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1. 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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2. 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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3. 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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4. 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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5. 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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7. 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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8. 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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9. 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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10. 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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12. 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

13. 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

14. 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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15. 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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16. 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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17. 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

18. 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

20. 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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21. 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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22. 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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