Author: "Patrice Agnamey" - Searchworks@Jio Institute Digital Library Search Results

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1. Design, Synthesis, and In Vitro Antimalarial Evaluation of New 1,3,5-Tris[(4-(Substituted-Aminomethyl)Phenoxy)Methyl]Benzenes

Author: Sandra Albenque-Rubio, Jean Guillon, Patrice Agnamey, Céline Damiani, Solène Savrimoutou, Romain Mustière, Noël Pinaud, Stéphane Moreau, Jean-Louis Mergny, Luisa Ronga, Ioannis Kanavos, Mathieu Marchivie, Serge Moukha, Pascale Dozolme, Pascal Sonnet, and Anita Cohen
Subjects: antimalarial activity, 1,3,5-tris[(4-(substituted-aminomethyl)phenoxy)methyl]benzene, G-quadruplexes, synthesis, Pharmacy and materia medica, RS1-441, Chemistry, QD1-999
Abstract: By taking into account our previously described series of 1,3,5-tris[(4-(substituted-aminomethyl)phenyl)methyl]benzene compounds, we have now designed, prepared, and evaluated in vitro against Plasmodium falciparum a novel series of structural analogues of these molecules, i.e., the 1,3,5-tris[(4-(substituted-aminomethyl)phenoxy)methyl]benzene derivatives. The pharmacological data showed antimalarial activity with IC50 values in the sub and μM range. The in vitro cytotoxicity of these new nitrogen polyphenoxymethylbenzene compounds was also evaluated on human HepG2 cells. The 1,3,5-tris[(4-(substituted-aminomethyl)phenoxy)methyl]benzene derivative 1m was found as one of the most potent and promising antimalarial candidates with favorable cytotoxic to antiprotozoal properties in the P. falciparum strains W2 and 3D7. In conclusion, this 1,3,5-tris[(4-(pyridin-3-ylmethylaminomethyl)phenoxyl)methyl]benzene 1m (IC50 = 0.07 μM on W2, 0.06 μM on 3D7, and 62.11 μM on HepG2) was identified as the most promising antimalarial derivative with selectivity indexes (SI) of 887.29 on the W2 P. falciparum chloroquine-resistant strain, and of 1035.17 on the chloroquine-sensitive and mefloquine decreased sensitivity strain 3D7. It has been previously described that the telomeres of P. falciparum could represent potential targets for these types of polyaromatic compounds; therefore, the capacity of our novel derivatives to stabilize the parasitic telomeric G-quadruplexes was assessed using a FRET melting assay. However, with regard to the stabilization of the protozoal G-quadruplex, we observed that the best substituted derivatives 1, which exhibited some interesting stabilization profiles, were not the most active antimalarial compounds against the two Plasmodium strains. Thus, there were no correlations between their antimalarial activities and selectivities of their respective binding to G-quadruplexes.
Published: 2024
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2. Synthesis and Antimalarial Evaluation of New 1,3,5-tris[(4-(Substituted-aminomethyl)phenyl)methyl]benzene Derivatives: A Novel Alternative Antiparasitic Scaffold

Author: Sandra Albenque-Rubio, Jean Guillon, Anita Cohen, Patrice Agnamey, Solène Savrimoutou, Stéphane Moreau, Jean-Louis Mergny, Luisa Ronga, Ioannis Kanavos, Serge Moukha, Pascale Dozolme, and Pascal Sonnet
Subjects: antimalarial activity, 1,3,5-tris[(4-(substituted-aminomethyl)phenyl)methyl]benzene, antileishmanial activity, Pharmacy and materia medica, RS1-441, Chemistry, QD1-999
Abstract: A series of new 1,3,5-tris[(4-(substituted-aminomethyl)phenyl)methyl]benzene compounds were designed, synthesized, and evaluated in vitro against two parasites (Plasmodium falciparum and Leishmania donovani). The biological results showed antimalarial activity with IC50 values in the sub and μM range. The in vitro cytotoxicity of these new aza polyaromatic derivatives was also evaluated on human HepG2 cells. The 1,3,5-tris[(4-(substituted-aminomethyl)phenyl)methyl]benzene 1m was found as one of the most potent and promising antimalarial candidates with a ratio of cytotoxic to antiprotozoal activities of 83.67 against the P. falciparum CQ-sensitive strain 3D7. In addition, derivative 1r was also identified as the most interesting antimalarial compound with a selectivity index (SI) of 17.28 on the W2 P. falciparum CQ-resistant strain. It was previously described that the telomeres of P. falciparum could be considered as potential targets of these kinds of aza heterocycles; thus, the ability of these new derivatives to stabilize the parasitic telomeric G-quadruplexes was measured through a FRET melting assay.
Published: 2023
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3. Design, synthesis, and antiprotozoal evaluation of new 2,4-bis[(substituted-aminomethyl)phenyl]quinoline, 1,3-bis[(substituted-aminomethyl)phenyl]isoquinoline and 2,4-bis[(substituted-aminomethyl)phenyl]quinazoline derivatives

Author: Jean Guillon, Anita Cohen, Clotilde Boudot, Alessandra Valle, Vittoria Milano, Rabindra Nath Das, Aurore Guédin, Stéphane Moreau, Luisa Ronga, Solène Savrimoutou, Maxime Demourgues, Elodie Reviriego, Sandra Rubio, Sandie Ferriez, Patrice Agnamey, Cécile Pauc, Serge Moukha, Pascale Dozolme, Sophie Da Nascimento, Pierre Laumaillé, Anne Bouchut, Nadine Azas, Jean-Louis Mergny, Catherine Mullié, Pascal Sonnet, and Bertrand Courtioux
Subjects: antimalarial activity, quinoline-like derivatives, antitrypanosomal activity, antileishmanial activity, g-quadruplex, Therapeutics. Pharmacology, RM1-950
Abstract: A series of new 2,4-bis[(substituted-aminomethyl)phenyl]quinoline, 1,3-bis[(substituted-aminomethyl)phenyl]isoquinoline, and 2,4-bis[(substituted-aminomethyl)phenyl]quinazoline derivatives was designed, synthesised, and evaluated in vitro against three protozoan parasites (Plasmodium falciparum, Leishmania donovani, and Trypanosoma brucei brucei). Biological results showed antiprotozoal activity with IC50 values in the µM range. In addition, the in vitro cytotoxicity of these original molecules was assessed with human HepG2 cells. The quinoline 1c was identified as the most potent antimalarial candidate with a ratio of cytotoxic to antiparasitic activities of 97 against the P. falciparum CQ-sensitive strain 3D7. The quinazoline 3h was also identified as the most potent trypanosomal candidate with a selectivity index (SI) of 43 on T. brucei brucei strain. Moreover, as the telomeres of the parasites P. falciparum and Trypanosoma are possible targets of this kind of nitrogen heterocyclic compounds, we have also investigated stabilisation of the Plasmodium and Trypanosoma telomeric G-quadruplexes by our best compounds through FRET melting assays.
Published: 2020
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4. Design, Synthesis, and Antiprotozoal Evaluation of New Promising 2,9-Bis[(substituted-aminomethyl)]-4,7-phenyl-1,10-phenanthroline Derivatives, a Potential Alternative Scaffold to Drug Efflux

Author: Jean Guillon, Anita Cohen, Clotilde Boudot, Sarah Monic, Solène Savrimoutou, Stéphane Moreau, Sandra Albenque-Rubio, Camille Lafon-Schmaltz, Alexandra Dassonville-Klimpt, Jean-Louis Mergny, Luisa Ronga, Mikel Bernabeu de Maria, Jeremy Lamarche, Cristina Dal Lago, Eric Largy, Valérie Gabelica, Serge Moukha, Pascale Dozolme, Patrice Agnamey, Nadine Azas, Catherine Mullié, Bertrand Courtioux, and Pascal Sonnet
Subjects: antimalarial activity, phenanthroline, G-quadruplex, antileishmanial activity, antitrypanosomal activity, Medicine
Abstract: A series of novel 2,9-bis[(substituted-aminomethyl)]-4,7-phenyl-1,10-phenanthroline derivatives was designed, synthesized, and evaluated in vitro against three protozoan parasites (Plasmodium falciparum, Leishmania donovani and Trypanosoma brucei brucei). Pharmacological results showed antiprotozoal activity with IC50 values in the sub and μM range. In addition, the in vitro cytotoxicity of these original molecules was assessed with human HepG2 cells. The substituted diphenylphenanthroline 1l was identified as the most potent antimalarial derivative with a ratio of cytotoxic to antiparasitic activities of 505.7 against the P. falciparum CQ-resistant strain W2. Against the promastigote forms of L. donovani, the phenanthrolines 1h, 1j, 1n and 1o were the most active with IC50 from 2.52 to 4.50 μM. The phenanthroline derivative 1o was also identified as the most potent trypanosomal candidate with a selectivity index (SI) of 91 on T. brucei brucei strain. FRET melting and native mass spectrometry experiments evidenced that the nitrogen heterocyclic derivatives bind the telomeric G-quadruplexes of P. falciparum and Trypanosoma. Moreover, as the telomeres of the parasites P. falciparum and Trypanosoma could be considered to be possible targets of this kind of nitrogen heterocyclic derivatives, their potential ability to stabilize the parasitic telomeric G-quadruplexes have been determined through the FRET melting assay and by native mass spectrometry.
Published: 2022
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5. Understanding human-Plasmodium falciparum immune interactions uncovers the immunological role of worms.

Author: Christian Roussilhon, Philippe Brasseur, Patrice Agnamey, Jean-Louis Pérignon, and Pierre Druilhe
Subjects: Medicine, Science
Abstract: BACKGROUND: Former studies have pointed to a monocyte-dependent effect of antibodies in protection against malaria and thereby to cytophilic antibodies IgG1 and IgG3, which trigger monocyte receptors. Field investigations have further documented that a switch from non-cytophilic to cytophilic classes of antimalarial antibodies was associated with protection. The hypothesis that the non-cytophilic isotype imbalance could be related to concomittant helminthic infections was supported by several interventions and case-control studies. METHODS AND FINDINGS: We investigated here the hypothesis that the delayed acquisition of immunity to malaria could be related to a worm-induced Th2 drive on antimalarial immune responses. IgG1 to IgG4 responses against 6 different parasite-derived antigens were analyzed in sera from 203 Senegalese children, half carrying intestinal worms, presenting 421 clinical malaria attacks over 51 months. Results show a significant correlation between the occurrence of malaria attacks, worm carriage (particularly that of hookworms) and a decrease in cytophilic IgG1 and IgG3 responses and an increase in non-cytophilic IgG4 response to the merozoite stage protein 3 (MSP3) vaccine candidate. CONCLUSION: The results confirm the association with protection of anti-MSP3 cytophilic responses, confirm in one additional setting that worms increase malaria morbidity and show a Th2 worm-driven pattern of anti-malarial immune responses. They document why large anthelminthic mass treatments may be worth being assessed as malaria control policies.
Published: 2010
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6. Synthesis and Antiprotozoal Evaluation of New 2,9-bis[(pyridinylalkylaminomethyl) phenyl]-1,10-Phenanthroline Derivatives by Targeting G-quadruplex, an Interesting Pharmacophore Against Drug Efflux

Author: Jean Guillon, Anita Cohen, Sarah Monic, Clotilde Boudot, Solène Savrimoutou, Sandra Albenque-Rubio, Stéphane Moreau, Alexandra Dassonville-Klimpt, Jean-Louis Mergny, Luisa Ronga, Mikel Bernabeu de Maria, Nikita Tyurin-Schmitt, Paul Parrens, Adrien Labarthe, Valentin Gomez, Serge Moukha, Pascale Dozolme, Nadine Azas, Valérie Gabelica, Patrice Agnamey, Céline Damiani, Anne Totet, Catherine Mullié, Bertrand Courtioux, and Pascal Sonnet
Subjects: General Materials Science
Published: 2023
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7. Assessing The In Vitro Inhibition of β-Hematin Formation to Elucidate the Mechanism of Action of New Arylamino Alcohols

Author: Céline Damiani, Floriane Soler, Yohann Le Govic, Anne Totet, Guillaume Bentzinger, Anne Bouchut, Patrice Agnamey, Alexandra Dassonville-Klimpt, and Pascal Sonnet
Published: 2023
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8. Design, Synthesis, and Antiprotozoal Evaluation of New Promising 2,9-Bis[(substituted-aminomethyl)]-4,7-phenyl-1,10phenanthroline Derivatives, a Potential Alternative Scaffold to Drug Efflux

Author: Jean Guillon, Anita Cohen, Clotilde Boudot, Sarah Monic, Solène Savrimoutou, Stéphane Moreau, Sandra Albenque-Rubio, Camille Lafon-Schmaltz, Alexandra Dassonville-Klimpt, Jean-Louis Mergny, Luisa Ronga, Mikel Bernabeu de Maria, Jeremy Lamarche, Cristina Dal Lago, Eric Largy, Valérie Gabelica, Serge Moukha, Pascale Dozolme, Patrice Agnamey, Nadine Azas, Catherine Mullié, Bertrand Courtioux, Pascal Sonnet, Acides Nucléiques : Régulations Naturelle et Artificielle (ARNA), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), Neuroépidémiologie Tropicale (NET), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Laboratoire d'Optique et Biosciences (LOB), École polytechnique (X)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Polytechnique de Paris (IP Paris), Institut des sciences analytiques et de physico-chimie pour l'environnement et les materiaux (IPREM), Université de Pau et des Pays de l'Adour (UPPA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Environnement, Santé/Stic (E2S), Université de Bourgogne (UB), Université de Pau et des Pays de l'Adour (UPPA), Institut Européen de Chimie et Biologie (IECB), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Mergny, Jean-Louis, Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Unité de recherche Mycologie et Sécurité des Aliments (MycSA), and Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Microbiology (medical), General Immunology and Microbiology, G-quadruplex, antimalarial activity, phenanthroline, antileishmanial activity, antitrypanosomal activity, [SDV.BBM.BP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Infectious Diseases, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Immunology and Allergy, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Molecular Biology, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM]
Abstract: International audience; A series of novel 2,9-bis[(substituted-aminomethyl)]-4,7-phenyl-1,10-phenanthroline derivatives was designed, synthesized, and evaluated in vitro against three protozoan parasites (Plasmodium falciparum, Leishmania donovani and Trypanosoma brucei brucei). Pharmacological results showed antiprotozoal activity with IC50 values in the sub and μM range. In addition, the in vitro cytotoxicity of these original molecules was assessed with human HepG2 cells. The substituted diphenylphenanthroline 1l was identified as the most potent antimalarial derivative with a ratio of cytotoxic to antiparasitic activities of 505.7 against the P. falciparum CQ-resistant strain W2. Against the promastigote forms of L. donovani, the phenanthrolines 1h, 1j, 1n and 1o were the most active with IC50 from 2.52 to 4.50 μM. The phenanthroline derivative 1o was also identified as the most potent trypanosomal candidate with a selectivity index (SI) of 91 on T. brucei brucei strain. FRET melting and native mass spectrometry experiments evidenced that the nitrogen heterocyclic derivatives bind the telomeric G-quadruplexes of P. falciparum and Trypanosoma. Moreover, as the telomeres of the parasites P. falciparum and Trypanosoma could be considered to be possible targets of this kind of nitrogen heterocyclic derivatives, their potential ability to stabilize the parasitic telomeric G-quadruplexes have been determined through the FRET melting assay and by native mass spectrometry.
Published: 2022
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9. Design, synthesis, and characterization of novel aminoalcohol quinolines with strong in vitro antimalarial activity

Author: Catherine Mullié, Mathieu Marchivie, Patrice Agnamey, Anne Totet, Bruno Pradines, Anita Cohen, Alexandra Dassonville-Klimpt, Jérôme Dormoi, Jean Guillon, Nadine Azas, Céline Damiani, Pascal Sonnet, Jeremy Schneider, N. Taudon, C. Tisnerat, Toulin, Stéphane, Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), Institut de Chimie de la Matière Condensée de Bordeaux (ICMCB), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Acides Nucléiques : Régulations Naturelle et Artificielle (ARNA), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche Biomédicale des Armées (IRBA), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Centre National de Référence du Paludisme [IRBA, Marseille] (CNRP), Institut de Recherche Biomédicale des Armées [Antenne Marseille] (IRBA)-Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), The authors would like to thank Philippe Grellier, department RDDM at Muséum National d’Histoire Naturelle (Paris, France), for providing generously the 3D7 and W2 P. falciparum strains and Sylvie Klieber and Alain Pellet, Sanofi R et D France, for in vitro ADMET study (Papp, hERG activity, microsomal and hepatic clearance and CY3A4 activity)., Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), and ANR-21-ASM1-0003,MORHOC'H 2,Modélisation de l'interaction de la houle et d'un courant inhomogène en zone côtière(2021)
Subjects: Plasmodium falciparum, P. falciparum, mefloquine analogs, Cell Line, 03 medical and health sciences, Antimalarials, Mice, Structure-Activity Relationship, Cricetulus, Pharmacokinetics, Parasitic Sensitivity Tests, In vivo, Drug Discovery, Ic50 values, Animals, Humans, antimalarial drug resistance, aminoalcohol quinolines, 030304 developmental biology, Pharmacology, 0303 health sciences, Mice, Inbred BALB C, [CHIM.MATE] Chemical Sciences/Material chemistry, Dose-Response Relationship, Drug, Molecular Structure, 030306 microbiology, Chemistry, Organic Chemistry, General Medicine, [CHIM.MATE]Chemical Sciences/Material chemistry, Combinatorial chemistry, Amino Alcohols, In vitro, Ether-A-Go-Go Potassium Channels, 3. Good health, Malaria, Design synthesis, Novel agents, Drug Design, Microsomes, Liver, Quinolines, Female, Selectivity
Abstract: International audience; Malaria is the fifth most lethal parasitic infections in the world. Herein, five new series of aminoalcohol quinolines including fifty-two compounds were designed, synthesized and evaluated in vitro against Pf3D7 and PfW2 strains. Among them, fourteen displayed IC50 values below or near of 50.0 nM whatever the strain with selectivity index often superior to 100. 17b was found as a promising antimalarial candidate with IC50 values of 14.9 nM and 11.0 nM against respectively Pf3D7 and PfW2 and a selectivity index higher than 770 whatever the cell line is. Further experiments were achieved to confirm the safety and to establish the preliminary ADMET profile of compound 17b before the in vivo study performed on a mouse model of P. berghei ANKA infection. The overall data of this study allowed to establish new structure-activity relationships and the development of novel agents with improved pharmacokinetic properties
Published: 2022
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10. Novel antimalarial enantiopure arylaminoalcohols as efflux pump substrates to fight resistant P. falciparum

Author: Camille Tisnerat, Jérémy Schneider, Céline Damiani, Patrice Agnamey, Catherine Mullié, Anne Totet, Emmanuel Sevin, Alexandra Dassonville-Klimpt, Fabien Gosselet, and Pascal Sonnet
Published: 2021
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11. Novel enantiopure arylaminoalcohols as promising antimalarial drugs to struggle resistant P. falciparum

Author: Pascal Sonnet, Fabien Gosselet, Alexandra Dassonville-Klimpt, Catherine Mullié, Patrice Agnamey, Anne Totet, DAMIANI DAMIANI, Jérémy Schneider, and Camille Tisnerat
Published: 2021
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12. Synthesis and biological evaluation of new enantiopure 4-aminoalcohol-quinoline and -fluorene hybrids as antimalarial drugs

Author: Alexandra Dassonville-Klimpt, Céline Damiani, Jeremy Schneider, Catherine Mullié, Anne Totet, Pascal Sonnet, Camille Tisnerat, René Pemha, and Patrice Agnamey
Subjects: chemistry.chemical_compound, Enantiopure drug, chemistry, Quinoline, Fluorene, Combinatorial chemistry, Biological evaluation
Published: 2020
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13. Pollution of Water Resources and Environmental Impacts in Urban Areas of Developing Countries: Case of the City of Les Cayes (Haiti)

Author: Evens Emmanuel, Christian Raccurt, Ketty Balthazard-Accou, Patrice Agnamey, Université Quisqueya, Centre de Recherche et d'Appui aux Politiques Urbaines (CRAPU), Université Quisqueya, Centre de Recherche et d'Appui aux Politiques Urbaines, Port-au-Prince, Haïti. (uniQ), Anofel Cryptosporidium National Network, Department of Medical Parasitology and Mycology, and Departments of Medical Parasitology and Mycology
Subjects: Pollution, 0303 health sciences, 030306 microbiology, [SDE.IE]Environmental Sciences/Environmental Engineering, media_common.quotation_subject, InformationSystems_INFORMATIONSTORAGEANDRETRIEVAL, 1. No poverty, Developing country, 010501 environmental sciences, 01 natural sciences, [SDE.ES]Environmental Sciences/Environmental and Society, Water resources, 03 medical and health sciences, Geography, 11. Sustainability, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Environmental planning, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), ComputingMilieux_MISCELLANEOUS, 0105 earth and related environmental sciences, media_common
Abstract: International audience
Published: 2019
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14. Asymmetric synthesis of new antimalarial aminoquinolines through Sharpless aminohydroxylation

Author: Pascal Sonnet, Alexandra Dassonville-Klimpt, Wesley De Souza, Patrice Agnamey, Guillaume Bentzinger, and Catherine Mullié
Subjects: 0301 basic medicine, biology, Chemistry, Stereochemistry, Mefloquine, 030106 microbiology, Organic Chemistry, Quinoline, Enantioselective synthesis, Biological activity, Plasmodium falciparum, biology.organism_classification, Catalysis, Inorganic Chemistry, 03 medical and health sciences, chemistry.chemical_compound, Enantiopure drug, medicine, Physical and Theoretical Chemistry, Enantiomer, Aminoquinolines, medicine.drug
Abstract: Recently, the asymmetric synthesis and biological activity of ( R )- and ( S )-4-aminoquinolinemethanols 1 as mefloquine analogues were reported. Several compounds showed very promising antimalarial activity, in the nanomolar range, against Plasmodium falciparum 3D7 and W2. Enantiomers with an ( S )-absolute configuration were more active than their ( R )-counterparts by a factor ranging from 2 to 15-fold, according to the compound and the plasmodial strain considered. In continuation of our work, three novel series of enantiopure aminoquinolines 2a , 2b, and 3 were synthesized via an asymmetric aminohydroxylation reaction. These compounds were obtained in 2 or 4 steps from a common amidoalcohol key-intermediate 4 . They displayed IC 50 values close to the micromolar against the two P. falciparum strains 3D7 and W2. The study of the structure–activity relationships allows us to better understand the importance of the substitution and of the stereochemistry at C11 and C12 position of the quinoline and gives tracks for the design of new compounds more active against the plasmodial strains.
Published: 2016
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15. Enantiopure substituted pyridines as promising antimalarial drug candidates

Author: Etienne Pair, Alexandra Dassonville-Klimpt, Catherine Mullié, Guillaume Bentzinger, Jean Guillon, Mathieu Marchivie, Patrice Agnamey, Pascal Sonnet, Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Régulations Naturelles et Artificielles (ARNA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux Ségalen [Bordeaux 2], Institut de Chimie de la Matière Condensée de Bordeaux (ICMCB), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and This project was financed in part from DGA (Direction Générale de l’Armement, Ministère de la Défense, France), ANR Astrid (project ANR-12-STR-003), région Picardie and the SATT Nord. G. B. was the recipient of a grant from Région Picardie. The authors thank Philippe Grellier (Muséum National d’Histoire Naturelle) who graciously provided P. falciparum strains. We thank Sophie Da Nascimento for mass spectra recording.
Subjects: Drug, Enpiroline, media_common.quotation_subject, 010402 general chemistry, 01 natural sciences, Biochemistry, Drug Discovery, medicine, Arylaminoalcohols, Alkyl, media_common, chemistry.chemical_classification, 010405 organic chemistry, Chemistry, Mefloquine, Organic Chemistry, Enantioselective synthesis, Regioselectivity, Asymmetric synthesis, [CHIM.MATE]Chemical Sciences/Material chemistry, Combinatorial chemistry, 3. Good health, 0104 chemical sciences, Enantiopure drug, Malaria P. falciparum, Wittig reaction, SN2 reaction, medicine.drug
Abstract: International audience; We describe the enantioselective synthesis and biological evaluation of 4-(2-amino-1-hydroxyethyl)pyridines (4 AHPs) as new antimalarial drug candidates. In particular, two routes to obtain the key-intermediate 4-vinyl-pyridine were studied. These routes are based on a Kröhnke-type cyclization or on metal-catalyzed reactions. The Kröhnke-type cyclization route is faster but only efficient at low scale since this pathway involves a Wittig reaction that requires severe temperature-control. Consequently, we designed a second route based on metal-catalyzed reactions. This way is longer but the 4-vinyl-pyridine can be obtained on a 5 g scale at least. Finally, a regioselective SN2 ring-opening of enantiopure epoxides by alkyl primary amines allowed the synthesis of eight 4-AHPs with global yields up to 41%. These compounds show strong in vitro antimalarial activity against P. falciparum strains and are more active that chloroquine and mefloquine. These results demonstrate that 4-AHPs are promising antimalarial drug candidates.
Published: 2020
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16. Human cryptosporidiosis in immunodeficient patients in France (2015–2017)

Author: Damien Costa, Romy Razakandrainibe, Marc Sautour, Stéphane Valot, Louise Basmaciyan, Gilles Gargala, Denis Lemeteil, Loïc Favennec, Frédéric Dalle, Anne Debourgogne, Adela Angoulvant, Patrice Agnamey, Julie bonhomme, Brigitte Degeilh, Cathy Chemla, Cécile Garnaud, Coralie Lollivier, Cécile angebault, Pascal Delaunay, Guillaume Desoubeaux, Emilie Fréalle, Frédéric Grenouillet, Florent Morio, Françoise Botterel, Ghania Belkadi, Hélène Yera, Gilles Nevez, Xavier Iriart, Isabelle Accoceberry, Julie Brunet, Marc Thellier, Meja Rabodonirina, Milene Sasso, Charline Miossec, Murielle Nicolas, Nicole Desbois, Philippe Poirier, Christelle Pomares, Sandrine Houze, Yohann Le govic, Anne Pauline Bellanger, Franck Labbe, Marie Laure Darde, Olivier Duquesnoy, Pierre Flori, Patrick Bastien, Thomas Gueudet, Isabelle Villena, Dominique Aubert, Estelle Cateau, Marie-Elisabeth Bougnoux, Nathalie Kapel, Eric Dannaoui, Alexis Valentin, Anne Totet, Jean Menotti, Denis Blanchet, Magalie Demar, Emmanuel Dutoit, Renaud Piarroux, Emilie Sitterle, Denis Magne, Samsa Hamane, Antoine Berry, Cecile Ramade, CHU Rouen, Normandie Université (NU), Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire de parasitologie mycologie (CHU de Dijon), Infections Parasitaires : Transmission, Physiopathologie et Thérapeutiques (IP-TPT), Service de Santé des Armées-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Institut de Recherche pour le Développement (IRD), Epidémiosurveillance de protozooses à transmission alimentaire et vectorielle (ESCAPE), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Reims Champagne-Ardenne (URCA), Appareil Digestif Environnement Nutrition (ADEN ), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Service de Parasitologie-Mycologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Stress, Immunité, Pathogènes (SIMPA), Université de Lorraine (UL), Anofel Cryptosporidium National Network, Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Université de Caen Normandie (UNICAEN), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES), Centre Hospitalier Universitaire de Reims (CHU Reims), Université Grenoble Alpes - UFR Pharmacie (UGA UFRP), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université Paris Descartes - Paris 5 (UPD5), Laboratoire de Parasitologie-Mycologie, Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital l'Archet, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut Pasteur de Dakar, Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre hospitalier universitaire de Nantes (CHU Nantes), École nationale vétérinaire d'Alfort (ENVA), Service de parasitologie-mycologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), Université de Brest (UBO), CHU Bordeaux [Bordeaux], Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Dynamique des interactions Hôte pathogène, Université de Strasbourg (UNISTRA), Immunité et Infection, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Parasitologie et Mycologie, Hospices Civils de Lyon (HCL), Biologie, Génétique et Pathologie des Pathogènes Eucaryotes (MIVEGEC-BioGEPPE), Pathogènes, Environnement, Santé Humaine (EPATH), 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]), Laboratoire de Parasitologie-Mycologie-Sérologies Bactériennes et Parasitaires [CHU de la Martinique], Centre Hospitalier Universitaire de la Martinique - CHU Martinique, Parasitologie-Mycologie Fort de France, CHU Fort de France, Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Hôpital Bichat - Claude Bernard, Service de parasitologie et mycologie [CHRU de Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Neuroépidémiologie Tropicale (NET), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Groupe Immunité des Muqueuses et Agents Pathogènes (GIMAP), Université Jean Monnet [Saint-Étienne] (UJM), CHU Clermont-Ferrand, Laboratoire de Parasitologie-Mycologie (LPM), IFR 53, Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA)-CHU Maison Blanche-UPRES EA 2070, Centre de formation et de recherche sur l'environnement marin (CEFREM), Université de Perpignan Via Domitia (UPVD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Ecologie et biologie des interactions (EBI), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Departments of Medical Parasitology and Mycology, Service de réanimation médicale, Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Laboratoire Hospitalo-Universitaire de Parasitologie-Mycologie, Université des Antilles (UA)-Coordination Régionale de la lutte contre le Virus de L'Immunodéficience Humaine (COREVIH)-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Université de la Méditerranée - Aix-Marseille 2, Laboratoire de parasitologie mycologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe hospitalier Albert Chenevier – Henri Mondor, 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], Région Haute Normandie, Projet COS Sesa, 2015-2018, Université de Reims Champagne-Ardenne (URCA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Coordination Régionale de la lutte contre le Virus de L'Immunodéficience Humaine (COREVIH)-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-Université des Antilles (UA), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Service de Santé des Armées, Université de Rennes (UR), Laboratoire Chrono-environnement (UMR 6249) (LCE), École nationale vétérinaire - Alfort (ENVA), Microbiologie Fondamentale et Pathogénicité (MFP), Université Jean Monnet - Saint-Étienne (UJM), Université de Toulouse (UT), 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], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: 0301 basic medicine, Male, Pediatrics, Epidemiology, Cryptosporidiosis, 0302 clinical medicine, Risk Factors, Child, Immunodeficiency, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, biology, Mortality rate, Cryptosporidium, General Medicine, Middle Aged, 3. Good health, Diarrhea, Infectious Diseases, Cryptosporidium parvum, Child, Preschool, Protozoan, Cyclosporine, Female, Immunotherapy, France, medicine.symptom, Cryptosporidium hominis, Immunosuppressive Agents, Adult, medicine.medical_specialty, Adolescent, 030231 tropical medicine, 030106 microbiology, Immunology, Context (language use), Tacrolimus, 03 medical and health sciences, Immunocompromised Host, Young Adult, medicine, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Immunocompromised, Aged, Immunosuppression Therapy, Infant, Newborn, Infant, Mycophenolic Acid, medicine.disease, biology.organism_classification, Parasitology
Abstract: International audience; Cryptosporidiosis is a common disease in children and immunodeficient individuals. In 2006, a national network was set up on the surveillance of human cryptosporidiosis in France. Since January 2015, the 41 tertiary care hospitals and the 3 private laboratories of the French National Network on the surveillance of human cryptosporidiosis have been able to declare confirmed cases of cryptosporidiosis online. Between 2015 and 2017, 210 cases of cryptosporidiosis were declared in immunodeficient patients in France; Cryptosporidium parvum and Cryptosporidium hominis represented 66% and 22% of cases, respectively. A peak was observed in autumn. Cryptosporidiosis occurred mainly in a context of solid organ transplantation (SOT) (49%) and of HIV infection (30%). In SOT recipients, cryptosporidiosis appeared more frequently in the first 6 months post transplantation. Regarding cases declared in SOT recipients, mycophenolate mofetil was used in 68%. A mortality rate of 6% was observed. Present results underline the importance of screening for cryptosporidiosis in immunocompromised patients suffering from diarrhea, especially in the course of major cell mediated immunodeficiency or even systematic screening before SOT. Exclusive Cryptosporidium free water feeding could be suggested during major cell mediated immunodeficiency.
Published: 2018
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17. Synthesis and Antimalarial Activity of New Enantiopure Aminoalcoholpyrrolo[1,2-a]quinoxalines

Author: Pascal Sonnet, Jean Guillon, Jeremy Schneider, Patrice Agnamey, Catherine Mullié, Solène Savrimoutou, Stéphane Moreau, Anita Cohen, Sébastien Hutter, Alexandra Dassonville-Klimpt, Guillaume Bentzinger, Nadine Azas, Alexia Jonet, Nicolas Taudon, Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche Biomédicale des Armées (IRBA)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU), Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), and Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA)
Subjects: Stereochemistry, [SDV]Life Sciences [q-bio], Plasmodium falciparum, CHO Cells, 010402 general chemistry, 01 natural sciences, chemistry.chemical_compound, Antimalarials, Quinoxaline, Cricetulus, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Cell Line, Tumor, Quinoxalines, Drug Discovery, parasitic diseases, [CHIM]Chemical Sciences, Animals, Humans, Pyrroles, biology, 010405 organic chemistry, Quinoline, Enantioselective synthesis, Chloroquine, Stereoisomerism, biology.organism_classification, Amino Alcohols, 0104 chemical sciences, 3. Good health, Mefloquine, Enantiopure drug, chemistry, Enantiomer, Selectivity, Sharpless asymmetric dihydroxylation
Abstract: International audience; Background: We prepared a novel series of enantiopure mefloquine analogues with pyrrolo[1,2-a]quinoxaline core in order to fight Plasmodium falciparum resistant strain. Objectives: To observe the influence of pyrrolo[1,2-a]quinoxaline core versus quinoline core on the antimalarial activity. Method: Four enantiopure aminoalcoholpyrrolo[1,2-a]quinoxalines 2 were synthetized via Sharpless asymmetric dihydroxylation reaction in eight steps. Their antimalarial activity was evaluated on two Plasmodium falciparum strains 3D7 and W2 with a SYBR Green I fluorescence-based method and their cytotoxicity was measured on four cell lines HepG2, THP-1, CHO and HFF. Results: IC50 values of the four compounds 2 were close to the micromolar against the two P. falciparum strains. They were more active against P. falciparum strain W2 vs. P. falciparum strain 3D7. (R)-enantiomers were always more active than their (S)-counterpart whatever the strain. Selectivity indexes of compounds 2 were lower than 100. Conclusion: A novel series of enantiopure aminoalcohols with pyrrolo[1,2-a]quinoxaline core were synthesized in eight steps. They displayed IC50 values close to the micromolar against two P. falciparum strains 3D7 and W2. Although, In this series, 2,8-bistrifluoromethylquinoline was a best core than pyrrolo[1,2-a]quinoxaline for an optimal antimalarial activity, the pyrroloquinoxaline 2b showed an interesting antimalarial activity.
Published: 2018
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18. Design, synthesis and biological evaluation of novel 4-alkapolyenylpyrrolo[1,2-a]quinoxalines as antileishmanial agents – Part III

Author: Luisa Ronga, Noël Pinaud, Patrice Le Pape, Philippe Vincendeau, Solène Savrimoutou, Patrice Agnamey, Claire Soum, Sylvie Daulouède, Sébastien Hutter, Nadine Azas, Anita Cohen, Jean Guillon, Catherine Mullié, Natacha Farvacques, Fabrice Pagniez, Pascal Sonnet, Marco Del Favero, Université de Bordeaux (UB), Régulations Naturelles et Artificielles (ARNA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux Ségalen [Bordeaux 2], Aix-Marseille Université - Faculté de pharmacie (AMU PHARM), Aix Marseille Université (AMU), Cibles et Médicaments des Infections et de l'Immunité (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Université de Bordeaux, ARNA Laboratory (U869), Laboratoire de Glycochimie, des Antimicrobiens et des Agro-ressources - UMR CNRS 7378 (LG2A ), Université de Picardie Jules Verne (UPJV)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux Ségalen [Bordeaux 2], Laboratoire de parasitologie et de mycologie médicales [CHU Amiens], CHU Amiens-Picardie, Infections Parasitaires : Transmission, Physiopathologie et Thérapeutiques (IP-TPT), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Service de Santé des Armées, Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), and Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie
Subjects: Suzuki reaction, Antiparasitic, medicine.drug_class, Stereochemistry, Plasmodium falciparum, Trypanosoma brucei brucei, Antitrypanosomal activity, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Trypanosoma brucei, Antimalarial activity, Synthesis, Mice, Structure-Activity Relationship, chemistry.chemical_compound, Quinoxaline, Parasitic Sensitivity Tests, Pyrrolo[1, Quinoxalines, 2-a] quinoxaline, parasitic diseases, Drug Discovery, medicine, Animals, Humans, [CHIM]Chemical Sciences, Cytotoxicity, Cell Proliferation, Leishmania, Pharmacology, Dose-Response Relationship, Drug, Molecular Structure, biology, Chemistry, Macrophages, Alkaloid, Organic Chemistry, Hep G2 Cells, General Medicine, Antileishmanial activity, biology.organism_classification, Trypanocidal Agents, Combinatorial chemistry, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Trypanosomiasis, African, Drug Design, Antiprotozoal, Female
Abstract: cited By 8; International audience; A series of new 4-alkapolyenylpyrrolo[1,2-a]quinoxaline derivatives, original and structural analogues of alkaloid chimanine B and of previously described 4-alkenylpyrrolo[1,2-a]quinoxalines, was synthesized in good yields using efficient palladium-catalyzed Suzuki-Miyaura cross-coupling reactions. These new compounds were tested for in vitro antiparasitic activity upon three Leishmania spp. strains. Biological results showed activity against the promastigote forms of L. major, L. mexicana and L. donovani with IC50 ranging from 1.2 to 14.7 μM. In attempting to investigate if our pyrrolo[1,2-a]quinoxaline derivatives are broad-spectrum antiprotozoal compounds activities toward one Trypanosoma brucei brucei strain and the W2 and 3D7 Plasmodium falciparum strains were also investigated. In parallel, the in vitro cytotoxicity of these molecules was assessed on the murine J774 and human HepG2 cell lines. Structure-activity relationships of these new synthetic compounds are here discussed. © 2014 Elsevier Inc. All rights reserved.
Published: 2014
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19. CryptosporidiumContamination of Surface and Water Supplies in Haiti

Author: Evens Emmanuel, Philippe Brasseur, Christian Raccurt, Patrice Agnamey, Michel Vaillant, Jean W. Pape, Centre Lillois d’Études et de Recherches Sociologiques et Économiques - UMR 8019 (CLERSÉ), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Anofel Cryptosporidium National Network, Centre de Recherche et d'Appui aux Politiques Urbaines (CRAPU), Université Quisqueya, Centre de Recherche et d'Appui aux Politiques Urbaines, Port-au-Prince, Haïti. (uniQ), CRP-Santé Luxembourg, Department of Medical Parasitology and Mycology, and Departments of Medical Parasitology and Mycology
Subjects: Veterinary medicine, Health, Toxicology and Mutagenesis, 030231 tropical medicine, Cryptosporidium, Water supply, Fresh Water, Microbial contamination, Toxicology, 03 medical and health sciences, 0302 clinical medicine, Port au prince, Water Supply, parasitic diseases, Humans, surface, water supplies, 030212 general & internal medicine, Port-au-Prince, ComputingMilieux_MISCELLANEOUS, General Environmental Science, biology, business.industry, Public Health, Environmental and Occupational Health, Contamination, Listed company, biology.organism_classification, Cryptosporidium oocysts, Haiti, 6. Clean water, 3. Good health, waters, Oocytes, Environmental science, Water quality, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Water Microbiology, business, environment, Surface water
Abstract: Cryptosporidiosis is one of the most frequent causes of diarrhea in Haiti. Transmission in children less than five years-old, HIV-infected individuals, and people living in low socio-economic conditions is frequently due to consumption of water or food contaminated by Cryptosporidium oocysts. This study examined the circulation of Cryptosporidium oocysts in surface waters and in public water supplies in the district of Port-au-Prince. Data were gathered from December 2000 to June 2002 in 37 sites. In the district of Port-au-Prince, 24/37 samples of water collected (65%) were contaminated by Cryptosporidium oocysts and 10/11 (91%) of those collected in reservoirs used by people living in peripheral areas. The rate of contamination was 7/13 (54%) in water from public standpipes provided by the public company of water distribution. All surface water (4/4) collected was highly contaminated.
Published: 2011
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20. Presence of Cryptosporidium Oocysts and Giardia Cysts in the Surface Water and Groundwater in the City of Cayes, Haiti

Author: Evens Emmanuel, Obicson Lilite, Christian Raccurt, Philippe Brasseur, Ketty Balthazard-Accou, Anne Totet, and Patrice Agnamey
Subjects: Hydrology, biology, Giardia, Cryptosporidium, General Medicine, biology.organism_classification, Surface water, Groundwater
Published: 2009
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21. Time and Temperature Effects on the Viability and Infectivity of Cryptosporidium parvum Oocysts in Chlorinated Tap Water

Author: Xunde Li, Chu Clemenceau, Philippe Brasseur, Jean Jacques Ballet, and Patrice Agnamey
Subjects: Cryptosporidium parvum, Infectivity, Time Factors, Survival, animal diseases, Oocysts, Temperature, Public Health, Environmental and Occupational Health, Biology, biology.organism_classification, Microbiology, Apicomplexa, Mice, Animal science, Animals, Newborn, Tap water, Water Supply, In vivo, parasitic diseases, Animals, Environmental Chemistry, Bioassay, Biological Assay, General Environmental Science
Abstract: The authors compared the viability and infectivity of Cryptosporidium parvum oocysts in chlorinated tap water at various storage durations (i.e., 2 wk, 4 wk, 6 wk, or 8 wk) and at 2 cool temperatures (i.e., 10 degrees C and 4 degrees C), using in vitro (excystation) and in vivo (suckling mouse) methods. After 8 wk, mean oocyst excystation decreased to 33.4% and 26.7% at 10 degrees C and 4 degrees C, respectively. Suckling mice infectivity was higher after storage at 10 degrees C than after storage at 4 degrees C. These data suggest that Cryptosporidium parvum oocysts can survive and remain infectious for 8 wk in cool chlorinated tap water.
Published: 2004
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22. Evaluation of Four Commercial Rapid Immunochromatographic Assays for Detection of Cryptosporidium Antigens in Stool Samples: a Blind Multicenter Trial

Author: Meja Rabodoniriina, Claudine Sarfati, Cécile Garnaud, Jean-François Garin, Momar Diouf, Nathalie Kapel, Patrice Agnamey, Claudine Pinel, Emmanuel Dutoit, Francis Derouin, and Anne Totet
Subjects: Microbiology (medical), animal diseases, Cryptosporidiosis, Cryptosporidium, Antigens, Protozoan, Sensitivity and Specificity, Cryptosporidium species, Microbiology, Feces, Antigen, Multicenter trial, parasitic diseases, Humans, Medicine, Immunochromatographic Assays, Immunoassay, biology, Clinical Laboratory Techniques, business.industry, Assay sensitivity, biology.organism_classification, Cryptosporidium parvum, Multicenter study, Parasitology, business
Abstract: In a multicenter study, potassium dichromate-preserved stools from patients infected with Cryptosporidium parvum ( n = 20), C. hominis ( n = 20), and other Cryptosporidium species ( n = 10) and 60 controls were examined using four immunochromatographic assays. Assay sensitivity ranged between 50.1% and 86.7% for C. parvum and C. hominis but was
Published: 2011
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23. Enantiomerically pure amino-alcohol quinolines: in vitro anti-malarial activity in combination with dihydroartemisinin, cytotoxicity and in vivo efficacy in a Plasmodium berghei mouse model

Author: Catherine Mullié, Alexia Jonet, Camille Degrouas, Patrice Agnamey, Nicolas Taudon, Pascal Sonnet, Aurélie Pascual, Laboratoire de Glycochimie, des Antimicrobiens et des Agro-ressources - UMR CNRS 7378 (LG2A ), Université de Picardie Jules Verne (UPJV)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Infections Parasitaires : Transmission, Physiopathologie et Thérapeutiques (IP-TPT), Service de Santé des Armées-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Institut de Recherche pour le Développement (IRD), 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, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Laboratoire de parasitologie et de mycologie médicales [CHU Amiens], CHU Amiens-Picardie, Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Service de Santé des Armées, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, and HAL AMU, Administrateur
Subjects: Erythrocytes, Plasmodium berghei, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Quinoline, Pharmacology, 0302 clinical medicine, Parasitic Sensitivity Tests, Isobologram, Artemisinin, ComputingMilieux_MISCELLANEOUS, Mice, Inbred BALB C, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Enantiomer, biology, Anti-malarial activity, Drug Synergism, Haemolysis, Artemisinins, 3. Good health, in vivo, Treatment Outcome, Dihydroartemisinin, Infectious Diseases, Combination, Quinolines, Drug Therapy, Combination, Female, medicine.drug, Combination therapy, Plasmodium falciparum, 030231 tropical medicine, Hemolysis, Antimalarials, Inhibitory Concentration 50, 03 medical and health sciences, In vivo, parasitic diseases, medicine, Animals, 030306 microbiology, Research, biology.organism_classification, Survival Analysis, In vitro, Malaria, Disease Models, Animal, Parasitology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Background: As resistance to marketed anti-malarial drugs continues to spread, the need for new molecules active on Plasmodium falciparum-resistant strains grows. Pure (S) enantiomers of amino-alcohol quinolines previously displayed a good in vitro anti-malarial activity. Therefore, a more thorough assessment of their potential clinical use through a rodent model and an in vitro evaluation of their combination with artemisinin was undertaken. Methods: Screening on a panel of P. falciparum clones with varying resistance profiles and regional origins was performed for the (S)-pentyl and (S)-heptyl substituted quinoline derivatives, followed by an in vitro assessment of their combination with dihydroartemisinin (DHA) on the 3D7 clone and an in vivo assay in a mouse model infected with Plasmodium berghei. Their haemolytic activity was also determined. Results: A steady anti-malarial activity of the compounds tested was found, whatever the resistance profile or the regional origin of the strain. (S)-quinoline derivatives were at least three times more potent than mefloquine (MQ), their structurally close parent. The in vitro combination with DHA yielded an additive or synergic effect for both that was as good as that of the DHA/MQ combination. In vivo, survival rates were similar to those of MQ for the two compounds at a lower dose, despite a lack of clearance of the parasite blood stages. A 50% haemolysis was observed for concentrations at least 1,000-fold higher than the antiplasmodial IC 50 s. Conclusions: The results obtained make those two (S)-amino-alcohol quinoline derivatives good candidates for the development of new artemisinin-based combination therapy (ACT), hopefully with fewer neurologic side effects than those currently marketed ACT, including MQ.
Published: 2014
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24. Influence of ionic strength and soil characteristics on the behavior of Cryptosporidium oocysts in saturated porous media

Author: Justin André Casimir, Ketty Balthazard-Accou, Patrice Agnamey, Evens Emmanuel, Philippe Brasseur, Urbain Fifi, Université Quisqueya, Laboratoire LAQUE, Université de Quisqueya, Anofel Cryptosporidium National Network, Centre Lillois d’Études et de Recherches Sociologiques et Économiques - UMR 8019 (CLERSÉ), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche et d'Appui aux Politiques Urbaines (CRAPU), and Université Quisqueya, Centre de Recherche et d'Appui aux Politiques Urbaines, Port-au-Prince, Haïti. (uniQ)
Subjects: Environmental Engineering, Soil test, Health, Toxicology and Mutagenesis, 0207 environmental engineering, 02 engineering and technology, Electrolyte, 010501 environmental sciences, 01 natural sciences, Soil, Adsorption, Soil pH, Environmental Chemistry, Animals, 020701 environmental engineering, ComputingMilieux_MISCELLANEOUS, 0105 earth and related environmental sciences, Cryptosporidium parvum, Chemistry, [SDE.IE]Environmental Sciences/Environmental Engineering, Osmolar Concentration, Public Health, Environmental and Occupational Health, Oocysts, General Medicine, General Chemistry, Pollution, Ionic strength, Environmental chemistry, Soil water, Porous medium, Porosity, Groundwater
Abstract: The physico-chemical behavior of Cryptosporidium oocysts was investigated during their transfer through an alluvial formation from Les Cayes (Haiti) via batch tests. Five approximately 3 kg soil samples were collected and combined prior to batch tests from the alluvial formations. The experiments were carried out at soil pH by equilibrating different ranges of pure oocysts concentrations and soil samples with 3 mM CaCl 2 and 1 mM NaBr as electrolyte. We used the Debye–Huckel equation describing ion activity in a solution for a given ionic strength. The equilibrium adsorption mechanism is used to enumerate the oocysts in the soil. The results suggest that the oocysts behavior in porous media depends on soil characteristics such as soil pH, the nature of the mineral and organic constituents of the soil and the ionic strength and activities in solution. These results show that a total transfer in batch containing NaBr solutions against a partial one in batch containing CaCl 2 solutions depends on the oocysts media concentration. To confirm the oocysts number retained in soil, confocal microscopy was successfully used and the images demonstrate that the majority of oocysts were retained at the range of concentrations tested. The findings from this study demonstrated that the retention of C. Parvum in soils may be influenced by chemical conditions and soils characteristics, which are important for groundwater risk assessment.
Published: 2014
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25. Digestive Cryptosporidiosis in an Allogeneic Hematopoietic Stem Cell Transplant Recipient: A Case Report

Author: Denis Chatelain, Marjorie Cornu, ine Charbonnier, Anne Totet, and Patrice Agnamey
Subjects: biology, business.industry, Transplant recipient, Nitazoxanide, Cryptosporidium, Delayed diagnosis, biology.organism_classification, Immune system, Immunology, medicine, Allogeneic hematopoietic stem cell transplant, medicine.symptom, Stem cell, business, Confusion, medicine.drug
Abstract: Cryptosporidium has emerged as a major cause of diarrheal illness worldwide, especially among young children and patients with infectious or iatrogenic immune deficiencies. The authors report a case of mild cryptosporidiosis with delayed diagnosis in a stem cell transplant recipient probably due to confusion between digestive cryptosporidiosis and acute gastrointestinal graft-versus-host-disease. Clinical and parasitologic improvement was observed after a 3-day course of nitazoxanide and especially a reduction of immunosuppressive therapy.
Published: 2014
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26. Inhibition of complete development ofCryptosporidium parvum in Caco-2 cells

Author: M. Egraz-Bernard, Loïc Favennec, Patrice Agnamey, Philippe Brasseur, and J. J. Ballet
Subjects: Microbiology (medical), medicine.medical_specialty, Infectious Diseases, Medical microbiology, Cryptosporidium parvum, biology, Caco-2, Chemistry, medicine, General Medicine, biology.organism_classification, Microbiology
Published: 1996
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27. Cross-Sectional Serological Survey of Human Fascioliasis in Haiti

Author: Anne Totet, Patrice Agnamey, C. P. Raccurt, E. Fortes-Lopes, and J. Boncy
Subjects: Veterinary medicine, Pathology, medicine.medical_specialty, biology, Article Subject, business.industry, Serum samples, biology.organism_classification, Serology, lcsh:Infectious and parasitic diseases, Infectious Diseases, Caribbean region, Human fascioliasis, Medicine, Fasciola hepatica, Population study, Parasitology, lcsh:RC109-216, business, Martinique, Research Article
Abstract: Fasciola hepatica, the aetiological agent of fascioliasis in the Caribbean region, occurs throughout the major islands of the Greater Antilles and in localised zones on two islands (Martinique and Saint Lucia) of the Lesser Antilles. However, apart from Puerto Rico, information regarding human fascioliasis in islands of the Caribbean is out of date or unavailable, or even nonexistent as in Haiti. The authors conducted a retrospective, cross-sectional serological survey in Port-au-Prince using a Western blotting test (LDBIO Diagnostics) on human fascioliasis in Haiti. A total of 216 serum samples obtained from apparently healthy adults were tested. The frequency of antibodies in serum samples of the study population was 6.5% (14/216). The immunodominant bands recognised in Western blots were 27-28 kDa (100%), 42 kDa (64%), 60 kDa, and 8-9 kDa (28%). This is the first survey to reveal a relatively low proportion of asymptomaticF. hepatica-infected humans in Haiti.
Published: 2012

28. Changing patterns of malaria during 1996-2010 in an area of moderate transmission in Southern Senegal

Author: M. Badiane, Patrice Agnamey, M. Cisse, Philippe Brasseur, Michel Vaillant, and Piero Olliaro
Subjects: Adult, Male, medicine.medical_specialty, Pediatrics, lcsh:Arctic medicine. Tropical medicine, Adolescent, lcsh:RC955-962, Amodiaquine, lcsh:Infectious and parasitic diseases, law.invention, Antimalarials, Young Adult, law, parasitic diseases, Epidemiology, medicine, Humans, lcsh:RC109-216, Child, Aged, Rapid diagnostic test, business.industry, Incidence, Research, Incidence (epidemiology), Infant, Newborn, Infant, Middle Aged, medicine.disease, Artemisinins, Senegal, Malaria, Dispensary, Drug Combinations, Infectious Diseases, Transmission (mechanics), Child, Preschool, Tropical medicine, Female, Parasitology, business, Demography, medicine.drug
Abstract: Background Malaria is reportedly receding in different epidemiological settings, but local long-term surveys are limited. At Mlomp dispensary in south-western Senegal, an area of moderate malaria transmission, year-round, clinically-suspected malaria was treated with monotherapy as per WHO and national policy in the 1990s. Since 2000, there has been a staggered deployment of artesunate-amodiaquine after parasitological confirmation; this was adopted nationally in 2006. Methods Data were extracted from clinic registers for the period between January 1996 and December 2010, analysed and modelled. Results Over the 15-year study period, the risk of malaria decreased about 32-times (from 0.4 to 0.012 episodes person-year), while anti-malarial treatments decreased 13-times (from 0.9 to 0.07 treatments person-year) and consultations for fever decreased 3-times (from 1.8 to 0.6 visits person-year). This was paralleled by changes in the age profile of malaria patients so that the risk of malaria is now almost uniformly distributed throughout life, while in the past malaria used to concern more children below 16 years of age. Conclusions This study provides direct evidence of malaria risk receding between 1996-2010 and becoming equal throughout life where transmission used to be moderate. Infection rates are no longer enough to sustain immunity. Temporally, this coincides with deploying artemisinin combinations on parasitological confirmation, but other contributing causes are unclear.
Published: 2011
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29. Childhood Cryptosporidiosis: A Case Report

Author: Anne Totet, C. da Costa, Patrice Agnamey, A. Vanrenterghem, D. Djeddi, N. Brahimi, and A. Diallo
Subjects: Pathology, medicine.medical_specialty, Pediatrics, biology, business.industry, Cryptosporidium, Nitazoxanide, Case Report, biology.organism_classification, lcsh:Infectious and parasitic diseases, Infectious Diseases, Pharmacotherapy, Immune system, Medicine, lcsh:RC109-216, Parasitology, business, medicine.drug
Abstract: Cryptosporidiumhas emerged as an important cause of diarrheal illness worldwide, especially amongst young children and patients with infectious or iatrogenic immune deficiencies. The authors describe a case of mild cryptosporidiosis in a well-nourished, immunocompetent, one-year-old child. Rapid clinical and parasitological improvement was observed after a 3-day course of nitazoxanide.
Published: 2010

30. Laboratory-based surveillance for Cryptosporidium in France, 2006-2009

Author: D. Haouchine, Sandrine Houzé, Didier Basset, Adela Angoulvant, C. Chartier, Eric Dannaoui, Christine Aznar, Francis Derouin, Gabriela Certad, Frédéric Dalle, B. Degeilh, Jean-Marc Dewitte, Françoise Botterel, Marie-Laure Dardé, Chantal Duhamel, A. Berry, Marie-Elisabeth Bougnoux, M. Cambon, Patrice Agnamey, G. Belkadi, B. Couprie, Bernard Carme, Patrice Bourée, Pierre Buffet, Pascal Beaudeau, E. Dei Cas, Thanh Hai Duong, Alain Bonnin, Karine Guyot, Dominique Aubert, Frédéric Grenouillet, Pierre Flori, Jean Dupouy-Camet, Loïc Favennec, Gilles Gargala, N. Desbois, Nausicaa Gantois, Ml Grillot, Alexandra Faussart, Anofel Cryptosporidium National Network, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Service des maladies infectieuses et tropicales [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Laboratoire Hospitalo-Universitaire de Parasitologie-Mycologie, Coordination Régionale de la lutte contre le Virus de L'Immunodéficience Humaine (COREVIH)-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-Université des Antilles (UA), Laboratoire de Parasitologie-Mycologie, Centre Hospitalier Universitaire Lapeyronnie, Département santé environnement, Institut de Veille Sanitaire (INVS), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de parasitologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service de Parasitologie - Mycologie [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Immunité et Infection, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), Epidémiologie des parasitoses et mycoses tropicales, Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris (AP-HP), Centre National de Référence (CNR) Toxoplasmose/Toxoplasma Biological Resource Center (BRC) (CNR Toxoplasmose-Toxoplasma BRC), CHU Limoges, Université de Limoges (UNILIM), Neuroépidémiologie Tropicale et Comparée (NETEC), Université de Limoges (UNILIM)-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Parasitologie-Mycologie Fort de France, CHU Fort de France, Groupe Immunité des Muqueuses et Agents Pathogènes (GIMAP), Université Jean Monnet [Saint-Étienne] (UJM), Appareil Digestif Environnement Nutrition (ADEN ), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), The ANOFEL Cryptosporidium National Network (ACNN) is supported by a grant from InVS and ANOFEL. The genotyping was also supported financially by the French Ministry of Research (EA 3609)., We thank Nathalie Lelieur for providing useful assistance in data analysis, Anthony Pinon for his advice on statistics and Annie Sulahian for English revision of the manuscript., Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Service de parasitologie - mycologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR113-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre d’Infection et d’Immunité de Lille (CIIL) - U1019 - UMR 8204 ( CIIL ), Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR142-Université de Lille-Centre National de la Recherche Scientifique ( CNRS ), CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Coordination Régionale de la lutte contre le Virus de L'Immunodéficience Humaine (COREVIH)-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-Université des Antilles ( UA ), Institut de Veille Sanitaire, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Hôpital Necker, Assistance publique - Hôpitaux de Paris (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Université Pierre et Marie Curie - Paris 6 ( UPMC ) -IFR113-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université des Antilles et de la Guyane ( UAG ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre National de Référence (CNR) Toxoplasmose/Toxoplasma Biological Resource Center (BRC) ( CNR Toxoplasmose-Toxoplasma BRC ), Université de Limoges ( UNILIM ), Neuroépidémiologie Tropicale et Comparée ( NETEC ), Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Université de Limoges ( UNILIM ), Groupe Immunité des Muqueuses et Agents Pathogènes ( GIMAP ), Université Jean Monnet [Saint-Étienne] ( UJM ), Appareil Digestif Environnement Nutrition ( ADEN ), Université de Rouen Normandie ( UNIROUEN ), Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Jean Monnet - Saint-Étienne (UJM), and Laboratoire Chrono-environnement (UMR 6249) (LCE)
Subjects: Male, Veterinary medicine, MESH: Cryptosporidium, Epidemiology, MESH : Aged, Cryptosporidiosis, MESH : Child, Preschool, 0302 clinical medicine, MESH: Aged, 80 and over, MESH : Child, MESH: Child, Genotype, MESH : Population Surveillance, MESH : Female, Child, Aged, 80 and over, MESH: Aged, 0303 health sciences, MESH: Middle Aged, Incidence (epidemiology), MESH: Infant, Newborn, Cryptosporidium, MESH : Infant, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, Middle Aged, MESH : Adult, MESH: Infant, 3. Good health, MESH : Cryptosporidium, Canis, MESH: Young Adult, Child, Preschool, Population Surveillance, Female, France, Adult, medicine.medical_specialty, Adolescent, MESH : Male, MESH: Disease Notification, 030231 tropical medicine, MESH : Young Adult, Biology, MESH : Infant, Newborn, MESH: Population Surveillance, Young Adult, 03 medical and health sciences, Virology, MESH : Adolescent, medicine, Humans, MESH : Middle Aged, MESH : France, MESH : Aged, 80 and over, MESH : Cryptosporidiosis, Disease Notification, Genotyping, Aged, 030304 developmental biology, MESH: Adolescent, MESH: Humans, Public health, MESH : Humans, MESH: Child, Preschool, MESH: Cryptosporidiosis, Infant, Newborn, Public Health, Environmental and Occupational Health, Infant, MESH : Disease Notification, MESH: Adult, biology.organism_classification, MESH: Male, MESH: France, Parasitology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Female, Demography
Abstract: International audience; In 2002, the French Food Safety Agency drew attention to the lack of information on the prevalence of human cryptosporidiosis in the country. Two years later, the ANOFEL Cryptosporidium National Network (ACNN) was set up to provide public health authorities with data on the incidence and epidemiology of human cryptosporidiosis in France. Constituted on a voluntary basis, ACNN includes 38 hospital parasitology laboratories (mainly in university hospitals). Each laboratory is engaged to notify new cases of confirmed human cryptosporidiosis, store specimens (e.g. stools, duodenal aspirates or biopsies) and related clinical and epidemiological data, using data sheet forms. From January 2006 to December 2009, 407 cryptosporidiosis cases were notified in France and 364 specimens were collected. Of the notified cases, 74 were children under four years of age, accounting for 18.2%. HIV-infected and immunocompetent patients represented 38.6% (n=157) and 28% (n=114) of cases, respectively. A marked seasonal pattern was observed each year, with increased number of cases in mid to late summer and the beginning of autumn. Genotyping of 345 isolates from 310 patients identified C. parvumin 168 (54.2%) cases, C. hominis in 113 (36.4%) and other species in 29 (9.4%), including C. felis (n=15), C. meleagridis (n=4), C. canis (n=4), Cryptosporidium chipmunk genotype (n=1), Cryptosporidium rabbit genotype (n=1) and new Cryptosporidium genotypes (n=4). These data represent the first multisite report of laboratory-confirmed cases of cryptosporidiosis in France.
Published: 2010
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31. Seroprevalence of human Taenia solium cysticercosis in Haiti

Author: Patrice Agnamey, Christian Raccurt, Anne Totet, Jean Hugues Henrys, and J. Boncy
Subjects: Adult, medicine.medical_specialty, Veterinary medicine, Neurocysticercosis, Blotting, Western, Prevalence, Helminthiasis, Antibodies, Helminth, Enzyme-Linked Immunosorbent Assay, Serology, Seroepidemiologic Studies, Taenia solium, medicine, Seroprevalence, Animals, Humans, business.industry, Cysticercosis, Public health, General Medicine, medicine.disease, Haiti, medicine.drug_formulation_ingredient, Cross-Sectional Studies, Animal Science and Zoology, Parasitology, business
Abstract: Human Taenia solium cysticercosis is common in developing countries due to poor sanitary conditions and economics based on breeding livestock, especially pigs, with low hygiene standards. Neurocysticercosis, caused by migration of the larvae of the tapeworm in the nervous system, is the leading cause of acquired epilepsy in adults in Central and South America, sub-Saharan Africa, and East and South Asia. This makes neurocysticercosis a large public health problem in developing countries. Two clinical cases of neurocysticercosis have been observed recently in Haiti. In order to evaluate the prevalence of human T. solium cysticercosis in this country, in 2007 we conducted a cross-sectional serological retrospective survey using a Western blotting test (LDBIO Diagnostics®) in Port-au-Prince, where sewage systems are rare and swine usually roam freely throughout the area. A total of 216 serum samples, obtained from healthy adults seen in the work setting of periodical medical visits, were tested after storage at − 20°C. The frequency of antibodies in serum samples of the study population was 2.8% (6/216). The immunodominant bands recognized in Western blots were 23–26 kDa (100%), 39 kDa (67%), 45 kDa and 6–8 kDa (50%), 50–55 kDa (33%). These results confirm for the first time an endemic situation of cysticercosis in humans in Haiti, with similar prevalence as that reported in other Latin American and African countries. It reinforces the urgent need for control and prevention measures to be taken by local public health services.
Published: 2009

32. Dosing accuracy of artesunate and amodiaquine as treatment for falciparum malaria in Casamance, Senegal

Author: Piero Olliaro, Walter R. J. Taylor, M. Badiane, M. Cisse, Philippe Brasseur, Michel Vaillant, Oumar Gaye, and Patrice Agnamey
Subjects: Adult, Male, medicine.medical_specialty, Combination therapy, Adolescent, Artesunate, Amodiaquine, Pharmacology, Gastroenterology, Severity of Illness Index, amodiaqine, Drug Administration Schedule, chemistry.chemical_compound, Antimalarials, Pharmacotherapy, Internal medicine, Medicine, Humans, Dosing, Risk factor, Malaria, Falciparum, Child, business.industry, Body Weight, Public Health, Environmental and Occupational Health, Artemisinins, dosing, Senegal, Drug Combinations, Infectious Diseases, Treatment Outcome, Tolerability, chemistry, Relative risk, Child, Preschool, falciparum malaria, Parasitology, Female, artesunate, business, presentation, medicine.drug
Abstract: Summary objectives Several products of artesunate plus amodiaquine (AS + AQ) are being deployed in malariaendemic countries for treating uncomplicated falciparum malaria but dosing accuracy and consequential effects on efficacy and tolerability have not been examined. methods Patients with parasitologically confirmed, uncomplicated falciparum malaria were treated and followed by research teams or local health centre staff in Casamance, Senegal. AS + AQ was given as: (i) loose combination (AS 50 mg, AQ 200 mg), dosed on body weight, or (ii) co-blistered product (AS 50 mg, AQ 153 mg) dosed by weight or age. Target doses were: (i) AS 4 (2‐10) mg ⁄kg ⁄day and (ii) AQ 10 (7.5‐15) mg ⁄kg ⁄day. Patients receiving therapeutic doses defined dosing accuracy. Treatmentemergent signs and symptoms (TESS) were recorded. results A total of 3277 patients were treated with loose (n = 1972, weight-dosed) or co-blistered (n = 1305, 962 age-dosed, 343 weight-dosed) AS + AQ by the research team (n = 966) or clinic staff (n = 2311). AS was dosed correctly in >99% with all regimens. Loose AQ by weight was 98% correct. The co-blister AQ overdosed 18% of patients when dosed by age and underdosed 13% by weight. Low weight was an independent risk factor for overdosing. The co-blister had significantly more TESS than the loose product [117 ⁄1305 (9%) vs. 41 ⁄1972 (2%), relative risk = 4.3 (95% CI: 3.0‐6.1, P < 0.0001)]. Age-based dosing accounted for the difference. TESS occurred mostly within one day (72%) and were mild or moderate (75%). conclusion Artesunate is easier to dose than AQ. Currently available age-dosed, co-blistered AS + AQ tends to overdose AQ and is less well tolerated than loose tablets. It is not the optimal presentation of AS + AQ.
Published: 2008

33. Efficacy and safety of artesunate plus amodiaquine in routine use for the treatment of uncomplicated malaria in Casamance, southern Sénégal

Author: Philippe Brasseur, Michel Vaillant, Walter R. J. Taylor, Oumar Gaye, Piero Olliaro, and Patrice Agnamey
Subjects: medicine.medical_specialty, lcsh:Arctic medicine. Tropical medicine, Combination therapy, lcsh:RC955-962, Plasmodium falciparum, Artesunate, Amodiaquine, lcsh:Infectious and parasitic diseases, Antimalarials, chemistry.chemical_compound, Pharmacotherapy, Internal medicine, Outpatients, medicine, Animals, Humans, lcsh:RC109-216, Malaria, Falciparum, Artemisinin, Adverse effect, business.industry, Research, medicine.disease, Artemisinins, Senegal, Surgery, Drug Combinations, Treatment Outcome, Infectious Diseases, chemistry, Vomiting, Parasitology, Safety, medicine.symptom, business, Sesquiterpenes, Malaria, medicine.drug
Abstract: Background There are no data on the long term use of an artemisinin combination treatment in moderate or high transmission areas of Africa. Methods and findings Artesunate plus amodiaquine (AS+AQ) was used to treat slide-proven Plasmodium falciparum-infected patients of all ages in the Oussouye district, Casamance, Senegal, over a period of six years (2000 to 2005). Efficacy, by Kaplan Meier survival analysis (n = 966), and safety (adverse event rates, n = 752) were determined over 28 days. A weight-based dosing regimen was used for the loose tablets during 2000–2003 (n = 731) and a commercially available co-blister was used during 2004–2005 (n = 235). Annual crude (non PCR corrected) rates remained stable over the study period [range 88.5–96.7%; overall 94.6 (95% CI 92.9–95.9)]. Nine co-blister treated patients (0.9%) withdrew because of drug-related adverse events; seven had gastrointestinal complaints of whom two were hospitalized for vomiting. By Day 28, the mean total bilirubin (n = 72), AST (n = 94) and ALT (n = 95) values decreased. Three patients had Day 28 AST/ALT values > 40 < 200 IU/L. Changes in white cell counts were unremarkable (n = 87). Conclusion AS+AQ in combination was highly efficacious and well-tolerated in this area and justifies the decision to use it as first line treatment. Long-term monitoring of safety and efficacy should continue.
Published: 2007
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34. [Human cryptosporidiosis and Cryptosporidium spp. in Haiti]

Author: Christian P, Raccurt, Philippe, Brasseur, Rose I, Verdier, Xunde, Li, Etna, Eyma, Christine Pannier, Stockman, Patrice, Agnamey, Karine, Guyot, Anne, Totet, Bernard, Liautaud, Gilles, Nevez, Eduardo, Dei-Cas, and Jean W, Pape
Subjects: Adult, Cryptosporidium parvum, Diarrhea, AIDS-Related Opportunistic Infections, Genotype, Oocysts, Cryptosporidiosis, Cryptosporidium, Haiti, Feces, Species Specificity, Animals, Humans, Prospective Studies, Child
Abstract: Contamination by water-born infectious diseases is closely linked to urban slums conditions such as overcrowding and high level of faecal pollution by animal and human excreta. In this environment, cryptosporidiosis is a major cause of acute diarrhoea in children and chronic persistent diarrhoea in AIDS patients, resulting in increased morbidity and mortality in both populations. The aims of this study conducted in Port-au-Prince, Haiti were to: (i) determine the frequency of Cryptosporidium infection in two populations of patients with diarrhoea, children and AIDS patients, and the existence of Cryptosporidium carriage in healthy adults living in close contact with them; (ii) identify by molecular genotyping the Cryptosporidium species involved; and (iii) evaluate the viability of Cryptosporidium oocysts isolated from human stools. From January 2000 to January 2001, 158 of 1529 diarrhoea stool samples collected from 93 patients with diarrhoea, 57 adults followed at Centres GHESKIO and 36 children admitted at the University Hospital in Port-au-Prince contained Cryptosporidium oocysts (10.3%). The majority of adult patients (98%) were HIV-infected whereas the majority of children (81%) tested negative for HIV. Cryptosporidium was documented in only 1/102 healthy persons living in contact with Cryptosporidium infected patients and infection was with the same genotype as that of the contact patient. Among the 69 Cryptosporidium isolates studied for genotyping, three species were identified: C. hominis (59%), C. parvum (38%) and C. felis (3%). The two C. felis cases are the first reported from AIDS patients in the Caribbean. Most of the children regardless of their HIV status were infected with C. hominis (72%), whereas AIDS patients were more likely to be infected by either human or animal genotypes. These data confirm that immunocompromised individuals are susceptible to a wide range of Cryptosporidium spp. Viability of Cryptosporidium oocysts were determined in an experimental mouse model for 17/18 specimen studied including in 12/13 C. hominis, 4/4 C. parvum and 1/1 C. felis. Infectivity in newborn mice was found to be dose-dependent and more effective with C. parvum than the other two genotypes. Cryptosporidiosis remains a frequent hazard for both AIDS patients and young children in Haiti because of poor hygiene, particularly contaminated water and overcrowded conditions associated with urban slums.
Published: 2006

35. Cryptosporidiose humaine et espèces en cause en Haïti

Author: Etna Eyma, Bernard Liautaud, Christian Raccurt, Karine Guyot, Rose Irene Verdier, Patrice Agnamey, Gilles Nevez, Philippe Brasseur, Anne Totet, Jean W. Pape, Christine Pannier Stockman, Eduardo Dei-Cas, Xunde Li, Laboratoire de parasitologie et de mycologie médicales [CHU Amiens], CHU Amiens-Picardie, Service des maladies infectieuses et tropicales [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Groupe Haïtien d'Étude du Syndrome de Kaposi et des Infections Opportunistes (GHESKIO), Groupe Haïtien d'Étude du Syndrome de Kaposi et des Infections Opportunistes, Ecologie du parasitisme - EA 3609 (ECOPA), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille, Droit et Santé, Weill Medical College of Cornell University [New York], EA3609, Laboratoire ECOPA, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)
Subjects: medicine.medical_specialty, Cryptosporidium infection, animal diseases, 030231 tropical medicine, Cryptosporidium felis, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, parasitic diseases, Haïti, Medicine, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Sida, Genotyping, Feces, Cryptosporidium parvum, patients SIDA, 0303 health sciences, biology, 030306 microbiology, business.industry, Public Health, Environmental and Occupational Health, cryptosporidiose, péril fécal, Cryptosporidium, medicine.disease, biology.organism_classification, Virology, 3. Good health, Infectious Diseases, Tropical medicine, Parasitology, business, Cryptosporidium hominis
Abstract: Contamination by water-born infectious diseases is closely linked to urban slums conditions such as overcrowding and high level of faecal pollution by animal and human excreta. In this environment, cryptosporidiosis is a major cause of acute diarrhoea in children and chronic persistent diarrhoea in AIDS patients, resulting in increased morbidity and mortality in both populations. The aims of this study conducted in Port-au-Prince, Haiti were to: (i) determine the frequency of Cryptosporidium infection in two populations of patients with diarrhoea, children and AIDS patients, and the existence of Cryptosporidium carriage in healthy adults living in close contact with them; (ii) identify by molecular genotyping the Cryptosporidium species involved; and (iii) evaluate the viability of Cryptosporidium oocysts isolated from human stools. From January 2000 to January 2001, 158 of 1529 diarrhoea stool samples collected from 93 patients with diarrhoea, 57 adults followed at Centres GHESKIO and 36 children admitted at the University Hospital in Port-au-Prince contained Cryptosporidium oocysts (10.3%). The majority of adult patients (98%) were HIV-infected whereas the majority of children (81%) tested negative for HIV. Cryptosporidium was documented in only 1/102 healthy persons living in contact with Cryptosporidium infected patients and infection was with the same genotype as that of the contact patient. Among the 69 Cryptosporidium isolates studied for genotyping, three species were identified: C. hominis (59%), C. parvum (38%) and C. felis (3%). The two C. felis cases are the first reported from AIDS patients in the Caribbean. Most of the children regardless of their HIV status were infected with C. hominis (72%), whereas AIDS patients were more likely to be infected by either human or animal genotypes. These data confirm that immunocompromised individuals are susceptible to a wide range of Cryptosporidium spp. Viability of Cryptosporidium oocysts were determined in an experimental mouse model for 17/18 specimen studied including in 12/13 C. hominis, 4/4 C. parvum and 1/1 C. felis. Infectivity in newborn mice was found to be dose-dependent and more effective with C. parvum than the other two genotypes. Cryptosporidiosis remains a frequent hazard for both AIDS patients and young children in Haiti because of poor hygiene, particularly contaminated water and overcrowded conditions associated with urban slums.
Published: 2006
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36. Economic evaluation of a policy change from single-agent treatment for suspected malaria to artesunate-amodiaquine for microscopically confirmed uncomplicated falciparum malaria in the Oussouye District of south-western Senegal

Author: Philippe Brasseur, M. Cisse, Patrice Agnamey, Oumar Gaye, Jean Dumoulin, J. Rigal, Piero Olliaro, and Walter R. J. Taylor
Subjects: Adult, Male, Adolescent, Artesunate, Amodiaquine, Rural Health, Indirect costs, chemistry.chemical_compound, Antimalarials, Chloroquine, Environmental health, parasitic diseases, medicine, Humans, Artemisinin, Malaria, Falciparum, Child, Quinine, Traditional medicine, business.industry, Health Policy, Artesunate/amodiaquine, Public Health, Environmental and Occupational Health, Infant, Health Care Costs, medicine.disease, Artemisinins, Senegal, Infectious Diseases, chemistry, Child, Preschool, Parasitology, Drug Therapy, Combination, Female, business, Sesquiterpenes, Malaria, medicine.drug
Abstract: Senegal is changing policy for case management of uncomplicated falciparum malaria, which hitherto is diagnosed clinically and treated with chloroquine or intramuscular quinine. The WHO recommends artemisinin-based combinations for treating falciparum malaria, preferably based on a parasitological diagnosis. There are no economic projections if such a policy were introduced in Senegal. We have conducted a preliminary economic assessment of such a policy change. The study took place in the chloroquine-resistant district of Oussouye in south-western Senegal. We reviewed clinic registers of the district health posts (n=5) from 1996 to 2001, and piloted artesunate combined with amodiaquine (at 4 and 10 mg/kg/day x 3 days respectively) (AS--AQ) for treating slide-proven falciparum malaria during two rainy seasons (2000 and 2001) at one health centre. These data were used to calculate current direct patient costs (clinic visit, diagnosis, drugs) of malaria treatment and project future costs for the district. The robustness of the model was tested by allowing for different drug failure rates and costs of diagnosis. During 1996--2001, the mean number of primary treatments per year was 7654 for a mean, direct cost of 17,452 US dollars to the community. Clinical diagnosis resulted in over-treatment: 56% and 66% in the wet and dry seasons respectively. Current policy leads to substantial drug wastage and excess direct costs for the community. The direct costs of implementing AS-AQ for slide-proven malaria would be 8,150 US dollars (53% less expensive). Studies examining the public health effect and economics of deploying AS--AQ on a wider scale are underway in Senegal.
Published: 2005

37. Sensitivity of Plasmodium falciparum to amodiaquine and chloroquine in central Africa: a comparative study in vivo and in vitro

Author: Gaston Samba, Jonas Kouamouo, Patrice Agnamey, Albert Same Ekobo, Loïc Favennec, and Philippe Brasseur
Subjects: Adult, Male, Adolescent, Nausea, medicine.medical_treatment, Plasmodium falciparum, Drug Resistance, Amodiaquine, Pharmacology, Antimalarials, In vivo, Chloroquine, parasitic diseases, medicine, Animals, Humans, Cameroon, Malaria, Falciparum, Child, Chemotherapy, biology, Traditional medicine, business.industry, Pruritus, Public Health, Environmental and Occupational Health, Infant, General Medicine, Middle Aged, biology.organism_classification, medicine.disease, In vitro, Infectious Diseases, Congo, Child, Preschool, Female, Parasitology, medicine.symptom, business, Malaria, medicine.drug
Abstract: A comparative study in vivo of amodiaquine efficacy (35 mg/kg over 3 d) and chloroquine (25 mg/kg over 3 d) was conducted in 1991 and 1992 in Cameroon and Congo in 123 patients with uncomplicated Plasmodium falciparum malaria. Amodiaquine was more effective than chloroquine, with parasite clearance by day 7 in 79.7% of the patients compared with 59.4%. Sixteen of 32 (50%) P. falciparum isolates tested in vitro were resistant to chloroquine and only 3 of 34 (9%) were resistant to amodiaquine. 5.3% of patients treated with amodiaquine complained of pruritus and 18.7% of nausea, compared with 15.7% and 5% respectively of those treated with chloroquine.
Published: 1995
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38. Long-lasting anticryptosporidial activity of nitazoxanide in an immunosuppressed rat model

Author: Patrice Agnamey, Xunde Li, Ballet Jj, Logic Favennec, Philippe Brasseur, Denis Lemeteil, and Jean-Francois Rossignol
Subjects: Long lasting, Male, Adenosine, Paromomycin, Rat model, Antiprotozoal Agents, Early Relapse, Cryptosporidiosis, Pharmacology, Rats, Sprague-Dawley, Feces, Immunocompromised Host, parasitic diseases, medicine, Animals, Parasite Egg Count, Cryptosporidium parvum, biology, Nitazoxanide, Chronic diarrhoea, biology.organism_classification, Nitro Compounds, Virology, Discontinuation, Rats, Disease Models, Animal, Thiazoles, Parasitology, medicine.drug
Abstract: Cryptosporidium parvum, Tyzzer, 1912 is identified as a common cause of diarrhoea in immunocompetent individuals. In immunocompromised, especially HIV-infected subjects, cryptosporidiosis causes severe chronic diarrhoea. In this study, nitazoxanide (NTZ) was compared for curative activity with sinefungin (SNF) and paromomycin (PRM) in immunosuppressed rats, a screening model for anticryptosporidial agents. NTZ at either 50 mg/kg/day, 100 mg/kg/day or 200 mg/kg/day resulted in seven days in a dose-dependent inhibition of oocyst shedding similar to that obtained with SNF (10 mg/kg/day) and PRM (100 mg/kg/day). Further discontinuation of SNF or PRM 100 mg/kg/day therapy resulted in early relapse of oocyst shedding which reached the pre-treatment levels in 2-4 days. In contrast, seven days after discontinuation of therapy, shedding inhibition was unchanged in NTZ-treated rats. Data prompt further assessment of the activity of NTZ on sequestered C. parvum.
Published: 2003

39. Amodiaquine-artesunate versus amodiaquine for uncomplicated Plasmodium falciparum malaria in African children: a randomised, multicentre trial

Author: Sanjeev Krishna, S. Gikunda, Paul Garner, Diallo S, Bertrand Lell, Peter G. Kremsner, J. Mwanza, Walter R. J. Taylor, Frank Cobelens, Steffen Borrmann, Michel A. Missinou, P. Osimbo, Eliab Some, M. Loolpapit, Philippe Brasseur, Patrice Agnamey, Martin Adjuik, Philipp Rezbach, Piero Olliaro, Francine Ntoumi, M. Cisse, Abdel Babiker, Jean-François Faucher, Pierre-Blaise Matsiegui, Global Health, and Infectious diseases
Subjects: Male, medicine.medical_specialty, Plasmodium falciparum, Artesunate, Amodiaquine, Pharmacology, Drug Administration Schedule, Antimalarials, chemistry.chemical_compound, Chloroquine, Internal medicine, parasitic diseases, Gametocyte, Animals, Humans, Medicine, Gabon, Artemether, Malaria, Falciparum, Child, biology, business.industry, Artesunate/amodiaquine, Infant, General Medicine, biology.organism_classification, medicine.disease, Kenya, Artemisinins, Senegal, Treatment Outcome, chemistry, Child, Preschool, Drug Therapy, Combination, Female, business, Sesquiterpenes, Malaria, medicine.drug
Abstract: Increasing drug resistance limits the choice of efficacious chemotherapy against Plasmodium falciparum malaria in Africa. Amodiaquine still retains efficacy against P falciparum in many African countries. We assessed the safety, treatment efficacy, and effect on gametocyte carriage of adding artesunate to amodiaquine in three randomised trials in Kenya, Sénégal, and Gabon. We enrolled 941 children (400 in Kenya, 321 in Sénégal, and 220 in Gabon) who were 10 years or older and who had uncomplicated P falciparum malaria. Patients were randomly assigned amodiaquine (10 mg/kg per day for 3 days) plus artesunate (4 mg/kg per day for 3 days) or amodiaquine (as above) and placebo (for 3 days). The primary endpoints were parasitological cure rates at days 14 and 28. Analysis was by intention to treat and by an evaluability method. Both regimens were well tolerated. Six patients in the amodiaquine-artesunate group and five in the amodiaquine group developed early, drug-induced vomiting, necessitating alternative treatment. By intention-to-treat analysis, the day-14 cure rates for amodiaquine-artesunate versus amodiaquine were: 175/192 (91%) versus 140/188 (74%) in Kenya (D=16.7% [95% CI 9.3-24.1], p
Published: 2002

40. Fréquence de Cryptosporidium sp dans la gastroentérite aiguë de l’enfant

Author: D. Djeddi, André Léké, Guy Kongolo, J. Mounard, Patrice Agnamey, C Wallois, A. Vanrenterghem, and F Raccurt
Subjects: Pediatrics, Perinatology and Child Health, Biology, Molecular biology
Published: 2010
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41. Presence of Enterocytozoon bieneusi Associated with Intestinal Coccidia in Patients with Chronic Diarrhea Visiting an HIV Center in Haiti

Author: Anne Totet, Bernadette Fouché, Jean Menotti, Christian Raccurt, Jean W. Pape, Taïeb Chouaki, and Patrice Agnamey
Subjects: Adult, Diarrhea, Male, Adolescent, Cyclospora cayetanensis, fluids and secretions, Acquired immunodeficiency syndrome (AIDS), Virology, HIV Seropositivity, parasitic diseases, medicine, Humans, Enterocytozoon bieneusi, Intestinal Diseases, Parasitic, Child, Sida, Human feces, biology, Coccidiosis, fungi, Infant, virus diseases, Cryptosporidium, Enterocytozoon, Middle Aged, biology.organism_classification, medicine.disease, Isospora, Infectious Diseases, Child, Preschool, Chronic Disease, Female, Parasitology, medicine.symptom
Abstract: This study investigated the presence of Enterocytozoon bieneusi as a possible cause of chronic diarrhea in Haitian patients attending the GHESKIO AIDS clinic in Port-au-Prince, Haiti. Coccidian oocysts were found by polymerase chain reaction (PCR) in the stools of 58/74 patients with chronic diarrhea and included the following agents: 45 (60%) Cryptosporidium spp., 27 (34%) Cyclospora cayetanensis, and 11 (15%) Isospora belli. Four patients (5.5%) were co-infected with E. bieneusi and one (1.4%) had E. bieneusi alone. The PCR-restriction fragment length polymorphism (RFLP) method made it possible to document the presence in human feces of E. bieneusi in Haiti. As in sub-Saharan Africa, the association of E. bieneusi with coccidian parasites found in Haitian patients with diarrhea is probably caused by the high level of fecal contamination of soils and surface waters usually associated with countries with low hygienic standards.
Published: 2008
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42. Understanding Human-Plasmodium falciparum Immune Interactions Uncovers the Immunological Role of Worms

Author: Patrice Agnamey, Pierre Druilhe, Christian Roussilhon, Jean-Louis Pérignon, and Philippe Brasseur
Subjects: Infectious Diseases/Epidemiology and Control of Infectious Diseases, Male, Adolescent, Plasmodium falciparum, Helminthiasis, Protozoan Proteins, Antibodies, Protozoan, lcsh:Medicine, Antigens, Protozoan, Comorbidity, Host-Parasite Interactions, Th2 Cells, Immune system, Antigen, Immunity, Helminths, parasitic diseases, medicine, Animals, Humans, Prospective Studies, Malaria, Falciparum, Child, lcsh:Science, Infectious Diseases/Helminth Infections, Multidisciplinary, biology, lcsh:R, Infectious Diseases/Protozoal Infections, Infant, medicine.disease, biology.organism_classification, Virology, Senegal, Vaccination, Child, Preschool, Immunoglobulin G, Immunology, biology.protein, Female, lcsh:Q, Antibody, Malaria, Research Article
Abstract: Background Former studies have pointed to a monocyte-dependant effect of antibodies in protection against malaria and thereby to cytophilic antibodies IgG1 and IgG3, which trigger monocyte receptors. Field investigations have further documented that a switch from non-cytophilic to cytophilic classes of antimalarial antibodies was associated with protection. The hypothesis that the non-cytophilic isotype imbalance could be related to concomittant helminthic infections was supported by several interventions and case-control studies. Methods and Findings We investigated here the hypothesis that the delayed acquisition of immunity to malaria could be related to a worm-induced Th2 drive on antimalarial immune responses. IgG1 to IgG4 responses against 6 different parasite-derived antigens were analyzed in sera from 203 Senegalese children, half carrying intestinal worms, presenting 421 clinical malaria attacks over 51 months. Results show a significant correlation between the occurrence of malaria attacks, worm carriage (particularly that of hookworms) and a decrease in cytophilic IgG1 and IgG3 responses and an increase in non-cytophilic IgG4 response to the merozoite stage protein 3 (MSP3) vaccine candidate. Conclusion The results confirm the association with protection of anti-MSP3 cytophilic responses, confirm in one additional setting that worms increase malaria morbidity and show a Th2 worm-driven pattern of anti-malarial immune responses. They document why large anthelminthic mass treatments may be worth being assessed as malaria control policies.
Published: 2010
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43. Effets sur l’épidémiologie du paludisme non compliqué du déploiement de la combinaison d’artésunate et amodiaquine à Oussouye, district de Casamance, Sénégal (Recherche-Action)

Author: Oumar Gaye, Michel Vaillant, Piero Olliaro, Patrice Agnamey, Walter R. J. Taylor, and Philippe Brasseur
Subjects: Epidemiology, Public Health, Environmental and Occupational Health
Published: 2009
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44. P9-11 - Rapports de moyennes géométriques pour évaluer la sensibilité in vitro de Plasmodium falciparum aux antipaludéens en Casamance (Sud-Ouest du Sénégal)

Author: Patrice Agnamey, Piero Olliaro, Michel Vaillant, Philippe Brasseur, and P. Eldin de Pecoulas
Subjects: Epidemiology, Public Health, Environmental and Occupational Health
Published: 2006
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45. Microbiological contamination of groundwater by Cryptosporidium oocysts in Haiti. Health risk assessment for population

Author: Ketty Balthazard-Accou, Evens Emmanuel, Momar Diouf, Patrice Agnamey, Université Quisqueya, Centre de Recherche et d'Appui aux Politiques Urbaines (CRAPU), Université Quisqueya, Centre de Recherche et d'Appui aux Politiques Urbaines, Port-au-Prince, Haïti. (uniQ), Direction de la recherche clinique et de l'innovation [CHU Amiens], CHU Amiens-Picardie, Anofel Cryptosporidium National Network, and Université de Picardie Jules Verne (UPJV)
Subjects: [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, biological hazards, evaluación de los riesgos, risk assessment, health, Cryptosporidium spp, risques biologiques, Eaux souterraines, contamination microbiologique, salud, Cryptosporidium sp, microbiological contamination, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, aguas subterráneas, riesgos biológicos, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, évaluation des risques, santé, Groundwater, contaminación microbiológica
Abstract: International audience; Contamination of natural aquatic ecosystems by Cryptosporidium is a major environmental and human health issue. In Haiti, environmental Cryptosporidium oocysts pollution has been well documented by previous studies conducted in several cities of the country. In groundwater from Les Cayes of Haiti, significant concentrations from 1 to 989 oocysts in 100 liters of filtered water were calculated. Results of these studies revealed high level of Cryptosporidium oocysts pollution in surface water and groundwater. Therefore, regarding cryptosporidiosis, contaminated water resources constitute a real sanitary risk mainly for children and immunocompromised individuals. So, it is necessary to assess the biological risk for populations served by those polluted water resources. The aim of this study is to present: (i) the steps of a procedure intended to evaluate risks to human health linked to the consumption of water from groundwater; and (ii) the results of its application on groundwater from Les Cayes, city located in southwestern Haiti. The procedure is based on a scenario that describes the existence of an uncontrolled landfill leachate which are neither collected nor treated. The refuse has a close contact with the soil making easy the transfer of various pollutants from the surface to groundwater. Moreover, latrines and septic tanks are often discharged into the unsaturated zone of the geological matrix are also retained. Risk estimation was calculated for two groups in the exposed population: immunocompetent and immunocompromised individuals. As expected, the study revealed a high risk for individuals in the immunocompromised group.; La contaminación de los ecosistemas acuáticos naturales por Cryptospridium parvum constituye una verdadera preocu-pación de salud humana e ambiental principalmente en los países en desarrollo. En Haití, los oocitos de cryptosporidios se han encontrado en muchas ciudades del país en las aguas de superficie y las aguas destinadas al consumo humano. En las aguas subterráneas en Les Cayes de Haití, concentraciones significativas de 1 a 989 oocitos en 100 litros de agua filtrada han sido determinadas. Los resultados de estos estudios han revelado un nivel elevado de polución por oocitos de Cryptosporidium en las aguas de superficie y aguas subterráneas. Por ende, los recursos en agua contaminados por oocitos constituyen un verdadero riesgo sanitario para los niños y las personas inmunodeprimidas. Así, se hace necesario evaluar el riesgo biológico para las poblaciones que se abastecen de estos recursos en agua contaminados. El objetivo de este estudio es presentar: (i) las etapas de un procedimiento destinado a evaluar los riesgos para la salud humana ligados al consumo de agua proveniente de las aguas subterráneas; et (ii) los resultados de la aplicación de este proced-imiento en las aguas subterráneas en Les Cayes, ciudad situada en el suroeste de Haití. El procedimiento está basado en un escenario que describe la existencia de una descarga violenta en donde los lixiviados no son ni recolectados ni tratados. Las basuras están directamente en contacto con el suelo y siguen los mecanismos de transferencia hacia la capa de agua subterránea. Además, las letrinas y fosas sépticas, rechazando sus efluentes en la zona no saturada de la matriz geológica, están igualmente retenidas. La estimación del riesgo ha sido calculada para dos grupos en la población expuesta: inmunodeprimida y immunocompetente. Este aparece como un riesgo elevado para los inmunodeprimidos.; La contamination des écosystèmes aquatiques naturels par Cryptospridium parvum constitue une véritable préoccupa-tion de santé hu et environnementale principalement dans les pays en développement. En Haïti, des oocytes de cryptosporidies ont été retrouvés dans plusieurs villes du pays dans les eaux de surface et dans les eaux destinées à la consommation humaine. Dans les eaux souterraines Les Cayes d'Haïti, des concentrations significatives de 1 à 989 oo-cystes dans 100 litres d'eau filtrée ont été déterminées. Les résultats de ces études ont révélé un niveau élevé de pollution par des oocystes de Cryptosporidium dans les eaux de surface et des eaux souterraines. Par conséquent, les ressources en eau contaminés par des oocystes constituent un véritable risque sanitaire principalement pour les enfants et les per-sonnes immunodéprimées. Ainsi, il apparaît nécessaire d'évaluer le risque biologique pour les populations desservies par ces ressources en eau polluées. Le but de cette étude est de présenter: (i) les étapes d'une procédure destinée à évaluer les risques pour la santé humaine liés à la consommation d'eau provenant des eaux souterraines; et (ii) les résultats de l'application de cette procédure sur les eaux souterraines Les Cayes, ville située dans le sud-ouest Haïti. La procédure est basée sur un scénario qui décrit l'existence d'une décharge sauvage où les lixiviats ne sont ni collectés, ni traités. Les déchets sont directement en contact avec le sol et suivent les mécanismes de transfert vers la nappe. En outre, les latrines et fosses septiques, rejetant leurs effluents dans la zone non saturée de la matrice géologique, sont également retenues. L'estimation du risque a été calculée pour deux groupes dans la population exposée: immunodéprimé et immunocompétent. Il apparaît comme attendu un risque élevé pour les immunodéprimés.

46. Synthesis and evaluation of new enantiopure pyridine-based arylaminoalcohols as antimalarial drugs

Author: Etienne Pair, Alexandra Dassonville-Klimpt, Guillaume Bentzinger, Pauline Loupias, Anne Bouchut, Catherine Mullie, Patrice Agnamey, Pascal Sonnet, and DESSAIVRE, Louise
Subjects: [SDV] Life Sciences [q-bio]

47. Mortality from malaria in France, 2005 to 2014

Author: Kendjo, Eric, Thellier, Marc, Noël, Harold, Jauréguiberry, Stéphane, Septfons, Alexandra, Mouri, Oussama, Gay, Frédérick, Tantaoui, Ilhame, Caumes, Eric, Houzé, Sandrine, Piarroux, Renaud, Musset, Lise, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Référence du Paludisme [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Santé publique France Guyane, Santé publique France - French National Public Health Agency [Saint-Maurice, France], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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 de Paris (UP), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Parasitologie [Cayenne, Guyane française], Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 261), Institut de Recherche pour le Développement (IRD)-Université Paris Cité (UPCité), Réseau International des Instituts Pasteur (RIIP), Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR - laboratoire associé), Centre Collaborateur OMS pour la surveillance de la résistance aux antipaludiques [Cayenne, Guyane française] (CCOMS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), The French imported malaria Study group: C. Strady (CHU Reims), Caroline Lohmann (CH du Moenchsberg, Mulhouse), Celine Arriuberge (CH Trousseau, Paris), Emmanuel Grimprel (CH Trousseau, Paris), Jean-Marie Delarbre (CH du Moenchsberg, Mulhouse), Michel Thibault (CH René Dubos, Pontoise), Mohamadou Niang (CHR Orléans), A. Barrans (CH Sète), A. Martin (CH Périgueux), A. Spiegel (DESP Nord), A. Valentin (CHU Toulouse), A.S. Le Guern (Institut Pasteur, Paris), Adela Angoulvant (CHU Kremlin-Bicêtre, Paris), Adeline Dubois (CH Alès), Adrien Genin (CH Pays d'Aix), Agathe Lebuisson (CHU Cochin), Agnes Riche (CH Angoulême), Agnès Durand (Institut Pasteur, Paris), Agnès Fromont (CH Auxerre), Ahmed Aboubacar (CHU de Strasbourg), Ahmed Fateh Ousser (CH Louis Mourier), Aida Taieb (INTS, Paris), Alain Domergue (CH Alès - Cévennes), Alain Gravet (CH du Moenchsberg, Mulhouse), Alain Lecoustumier (CH de Cahors), Albert Faye (CHU Robert Debré, Paris), Alexander Pfaff (CHU de Strasbourg), Alexandra Faussart (CHU Bichat-Claude Bernard, Paris), Alexandre Chlilek (CHU Nîmes), Alice Borel (CHU Amiens), Alice Pérignon (CHU Pitié-Salpêtrière, Paris), Ana Mendes-Mreira (CH La Rochelle), André Gardrat (CH d’Evreux), Ange Kissila (CH Provins), Angèle LI (CH Creil (Laënnec)), Anne Cady (CH Bretagne Atlantique), Anne Debourgogne (CHU de Nancy), Anne Delaval (CHI Robert Ballanger, Aulnay-sous-Bois), Anne Goepp (CHI Villeneuve St Georges), Anne Marfaing-Koka (Hôpital Antoine-Béclère), Anne Pauline Bellanger (CHU Besançon, Jean Minjoz), Anne Vincenot-Blouin (CH Meaux), Anne-Marie Teychene-Coutet (CH Bondy-Jean Verdier), Anne-Sophie Deleplancque (CH Lille), Annick Verhaeghe (CH de Dunkerque), Annie Motard-Picheloup (CHI Fréjus St Raphaël), Antoine Berry (CHU Toulouse), Antoine Huguenin (CHU Reims), Arnaud Bouvet (CH Bretagne Atlantique), Audrey Merens (HIA Begin), Aurelie Roide (CHU Lariboisière, Paris), Aurore Sanson (CH Jacques Cœur, Bourges), Aurélie Fricot (CHU Necker), Aurélie Guigon (CHR Orléans), Benfatallah Dhouha (CHU Necker, Paris), Benjamin Wyplosz (CHU Kremlin-Bicêtre, Paris), Benoît Henri (INTS, Paris), Bernadette Buret (CH Niort), Bernadette Cuisenier (CHU Dijon), Bernadette Worms (CHU Dijon), Bernard Faugère (CH Timone, Marseille), Biligui Sylvestre (CHU Pitié-Salpêtrière, Paris), Boualem Sendid (CH Lille), Bruno Megarbane (CHU Lariboisière, Paris), Bruno Pradines (Département Microbiologie et Maladies Infectieuses, Institut de Recherche Biomédicale des Armées, 13005 Marseille, France, Aix Marseille University, IRD, SSA, AP-HM, VITROME, 13005 Marseille, France, IHU Méditerranée Infection, 13005 Marseille, France, Centre National de Référence du Paludisme, Institut de Recherche Biomédicale des Armées, 13005 Marseille, France), Béatrice Quinet (CH Trousseau, Paris), C. Braidy (CH du Sud Seine et Marne), C. Farrugia (CH de Dourdan), C. Finot (CH de Dreux), Camille Roussel (INTS, Paris), Camille Runel-Belliard (CHU de Bordeaux), Caren Brump (CHU Lariboisière, Paris), Carine Dokoula (CH Jacques Cœur, Bourges), Carmina Camal (CH Louis Mourier), Carole Mackosso (CHU Bichat-Claude Bernard, Paris), Carole Poupon (CH de Gonesse), Caroline Garandeau (CH Angoulême), Catherine Benoit (CH du Sud Seine et Marne), Catherine Branger (CH Louis Mourier), Catherine Brehant (CH La Rochelle), Catherine Desideri-Vaillant (HIA Clermont Tonnerre, Brest), Catherine Kauffmann Lacroix (CH Poitiers), Catherine Lafaurie (CH d’Epernay), Cecile Hombrouck-Alet (CH Blois), Cecile Ramade (Lyon-Croix-Rousse), Celine Damiani (CHU Amiens), Celine Gourmel (CHU Lariboisière, Paris), Chantal Duhamel (CHU Côte de Nacre), Chantal Garabedian (CH Pays d'Aix), Chralotte Chambrion (INTS, Paris), Christelle Morelle (CHU Montpellier), Christelle Pomares Estran (CH Universitaire de Nice), Christelle Prince (CH de Cayenne Andrée Rosemon), Christian Durand (CH Provins), Christian Fulleda (CHU Lariboisière, Paris), Christian Raccurt (CHU Amiens), Christine Chaigneau (GHPSO, Creil), Christine Chemla (CHRU de Reims), Christine Van batten (CH Laënnec, Creil), Christophe Martinaud (HIA Percy, Clamart), Christophe Rapp (HIA Begin), Claire Augé (CHU Bichat-Claude Bernard, Paris), Claire Malbrunot (CH Corbeil Essonne), Claudine Febvre (CH de Montbéliard), Claudine Sarfati (Hôpital Saint-Louis, Paris), Coralie l'Ollivier (CH de la Timone, Marseille), Corinne Huet (Hôpital Louis-Pasteur, Cherbourg-Octeville), Cournac Jean-Marie (HIA Percy, Clamart), Cynthia Pianetti (CH Gabriel Martin, La Réunion), Cécile Angebault (CHU Necker, Paris), Cécile Ficko (HIA Begin), Cécile Garnaud (CHU de Grenoble), Cécile Leprince (CHI Robert Ballanger, Aulnay-sous-Bois), Céliat Merat (CHU Nantes), Céline Dard (CHU de Grenoble), Céline Nourrisson (CHRU Clermont-Ferrand), Céline Tournus (Hôpital Delafontaine, Saint-Denis), Daniel Azjenberg (CHU Dupuytren, Limoges), Daniel Camus (CH Lille), Daniel Lusina (CHI Robert Ballanger, Aulnay-sous-Bois), Daniel Parzy (IMTSSA, Marseille), Denis Pons (CHRU Clermont-Ferrand), Denis Filisetti (CHU Strasbourg), Denis Malvy (CHU de Bordeaux), Didier Basset (CHU Montpellier), Didier Jan (CH Laval), Didier Poisson (CHR Orléans), Didier Raffenot (CH Chambéry), Dieudonné Bemba (CH Bondy-Jean Verdier), Dominique Maubon (CHU de Grenoble), Dominique Mazier (CHU Pitié-Salpêtrière, Paris), Dominique Popjora (CH Trousseau, Paris), Dominique Toubas (CHRU de Reims), Dorothée Quino (CHRU Morvan, Brest), Alioune Ndour (INTS, Paris), Ducout Louis (CH de la Côte Basque), Duong Thanh Hai (CHRU Bretonneau), E. Boyer (CH Le Mans), Edgar Ombandza (CH Provins), Edith Mazars (CH de Valenciennes), Elisabeth Buffet (CH de Epernay), Elodie Collin (CHI Robert Ballanger, Aulnay-sous-Bois), Elodie Meynet (CH Annecy Genevois), Emeline Scherer (CHU Besançon, Jean Minjoz), Emilie Fréalle (CH Lille), Emilie Klein (CHU Lariboisière, Paris), Emilie Sitterle (CHU Necker, Paris), Emily Ronez (CHU Lariboisière, Paris), Emmanuel Dutoit (CH Lille), Enrique Casalino (CHU Bichat-Claude Bernard, Paris), Eric Caumes (CHU Pitié-Salpêtrière, Paris), Eric Dannaoui (Hôpital Européen Georges Pompidou, Paris), Eric Gardien (CH de Draguignan, Bordeaux), Eric Kendjo (CHU Pitié-Salpêtrière, Paris),Eric d'Ortenzio (CHU Bichat-Claude Bernard, Paris), Ermanno Candolfi (CHU de Strasbourg), Estelle Perraud-Cateau (CH Poitiers), Eterne Twizeyimana (CH du Cotentin), F. Roblot (CH Poitiers), Fabienne Pateyron (CH Provins), Fabrice Bruneel (CH de Versailles, André Mignot), Fabrice Legros (CNR du paludisme), Fabrice Simon (HIA Laveran), Fakhri Jeddi (CHU Nantes), Farida M. Benaoudia (CH Troyes), Faïzi Ajana (CH Tourcoing), Felix Djossou (CH de Cayenne Andrée Rosemon), Firouze Banisadr (CHRU de Reims), Florent Morio (CHU Nantes), Francis Derouin (Hôpital Saint-Louis, Paris), Francois Moussel (CH François-Quesnay, Mantes-La-Jolie), Francoise Foulet (CHU Henri Mondor), François Peyron (Lyon-Croix-Rousse), Françoise Benoit-Vical (CHU Toulouse), Françoise Botterel (CHU Henri Mondor), Françoise Gayandrieu (CHU Nantes), Françoise Schmitt (CH du Moenchsberg, Mulhouse), Frederic Ariey (CHU Cochin, Paris), Frédéric Grenouillet (CHU Jean Minjoz, Besançon), Frédéric Sorge (CHU Necker), Frédérique Gay (CHU Pitié-Salpêtrière, Paris), Frédérique Foudrinier (CHRU de Reims), G. Courrouble (CH Blois), G. Gallou (CH de Falaise), G. Julienne (CH Belfort), G. Philippon (Centre Médical CMETE, Paris), Gauthier Pean-de-Ponfilly (CHU Lariboisière, Paris), Geneviève Grise (CH d’Elbeuf), Ghania Belkacem Belkadi (CH Tenon), Gilbert Lorre (CHD La Roche-sur-Yon), Gilles Gargala (CHU Rouen), Gilles Nevez (CHRU Morvan, Brest), Gisele Dewulf (CH de Valenciennes), Guillaume Désoubeaux (CHRU Bretonneau, Tours), Guillaume Escriou (CHU Bichat-Claude Bernard, Paris), Guillaume Le Loup (CH Tenon, Paris), Guillaume Menard (HIA Saint-Anne, Toulon), Guy Carroger (CH Jacques Cœur, Bourges), Guy Galeazzi (CH Louis Mourier), Gwénaël le Moal (CH Poitiers), Hana Talabani (CHU Cochin, Paris), Hanene Abid (CHU Necker, Paris), Helene Broutier (CHI Robert Ballanger, Aulnay-sous-Bois), Herve Pelloux (CHU de Grenoble), Houria Ichou (CH Louis Mourier), Hugo Laurent (CHU Lariboisière, Paris), Hélène Broutier (CH Meaux), Hélène Lapillonne (CH Trousseau, Paris), Hélène Yera (CHU Cochin, Paris), Hélène savini (HIA Laveran), I. Hermes (CH Saint-Malo), Ilhame Tantaoui (CHU Pitié-Salpêtrière, Paris), Isabelle Poilane (CH Bondy-Jean Verdier), Isabelle Amouroux (Hôpital Antoine-Béclère), Isabelle Mazurier (Hôpitaux Civils de Colmar), Isabelle Salimbeni (CH de Cannes), Isabelle Tawa (Centre Médical CMETE, Paris), J Cuziat (CH Saint-Nazaire), J. Bernard Poux (CH de Val d'Ariège - Foix), J. Heurtet (CH Beauvais), J. Rome (CH de Fougères), J. Truchot (CHU Lariboisière, Paris), J.M. Segalin (CHR Orleans), Jacques Gaillat (CH Annecy Genevois), Jacques Le bras (CHU Bichat-Claude Bernard, Paris), Jacques Thevenot (Centre Médical CMETE, Paris), Jacques Vaucel (CH Saint-Brieuc), Jean Dunand (Hôpital Ambroise Paré), Jean Benjamin Murat (CH de Roanne), Jean Marie Trapateau (CH Angoulême), Jean Yves Peltier (CHI Poissy-st-germain), Jean-Etienne Pilo (HIA Begin), Jean-Francois Magnaval (CHU Toulouse), Jean-François Faucher (CHU Jean Minjoz, Limoge), Jean-Paul Boutin (DESP Sud), Jean-Paul Couaillac (CH de Cahors), Jean-Philippe Breux (CH Cholet), Jean-Pierre Hurst (CH Jacques Monod, Le Havre), Jean-Yves Siriez (CHU Robert Debré, Paris), Jean-philippe Bouchara (CHU Angers), Jerome Clain (CHU Bichat-Claude Bernard, Paris), Jerome Naudin (CHU Robert Debré, Paris), Jordan Leroy (CH Lille), Josette Jehan (CH du Cotentin), Joudia Najid (CHU Pitié-Salpêtrière, Paris), Judith Gorlicki (CHU Lariboisière, Paris), Julie Bonhomme (CHU Côte de Nacre), Julie Brunet (CHU de Strasbourg), Jérome Guinard (CHR Orleans), Karima Cheikh (CHU Henri Mondor), L. Pougnet (HIA Clermont Tonnerre, Brest), Lauren Pull (CHU Robert Debré, Paris), Laurence Millon (CHU Jean Minjoz, Besançon), Laurence Campergue-Mayer (CH Avignon), Laurence Estepa (CH Blois), Laurence Lachaud (CHU Nîmes), Laurent Aaron (CH Jacques Cœur, Bourges), Laurent Bret (CHR Orléans), Laurent Guillaume (CH Blois), Liliane Ciceron (CHU Pitié-Salpêtrière, Paris), Lionnel Bertaux (CNR du paludisme), Lise Musset (Institut Pasteur, Guyane), Louise Basmacyan (CHU Dijon), Loïc Favennec (CHU Rouen), Luce Landraud (CH Louis Mourier), Lucile Cadot (CH Alès - Cévennes), Ludovic de Gentile (CHU Angers), Luis Macias (CHU Bichat-Claude Bernard, Paris), Luu-ly Pham (CHU Kremlin-Bicêtre, Paris), M. Cambon (CHRU Clermont-Ferrand), M.F. Biava (CHU de Nancy), M.H. Kiefer (CH du Moenchsberg), M.P. Carlotti (CNR du paludisme), Madeleine Fontrouge (CH de Gonesse), Marc Pihet (CHU Angers), Marc Thellier (CHU Pitié-Salpêtrière, Paris), Marie-Catherine Receveur (CHU de Bordeaux), Marie-Claire Machouart (CHU de Nancy), Marie-Elisabeth Bougnoux (CHU Necker, Paris), Marie-Laure Bigel (CH François-Quesnay, Mantes-la-Jolie), Marie-Laure Darde (CHU Dupuyrien, Limoges), Marie-Nadège Bachelier (CH Jacques Cœur, Bourges), Marion Almeras (CH Béziers), Marion Leterrier (CHU Nantes), Marion Leterrier (CHD La Roche-sur-Yon), Martin Danis (CHU Pitié-Salpêtrière, Paris), Martin G (CH du Cotentin), Martine Bloch (CH Louis Mourier), Martine Liance (CHU Henri Mondor, Paris), Marylin Madamet (IMTSSA, Marseille), Matthieu Revest (CHU Pontchaillou, Rennes),Matthieu Mechain (CHU de Bordeaux), Maxime Thouvenin (CH Troyes), Mermond Sylvain (Institut Pasteur, Nouméa), Michel Develoux (CH Tenon, Paris), Michel Miegeville (CHU Nantes), Milène Sasso (CHU Nîmes), Mohamed Diaby (CH Vernon), Monique Marty (CH La Rochelle), Monique Greze (CH Albi), Monique Lemoine (CHU Bichat-Claude Bernard, Paris), Mouri Oussama (CHU Pitié-Salpêtrière, Paris), Muriel Cornet (Hôpital Hôtel-Dieu, Paris), Muriel Mimoun Ayache (CH Trousseau), Muriel Nicolas (CHU Pointe-à-Pitre / Abymes), Muriel Roumier (CH Arles), Muriel Silva (CH Jacques Monod), Mylène Penot (CERBA), Myriam Gharbi (CHU Bichat-Claude Bernard, Paris), Nadia Guennouni (CHU Bichat-Claude Bernard, Paris), Nadine Godineau (Hôpital Delafontaine, Saint-Denis), Naima Dahane (CHU Cochin, Paris), Nathalie Bourgeois (CHU Montpellier), Nathalie Desuremain (CH Trousseau, Paris), Nathalie Fauchet (CHI de Créteil), Nathalie Parez (CH Louis Mourier), Nathalie Wilhelm (CH de Cahors), Nawel Ait-Ammar (Hôpital Ambroise Paré), Nayla Nassar (CH Auxerre), Nicolas Argy (CHU Bichat-Claude Bernard, Paris), Nicolas Blondiaux (CH Tourcoing), Nicolas Taudon (CERBA), Nicole Desbois-Nogard (CHU de la Martinique), Noura Hassouni (CHU Necker), Odile Bouret-Dubouis (CH Bretagne Atlantique), Odile Eloy (CH de Versailles, André Mignot), Odile Falguiere (CH Béziers), Odile Fenneteau (CHU Robert Debré, Paris), Olivia Bandin (Hôpital Saint-Camille/Bry-sur-Marne), Olivier Albert (CHU de Bordeaux), Olivier Bouchaud (CH Bobigny-Avicenne), Olivier Patey (CHI Villeneuve St. Georges), Olivier Rogeaux (CH Chambéry), P. Clergeau (CH Sallanches), P. Daumain (CH de Dourdan), P.H. Consigny (Institut Pasteur, Paris), Paméla Chauvin (CHU Toulouse), Pascal Delaunay (CH Universitaire de Nice), Pascal Hazera (CH Saint-Lo), Pascal Houze (Hôpital Saint Louis, Paris), Pascal Millet (CHU de Bordeaux), Pascal Pouedras (CH Bretagne Atlantique), Pascale Penn (CH Le Mans), Patrice Agnamey (CHU Amiens), Patrice Bourrée (CHU Kremlin-Bicêtre, Paris), Patricia Barbut (CH Longjumeau), Patricia Brugel (CH Antibes Juan-Les-Pins), Patricia Roux (CH Saint-Antoine, Paris), Patrick Leguen (HIA Clermont Tonnerre, Brest), Patrick Valayer (CH Notre-Dame de la Miséricorde), Pauline Caraux-Paz (CHI Villeneuve St Georges), Pauline Touroultjupin (CH Cholet), Philippe Abboud (CHU Rouen), Philippe Cormier (CH d’Evry), Philippe Minodier (CH Marseille Nord), Philippe Moskovtchenko (Hôpitaux Civils de Colmar), Philippe Parola (CH Marseille Nord), Philippe Poirier (CHRU Clermont-Ferrand), Philippe Stolidi (CH Aubagne), Pierre Patoz (CH Tourcoing), Pierre Buffet (INTS, Paris), Pierre Buffet (CHU Pitié-Salpêtrière, Paris), Pierre Flori (CH Saint-Etienne), Pierre Marty (CH Universitaire de Nice), Pierre Mornand (CH Trousseau, Paris), Pinel Claudine (CHU de Grenoble), R. Dahan (CHU de Strasbourg), R. Devallière (CH Saint-Nazaire), R. Mazataud (CH Vitry le François), Rahaf Haj Hamid (CH Louis Mourier), Regis Courtin (CHU Pitié-Salpêtrière, Paris), Renaud Blonde (CHU Robert Debré, Paris), René Nabias (CHI Poissy-st-germain), Roland Fabre (HIA Begin), Rose-Anne Lavergne (CHU Nantes), Roxane Courtois (CH Cholet), Rym Chouk Turki (CHU Henri Mondor), Rémy Durand (CH Bobigny-Avicenne), Réné Nabias (CHU Necker, Paris), Sabah Kubab (CH Corbeil Essonne), Sabine Lasserre (CH Trousseau, Paris), Samia Hamane (Hôpital Saint-Louis, Paris), Sandrine Cojean (CHU Bichat-Claude Bernard, Paris), Sandrine Houze (CHU Bichat-Claude Bernard, Paris), Sophie Matheron (CHU Bichat-Claude Bernard, Paris), Sorya Belaz (CHU Pontchaillou, Rennes), Stephane Jaureguiberry (CHU Pitié-Salpêtrière, Paris), Stephane Ranque (CH de la Timone, Marseille), Stephanie Dulucq (CHU de Bordeaux), Stéphane Bretagne (Hôpital Saint-Louis, Paris), Stéphane Pelleau (Institut Pasteur, Guyane), Stéphane Picot (Hospices Civils de Lyon), Sylvain Clauser (Hôpital Ambroise Paré), Sylviane Chevrier (CHU Pontchaillou, Rennes), Sylviane Dydymski (CHRU Clermont-Ferrand), Sylvie Lariven (CHU Bichat-Claude Bernard, Paris), Sylvie Lhopital (CH Vernon), Sylvie Maurellet Evrard (CHI Villeneuve St Georges), Sylvie Roulaud (CH Angouleme), Sébastien Larréché (HIA Begin), Thi-Hai-Chau Trinh (CHR Orléans), Thierry Ancelle (CHU Cochin, Paris), Thierry Pistone (CHU de Bordeaux), Thomas Hanslik (Hôpital Ambroise Paré), Thomas Guimard (CHD La Roche-sur-Yon), Timothée Klopfenstein (CHU Besançon, Jean Minjoz), Valerie Fuster-Dumas (CHU de Bordeaux), Veronique Blanc-Amrane (CH Antibes Juan-Les-Pins), Veronique Delcey (CHU Lariboisière, Paris), Veronique Sarrasin-Hubert (CHU Bichat-Claude Bernard, Paris), Vincent Foissaud (HIA Percy, Clamart), Virginie Mouton-Rioux (CH Bretagne Atlantique), Virginie Vitrat (CH Annecy Genevois), Véronique Jan-Lasserre (CH Lagny-sur-Marne), Xavier Nicolas (HIA Clermont Tonnerre, Brest), Y. Costa (CH Lagny-sur-Marne), Yassamine Lazrek (Institut Pasteur, Guyane), Yaye Senghor (Hôpital Saint Joseph, Paris), Yohann Le Govic (CHU Angers), Yves Guimard (CH Jacques Cœur, Bourges), Yves Poinsignon (CH Bretagne Atlantique), Claude flamand (Institut Pasteur, Guyane), C.N. guyen (CH Trousseau, Paris), G. Noël (CH Marseille Nord), G. Soula (CH Marseille Nord), J.M.Didier (CH Vesoul), M.F. Raynaud (CH Antibes Juan-Les-Pins), M. Julien (CH Béziers), M. Morillon (HIA Laveran), M.P. Carlotti (IMTSSA), P. Chantelat (CH Vesoul), P. Dussert (CH Belfort), P. Ralaimazava (CH Bobigny-Avicenne), S. Zaouche (CHU Necker, Paris), Élodie Lesteven (CHU Lariboisière, Paris)., Musset, Lise, Centre National de Référence du Paludisme [CHU Pitié-Salpétrière] (CNRpalu), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Plasmodium, Epidemiology, FNRCm, MESH: Hospitalization, Mark and recapture, 0302 clinical medicine, MESH: Aged, 80 and over, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Child, 030212 general & internal medicine, MESH: Incidence, MESH: Travel, Imported malaria, media_common, MESH: Aged, MESH: Middle Aged, MESH: Infant, 3. Good health, MESH: Young Adult, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, surveillance, France, Sex ratio, MESH: Medical Record Linkage, MESH: Disease Notification, 030231 tropical medicine, Notifiable disease, MESH: Malaria, capture-recapture, malaria, MESH: Population Surveillance, 03 medical and health sciences, MESH: Cross-Sectional Studies, Virology, parasitic diseases, medicine, media_common.cataloged_instance, European union, MESH: Communicable Diseases, Imported, MESH: Adolescent, MESH: Hospitals, University, MESH: Humans, business.industry, MESH: Child, Preschool, Public Health, Environmental and Occupational Health, MESH: Adult, medicine.disease, Confidence interval, MESH: Male, Metropolitan France, MESH: France, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, travellers, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Female, Malaria, Demography
Abstract: Introduction Malaria is a notifiable disease in all European Union and European Economic Area countries except Belgium and France, where only autochthonous malaria is notifiable. Although morbidity caused by malaria has been assessed, little is known about mortality incidence. Objective Our aim was to estimate the number of imported malaria-related deaths in hospital in metropolitan France. Methods We matched individual deaths reported between 1 January 2005 and 31 December 2014 to the French National Reference Centre for malaria (FNRCm) with malaria-related deaths from two other sources: the French National Registry on medical causes of death and the French national hospital discharge database. A capture–recapture method with log-linear modelling was used. Age, sex and place of death stratification were applied to remove heterogeneity. Results The estimated malaria-related deaths in metropolitan France during the study period were 205 (95% confidence interval (CI): 191–219). The annual mean number of malaria-related deaths was estimated at 21 (95% CI: 19–22). The FNRCm malaria-related deaths surveillance had a 38% sensitivity (95% CI: 32–44). Among 161 in-hospital individual malaria-related deaths reported from three data sources, the sex ratio (male to female) was 2.6. Median age of the patients was 57 years, ranging from 1 to 89 years. Conclusion The pertinent finding of this report is that malaria-related death records were significantly less* complete than case records. Therefore, data comparison of imported malaria morbidity and mortality between countries should imperatively be assessed using standard indicators weighted according to the completeness of health surveillance systems.
Published: 2020
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48. Absence of association between Plasmodium falciparum small sub-unit ribosomal RNA gene mutations and in vitro decreased susceptibility to doxycycline

Author: Jacques Lebras, François Nosten, Bruno Pradines, Tiphaine Gaillard, Chirapat Wangsing, Véronique Hubert, Sandrine Houzé, Nathalie Wurtz, Sébastien Briolant, Kanlaya Sriprawat, UL, SIMPA, Hôpital d'Instruction des Armées Sainte Anne, Service de Santé des Armées, Institut de Recherches Biomédicales des Armées, Unité de Recherche sur les Maladies Infectieuses Tropicales Emergentes (URMITE), 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)-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, 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), PRES Sorbonne Paris Cité, Mahidol University [Bangkok], University of Oxford, Direction Interarmées du Service de Santé, Laboratoire de Parasitologie [Cayenne, Guyane française], Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), This study was supported by the Délégation Générale pour l’Armement (Grant number 10CO405) and the Institut national de Veille sanitaire (CNR paludisme). The Shoklo Malaria Research Unit is part of the Mahidol Oxford University Research Unit, supported by The Wellcome Trust of Great Britain., French National Reference Centre for Imported Malaria Study Group : Ahmed Aboubacar, Patrice Agnamey, Faïza Ajana, Roger Amira, Nicolas Argy, Sonia Baumard, Pauline Bellanger, Dieudonné Bemba, Jean Beytout, Marie-Laure Bigel, Martine Bloch, Richard Bonnet, Alice Borel, Olivier Bouchaud, Catherine Branger, Fabrice Bruneel, Monique Cambon, Daniel Camus, Enrique Casalino, Jérome Clain, Sandrine Cojean, Bernadette Cuisenier B, Ludovic De Gentile, Jean-Marie Delarbre, Anne Delaval, Rémy Durand, Emmanuel Dutoit, Odile Eloy, Jean-François Faucher, Albert Faye, Odile Fenneteau, Denis Filisetti, Christian Fulleda, Nadine Godineau, Frédéric Grenouillet, Jean-Pierre Hurst, Houria Ichou, Elizabeth Klein E, Sylvie Lariven, Magalie Lefevre, Monique Lemoine, Olivier Lesens, Caroline Lohmann, Daniel Lusina, Marie-Claude Machouart, Robert Mary, Sophie Matheron, Denis Mechali, Audrey Merrens, Laurence Millon, Sébastien Monnier, Emmanuel Mortier, François Moussel, Olivier Pageot, Nathalie Parez, Pierre Patoz, Alexander Pfaff, Marc Pihet, Jean-Etienne Pilo, Isabelle Poilane, Denis Pons, Marie Poupart, Marc Prevel, Lauren Pull, Christophe Rapp, Alexandre Rivier, Emily Ronez, Daniel Rotten, Anne-Laure Simonet, Jean-Yves Siriez, Christophe Strady, Audrey Therby, Michel Thibault, Maxime Thouvenin, Dominique Toubas., INSB-INSB-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), University of Oxford [Oxford], Unité de Recherche sur les Maladies Infectieuses Tropicales Emergentes ( URMITE ), 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, INSB-INSB-Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR48, INSB-INSB-Centre National de la Recherche Scientifique ( CNRS ), Mère et enfant face aux infections tropicales ( MERIT - UMR_D 216 ), Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ), Laboratoire de parasitologie [Cayenne], Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ), Fédération des Laboratoires, Hôpital d'instruction des armées Sainte-Anne, Service de Parasitologie Mycologie [AP-HP Hôpital Bichat - Claude Bernard], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Shoklo Malaria Research Unit [Mae Sot, Thailand] (Faculty of Tropical Medicine), Mahidol University [Bangkok]-Mahidol Oxford Tropical Medicine Research Unit (MORU), University of Oxford [Oxford]-Mahidol University [Bangkok]-Wellcome Trust-University of Oxford [Oxford]-Wellcome Trust, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Descartes - Paris 5 (UPD5), Unité de Recherche en Biologie et Epidémiologie Parasitaires, Institut de Médecine Tropicale du Service de Santé des Armées-Centre National de la Recherche Scientifique (CNRS), Groupe d'Etude des Interactions Hôte-Parasite (GEIHP), and Université d'Angers (UA)
Subjects: Genes, Protozoan, Drug Resistance, Drug resistance, Molecular marker, chemistry.chemical_compound, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Doxycycline, Malaria, Falciparum, ComputingMilieux_MISCELLANEOUS, MESH: Plasmodium falciparum, MESH: Inhibitory Concentration 50, Doxycycline, Quinine, biology, MESH: Malaria, Falciparum, 3. Good health, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Genes, Protozoan, MESH: Drug Resistance, [SDV.IMM]Life Sciences [q-bio]/Immunology, medicine.drug, [SDV.IMM] Life Sciences [q-bio]/Immunology, pfssrRNA, Plasmodium falciparum, Antimalarials, Inhibitory Concentration 50, In vitro, parasitic diseases, MESH: Genes, rRNA, medicine, Humans, [SDV.EE.SANT] Life Sciences [q-bio]/Ecology, environment/Health, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, 16S rRNA, Gene, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, MESH: Humans, Research, Genes, rRNA, Ribosomal RNA, biology.organism_classification, medicine.disease, Virology, Small ribosomal sub-unit RNA gene, MESH: Antimalarials, Malaria, chemistry, Artesunate, Parasitology, Anti-malarial
Abstract: International audience; Background: Doxycycline is an antibiotic used in combination with quinine or artesunate for malaria treatment or alone for malaria chemoprophylaxis. Recently, one prophylactic failure has been reported, and several studies have highlighted in vitro doxycycline decreased susceptibility in Plasmodium falciparum isolates from different areas. The genetic markers that contribute to detecting and monitoring the susceptibility of P. falciparum to doxycycline, the pfmdt and pftetQ genes, have recently been identified. However, these markers are not sufficient to explain in vitro decreased susceptibility of P. falciparum to doxycycline. In this paper, the association between polymorphism of the small sub-unit ribosomal RNA apicoplastic gene pfssrRNA (PFC10_API0057) and in vitro susceptibilities of P. falciparum isolates to doxycycline were investigated.Methods: Doxycycline IC50 determinations using the hypoxanthine uptake inhibition assay were performed on 178 African and Thai P. falciparum isolates. The polymorphism of pfssrRNA was investigated in these samples by standard PCR followed by sequencing.Results: No point mutations were found in pfssrRNA in the Thai or African isolates, regardless of the determined IC50 values.Conclusions: The pfssrRNA gene is not associated with in vitro decreased susceptibility of P. falciparum to doxycycline. Identifying new in vitro molecular markers associated with reduced susceptibility is needed, to survey the emergence of doxycycline resistance.
Published: 2015
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