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1. Misdiagnosis of imported falciparum malaria from African areas due to an increased prevalence of pfhrp2/pfhrp3 gene deletion: the Djibouti case

Author: Xavier Iriart, Sandie Menard, Pamela Chauvin, Hasna S. Mohamed, Elena Charpentier, Mohamed A. Mohamed, Antoine Berry, and Mohamed H. Aboubaker
Subjects: Plasmodium falciparum, histidine-rich protein 2, deletion, Djibouti, rapid diagnostic test, Infectious and parasitic diseases, RC109-216, Microbiology, QR1-502
Abstract: ABSTRACTFollowing the diagnosis of a falciparum malaria case imported from Djibouti and not detected by a pfHRP2-based rapid diagnostic test (RDT), we investigated the prevalence of the pfhrp2/pfhrp3-deleted parasites in Djibouti using 378 blood samples collected between January and May 2019, from Djiboutian patients with suspected malaria. Malaria diagnosis by quantitative PCR confirmed the presence of Plasmodium falciparum for 20.9% (79/378) samples while RDTs did not detect HRP2 antigen in 83.5% (66/79) of these samples. Quantitative PCRs targeting the pfhrp2/pfhrp3 genes confirmed the absence of both genes for 86.5% of P. falciparum strains. The very large number (86.5%) of falciparum parasites lacking the pfhrp2/pfhrp3 genes observed in this study, now justifies the use of non-HRP2 alternative RDTs in Djibouti. In this area and in most countries where HRP2-based RDTs constitute the main arsenal for falciparum malaria diagnosis, it is important to implement a systematic surveillance and to inform biologists and clinicians about the risk of malaria misdiagnosis. Further investigations are needed to better understand the mechanism of selection and diffusion of the pfhrp2/pfhrp3-deleted parasites.
Published: 2020
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2. The Rare, the Best: Spread of Antimalarial-Resistant Plasmodium falciparum Parasites by Anopheles Mosquito Vectors

Author: Antoine Berry, Sandie Menard, Sandrine E. Nsango, Luc Abate, Didier Concordet, Majoline Tchioffo Tsapi, Xavier Iriart, Parfait H. Awono-Ambéné, Benjamin Roche, and Isabelle Morlais
Subjects: malaria, Anopheles, transmission, Plasmodium falciparum, resistance, antimalarials, Microbiology, QR1-502
Abstract: ABSTRACT The emergence of resistance to antimalarials has prompted the steady switch to novel therapies for decades. Withdrawal of antimalarials, such as chloroquine in sub-Saharan Africa in the late 1990s, led to rapid declines in the prevalence of resistance markers after a few years, raising the possibility of reintroducing them for malaria treatment. Here, we provide evidence that the mosquito vector plays a crucial role in maintaining parasite genetic diversity. We followed the transmission dynamics of Plasmodium falciparum parasites through its vector in natural infections from gametocytes contained in the blood of asymptomatic volunteers until sporozoites subsequently developed in the mosquito salivary glands. We did not find any selection of the mutant or wild-type pfcrt 76 allele during development in the Anopheles mosquito vector. However, microsatellite genotyping indicated that minority genotypes were favored during transmission through the mosquito. The analysis of changes in the proportions of mutant and wild-type pfcrt 76 alleles showed that, regardless of the genotype, the less-represented allele in the gametocyte population was more abundant in mosquito salivary glands, indicating a selective advantage of the minority allele in the vector. Selection of minority genotypes in the vector would explain the persistence of drug-resistant alleles in the absence of drug pressure in areas with high malaria endemicity and high genetic diversity. Our results may have important epidemiological implications, as they predict the rapid re-emergence and spread of resistant genotypes if antimalarials that had previously selected resistant parasites are reintroduced for malaria prevention or treatment. IMPORTANCE Drug selection pressure in malaria patients is the cause of the emergence of resistant parasites. Resistance imposes a fitness cost for parasites in untreated infections, so withdrawal of the drug leads to the return of susceptible parasites. Little is known about the role of the malaria vector in this phenomenon. In an experimental study conducted in Cameroon, an area of high malaria transmission, we showed that the vector did not favor the parasites based on sensitivity or resistance criteria, but it did favor the selection of minority clones. This finding shows that the vector increases the diversity of plasmodial populations and could play an important role in falciparum malaria epidemiology by maintaining resistant clones despite the absence of therapeutic pressure.
Published: 2021
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3. Young Sprague Dawley rats infected by Plasmodium berghei: A relevant experimental model to study cerebral malaria.

Author: Sokhna Keita Alassane, Marie-Laure Nicolau-Travers, Sandie Menard, Olivier Andreoletti, Jean-Pierre Cambus, Noémie Gaudre, Myriam Wlodarczyk, Nicolas Blanchard, Antoine Berry, Sarah Abbes, David Colongo, Babacar Faye, Jean-Michel Augereau, Caroline Lacroux, Xavier Iriart, and Françoise Benoit-Vical
Subjects: Medicine, Science
Abstract: Cerebral malaria (CM) is the most severe manifestation of human malaria yet is still poorly understood. Mouse models have been developed to address the subject. However, their relevance to mimic human pathogenesis is largely debated. Here we study an alternative cerebral malaria model with an experimental Plasmodium berghei Keyberg 173 (K173) infection in Sprague Dawley rats. As in Human, not all infected subjects showed cerebral malaria, with 45% of the rats exhibiting Experimental Cerebral Malaria (ECM) symptoms while the majority (55%) of the remaining rats developed severe anemia and hyperparasitemia (NoECM). These results allow, within the same population, a comparison of the noxious effects of the infection between ECM and severe malaria without ECM. Among the ECM rats, 77.8% died between day 5 and day 12 post-infection, while the remaining rats were spontaneously cured of neurological signs within 24-48 hours. The clinical ECM signs observed were paresis quickly evolving to limb paralysis, global paralysis associated with respiratory distress, and coma. The red blood cell (RBC) count remained normal but a drastic decrease of platelet count and an increase of white blood cell numbers were noted. ECM rats also showed a decrease of glucose and total CO2 levels and an increase of creatinine levels compared to control rats or rats with no ECM. Assessment of the blood-brain barrier revealed loss of integrity, and interestingly histopathological analysis highlighted cyto-adherence and sequestration of infected RBCs in brain vessels from ECM rats only. Overall, this ECM rat model showed numerous clinical and histopathological features similar to Human CM and appears to be a promising model to achieve further understanding the CM pathophysiology in Humans and to evaluate the activity of specific antimalarial drugs in avoiding/limiting cerebral damages from malaria.
Published: 2017
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4. Effect of sulfadoxine-pyrimethamine chemoprophylaxis in pregnant women on selection of the newP. falciparum dhpsquintuple mutant carrying the I431V mutation

Author: Olivia Cohen, Emilie Guemas, Sandie Menard, Martial Tsague Kenfack, Carine Talom Ngassa, Xavier Iriart, Marlise Bidzogo Lebobo, Celestin Ondobo Ekae, Carole Eboumbou, Calvin Tiyou Kenmeni, and Antoine Berry
Subjects: Pharmacology, Microbiology (medical), Infectious Diseases, Pharmacology (medical)
Abstract: BackgroundA new mutation in the Plasmodium falciparum dihydropteroate synthetase gene (pfdhps), I431V, has been identified in several countries of Central and West Africa. This mutation is mostly found in association with four other SNPs on pfdhps (S436A, A437G, A581G and A613S), forming a quintuple mutant (vagKgs) and almost always associated with the Plasmodium falciparum dihydrofolate reductase gene (pfdhfr) CirnI (C50R, N51I, S108N) triple mutant. To date, nothing is known about the impact of this new pfdhps genotype on sulfadoxine-pyrimethamine (SP) resistance.ObjectivesWe sought to assess the prevalence of this pfdhps vagKgs quintuple mutant in two groups of pregnant women with malaria, one that took intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) and one that did not.MethodsThe pfdhfr and pfdhps genes from Plasmodium falciparum isolates collected in Yaoundé (Cameroon) from pregnant women with symptomatic malaria under IPTp-SP or not, were sequenced.ResultsOf 159 patients evaluated, 70 had already taken SP during pregnancy and 89 had never taken SP. Only the vagKgs allele was significantly overrepresented in the SP+ group (21.4% versus 3.4%; P ConclusionsWe found a strong overrepresentation of the CirnI/vagKgs haplotype in the IPTp-SP pregnant group, suggesting a high level of resistance of this mutant to SP. This could compromise not only the effectiveness of IPTp-SP but also the seasonal malaria chemoprevention of young children, now widely implemented.
Published: 2023
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5. Efficacy of dihydroartemisinin/piperaquine in patients with non-complicated Plasmodium falciparum malaria in Yaoundé, Cameroon

Author: Xavier Iriart, Benoit Witkowski, Melissa Mairet-Khedim, Lawrence Ayong, Laure Otam, Sandrine E. Nsango, Christelle Ngou, Antoine Berry, Peggy Gandia, Isabelle Morlais, Nimol Khim, Camille Roesch, Sandie Menard, Sreynet Srun, Thomas Lanot, Francis Abega, Malaria Molecular Epidemiology, Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Microbiologie structurale - Structural Microbiology (Microb. Struc. (UMR_3528 / U-Pasteur_5)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Université de Douala, Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur (RIIP), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Université de Ngaoundéré/University of Ngaoundéré [Cameroun] (UN), Innovations Thérapeutiques et Résistances (InTheRes), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, This work was sponsored in part by the Institut National de la Santée de la Recherche Médicale, the ParaFrap Consortium and core funding from the Institut de Recherche pour le Développement & Pasteur Institute of Cambodia. S.N. was supported by an Institut Pasteur International Network Calmette & Yersin mobility grant, We would like to thank all the technical teams from the Malaria Research Unit of the Centre Pasteur of Cameroon, the Malaria Molecular Epidemiology Unit of the Pasteur Institute of Cambodia and the Eukaryotic Intracellular Parasites: Immunity and Chemoresistance Unit of the Centre for Physiopathology of Toulouse Purpan., Malaria Molecular Epidemiology (MMEU), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Dispensaire Nkol Eton, Yaounde, Cameroon, Transmission-Interactions-Adaptations hôtes/vecteurs/pathogènes (MIVEGEC-TRIAD), Evolution des Systèmes Vectoriels (ESV), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université de Toulouse (UT)-Université de Toulouse (UT)
Subjects: Microbiology (medical), medicine.medical_treatment, Plasmodium falciparum, MESH: Malaria, 030231 tropical medicine, Dihydroartemisinin, Pharmacology, Antimalarials, 03 medical and health sciences, 0302 clinical medicine, Dihydroartemisinin/piperaquine, Piperaquine, MESH: Artemisinins, parasitic diseases, medicine, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Pharmacology (medical), In patient, Cameroon, Clinical efficacy, Malaria, Falciparum, Artemisinin, MESH: Plasmodium falciparum, 030304 developmental biology, 0303 health sciences, MESH: Humans, biology, business.industry, MESH: Malaria, Falciparum, MESH: Cameroon, medicine.disease, biology.organism_classification, MESH: Antimalarials, Artemisinins, Malaria, 3. Good health, Infectious Diseases, Quinolines, business, MESH: Quinolines, medicine.drug
Abstract: Background Dihydroartemisinin/piperaquine is increasingly used for the treatment of uncomplicated Plasmodium falciparum malaria in Africa. The efficacy of this combination in Cameroon is poorly documented, while resistance to dihydroartemisinin/piperaquine readily spreads in Southeast Asia. Objectives This study evaluated the clinical efficacy of dihydroartemisinin/piperaquine in Cameroon, as well as the molecular profile and phenotypic susceptibility of collected isolates to dihydroartemisinin and piperaquine. Patients and methods Dihydroartemisinin/piperaquine efficacy in 42 days was followed-up for 138 patients presenting non-complicated falciparum malaria. Piperaquine concentration was determined at day 7 for 124 patients. kelch13 gene polymorphisms (n = 150) and plasmepsin2 gene amplification (n = 148) were determined as molecular markers of resistance to dihydroartemisinin and piperaquine, respectively. Parasite susceptibility to dihydroartemisinin and piperaquine was determined using validated in vitro survival assays. Results The efficacy of dihydroartemisinin/piperaquine treatment was 100% after PCR correction. The reinfections were not associated with a variation of piperaquine concentration at day 7. Ninety-six percent (144/150) of the samples presented a WT allele of the kelch13 gene. Two percent (3/150) presented the non-synonymous mutation A578S, which is not associated with resistance to dihydroartemisinin. No duplication of the plasmepsin2 gene was observed (0/148). All the samples tested in vitro by survival assays (n = 87) were susceptible to dihydroartemisinin and piperaquine. Conclusions Dihydroartemisinin/piperaquine has demonstrated excellent therapeutic efficacy with no evidence of emerging artemisinin or piperaquine resistance in Yaoundé, Cameroon. This observation suggests that dihydroartemisinin/piperaquine could be a sustainable therapeutic solution for P. falciparum malaria if implemented in areas previously free of artemisinin- and piperaquine-resistant parasites, unlike Southeast Asia.
Published: 2021
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6. Misdiagnosis of imported falciparum malaria from African areas due to an increased prevalence of pfhrp2/pfhrp3 gene deletion: the Djibouti case

Author: Mohamed Houmed Aboubaker, Xavier Iriart, Eléna Charpentier, Pamela Chauvin, Antoine Berry, Hasna S. Mohamed, Mohamed Ali Mohamed, and Sandie Menard
Subjects: 0301 basic medicine, Letter, Epidemiology, 030106 microbiology, Immunology, Plasmodium falciparum, Protozoan Proteins, Antigens, Protozoan, rapid diagnostic test, Microbiology, Sensitivity and Specificity, 03 medical and health sciences, Virology, Drug Discovery, parasitic diseases, Prevalence, Medicine, Humans, deletion, Diagnostic Errors, Malaria, Falciparum, Rapid diagnostic test, biology, business.industry, Diagnostic Tests, Routine, General Medicine, Gene deletion, biology.organism_classification, medicine.disease, histidine-rich protein 2, 030104 developmental biology, Infectious Diseases, Population Surveillance, Djibouti, Parasitology, business, Malaria, Gene Deletion
Abstract: Following the diagnosis of a falciparum malaria case imported from Djibouti and not detected by a pfHRP2-based rapid diagnostic test (RDT), we investigated the prevalence of the pfhrp2/pfhrp3-deleted parasites in Djibouti using 378 blood samples collected between January and May 2019, from Djiboutian patients with suspected malaria. Malaria diagnosis by quantitative PCR confirmed the presence of Plasmodium falciparum for 20.9% (79/378) samples while RDTs did not detect HRP2 antigen in 83.5% (66/79) of these samples. Quantitative PCRs targeting the pfhrp2/pfhrp3 genes confirmed the absence of both genes for 86.5% of P. falciparum strains. The very large number (86.5%) of falciparum parasites lacking the pfhrp2/pfhrp3 genes observed in this study, now justifies the use of non-HRP2 alternative RDTs in Djibouti. In this area and in most countries where HRP2-based RDTs constitute the main arsenal for falciparum malaria diagnosis, it is important to implement a systematic surveillance and to inform biologists and clinicians about the risk of malaria misdiagnosis. Further investigations are needed to better understand the mechanism of selection and diffusion of the pfhrp2/pfhrp3-deleted parasites.
Published: 2020

7. The Rare, the Best: Spread of Antimalarial-Resistant Plasmodium falciparum Parasites by Anopheles Mosquito Vectors

Author: Xavier Iriart, Antoine Berry, Parfait Awono-Ambene, Benjamin Roche, Isabelle Morlais, Sandrine E. Nsango, Didier Concordet, Luc Abate, Sandie Menard, Majoline Tchioffo Tsapi, Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Douala, Transmission-Interactions-Adaptations hôtes/vecteurs/pathogènes (MIVEGEC-TRIAD), Evolution des Systèmes Vectoriels (ESV), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Innovations Thérapeutiques et Résistances (InTheRes), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale (OCEAC), Unité de modélisation mathématique et informatique des systèmes complexes [Bondy] (UMMISCO), Université de Yaoundé I-Institut de la francophonie pour l'informatique-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cadi Ayyad [Marrakech] (UCA)-Sorbonne Université (SU)-Institut de Recherche pour le Développement (IRD [France-Nord]), Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM), Institut de Recherche pour le Developpemente - Institut de Medecine et d'Epidemiologie Appliquee MEA-AO-07French National Research Agency (ANR) European Commission ANR-11-BSV7-009-01MEA-AO-07, Baures, Simone, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique et évolution des maladies infectieuses (GEMI), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Génétique et évolution des maladies infectieuses (GEMI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Microbiology (medical), Physiology, [SDV]Life Sciences [q-bio], Population, Plasmodium falciparum, malaria, mosquito, Microbiology, resistance, antimalarials, Chloroquine, Genotype, parasitic diseases, Anopheles, Genetics, medicine, Gametocyte, education, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, education.field_of_study, General Immunology and Microbiology, Ecology, biology, transmission, Cell Biology, genetic diversity, biology.organism_classification, medicine.disease, Virology, QR1-502, [SDV] Life Sciences [q-bio], Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Vector (epidemiology), Malaria, medicine.drug
Abstract: International audience; The emergence of resistance to antimalarials has prompted the steady switch to novel therapies for decades. Withdrawal of antimalarials, such as chloroquine in sub-Saharan Africa in the late 1990s, led to rapid declines in the prevalence of resistance markers after a few years, raising the possibility of reintroducing them for malaria treatment. Here, we provide evidence that the mosquito vector plays a crucial role in maintaining parasite genetic diversity. We followed the transmission dynamics of Plasmodium falciparum parasites through its vector in natural infections from gametocytes contained in the blood of asymptomatic volunteers until sporozoites subsequently developed in the mosquito salivary glands. We did not find any selection of the mutant or wild-type pfcrt 76 allele during development in the Anopheles mosquito vector. However, microsatellite genotyping indicated that minority genotypes were favored during transmission through the mosquito. The analysis of changes in the proportions of mutant and wild-type pfcrt 76 alleles showed that, regardless of the genotype, the less-represented allele in the gametocyte population was more abundant in mosquito salivary glands, indicating a selective advantage of the minority allele in the vector. Selection of minority genotypes in the vector would explain the persistence of drug-resistant alleles in the absence of drug pressure in areas with high malaria endemicity and high genetic diversity. Our results may have important epidemiological implications, as they predict the rapid re-emergence and spread of resistant genotypes if antimalarials that had previously selected resistant parasites are reintroduced for malaria prevention or treatment.IMPORTANCE Drug selection pressure in malaria patients is the cause of the emergence of resistant parasites. Resistance imposes a fitness cost for parasites in untreated infections, so withdrawal of the drug leads to the return of susceptible parasites. Little is known about the role of the malaria vector in this phenomenon. In an experimental study conducted in Cameroon, an area of high malaria transmission, we showed that the vector did not favor the parasites based on sensitivity or resistance criteria, but it did favor the selection of minority clones. This finding shows that the vector increases the diversity of plasmodial populations and could play an important role in falciparum malaria epidemiology by maintaining resistant clones despite the absence of therapeutic pressure..
Published: 2021
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8. New Insights into Blood Circulating Lymphocytes in Human Pneumocystis Pneumonia

Author: Claire Cottrel, Nicolas Blanchard, Xavier Iriart, Emilie Guemas, Pamela Chauvin, Sophie Cassaing, Alexis Valentin, Judith Fillaux, Antoine Berry, Catherine Marques, Eléna Charpentier, Sandie Menard, Benson-Rumiz, Alicia, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Microbiology (medical), QH301-705.5, Lymphocyte, Context (language use), Plant Science, lymphocyte, Pneumocystis pneumonia, Article, Pneumocystis jirovecii, pneumocystosis, Immunophenotyping, immunophenotyping, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, T helper, medicine, Pneumocystosis, Biology (General), Ecology, Evolution, Behavior and Systematics, B cell, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, business.industry, biology.organism_classification, medicine.disease, respiratory tract diseases, medicine.anatomical_structure, Immunology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, business, CD8, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, B lymphocytes
Abstract: The host lymphocyte response is decisive in Pneumocystis pneumonia (PCP) pathophysiology but little is known of the specific roles of lymphocyte subpopulations in this fungal infection. Peripheral NK, NKT, B, TCD4+ and TCD8+ subpopulations were compared by immunophenotyping between 20 patients diagnosed with PCP (PCP(+)] and 20 uninfected immunosuppressed patients (PCP(−)). Among PCP(+) subjects, the lymphocyte populations were also compared between surviving and deceased patients. Low B cell count (&lt, 40 cells/µL) was more frequent in PCP(+) than in PCP(−) patients (p = 0.03), while there was no difference for the TCD4 count. Among the PCP(+) group, the 7 deceased patients had lower Th1 (p = 0.02) and Tc1 (p = 0.03) populations, higher Th2 response (p = 0.03), higher effector TCD8 (p &lt, 0.01), lower central memory TCD8 (p = 0.04) and reduced NK cells (p = 0.02) compared with the 13 survivors. Th1/Th2 ratio &lt, 17, CD8 Tc1 &lt, 44%, effector TCD8 &lt, 25%, central memory TCD8 &lt, 4%, NK cells &lt, 50 cells/µL and total lymphocytes &lt, 0.75 G/L were associated with a higher risk of mortality (p = 0.003, p = 0.007, p = 0.0007, p = 0.004, p = 0.02 and p = 0.019, respectively). The traditional analysis of TCD4 and TCD8 populations may be insufficient in the context of PCP. It could be completed by using B cells to predict the risk of PCP, and by using lymphocyte subpopulations or total lymphocyte count, which are easy to obtain in all health care facilities, to evaluate PCP prognosis.
Published: 2021
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9. Immune Response in Pneumocystis Infections According to the Host Immune System Status

Author: Xavier Iriart, Eléna Charpentier, Catherine Marques, Sandie Menard, Antoine Berry, Benson-Rumiz, Alicia, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Microbiology (medical), QH301-705.5, Lymphocyte, medicine.medical_treatment, 030106 microbiology, Inflammation, Pneumocystis, Plant Science, Review, lymphocyte, Pneumocystis pneumonia, immune response, pneumocystosis, 03 medical and health sciences, TCD4, Immune system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, TCD8, medicine, Macrophage, Biology (General), Ecology, Evolution, Behavior and Systematics, Immunodeficiency, B cells, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, immunosuppression, business.industry, Immunosuppression, medicine.disease, 030104 developmental biology, medicine.anatomical_structure, inflammation, Immunology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine.symptom, Pneumocystis Infections, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; The host immune response is critical in Pneumocystis pneumonia (PCP). Immunocompetent hosts can eliminate the fungus without symptoms, while immunodeficient hosts develop PCP with an unsuitable excessive inflammatory response leading to lung damage. From studies based on rodent models or clinical studies, this review aimed to better understand the pathophysiology of Pneumocystis infection by analysing the role of immune cells, mostly lymphocytes, according to the immune status of the infected host. Hence, this review first describes the immune physiological response in infected immunocompetent hosts that are able to eliminate the fungus. The objective of the second part is to identify the immune elements required for the control of the fungus, focusing on specific immune deficiencies. Finally, the third part concentrates on the effect of the different immune elements in immunocompromised subjects during PCP, to better understand which cells are detrimental, and which, on the contrary, are beneficial once the disease has started. This work highlights that the immune response associated with a favourable outcome of the infection may differ according to the immune status of the host. In the case of immunocompetency, a close communication between B cells and TCD4 within tertiary lymphocyte structures appears critical to activate M2 macrophages without much inflammation. Conversely, in the case of immunodeficiency, a pro-inflammatory response including Th1 CD4, cytotoxic CD8, NK cells, and IFNγ release seems beneficial for M1 macrophage activation, despite the impact of inflammation on lung tissue.
Published: 2021
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10. Identification of compounds active against quiescent artemisinin-resistant Plasmodium falciparum parasites via the quiescent-stage survival assay (QSA)

Author: Sandie Menard, Manel Ouji, Michel Nguyen, Lucie Paloque, Thibaud Reyser, Françoise Benoit-Vical, Jean-Michel Augereau, Benoit Witkowski, Laboratoire de chimie de coordination (LCC), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT), Malaria Molecular Epidemiology (MMEU), Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institut National de la Santé et de la Recherche Médicale (INSERM), CNRS, ANR-13-BSV3-0018,MALARTRES,Résistance de Plasmodium aux antipaludiques de la famille des artémisinines(2013), ANR-14-CE35-0003,CAP-G4,Development of photo-reactive probes to capture G-quadruplex DNA in complex with endogenous proteins and exogenous synthetic ligands(2014), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Malaria Molecular Epidemiology, Gulli, Marie-Hélène, Blanc 2013 - Résistance de Plasmodium aux antipaludiques de la famille des artémisinines - - MALARTRES2013 - ANR-13-BSV3-0018 - Blanc 2013 - VALID, Appel à projets générique - Development of photo-reactive probes to capture G-quadruplex DNA in complex with endogenous proteins and exogenous synthetic ligands - - CAP-G42014 - ANR-14-CE35-0003 - Appel à projets générique - VALID, Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), and Université Fédérale Toulouse Midi-Pyrénées
Subjects: Microbiology (medical), [CHIM.THER] Chemical Sciences/Medicinal Chemistry, Plasmodium falciparum, Drug Resistance, Protozoan Proteins, Context (language use), Drug resistance, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Pharmacology, 03 medical and health sciences, Antimalarials, Chloroquine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, parasitic diseases, medicine, Animals, Pharmacology (medical), Parasites, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Artemisinin, Malaria, Falciparum, 030304 developmental biology, 0303 health sciences, biology, 030306 microbiology, Drug discovery, biology.organism_classification, Artemisinins, 3. Good health, Infectious Diseases, Drug development, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Cambodia, Artemisinine, Atovaquone, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, medicine.drug
Abstract: Background Quiescence is an unconventional mechanism of Plasmodium survival, mediating artemisinin resistance. This phenomenon increases the risk of clinical failures following artemisinin-based combination therapies (ACTs) by slowing parasite clearance and allowing the selection of parasites resistant to partner drugs. Objectives To thwart this multiresistance, the quiescent state of artemisinin-resistant parasites must be taken into consideration from the very early stages of the drug discovery process. Methods We designed a novel phenotypic assay we have named the quiescent-stage survival assay (QSA) to assess the antiplasmodial activity of drugs on quiescent parasites. This assay was first validated on quiescent forms from different artemisinin-resistant parasite lines (laboratory strain and field isolates), using two reference drugs with different mechanisms of action: chloroquine and atovaquone. Furthermore, the efficacies of different partner drugs of artemisinins used in ACTs were investigated against both laboratory strains and field isolates from Cambodia. Results Our results highlight that because of the mechanism of quiescence and the respective pharmacological targets of drugs, drug efficacies on artemisinin-resistant parasites may be different between quiescent parasites and their proliferating forms. Conclusions These data confirm the high relevance of adding the chemosensitivity evaluation of quiescent parasites by the specific in vitro QSA to the antiplasmodial drug development process in the current worrisome context of artemisinin resistance.
Published: 2020
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11. Performance evaluation of different strategies based on microscopy techniques, rapid diagnostic test and molecular loop-mediated isothermal amplification assay for the diagnosis of imported malaria

Author: Catherine Armengol, Sandie Menard, Antoine Berry, Xavier Iriart, Judith Fillaux, A.-S. Salabert, Arnaud Pagès, H. Guegan, Emilie Guemas, Pamela Chauvin, Eléna Charpentier, E. Benichou, Alexis Valentin, Sophie Cassaing, CHU Toulouse [Toulouse], Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Toulouse Neuro Imaging Center (ToNIC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Service de Parasitologie et Mycologie, CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse], Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, CCSD, Accord Elsevier, and Institut Fédératif de Biologie (IFB) - Hôpital Purpan
Subjects: 0301 basic medicine, Plasmodium, Alethia, [SDV]Life Sciences [q-bio], Buffy coat, Rapid diagnostic test, MESH: Africa, MESH: Malaria / diagnosis, Gastroenterology, MESH: Communicable Diseases, Imported / diagnosis, MESH: Nucleic Acid Amplification Techniques / standards, 0302 clinical medicine, Communicable Diseases, Imported, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Diagnosis, MESH: Communicable Diseases, Imported / parasitology, Prospective Studies, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Imported malaria, MESH: Molecular Diagnostic Techniques / methods, Microscopy, Temperature, General Medicine, MESH: Temperature, 3. Good health, [SDV] Life Sciences [q-bio], Infectious Diseases, Real-time polymerase chain reaction, Molecular Diagnostic Techniques, MESH: Microscopy / methods, France, Nucleic Acid Amplification Techniques, Microbiology (medical), medicine.medical_specialty, 030106 microbiology, Loop-mediated isothermal amplification, Real-Time Polymerase Chain Reaction, Sensitivity and Specificity, QBC, 03 medical and health sciences, Thin smear, LAMP, Internal medicine, parasitic diseases, medicine, Humans, MESH: Molecular Diagnostic Techniques / standards, MESH: Malaria / parasitology, RDT, MESH: Microscopy / standards, Plasmodium species identification, MESH: Humans, business.industry, MESH: Plasmodium, Thick smear, medicine.disease, MESH: Nucleic Acid Amplification Techniques / methods, MESH: Prospective Studies, MESH: Sensitivity and Specificity, Malaria, MESH: France, MESH: Real-Time Polymerase Chain Reaction / standards, Blood smear, Africa, business
Abstract: Objectives Malaria is one of most common tropical diseases encountered in travellers and migrants. It requires an urgent and reliable diagnosis considering its potential severity. In this study, performance of five diagnostic assays were evaluated in a nonendemic region and compared prospectively to quantitative PCR (qPCR). Methods A prospective study was conducted at Toulouse Hospital from August 2017 to January 2018 and included all patients with initial Plasmodium screening. Thin and thick blood smears (TnS, TkS), quantitative buffy coat (QBC), rapid diagnostic tests (RDTs) and commercial loop-mediated isothermal amplification (LAMP) were independently performed on each blood sample and compared to our qPCR reference standard. Results The study encompassed 331 patients, mainly returning from Africa. qPCR detected 73 Plasmodium-positive samples (including 58 falciparum). Individually, LAMP had a 97.3% (71/73) sensitivity, far ahead of TnS (84.9%, 62/73), TkS (86.3%, 63/73), QBC (86.3%, 63/73) and RDT (86.3%, 63/73). RDT demonstrated a high sensitivity for falciparum (98.3%, 57/58) but missed all ovale, malariae and knowlesi infections. Specificity was excellent for all techniques (99.6–100%). The most sensitive diagnosis strategies were TnS + RDT (95.9%, 70/73), TnS + LAMP (97.3%, 71/73) and TnS + RDT + LAMP (100%, 73/73), about 10% higher than strategies using exclusively microscopy, TkS + TnS (87.7%, 64/73) or QBC + TnS (87.7%, 64/73). TnS remains necessary for Plasmodium species identification and quantification. Adding sequentially TnS only on LAMP-positive samples did not decrease TnS + LAMP strategy sensitivity. Conclusions In nonendemic countries, the currently recommended microscopy-based strategies seem unsatisfactory for malaria diagnosis considering RDT and LAMP performance, two rapid and sensitive assays that require limited training.
Published: 2020
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12. Multiple phenotypic and genotypic artemisinin sensitivity evaluation of Malian Plasmodium falciparum isolates

Author: Sandie Menard, Antoine Berry, Françoise Benoit-Vical, Pety Tor, Arba Pramundita Ramadani, Antoine Dara, Jean-Michel Augereau, Karamoko Niaré, Ogobara K. Doumbo, Lucie Paloque, Malaria Research and Training Center [Bamako, Mali], Université de Bamako, Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Division of Malaria Research, Institute for Global Health, University of Maryland School of Medicine, University of Maryland School of Medicine, University of Maryland System-University of Maryland System, Service de Parasitologie et Mycologie, CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Service de Parasitologie-Mycologie [Toulouse], and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse]
Subjects: 0301 basic medicine, Genotype, medicine.medical_treatment, Plasmodium falciparum, 030106 microbiology, 030231 tropical medicine, Drug Resistance, Dihydroartemisinin, Drug resistance, Microbiology, Antimalarials, 03 medical and health sciences, 0302 clinical medicine, Gentamicin protection assay, Virology, parasitic diseases, medicine, Humans, Parasite hosting, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Artemisinin, ComputingMilieux_MISCELLANEOUS, biology, Articles, biology.organism_classification, Artemisinins, 3. Good health, Phenotype, Infectious Diseases, Parasitology, Ex vivo, medicine.drug
Abstract: International audience; We assessed the ex vivo/in vitro sensitivity of 54 Malian Plasmodium falciparum isolates to artemisinin for the monitoring of drug resistance in this area. The artemisinin sensitivity of parasites was evaluated using 1) the ex vivo and in vitro parasite recrudescence detection after treatment of the ring stage with 1–200 nM artemisinin for 48 hours and 2) the in vitro parasite recrudescence kinetics assay over 7 days after 6-hour treatment of the ring stage with 700 nM dihydroartemisinin (DHA). In addition, as recommended by the World Health Organization for artemisinin resistance characterization, the ring-stage survival assay (RSA0–3 h) was performed and the parasite isolates were sequenced at the kelch 13 propeller locus. No clinical and molecular evidence of artemisinin resistance was observed. However, these isolates present different phenotypic profiles in response to artemisinin treatments. Despite all RSA0–3 h values less than 1.5%, six out of 46 (13.0%) isolates tested ex vivo and four out of six (66.7%) isolates tested in vitro were able to multiply after 48-hour treatments with 100 nM artemisinin. Moreover, five out of eight isolates tested showed faster parasite recovery after DHA treatment in kinetic assays. The presence of such phenotypes needs to be taken into account in the assessment of the efficacy of artemisinins in Mali. The assays presented here appear as valuable tools for the monitoring of artemisinin sensitivity in the field and thus could help to evaluate the risk of emergence of artemisinin resistance in Africa.
Published: 2018
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13. Prevalence ofPlasmodium falciparumparasites resistant to sulfadoxine/pyrimethamine in pregnant women in Yaoundé, Cameroon: emergence of highly resistantpfdhfr/pfdhpsalleles

Author: Antoine Berry, Sandrine E. Nsango, Sandie Menard, Pamela Chauvin, Luc Abate, Majoline T. Tchioffo, Xavier Iriart, Isabelle Morlais, Parfait Awono-Ambene, Service de Parasitologie et Mycologie, CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Douala, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Transmission-Interactions-Adaptations hôtes/vecteurs/pathogènes (MIVEGEC-TRIAD), Evolution des Systèmes Vectoriels (ESV), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Laboratoire d’Entomologie Médicale, and Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale
Subjects: Adult, Microbiology (medical), Sulfadoxine, medicine.medical_treatment, Plasmodium falciparum, Drug Resistance, Gene mutation, Biology, Antimalarials, Young Adult, Gene Frequency, Pregnancy, parasitic diseases, Prevalence, medicine, Humans, Pharmacology (medical), Cameroon, Malaria, Falciparum, Pregnancy Complications, Infectious, Allele, ComputingMilieux_MISCELLANEOUS, Pharmacology, Dihydropteroate Synthase, Polymorphism, Genetic, Sequence Analysis, DNA, medicine.disease, biology.organism_classification, Virology, Sulfadoxine/pyrimethamine, 3. Good health, Drug Combinations, Tetrahydrofolate Dehydrogenase, Pyrimethamine, Infectious Diseases, Mutation, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, Dihydropteroate synthase, Malaria, medicine.drug
Abstract: OBJECTIVES To determine, 6 years after the adoption of intermittent preventive treatment of pregnant women with sulfadoxine/pyrimethamine (IPTp-SP) in Cameroon, (i) the polymorphism and prevalence of Plasmodium falciparum dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) gene mutations associated with sulfadoxine/pyrimethamine resistance and (ii) the consequences of sulfadoxine/pyrimethamine use in the selection of pfdhfr/pfdhps alleles. METHODS pfdhfr and pfdhps genes from P. falciparum isolates collected in Yaounde (Cameroon) from pregnant women with symptomatic malaria before taking IPTp-SP [SP- group (control) (n = 51)] or afterwards [SP+ group (n = 49)] were sequenced. RESULTS The pfdhfr N51I, C59R, S108N triple mutant had a prevalence close to 100% (96/100) and no mutations at codons 50 and 164 were detected in either of the groups. The most frequent pfdhps mutation was A437G with a prevalence of 76.5% (39/51) in the SP- group, which was significantly higher in pregnant women who took sulfadoxine/pyrimethamine [95.9% (47/49)] (P = 0.012). Our study confirmed the presence of the pfdhps K540E mutation in Cameroon, but it remained rare. The prevalence of pfdhps A581G and A613S mutations had increased [5.9% (3/51) and 11.8% (6/51) in the control group, respectively] since the last studies in 2005. Surprisingly, the new pfdhps I431V mutation was detected, at a prevalence of 9.8% (5/51), and was found to be associated with other pfdhfr/pfdhps alleles to form an octuple N51I, C59R, S108N/I431V, S436A, A437G, A581G, A613S mutant. CONCLUSIONS Significant changes were found in pfdhps polymorphism. In particular, we observed several parasites carrying eight mutations in pfdhfr/pfdhps genes, which are very susceptible to having a high level of resistance to sulfadoxine/pyrimethamine.
Published: 2015
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14. Risk Factors of Pneumocystis Pneumonia in Solid Organ Recipients in the Era of the Common Use of Posttransplantation Prophylaxis

Author: Laurence Lavayssière, O. Roques, Jean-François Magnaval, Sandie Menard, Lionel Rostaing, A. Del Bello, Sophie Cassaing, Olivier Cointault, Antoine Berry, Judith Fillaux, Rose-Anne Lavergne, Isabelle Cardeau-Desangles, Pamela Chauvin, Nassim Kamar, Xavier Iriart, L. Esposito, T. Challan Belval, CHU Toulouse [Toulouse], Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Graft Rejection, Male, Antifungal Agents, [SDV]Life Sciences [q-bio], Cytomegalovirus, Pneumocystis carinii, Pneumocystis pneumonia, Clinical research, Postoperative Complications, Risk Factors, Immunology and Allergy, Pharmacology (medical), Univariate analysis, risk stratification, Pneumonia, Pneumocystis, Graft Survival, risk assessment, Middle Aged, complication: infectious, practice, Tissue Donors, 3. Good health, fungal, Cytomegalovirus Infections, Female, Risk assessment, infection and infectious agents, medicine.medical_specialty, infectious disease, lung, disease: infectious, Immunocompromised Host, Internal medicine, Trimethoprim, Sulfamethoxazole Drug Combination, medicine, Humans, Retrospective Studies, Transplantation, business.industry, Organ Transplantation, Odds ratio, Antibiotic Prophylaxis, medicine.disease, Transplant Recipients, Tacrolimus, Confidence interval, Surgery, Case-Control Studies, business, Follow-Up Studies
Abstract: International audience; Pneumocystis pneumonia (PCP) in solid organ transplant (SOT) recipients becomes rare in the immediate posttransplantation period thanks to generalized prophylaxis. We aimed to identify the predictive factors for PCP in the era of universal prophylaxis and to propose a strategy for preventing PCP beyond the first year after transplantation. In a retrospective case-control study, 33 SOT cases with PCP diagnosed between 2004 and 2010 were matched with two controls each to identify risk factors for PCP by uni- and multivariate analysis. All the patients benefited from 6 months of posttransplantation trimethoprim-sulfamethoxazole prophylaxis. Most PCP in SOT patients occurred during the second year posttransplantation (33%). By univariate analysis, age, nonuse of tacrolimus, total and CD4 lymphocyte counts, gamma-globulin concentration and cytomegalovirus (CMV) infection appeared to be PCP risk factors. In the final multivariate analysis, age (adjusted odds ratio [OR] 3.7, 95% confidence interval [CI]: 1.3-10.4), CMV infection (OR: 5.2, 95% CI: 1.8-14.7) and total lymphocyte count (OR: 3.9, 95% CI: 1.4-10.7) were found to be independently associated with PCP. The second year posttransplantation appeared to be the new period of highest risk of PCP. Age, CMV viremia and lymphocytes were the most pertinent predictive criteria to evaluate the risk of PCP in clinical practice.
Published: 2015
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15. Insight into k13-propeller gene polymorphism and ex vivo DHA-response profiles from Cameroonian isolates

Author: Francis A. Abega Mekongo, Isabelle Morlais, Antoine Berry, Xavier Iriart, Christelle Ngou Maffo, Joëlle Njila Tchoufack, Majoline Tchioffo Tsapi, Luc Abate, Parfait Awono-Ambene, Sandrine E. Nsango, Sandie Menard, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d’Entomologie Médicale, Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale, Faculté de Médecine et des Sciences Pharmaceutiques, Université de Douala, Service de Parasitologie et Mycologie, CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Transmission-Interactions-Adaptations hôtes/vecteurs/pathogènes (MIVEGEC-TRIAD), Evolution des Systèmes Vectoriels (ESV), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Dispensaire de Nkol-Eton, This study was supported in part by the French Agence Nationale de la Recherche (Grant ANR–13–BSV3–0018–0), by Institut National de la Santé et de la Recherche Médicale, by ParaFrap Consortium, and by core funding from the Institut de Recherche pour le Développement. JNT was supported by a scholarship from the Agence Universitaire de la Francophonie (AUF)., ANR-13-BSV3-0018,MALARTRES,Résistance de Plasmodium aux antipaludiques de la famille des artémisinines(2013), BMC, BMC, Blanc 2013 - Résistance de Plasmodium aux antipaludiques de la famille des artémisinines - - MALARTRES2013 - ANR-13-BSV3-0018 - Blanc 2013 - VALID, Service de Parasitologie et Mycologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Génétique et évolution des maladies infectieuses (GEMI), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Génétique et évolution des maladies infectieuses (GEMI), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Volunteers, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Resistance, Drug Resistance, Protozoan Proteins, Parasite load, 0302 clinical medicine, Parasitic Sensitivity Tests, Genotype, Prospective Studies, Cameroon, 030212 general & internal medicine, Malaria, Falciparum, Artemisinin, Child, K13, Middle Aged, Artemisinins, 3. Good health, [SDV] Life Sciences [q-bio], Treatment Outcome, Dihydroartemisinin, Infectious Diseases, Quinolines, Clearance, Female, medicine.drug, Adult, Ring-stage survival assay, Adolescent, Plasmodium falciparum, 030231 tropical medicine, Biology, Antimalarials, Young Adult, 03 medical and health sciences, parasitic diseases, medicine, Humans, Point Mutation, Survival rate, Polymorphism, Genetic, Research, biology.organism_classification, medicine.disease, Virology, Immunology, Parasitology, Ex vivo, Malaria
Abstract: International audience; Background.The spread of Plasmodium falciparum resistance to artemisinin derivatives in Southeast Asia is a major source of concern and the emergence of resistance in Africa would have dramatic consequences, by increasing malaria mortality and morbidity. It is therefore urgent to implement regular monitoring in sentinel sites in sub-Saharan Africa using robust and easy-to-implement tools. The prevalence of k13-propeller mutations and the phenotypic profiles are poorly known in sub-Saharan Africa. Here, the k13-propeller polymorphism was compared to both ex vivo susceptibility to DHA and early parasitological and clinical responses to artemisinin combination therapy (ACT).Methods. Plasmodium falciparum isolates were collected in 2015 in Yaoundé (Cameroon) from patients treated with dihydroartemisinin-piperaquine combination. Samples were analysed for their susceptibility to artemisinin using the k13-propeller sequencing, the ex vivo ring-stage survival assay, the in vivo parasite positive rate and the clinical statute at day 2.Results. None of the collected isolates revealed the presence of resistance mutations in the k13-propeller sequence. The median ring-stage survival rate for all the 64 interpretable isolates after a 6-hour pulse of 700 nM dihydroartemisinin was low, 0.49% (IQR: 0–1.3). Total parasite clearance was observed for 87.5% of patients and the remaining parasitaemic isolates (12.5%) showed a high reduction of parasite load, ranging from 97.5 to 99.9%. Clinical symptoms disappeared in 92.8% of cases.Conclusion. This study demonstrated the absence of k13-resistant genotypes in P. falciparum isolates from Cameroon. Only synonymous mutations were found with a low prevalence (4.3%). A good association between k13 genotypes and the ex vivo ring-stage survival assay or parasitological and clinical data was obtained. These results give a baseline for the long-term monitoring of artemisinin derivative efficacy in Africa.
Published: 2016
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16. A Worldwide Map of Plasmodium falciparum K13-Propeller Polymorphisms

Author: Benoit Witkowski, Hans-Peter Fuehrer, Garib Das Thakur, Céline Barnadas, Djibrine Djalle, Michael Ramharter, Mindy Leelawong, Wasif Ali-Khan, Harald Noedl, Bouasy Hongvanthong, Mohammad Shafiul-Alam, Hypolite Muhindo-Mavoko, Abdillahi Mohamed Hassan, Judith Straimer, Nimol Khim, Kigbafori D. Silué, Kaknika Loch, Barbara H. Stokes, Maria Dorina Bustos, Laura Berne, Dylan R. Pillai, Ayola A. Adegnika, Lin Hua Tang, Rotha Eam, Saorin Kim, Alioune Dieye, Mei Li, Carole E. Eboumbou-Moukoko, Lydie Canier, Marian Warsame, Didier Menard, David A. Fidock, Yap Boum, Lyndes Wini, Abdiqani Sheikh-Omar, Patrick Tshibangu-Wa-Tshibangu, Maman Laminou Ibrahim, Mohammad Jahirul-Karim, Malen Ken, Monique A. Dorkenoo, Sócrates Herrera, Odile Mercereau-Puijalon, Lise Musset, Valentine Duru, Eric Legrand, Maniphone Khanthavong, Pascal Ringwald, Bruno Pradines, Sandrine Houzé, Rachida Tahar, Olukemi K. Amodu, Johann Beghain, Sandie Menard, Liwang Cui, Colin J. Sutherland, Jun Hu Chen, Kesara Na-Bangchang, Khin Lin, Michael Nambozi, Rithea Leang, Jean Christophe Barale, Milijaona Randrianarivelojosia, Marcus V. G. Lacerda, Sophy Chy, Frédéric Ariey, Jean-Bosco Ouédraogo, Isabelle Morlais, Maria de Fátima Ferreira-da-Cruz, Lubin Jiang, Christophe Rogier, Jun Cao, Peter G. Kremsner, Bui Quang-Phuc, Inès Vigan-Womas, Din Syafruddin, Jetsumon Sattabongkot, Shigeyuki Kano, Abebe A. Fola, Louis Collet, Karamoko Niaré, Thierry Fandeur, Sedigheh Zakeri, Sodiomon B. Sirima, Antoine Berry, Jean Baptiste Mazarati, Fe Espino, Ghulam Rahim-Awab, Chanra Khean, Offianan Andre Toure, Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Génétique et Génomique des Insectes vecteurs, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Centre de Recherche Médicale de Lambaréné, Albert Schweitzer, Leiden University Medical Center (LUMC), Universiteit Leiden, International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), University of Ibadan, Nangarhar University, Mahidol University [Bangkok], The Walter and Eliza Hall Institute of Medical Research (WEHI), University of Melbourne, Papua New Guinea Institute for Medical Research (PNGIMR), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Mbarara University of Science and Technology [Mbarara] (MUST), Epicentre Ouganda [Mbarara] [Médecins Sans Frontières], Epicentre [Paris] [Médecins Sans Frontières], World Health Organization (WHO), country office for Thailand, Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), JiangSu University, National Institute of Parasitic Diseases, Center for Disease Control, China, Centre Hospitalier de Mayotte, Pennsylvania State University (Penn State), Penn State System, Epidemiology and Disease Control division (EDCD), Ministry of Public Health [Nepal], Institut Pasteur de Dakar, Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD), Institut Pasteur de Bangui, Université de Lomé [Togo], Université de Douala, Centre Pasteur du Cameroun, Research Institute for Tropical Medicine, Centre International de Recherches Médicales de Franceville (CIRMF), Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), University of Gondar, Institute of Parasitology [Vienna], University of Veterinary Medicine, Vienna, World Health Organisation (WHO), country office for Somalia, Caucaseco scientific research center = Centro de Investigación Científica Caucaseco, National Center for Malariology, Parasitology and Entomology, Ministry of Health [Mozambique], Hôpital Bichat - Claude Bernard, Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 216), Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), Centre de Recherche Médicale et Sanitaire (Niamey, Niger) (CERMES), Directorate General of Health Services (DGHS), Institut Pasteur de Shanghai, Académie des Sciences de Chine - Chinese Academy of Sciences (IPS-CAS), National Center for Global Health and Medicine [Japan] (NCGM), Institut Pasteur du Laos, Instituto Leônidas e Maria Deane - Fiocruz Amazônia [Manaus, Brésil] (ILMD), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Fundação de Medicina Tropical Doutor Heitor Vieira Dourado (FMT-HVD), National Center for Malaria Control, Parasitology and Entomology, Ministry of Health of Cambodgia, Henry M. Jackson Foundation for the Advancement of Military Medicine (HJM), U.S. Naval Medical Research, The Department of Medical Research (Upper Myanmar), Rwanda Biomedical Center (RBC), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement [Yaoundé, Cameroun] (IRD [Cameroun]), Institut de Recherche pour le Développement (IRD), University of Kinshasa (UNIKIN), University of Antwerp (UA), Institut Pasteur de la Guyane, Thammasat University (TU), Tropical Diseases Research Center (TDRC), Université de Bamako, Medizinische Universität Wien = Medical University of Vienna, Institut de Recherche en Sciences de la Santé (IRSS) / Centre Muraz, Medicines for Malaria Venture (MMV), Université de Genève = University of Geneva (UNIGE), Global Malaria Programme, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence du Paludisme, Institut Pasteur de Madagascar, Ministry of Health and Human Services [Somalia], Centre Suisse de Recherches Scientifiques en Cote d'Ivoire [Abidjan] (CSRS-CI), Université Félix Houphouët-Boigny (UFHB), Groupe de recherche action en santé (GRAS), London School of Hygiene and Tropical Medicine (LSHTM), University of Hasanuddin, Eijkman Institute for Molecular Biology [Jakarta], Institut Pasteur de Côte d'Ivoire, Ministry of Health and Medical Services, Institut Pasteur d'Iran, Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR - laboratoire associé), Microbiologie structurale - Structural Microbiology (Microb. Struc. (UMR_3528 / U-Pasteur_5)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Columbia University Irving Medical Center (CUIMC), Institut de Recherche Biomédicale des Armées [Antenne Marseille] (IRBA), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Supported by the Institut Pasteur Paris, Institut Pasteur International Division, Institut Pasteur Cambodia, and the World Health Organization, by a grant (ANR-10-LABX-62-IBEID) from the French Government Investissement d’Avenir program, Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases', a grant from Natixis Banques, a grant (R01I109023, to Dr. Fidock) from the National Institutes of Health, grants from the Fiocruz Fundação Oswaldo Cruz, Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro, Fundação de Amparo à Pesquisa do Estado do Amazonas, the Brazilian National Council for Scientific and Technological Development, the Agence Nationale de la Recherche (13-BSV3-0018-01 and11-BSV7-009-01), the Austrian Federal Ministry of Science, Research, and Econo-my, the Calgary Laboratory Services, the Centre International de Recherches Médicales de Franceville, the European and Developing Countries Clinical Trials Partnership (CT-2004-31070-001), the Drugs for Neglected Diseases Initiative, the Else Kroener Fresenius Stiftung, the Holger Poehlmann Stiftung, the European Community African–European Research Initiative 'IDEA' (HEALTH-F3-2009-241642), the Fonds Wetenschappelijk Onderzoek, the Vlaamse Interuniversitaire Raad–Universitaire Ontwikkelingssamenwerking, the Belgian Technical Cooperation in Democratic Republic of Congo, the European Community Seventh Framework Program (FP7/2007-2013, 242095, and 223601), the European Commission (REGPOT-CT-2011-285837-STRONGER), the Ministère de la Santé Publique du Niger (Laboratoire National de Référence Résistance aux Antipaludiques), the Foundation of National Science and Technology Major Program (2012ZX10004-220), the French Ministry of Health (Institut National de Veille Sanitaire), the Global Fund to Fight AIDS, Tuberculosis and Malaria, the 5% Initiative program (French Ministry of Foreign Affairs, France Expertise Internationale, 12INI109), the Institut Pasteur de Madagascar, the Government of the Philippines, the Institut de Recherche pour le Développement, the Foundation des Treilles, the Délégation Générale pour l’Armement (PDH-2-NRBC-4-B1-402), the Institut Pasteur de Bangui, the International Society for Health Research and Training, the Malaria Research Initiative Bandarban, Vienna, International Centre for Diarrhoeal Disease Research, Bangladesh, the Médecins sans Frontières (Centre Opérationnel Paris, France), Medicines for Malaria Venture, the National Research Council of Thailand, the Thammasat University, the National Natural Science Foundation of China (81271870, 81361120405, and 81271863), the Natural Science Foundation of Jiangsu Province (BK20130114 and BK20150001), the Jiangsu Science and Technology Department (BM2015024), the National Institutes of Health (R01 AI11646601, AI109023, and ICEMR U19AI089702, U19AI089672), the Pasteur Institute of Iran, the Malaria Division of the Iranian Center for Diseases Management and Control, Public Health England (Malaria Reference Service Contract), the Government of Rwanda, the U.S. Department of Defense Armed Forces Health Surveillance Center, Global Emerging Infections Surveillance and Response System (P0463-14-N6), the Fogarty International Center of the National Institutes of Health training (D43 TW007393), the Mahidol-Oxford Research Unit, the Government of Japan (Science and Technology Agency, Agency for Medical Research and Development, Japan International Cooperation Agency, and Science and Technology Research Partnership for Sustainable Development), and the President’s Malaria Initiative of the U.S. Agency for International Development., The KARMA Consortium, ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-13-BSV3-0018,MALARTRES,Résistance de Plasmodium aux antipaludiques de la famille des artémisinines(2013), ANR-13-BSV7-0009,NEBEDIV,Le rôle des ennemis naturels dans la diversité béta des arbres tropicaux(2013), European Project: CT-2004-31070-001,EDCCTP, European Project: HEALTH-F3-2009-24164,IDEA, European Project: FP7/2007-2013, 24209,FP7, European Project: FP7/2007-2013, 22360,FP7, European Project: 285837,EC:FP7:REGPOT,FP7-REGPOT-2011-1,STRONGER(2011), European Project: 242095,EC:FP7:HEALTH,FP7-HEALTH-2009-single-stage,EVIMALAR(2009), European Project: 223601,EC:FP7:HEALTH,FP7-HEALTH-2007-B,MALVECBLOK(2009), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), CHU Toulouse [Toulouse], Fundação Oswaldo Cruz (FIOCRUZ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Genève (UNIGE), INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR), Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Eberhard Karls Universität Tübingen, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia., Centre International de Recherches Médicales de Franceville, Caucaseco scientific research center, Mère et enfant face aux infections tropicales (MERIT - UMR_D 216), National Center for Global Health and Medicine (NCGM), Instituto Leônidas e Maria Deane (ILMD), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement [Yaoundé], Centre Suisse de Recherches Scientifiques en Côte d'Ivoire, Eijkman Institute for Molecular Biology, Laboratoire de Parasitologie, Centre National de Référence du Paludisme - Région Antilles-Guyane, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-WHO Collaborating Center for Surveillance of Antimalarial Drug Resistance, Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), ANR-10-LABX-62-IBEID,IBEID,Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases'(2010), Van geertruyden, Jean-Pierre, and KARMA Consortium
Subjects: 0301 basic medicine, Nonsynonymous substitution, MESH: Sequence Analysis, DNA, Endemic Diseases, MESH: Asia, Southeastern, Drug Resistance, Protozoan Proteins, Drug resistance, MESH: Genotype, Lactones, 0302 clinical medicine, Genotype, Artemisinin, Malaria, Falciparum, MESH: Protozoan Proteins, Asia, Southeastern, MESH: Plasmodium falciparum, Genetics, biology, MESH: Malaria, Falciparum, General Medicine, Artemisinins, MESH: China, 3. Good health, MESH: Endemic Diseases, MESH: Drug Resistance, Algorithms, MESH: Lactones, medicine.drug, China, MESH: Mutation, 030231 tropical medicine, 030106 microbiology, Plasmodium falciparum, MESH: Algorithms, 03 medical and health sciences, parasitic diseases, MESH: Artemisinins, MESH: Polymorphism, Genetic, medicine, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Allele, Polymorphism, Genetic, MESH: Humans, Haplotype, Sequence Analysis, DNA, medicine.disease, biology.organism_classification, Virology, Mutation, Human medicine, Malaria
Abstract: Comment inK13-Propeller Mutations and Malaria Resistance, http://www.nejm.org/doi/full/10.1056/NEJMe1604520; International audience; BACKGROUND:Recent gains in reducing the global burden of malaria are threatened by the emergence of Plasmodium falciparum resistance to artemisinins. The discovery that mutations in portions of a P. falciparum gene encoding kelch (K13)-propeller domains are the major determinant of resistance has provided opportunities for monitoring such resistance on a global scale.METHODS:We analyzed the K13-propeller sequence polymorphism in 14,037 samples collected in 59 countries in which malaria is endemic. Most of the samples (84.5%) were obtained from patients who were treated at sentinel sites used for nationwide surveillance of antimalarial resistance. We evaluated the emergence and dissemination of mutations by haplotyping neighboring loci.RESULTS:We identified 108 nonsynonymous K13 mutations, which showed marked geographic disparity in their frequency and distribution. In Asia, 36.5% of the K13 mutations were distributed within two areas--one in Cambodia, Vietnam, and Laos and the other in western Thailand, Myanmar, and China--with no overlap. In Africa, we observed a broad array of rare nonsynonymous mutations that were not associated with delayed parasite clearance. The gene-edited Dd2 transgenic line with the A578S mutation, which expresses the most frequently observed African allele, was found to be susceptible to artemisinin in vitro on a ring-stage survival assay.CONCLUSIONS:No evidence of artemisinin resistance was found outside Southeast Asia and China, where resistance-associated K13 mutations were confined. The common African A578S allele was not associated with clinical or in vitro resistance to artemisinin, and many African mutations appear to be neutral. (Funded by Institut Pasteur Paris and others.).
Published: 2016
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17. Contribution of molecular diagnosis to the management of cutaneous leishmaniasis in travellers

Author: Sandie Menard, Jean-François Magnaval, Sophie Cassaing, Guillaume Martin-Blondel, Alexis Valentin, Judith Fillaux, Rose-Anne Lavergne, Pamela Chauvin, S. Arnaud, Christine Roques-Malecaze, Xavier Iriart, Antoine Berry, Bruno Marchou, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Parasitologie et Mycologie, CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Service des maladies infectieuses et tropicales [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Laboratoire d'Anthropobiologie (LA), École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Service de Parasitologie et Mycologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service Maladies infectieuses et tropicales [CHU Toulouse], Pôle Inflammation, infection, immunologie et loco-moteur [CHU Toulouse] (Pôle I3LM Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Pagès, Nathalie, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Microbiology (medical), Adolescent, diagnosis, [SDV]Life Sciences [q-bio], 030231 tropical medicine, Direct examination, Leishmaniasis, Cutaneous, Polymerase Chain Reaction, Sensitivity and Specificity, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Cutaneous leishmaniasis, medicine, Humans, Child, leishmaniasis, Aged, Aged, 80 and over, Leishmania, Travel, 0303 health sciences, biology, cutaneous, 030306 microbiology, business.industry, Leishmaniasis, Sequence Analysis, DNA, sequencing, General Medicine, Middle Aged, medicine.disease, biology.organism_classification, Optimal management, 3. Good health, [SDV] Life Sciences [q-bio], PCR, Infectious Diseases, Molecular Diagnostic Techniques, Child, Preschool, Immunology, Female, Identification (biology), business
Abstract: International audience; Cutaneous leishmaniasis is one of the most frequent skin diseases occurring after travelling in endemic areas. Optimal management requires identification of the species of Leishmania involved. In this study we aimed to evaluate the use of molecular diagnosis as routine, in comparison with direct examination and culture. Thirty positive diagnoses were carried out between 2007 and 2013. Classical PCR enabled 11 positive cases to be identified that were found to be negative by conventional methods. Sequencing led to the identification of eight different species. Routine use of PCR and sequencing appears very efficient in the management of cutaneous leishmaniasis.
Published: 2014
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18. Induction of multidrug tolerance in plasmodium falciparum by extended artemisinin pressure

Author: Sandie Menard, Françoise Benoit-Vical, Christiane Bouchier, Antoine Berry, Xavier Iriart, Arba Pramundita Ramadani, Benoit Witkowski, Odile Mercereau-Puijalon, Johann Beghain, Tanila Ben Haddou, Frédéric Ariey, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées, Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], This study was supported in part by the French Agence Nationale de la Recherche (grant ANR-13-BSV3-0018-01) and the Centre National de la Recherche Scientifique. O.M.-P. and F.A. were supported by a grant from the Laboratory of Excellence Integrative Biology of Emerging Infectious Diseases (ANR-10-LABX-62-IBEID), and O.M.-P. was supported by Banque Natixis., ANR-13-BSV3-0018,MALARTRES,Résistance de Plasmodium aux antipaludiques de la famille des artémisinines(2013), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT), Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: Microbiology (medical), Drug, Multidrug tolerance, Epidemiology, media_common.quotation_subject, Plasmodium falciparum, malaria, lcsh:Medicine, drug pressure, parasites, Pharmacology, lcsh:Infectious and parasitic diseases, antifolate, Antimalarials, chemistry.chemical_compound, Antibiotic resistance, quinolone, parasitic diseases, multidrug tolerance, medicine, Humans, lcsh:RC109-216, [CHIM.COOR]Chemical Sciences/Coordination chemistry, antimicrobial resistance, Malaria, Falciparum, Artemisinin, Induction of Multidrug Tolerance in Plasmodium falciparum by Extended Artemisinin Pressure, Asia, Southeastern, media_common, biology, Research, lcsh:R, Drug Tolerance, atovaquone, biology.organism_classification, medicine.disease, Southeast Asia, Virology, Artemisinins, 3. Good health, Infectious Diseases, artemisinin, chemistry, Antifolate, Malaria, Atovaquone, medicine.drug
Abstract: Tolerance is not detected by current assays and represents a major threat to antimalarial drug policy., Plasmodium falciparum resistance to artemisinin derivatives in Southeast Asia threatens global malaria control strategies. Whether delayed parasite clearance, which exposes larger parasite numbers to artemisinins for longer times, selects higher-grade resistance remains unexplored. We investigated whether long-lasting artemisinin pressure selects a novel multidrug-tolerance profile. Although 50% inhibitory concentrations for 10 antimalarial drugs tested were unchanged, drug-tolerant parasites showed higher recrudescence rates for endoperoxides, quinolones, and an antifolate, including partner drugs of recommended combination therapies, but remained susceptible to atovaquone. Moreover, the age range of intraerythrocytic stages able to resist artemisinin was extended to older ring forms and trophozoites. Multidrug tolerance results from drug-induced quiescence, which enables parasites to survive exposure to unrelated antimalarial drugs that inhibit a variety of metabolic pathways. This novel resistance pattern should be urgently monitored in the field because this pattern is not detected by current assays and represents a major threat to antimalarial drug policy.
Published: 2015
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19. Molecular characterization of Babesia and Cytauxzoon species in wild South-African meerkats

Author: Antoine Berry, Sandie Menard, and Sarah Leclaire
Subjects: Carnivora, Zoology, Babesia, Animals, Wild, 18S ribosomal RNA, law.invention, Piroplasmida, South Africa, Phylogenetics, law, Babesiosis, parasitic diseases, Theileria, DNA, Ribosomal Spacer, medicine, RNA, Ribosomal, 18S, Animals, Protozoan Infections, Animal, Polymerase chain reaction, Phylogeny, biology, DNA, Protozoan, biology.organism_classification, medicine.disease, Cytauxzoon, Infectious Diseases, Molecular phylogenetics, Animal Science and Zoology, Parasitology
Abstract: Piroplasms, including Babesia, Cytauxzoon and Theileria species, frequently infect domestic and wild mammals. At present, there is no information on the occurrence and molecular identity of these tick-borne blood parasites in the meerkat, one of South Africa's most endearing wildlife celebrities. Meerkats live in territorial groups, which may occur on ranchland in close proximity to humans, pets and livestock. Blood collected from 46 healthy meerkats living in the South-African Kalahari desert was screened by microscopy and molecular methods, using PCR and DNA sequencing of 18S rRNA and ITS1 genes. We found that meerkats were infected by 2 species: one species related to Babesia sp. and one species related to Cytauxzoon sp. Ninety one percent of the meerkats were infected by the Cytauxzoon and/or the Babesia species. Co-infection occurred in 46% of meerkats. The pathogenicity and vectors of these two piroplasm species remains to be determined.
Published: 2014

20. pfmdr1 Amplification Associated with Clinical Resistance to Mefloquine in West Africa: Implications for Efficacy of Artemisinin Combination Therapies

Author: Jean-François Magnaval, Patrice Njomnang Soh, Benoit Witkowski, M. Alvarez, Sandie Menard, Françoise Benoit-Vical, Xavier Iriart, Veronique Naneix-Laroche, Antoine Berry, and Bruno Marchou
Subjects: Adult, Male, Microbiology (medical), Oncology, medicine.medical_specialty, Combination therapy, Drug Resistance, Gene Dosage, Case Reports, Drug resistance, Pharmacology, West africa, Inhibitory Concentration 50, Pharmacotherapy, Internal medicine, parasitic diseases, Genotype, medicine, Humans, Treatment Failure, Malaria, Falciparum, Artemisinin, Mefloquine, business.industry, medicine.disease, Artemisinins, Africa, Western, Drug Therapy, Combination, Multidrug Resistance-Associated Proteins, business, Malaria, medicine.drug
Abstract: We describe here a clinical failure in the treatment with mefloquine of acute falciparum malaria contracted in Africa and associated with in vitro mefloquine resistance and pfmdr1 copy number amplification. This case raises the question of the presence and the evolution of this genotype in Africa, which is also known to alter the susceptibility to artemisinin combination therapy (ACT).
Published: 2010
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21. Plasmodium falciparum Isolates with Increased pfmdr1 Copy Number Circulate in West Africa

Author: Jean-François Magnaval, Benoit Witkowski, Françoise Benoit-Vical, Patrice Njomnang Soh, Antoine Berry, Bruno Marchou, Sandie Menard, Xavier Iriart, Marie-Laure Nicolau, and M. Alvarez
Subjects: Artemisinins, Genotype, Plasmodium falciparum, Gene Dosage, Drug resistance, West africa, Apicomplexa, Antimalarials, Mechanisms of Resistance, parasitic diseases, medicine, Animals, Humans, Pharmacology (medical), Malaria, Falciparum, Artemisinin, Pharmacology, Genetics, biology, biology.organism_classification, Virology, Infectious Diseases, Africa, Protozoa, Multidrug Resistance-Associated Proteins, medicine.drug
Abstract: Amplification of pfmdr1 in Plasmodium falciparum is linked to resistance to aryl-amino-alcohols and in reduced susceptibility to artemisinins. We demonstrate here that duplicated pfmdr1 genotypes circulate in West Africa. The monitoring of this prevalence in Africa appears essential for determining the antimalarial policy and to maintain the efficiency of artemisinin-based combination therapy (ACT) for as long as possible.
Published: 2010
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22. A complementary tool for management of disseminated Histoplasma capsulatum var. capsulatum infections in AIDS patients

Author: Denis Blanchet, Sophie Cassaing, Jean-François Magnaval, Pamela Chauvin, Rose-Anne Lavergne, Pierre Couppié, Antoine Berry, Sandie Menard, Magalie Demar, Judith Fillaux, Bernard Carme, Marie-Hélène Bessières, Antoine Adenis, Christine Aznar, Xavier Iriart, and Mathieu Nacher
Subjects: Microbiology (medical), Adult, Male, Opportunistic infection, AIDS-Related Opportunistic Infections, Histoplasma, Aspergillosis, Microbiology, Sensitivity and Specificity, Histoplasmosis, Cohort Studies, Mannans, 03 medical and health sciences, Galactomannan, chemistry.chemical_compound, 0302 clinical medicine, Blood serum, Antigen, parasitic diseases, medicine, Humans, 030212 general & internal medicine, Antibodies, Fungal, 0303 health sciences, Acquired Immunodeficiency Syndrome, biology, 030306 microbiology, business.industry, Galactose, General Medicine, Middle Aged, South America, bacterial infections and mycoses, medicine.disease, biology.organism_classification, Virology, 3. Good health, French Guiana, Infectious Diseases, chemistry, Immunology, Female, business
Abstract: In South America, disseminated histoplasmosis due to Histoplasma capsulatum var. capsulatum (H. capsulatum), is a severe and frequent opportunistic infection in AIDS patients. In areas outside the USA where specific-Histoplasma antigen detection is not available, the diagnosis is difficult. With the galactomannan antigen (GM) detection, a test commonly used for invasive aspergillosis diagnosis, there is a cross-reactivity with H. capsulatum that can be helpful for the diagnosis of histoplasmosis. The aim of this study was to evaluate the GM detection for the diagnosis of disseminated histoplasmosis in AIDS patients. The performance of the GM detection was evaluated with serum collected in French Guiana where H. capsulatum is highly endemic. Sera from AIDS patients with disseminated histoplasmosis occurring from 2002 to 2009 and from control HIV-positive patients without histoplasmosis were tested with the GM detection and Histoplasma-specific antibody detection (IEP). In 39 AIDS patients with proven disseminated histoplasmosis, the sensitivity of the Histoplasma IEP was only 35.9% and was linked to the TCD4+ lymphocyte level. For the GM detection, the sensitivity (Se) was 76.9% and specificity (Sp) was 100% with the recommended threshold for aspergillosis diagnosis (0.5). The test was more efficient with a threshold of 0.4 (Se: 0.82 [95% CI: 0.66-0.92], Sp: 1.00 [95% CI: 0.86-1.00], LR+: >10, LR-: 0.18). This study confirms that the GM detection can be a surrogate marker for the diagnosis of disseminated histoplasmosis in AIDS patients in endemic areas where Histoplasma EIA is not available.
Published: 2013

23. An extraction method of positive blood cultures for direct identification of Candida species by Vitek MS matrix-assisted laser desorption ionization time of flight mass spectrometry

Author: Sophie Cassaing, Christine Roques-Malecaze, Jean-Fran Ç Ois Magnaval, Rose-Anne Lavergne, Sylvie Arnaud, Antoine Berry, Sandie Menard, Pamela Chauvin, Xavier Iriart, Alexis Valentin, Judith Fillaux, CHU Toulouse [Toulouse], Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD)
Subjects: Microbiological Techniques, MALDI-TOF, Time Factors, [SDV]Life Sciences [q-bio], Matrix assisted laser desorption ionization time of flight, Mycology, Biology, Mass spectrometry, blood culture, Sensitivity and Specificity, Microbiology, Specimen Handling, 03 medical and health sciences, medicine, Humans, Blood culture, 030304 developmental biology, Candida, 0303 health sciences, medicine.diagnostic_test, 030306 microbiology, Candidemia, General Medicine, 3. Good health, Infectious Diseases, Blood, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Candida spp, extraction, identification, Extraction methods, Subculture (biology), Time-of-flight mass spectrometry, Mixed infection
Abstract: International audience; Candida spp. are an important cause of nosocomial bloodstream infections. Currently, complete identification of yeasts with conventional methods takes several days. We report here the first evaluation of an extraction method associated with the Vitek MS matrix-assisted laser desorption ionization time of flight mass spectrometry for direct identification of Candida species from positive blood cultures. We evaluated this protocol with blood cultures that were inoculated with reference and routine isolates (eight reference strains, 30 patients isolates and six mixed cultures containing two strains of different Candida species), or from patients with candidemia (28 isolates). This method performed extremely well (97% correct identification) with blood cultures of single Candida spp. and significantly reduced the time of diagnosis. Nevertheless, subculture remains indispensable to test fungal resistance and to detect mixed infections.
Published: 2013
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24. A molecular marker of artemisinin-resistant Plasmodium falciparum malaria

Author: Valentine Duru, Laurence Ma, Jean Christophe Barale, Olivo Miotto, Socheat Duong, Sandie Menard, Antoine Berry, Blaise Genton, Pascal Ringwald, Benoit Witkowski, Anne-Claire Langlois, Rithea Leang, Nimol Khim, Saorin Kim, Françoise Benoit-Vical, Seila Suon, Denis Mey Bout, Frédéric Ariey, Odile Mercereau-Puijalon, Johann Beghain, Christiane Bouchier, Chanaki Amaratunga, Char Meng Chuor, Jacques Le Bras, Didier Menard, Sokunthea Sreng, William O. Rogers, Rick M. Fairhurst, Thierry Fandeur, Pharath Lim, Immunologie moléculaire des parasites, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'épidémiologie moléculaire, Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases-National Institutes of Health, Génomique (Plate-Forme) - Genomics Platform, Institut Pasteur [Paris], National Center for Parasitology, Entomology and Malaria Control, National Center for Parasitology, Entomology and Malaria Control [Phnom Penh, Cambodia] (CNM), Drug Monitoring in Cambodia, SSA WHO-National Center for Parasitology, Entomology and Malaria Control [Phnom Penh, Cambodia] (CNM), Service de Parasitologie et Mycologie, CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], US Naval Medical Research Unit n°2, Swiss Tropical and Public Health Institute [Basel], Unité de Parasitologie Médicale, Centre International de Recherches Médicales de Franceville (CIRMF), MRC Centre for Genomics and Global Health, University of Oxford [Oxford], Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University [Bangkok], The Wellcome Trust Sanger Institute [Cambridge], Global Malaria Program, Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre National de Référence du Paludisme, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-PRES Sorbonne Paris Cité, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées, Réseau International des Instituts Pasteur (RIIP), Clinical trials and sample collections were supported in part by the Global Fund Grant Malaria Program Rounds 6 (CAM-607-G10M-CNM3) and 9 (CAM-S10-G14-M), the Bill and Melinda Gates Foundation and USAID (through the World Health Organization), the US DOD Global Epidemic Information System, and the Intramural Research Program, NIAID, NIH. Laboratory work was supported by grants from Banque Natixis (to O.M.-P. and D.M.) and Laboratoire d'Excellence IBEID (Agence Nationale de la Recherche, France) and Institut Pasteur, Division International (ACIP A-10-2010). B.W. was supported by a postdoctoral fellowship from Institut Pasteur, Division International, J.B. by an Institut Pasteur Paris Master-Pro fellowship, and D.M. by the French Ministry of Foreign Affairs. We are grateful to the Wellcome Trust Sanger Institute and the MalariaGEN resource centre for sequencing, genotyping and population structure analysis of some Cambodian clinical samples, funded by the Wellcome Trust (098051, 090770/Z/09/Z) and the MRC (G0600718)., Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Service de Parasitologie et Mycologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), University of Oxford, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), and Université de Toulouse (UT)
Subjects: Genetic Markers, animal structures, Time Factors, Plasmodium falciparum, Drug Resistance, Protozoan Proteins, Drug resistance, Polymorphism, Single Nucleotide, Article, chemistry.chemical_compound, Antimalarials, Parasitic Sensitivity Tests, Molecular marker, Piperaquine, parasitic diseases, medicine, Animals, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Allele, Artemisinin, Malaria, Falciparum, Alleles, Genetics, Multidisciplinary, Blood Cells, biology, Artesunate/amodiaquine, biology.organism_classification, medicine.disease, Virology, Artemisinins, 3. Good health, Protein Structure, Tertiary, chemistry, Mutation, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Cambodia, Malaria, medicine.drug, Half-Life
Abstract: Plasmodium falciparum resistance to artemisinin derivatives in southeast Asia threatens malaria control and elimination activities worldwide. To monitor the spread of artemisinin resistance, a molecular marker is urgently needed. Here, using whole-genome sequencing of an artemisinin-resistant parasite line from Africa and clinical parasite isolates from Cambodia, we associate mutations in the PF3D7-1343700 kelch propeller domain ('K13-propeller') with artemisinin resistance in vitro and in vivo. Mutant K13-propeller alleles cluster in Cambodian provinces where resistance is prevalent, and the increasing frequency of a dominant mutant K13-propeller allele correlates with the recent spread of resistance in western Cambodia. Strong correlations between the presence of a mutant allele, in vitro parasite survival rates and in vivo parasite clearance rates indicate that K13-propeller mutations are important determinants of artemisinin resistance. K13-propeller polymorphism constitutes a useful molecular marker for large-scale surveillance efforts to contain artemisinin resistance in the Greater Mekong Subregion and prevent its global spread. © 2014 Macmillan Publishers Limited.
Published: 2013
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25. Diversity, host switching and evolution of Plasmodium vivax infecting African great apes

Author: Barthélémy Ngoubangoye, Benjamin Ollomo, Eric Willaume, A. Berry, Nil Rahola, Céline Arnathau, Franck Prugnolle, François Renaud, Didier Fontenille, Patrick Durand, Virginie Rougeron, Francisco J. Ayala, Sandie Menard, Christophe Paupy, Boris Makanga, Pierre Becquart, Centre International de Recherches Médicales de Franceville (CIRMF), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Institut de Recherche pour le Développement (IRD [France-Sud])-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Health, Emergence, Adaptation and Transmission (MIVEGEC-HEAT), Processus Écologiques et Évolutifs au sein des Communautés (PEEC), Institut de Recherche pour le Développement (IRD [France-Sud])-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut de Recherche pour le Développement (IRD [France-Sud])-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Institut de Recherche pour le Développement (IRD [France-Sud])-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut de Recherche pour le Développement (IRD [France-Sud])-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Diversity, ecology, evolution & Adaptation of arthropod vectors (MIVEGEC-DEEVA), Evolution des Systèmes Vectoriels (ESV), Parc of la Lékédi, University of California [Irvine] (UCI), University of California, Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), and Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])
Subjects: Male, Time Factors, Plasmodium vivax, DIVERSITE SPECIFIQUE, Polymerase Chain Reaction, 0302 clinical medicine, MITOCHONDRIE, PHYLOGENIE, Clade, Phylogeny, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, Genome, Multidisciplinary, biology, Transmission (medicine), Hominidae, Biological Sciences, ORIGINE DE LA MALADIE, Central African Republic, GENOME, ANALYSE GENETIQUE, Adult, TRANSMISSION, Molecular Sequence Data, 030231 tropical medicine, Zoology, [SDV.BID]Life Sciences [q-bio]/Biodiversity, DNA, Mitochondrial, Host Specificity, Laverania, SINGE, Evolution, Molecular, 03 medical and health sciences, Phylogenetics, parasitic diseases, medicine, ETUDE COMPARATIVE, Animals, Humans, PARASITE, 030304 developmental biology, Genetic diversity, Genetic Variation, PALUDISME, biology.organism_classification, medicine.disease, Virology, Malaria, Culicidae, Haplotypes, RESERVOIR
Abstract: Plasmodium vivax is considered to be absent from Central and West Africa because of the protective effect of Duffy negativity. However, there are reports of persons returning from these areas infected with this parasite and observations suggesting the existence of transmission. Among the possible explanations for this apparent paradox, the existence of a zoonotic reservoir has been proposed. May great apes be this reservoir? We analyze the mitochondrial and nuclear genetic diversity of P. vivax parasites isolated from great apes in Africa and compare it to parasites isolated from travelers returning from these regions of Africa, as well as to human isolates distributed all over the world. We show that the P. vivax sequences from parasites of great apes form a clade genetically distinct from the parasites circulating in humans. We show that this clade’s parasites can be infectious to humans by describing the case of a traveler returning from the Central African Republic infected with one of them. The relationship between this P. vivax clade in great apes and the human isolates is discussed.
Published: 2013
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26. Molecular monitoring of plasmodium falciparum drug susceptibility at the time of the introduction of artemisinin-based combination therapy in Yaoundé, Cameroon

Author: Xavier Iriart, Sandie Menard, Pembe Issamou Mayengue, Jean-François Magnaval, Brigitte Lemen, Isabelle Morlais, Leonardo K. Basco, Rachida Tahar, Parfait Awono-Ambene, Antoine Berry, Collins Sayang, Françoise Benoit-Vical, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 216), Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), CHU Bordeaux [Bordeaux], Service de Parasitologie et Mycologie, CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Laboratoire d'Anthropobiologie (LA), École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Laboratoire d’Entomologie Médicale, Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale, Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche Biomédicale des Armées (IRBA)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale (OCEAC), Université de la Méditerranée - Aix-Marseille 2, Anthropologie Moléculaire et Imagerie de Synthèse (AMIS), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Médecine légale [Hôpital de la Timone - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE), and Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA)
Subjects: Male, [SDV]Life Sciences [q-bio], Resistance, Drug Resistance, Protozoan Proteins, Drug resistance, pfmdr1copy number, 0302 clinical medicine, pfmdr1, Chloroquine, pfcrt, Prevalence, Cameroon, Artemisinin, Malaria, Falciparum, Child, 0303 health sciences, biology, pfmdr1 copy number, Middle Aged, Artemisinins, 3. Good health, Infectious Diseases, Child, Preschool, Drug Therapy, Combination, Female, Multidrug Resistance-Associated Proteins, medicine.drug, Adult, lcsh:Arctic medicine. Tropical medicine, Combination therapy, Adolescent, Genotype, lcsh:RC955-962, 030231 tropical medicine, Plasmodium falciparum, Mutation, Missense, Amodiaquine, Real-Time Polymerase Chain Reaction, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, Antimalarials, Young Adult, Pharmacotherapy, parasitic diseases, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, lcsh:RC109-216, LNA probes, 030306 microbiology, Research, Infant, Newborn, Infant, Membrane Transport Proteins, DNA, Protozoan, medicine.disease, biology.organism_classification, Virology, Malaria, LNA, Parasitology, probes, Sentinel Surveillance
Abstract: Background Regular monitoring of the levels of anti-malarial resistance of Plasmodium falciparum is an essential policy to adapt therapy and improve malaria control. This monitoring can be facilitated by using molecular tools, which are easier to implement than the classical determination of the resistance phenotype. In Cameroon, chloroquine (CQ), previously the first-line therapy for uncomplicated malaria was officially withdrawn in 2002 and replaced initially by amodiaquine (AQ) monotherapy. Then, artemisinin-based combination therapy (ACT), notably artesunate-amodiaquine (AS-AQ) or artemether-lumefantrine (AL), was gradually introduced in 2004. This situation raised the question of the evolution of P. falciparum resistance molecular markers in Yaoundé, a highly urbanized Cameroonian city. Methods The genotype of pfcrt 72 and 76 and pfmdr1 86 alleles and pfmdr1 copy number were determined using real-time PCR in 447 P. falciparum samples collected between 2005 and 2009. Results This study showed a high prevalence of parasites with mutant pfcrt 76 (83%) and pfmdr1 86 (93%) codons. On the contrary, no mutations in the pfcrt 72 codon and no samples with duplication of the pfmdr1 gene were observed. Conclusion The high prevalence of mutant pfcrt 76T and pfmdr1 86Y alleles might be due to the choice of alternative drugs (AQ and AS-AQ) known to select such genotypes. Mutant pfcrt 72 codon was not detected despite the prolonged use of AQ either as monotherapy or combined with artesunate. The absence of pfmdr1 multicopies suggests that AL would still remain efficient. The limited use of mefloquine or the predominance of mutant pfmdr1 86Y codon could explain the lack of pfmdr1 amplification. Indeed, this mutant codon is rarely associated with duplication of pfmdr1 gene. In Cameroon, the changes of therapeutic strategies and the simultaneous use of several formulations of ACT or other anti-malarials that are not officially recommended result in a complex selective pressure, rendering the prediction of the evolution of P. falciparum resistance difficult. This public health problem should lead to increased vigilance and regular monitoring.
Published: 2012
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27. Alveolar and blood T lymphocyte profiles in Pneumocystis jirovecii-positive patients: effects of HIV status

Author: Anne Huynh, Xavier Iriart, Antoine Blancher, Jean Tkaczuk, Sandie Menard, Françoise Huget, Benoit Witkowski, Christophe Hermant, Antoine Berry, M. Alvarez, Sophie Cassaing, Olivier Cointault, R. Escamilla, Marie-Denise Linas, Alexis Valentin, Laurence Lavayssière, Nassim Kamar, Sarah Abbes, Judith Fillaux, Bruno Marchou, and Jean-François Magnaval
Subjects: Adult, Male, Lymphocyte, HIV Infections, Pneumocystis pneumonia, Pneumocystis carinii, Immune system, T-Lymphocyte Subsets, medicine, Immunology and Allergy, Pneumocystis jirovecii, Humans, Aged, medicine.diagnostic_test, biology, business.industry, Pneumonia, Pneumocystis, virus diseases, T lymphocyte, Middle Aged, medicine.disease, biology.organism_classification, Pulmonary Alveoli, Pneumonia, Infectious Diseases, Bronchoalveolar lavage, medicine.anatomical_structure, Immunology, Female, business, CD8
Abstract: Background There are substantial differences in the risk evaluation, clinical presentation, and outcome of Pneumocystis pneumonia between human immunodeficiency virus (HIV)-positive and HIV-negative immunocompromised patients. To compare the host immune defenses against Pneumocystis jirovecii, the blood and alveolar lymphocyte profile was explored in these 2 populations. Methods The total, CD3(+), CD4(+), and CD8(+) T-lymphocyte counts were measured in the blood and alveoli of immunocompromised patients with a P. jirovecii DNA detected in their bronchoalveolar lavage samples, according to their HIV status. Results In blood and alveoli, the CD4(+) and CD8(+) T-lymphocyte counts were higher and lower, respectively, in the HIV-negative group. The threshold for initiating prophylaxis in HIV-positive persons, 200 CD4(+) T cells/μL, was not pertinent for HIV-negative patients. The P. jirovecii burden correlated with the blood CD4(+) T-cell counts in the HIV-positive but not in the HIV-negative group. Nevertheless, whatever the HIV status, a correlation was observed between alveolar CD4(+) T cells and the P. jirovecii burden. Conclusions The T-lymphocyte profile was different between HIV-positive and HIV-negative patients with P. jirovecii, suggesting a distinct pathogenesis. Alveolar CD4(+) T cells could be critical to explain the development of Pneumocystis pneumonia but may also be important for evaluation of disease risk, mostly among HIV-negative immunocompromised patients.
Published: 2011

28. Imported Plasmodium knowlesi malaria in a French tourist returning from Thailand

Author: Alain Le Coustumier, Nathalie Wilhelm, Xavier Iriart, David Olagnier, Jean-François Magnaval, Françoise Benoit-Vical, Sandie Menard, Stephane Sire, Antoine Berry, Benoit Witkowski, Sophie Cassaing, Judith Fillaux, and Alexis Valentin
Subjects: Male, Malaria/epidemiology, Antimalarials, Virology, parasitic diseases, medicine, Animals, Humans, Plasmodium knowlesi, Malaria epidemiology, Plasmodium knowlesi/isolation & purification, Travel, biology, fungi, Articles, Middle Aged, biology.organism_classification, medicine.disease, Thailand, Malaria, Infectious Diseases, Thailand/epidemiology, Antimalarials/therapeutic use, Macaca, Parasitology, France, Tourism
Abstract: We report a case of imported Plasmodium knowlesi malaria in a French tourist following a vacation in Thailand. This case shows, first, tourists may contract knowlesi malaria even only staying on the beach and second, the diagnosis remains difficult, even with polymerase chain reaction methods.
Published: 2011
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29. Evaluation of the Performance of the Novodiag® Stool Parasites Assay for the Detection of Intestinal Protozoa and Microsporidia

Author: Pamela Chauvin, Florie Barba, Emilie Guemas, Eléna Charpentier, Claire Cottrel, Judith Fillaux, Alexis Valentin, Sarah Baklouti, Sophie Cassaing, Sandie Ménard, Antoine Berry, and Xavier Iriart
Subjects: stool, protozoa, microsporidia, diagnosis, microscopy, qPCR, Medicine
Abstract: Objectives: We aimed to assess the performance of the Novodiag® Stool Parasites (NSP) assay in the diagnosis of the most common intestinal protozoan and microsporidia infections. Methods: A panel of 167 selected stool samples was retrospectively analysed with the NSP assay and compared to routine microscopy and qPCR methods for the detection of pathogenic protozoa and microsporidia. Results: Whereas specificity was high for all protozoa and microsporidia, NSP sensitivity was strongly dependent on the comparative method used as reference. When compared to microscopic methods, NSP sensitivity was high (96.7 to 100%) for Blastocystis hominis, Entamoeba histolytica and Cyclospora cayetanensis but was lower for Giardia intestinalis (85.2%) and ≤50% for Cystoisospora belli and Dientamoeba fragilis. In comparison to conventional qPCR, the NSP assay demonstrated lower sensitivity characteristics dependent on parasite loads, reaching 60 to 70% for G. intestinalis, D. fragilis, Cryptosporidium spp. and E. histolytica. Sensitivity was 100% for Enterocytozoon bieneusi, but none of the five samples containing Encephalitozoon spp. were detected. Conclusions: The overall performance of the NSP assay in the diagnosis of gastrointestinal protozoa and microsporidia seems to be better than or equivalent to that observed with microscopic methods but inferior to that obtainable with classical targeted qPCR.
Published: 2023
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30. New Insights into Blood Circulating Lymphocytes in Human Pneumocystis Pneumonia

Author: Eléna Charpentier, Catherine Marques, Sandie Ménard, Pamela Chauvin, Emilie Guemas, Claire Cottrel, Sophie Cassaing, Judith Fillaux, Alexis Valentin, Nicolas Blanchard, Antoine Berry, and Xavier Iriart
Subjects: Pneumocystis jirovecii, pneumocystosis, immunophenotyping, lymphocyte, T helper, B lymphocytes, Biology (General), QH301-705.5
Abstract: The host lymphocyte response is decisive in Pneumocystis pneumonia (PCP) pathophysiology but little is known of the specific roles of lymphocyte subpopulations in this fungal infection. Peripheral NK, NKT, B, TCD4+ and TCD8+ subpopulations were compared by immunophenotyping between 20 patients diagnosed with PCP (PCP(+)] and 20 uninfected immunosuppressed patients (PCP(−)). Among PCP(+) subjects, the lymphocyte populations were also compared between surviving and deceased patients. Low B cell count (p = 0.03), while there was no difference for the TCD4 count. Among the PCP(+) group, the 7 deceased patients had lower Th1 (p = 0.02) and Tc1 (p = 0.03) populations, higher Th2 response (p = 0.03), higher effector TCD8 (p < 0.01), lower central memory TCD8 (p = 0.04) and reduced NK cells (p = 0.02) compared with the 13 survivors. Th1/Th2 ratio < 17, CD8 Tc1 < 44%, effector TCD8 < 25%, central memory TCD8 < 4%, NK cells < 50 cells/µL and total lymphocytes < 0.75 G/L were associated with a higher risk of mortality (p = 0.003, p = 0.007, p = 0.0007, p = 0.004, p = 0.02 and p = 0.019, respectively). The traditional analysis of TCD4 and TCD8 populations may be insufficient in the context of PCP. It could be completed by using B cells to predict the risk of PCP, and by using lymphocyte subpopulations or total lymphocyte count, which are easy to obtain in all health care facilities, to evaluate PCP prognosis.
Published: 2021
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31. Immune Response in Pneumocystis Infections According to the Host Immune System Status

Author: Eléna Charpentier, Sandie Ménard, Catherine Marques, Antoine Berry, and Xavier Iriart
Subjects: Pneumocystis, lymphocyte, immune response, immunosuppression, TCD4, TCD8, Biology (General), QH301-705.5
Abstract: The host immune response is critical in Pneumocystis pneumonia (PCP). Immunocompetent hosts can eliminate the fungus without symptoms, while immunodeficient hosts develop PCP with an unsuitable excessive inflammatory response leading to lung damage. From studies based on rodent models or clinical studies, this review aimed to better understand the pathophysiology of Pneumocystis infection by analysing the role of immune cells, mostly lymphocytes, according to the immune status of the infected host. Hence, this review first describes the immune physiological response in infected immunocompetent hosts that are able to eliminate the fungus. The objective of the second part is to identify the immune elements required for the control of the fungus, focusing on specific immune deficiencies. Finally, the third part concentrates on the effect of the different immune elements in immunocompromised subjects during PCP, to better understand which cells are detrimental, and which, on the contrary, are beneficial once the disease has started. This work highlights that the immune response associated with a favourable outcome of the infection may differ according to the immune status of the host. In the case of immunocompetency, a close communication between B cells and TCD4 within tertiary lymphocyte structures appears critical to activate M2 macrophages without much inflammation. Conversely, in the case of immunodeficiency, a pro-inflammatory response including Th1 CD4, cytotoxic CD8, NK cells, and IFNγ release seems beneficial for M1 macrophage activation, despite the impact of inflammation on lung tissue.
Published: 2021
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31 results on '"Sandie Menard"'

1. Misdiagnosis of imported falciparum malaria from African areas due to an increased prevalence of pfhrp2/pfhrp3 gene deletion: the Djibouti case

2. The Rare, the Best: Spread of Antimalarial-Resistant Plasmodium falciparum Parasites by Anopheles Mosquito Vectors

3. Young Sprague Dawley rats infected by Plasmodium berghei: A relevant experimental model to study cerebral malaria.

4. Effect of sulfadoxine-pyrimethamine chemoprophylaxis in pregnant women on selection of the newP. falciparum dhpsquintuple mutant carrying the I431V mutation

5. Efficacy of dihydroartemisinin/piperaquine in patients with non-complicated Plasmodium falciparum malaria in Yaoundé, Cameroon

6. Misdiagnosis of imported falciparum malaria from African areas due to an increased prevalence of pfhrp2/pfhrp3 gene deletion: the Djibouti case

7. The Rare, the Best: Spread of Antimalarial-Resistant Plasmodium falciparum Parasites by Anopheles Mosquito Vectors

8. New Insights into Blood Circulating Lymphocytes in Human Pneumocystis Pneumonia

9. Immune Response in Pneumocystis Infections According to the Host Immune System Status

10. Identification of compounds active against quiescent artemisinin-resistant Plasmodium falciparum parasites via the quiescent-stage survival assay (QSA)

11. Performance evaluation of different strategies based on microscopy techniques, rapid diagnostic test and molecular loop-mediated isothermal amplification assay for the diagnosis of imported malaria

12. Multiple phenotypic and genotypic artemisinin sensitivity evaluation of Malian Plasmodium falciparum isolates

13. Prevalence ofPlasmodium falciparumparasites resistant to sulfadoxine/pyrimethamine in pregnant women in Yaoundé, Cameroon: emergence of highly resistantpfdhfr/pfdhpsalleles

14. Risk Factors of Pneumocystis Pneumonia in Solid Organ Recipients in the Era of the Common Use of Posttransplantation Prophylaxis

15. Insight into k13-propeller gene polymorphism and ex vivo DHA-response profiles from Cameroonian isolates

16. A Worldwide Map of Plasmodium falciparum K13-Propeller Polymorphisms

17. Contribution of molecular diagnosis to the management of cutaneous leishmaniasis in travellers

18. Induction of multidrug tolerance in plasmodium falciparum by extended artemisinin pressure

19. Molecular characterization of Babesia and Cytauxzoon species in wild South-African meerkats

20. pfmdr1 Amplification Associated with Clinical Resistance to Mefloquine in West Africa: Implications for Efficacy of Artemisinin Combination Therapies

21. Plasmodium falciparum Isolates with Increased pfmdr1 Copy Number Circulate in West Africa

22. A complementary tool for management of disseminated Histoplasma capsulatum var. capsulatum infections in AIDS patients

23. An extraction method of positive blood cultures for direct identification of Candida species by Vitek MS matrix-assisted laser desorption ionization time of flight mass spectrometry

24. A molecular marker of artemisinin-resistant Plasmodium falciparum malaria

25. Diversity, host switching and evolution of Plasmodium vivax infecting African great apes

26. Molecular monitoring of plasmodium falciparum drug susceptibility at the time of the introduction of artemisinin-based combination therapy in Yaoundé, Cameroon

27. Alveolar and blood T lymphocyte profiles in Pneumocystis jirovecii-positive patients: effects of HIV status

28. Imported Plasmodium knowlesi malaria in a French tourist returning from Thailand

29. Evaluation of the Performance of the Novodiag® Stool Parasites Assay for the Detection of Intestinal Protozoa and Microsporidia

30. New Insights into Blood Circulating Lymphocytes in Human Pneumocystis Pneumonia

31. Immune Response in Pneumocystis Infections According to the Host Immune System Status

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31 results on '"Sandie Menard"'

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