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1. Evaluation of two commercial kits and two laboratory-developed qPCR assays compared to LAMP for molecular diagnosis of malaria

Author

Azza Bouzayene, Rizwana Zaffaroullah, Justine Bailly, Liliane Ciceron, Véronique Sarrasin, Sandrine Cojean, Nicolas Argy, Sandrine Houzé, Valentin Joste, and the French National Malaria Reference Centre study group

Subjects
Malaria, Plasmodium, P. falciparum, Molecular diagnosis, qPCR, LAMP, Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Malaria is an infectious disease considered as one of the biggest causes of mortality in endemic areas. This life-threatening disease needs to be quickly diagnosed and treated. The standard diagnostic tools recommended by the World Health Organization are thick blood smears microscopy and immuno-chromatographic rapid diagnostic tests. However, these methods lack sensitivity especially in cases of low parasitaemia and non-falciparum infections. Therefore, the need for more accurate and reliable diagnostic tools, such as real-time polymerase chain reaction based methods which have proven greater sensitivity particularly in the screening of malaria, is prominent. This study was conducted at the French National Malaria Reference Centre to assess sensitivity and specificity of two commercial malaria qPCR kits and two in-house developed qPCRs compared to LAMP. Methods 183 blood samples received for expertise at the FNMRC were included in this study and were subjected to four different qPCR methods: the Biosynex Ampliquick® Malaria test, the BioEvolution Plasmodium Typage test, the in-house HRM and the in-house TaqMan qPCRs. The specificity and sensitivity of each method and their confidence intervals were determined with the LAMP-based assay Alethia® Malaria as the reference for malaria diagnosis. The accuracy of species diagnosis of the Ampliquick® Malaria test and the two in-house qPCRs was also evaluated using the BioEvolution Plasmodium Typage test as the reference method for species identification. Results The main results showed that when compared to LAMP, a test with excellent diagnostic performances, the two in-house developed qPCRs were the most sensitive (sensitivity at 100% for the in-house TaqMan qPCR and 98.1% for the in-house HRM qPCR), followed by the two commercial kits: the Biosynex Ampliquick® Malaria test (sensitivity at 97.2%) and the BioEvolution Plasmodium Typage (sensitivity at 95.4%). Additionally, with the in-house qPCRs we were able to confirm a Plasmodium falciparum infection in microscopically negative samples that were not detected by commercial qPCR kits. This demonstrates that the var genes of P. falciparum used in these in-house qPCRs are more reliable targets than the 18S sRNA commonly used in most of the developed qPCR methods for malaria diagnosis. Conclusion Overall, these results accentuate the role molecular methods could play in the screening of malaria. This may represent a helpful tool for other laboratories looking to implement molecular diagnosis methods in their routine analysis, which could be essential for the detection and treatment of malaria carriers and even for the eradication of this disease.

Published
2022
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2. Study of humoral immune response in mammals immunized with Plasmodium falciparum antigenic preparations

Author

Antonio B. Cruz Cubas, Flavia Cunha, Isére Kuiatse Nitcheu, Laurence Rolland, Liliane Ciceron, Alexandre B. Carvalho, André F. Furtado, and Loic Monjour

Subjects
Plasmodium falciparum, protein fractions, in vitro parasite inhibition, rhoptry proteins, Microbiology, QR1-502, Infectious and parasitic diseases, RC109-216
Abstract

Six Plasmodium falciparum protein fractions, isolated under reducing conditions, were used to immunize mice, rabbits and the squirrel monkey Saimiri sciureus. Five or seven subcutaneous injections of each antigenic preparation, in conjunction with Freund's complete or incomplete adjuvants, were administered. This led to the development of specific antibodies detected by IFAT, ELISA or immunobloting which inhibited merozoite reinvasion in in vitro P. falciparum cultures. This activity seems to be associated with rhoptry proteins contained in fractions Pf F2 and Pf F4.

Published
1992
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3. A plant-derived morphinan as a novel lead compound active against malaria liver stages.

Author

Maëlle Carraz, Akino Jossang, Jean-François Franetich, Anthony Siau, Liliane Ciceron, Laurent Hannoun, Robert Sauerwein, François Frappier, Philippe Rasoanaivo, Georges Snounou, and Dominique Mazier

Subjects
Medicine
Abstract

BACKGROUND: The global spread of multidrug-resistant malaria parasites has led to an urgent need for new chemotherapeutic agents. Drug discovery is primarily directed to the asexual blood stages, and few drugs that are effective against the obligatory liver stages, from which the pathogenic blood infection is initiated, have become available since primaquine was deployed in the 1950s. METHODS AND FINDINGS: Using bioassay-guided fractionation based on the parasite's hepatic stage, we have isolated a novel morphinan alkaloid, tazopsine, from a plant traditionally used against malaria in Madagascar. This compound and readily obtained semisynthetic derivatives were tested for inhibitory activity against liver stage development in vitro (P. falciparum and P. yoelii) and in vivo (P. yoelii). Tazopsine fully inhibited the development of P. yoelii (50% inhibitory concentration [IC50] 3.1 muM, therapeutic index [TI] 14) and P. falciparum (IC50 4.2 muM, TI 7) hepatic parasites in cultured primary hepatocytes, with inhibition being most pronounced during the early developmental stages. One derivative, N-cyclopentyl-tazopsine (NCP-tazopsine), with similar inhibitory activity was selected for its lower toxicity (IC50 3.3 muM, TI 46, and IC50 42.4 muM, TI 60, on P. yoelii and P. falciparum hepatic stages in vitro, respectively). Oral administration of NCP-tazopsine completely protected mice from a sporozoite challenge. Unlike the parent molecule, the derivative was uniquely active against Plasmodium hepatic stages. CONCLUSIONS: A readily obtained semisynthetic derivative of a plant-derived compound, tazopsine, has been shown to be specifically active against the liver stage, but inactive against the blood forms of the malaria parasite. This unique specificity in an antimalarial drug severely restricts the pressure for the selection of drug resistance to a parasite stage limited both in numbers and duration, thus allowing researchers to envisage the incorporation of a true causal prophylactic in malaria control programs.

Published
2006
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4. Postartesunate delayed hemolysis is a predictable event related to the lifesaving effect of artemisinins

Author

Dominique Mazier, Adela Angoulvant, Innocent Safeukui, Marc Thellier, Sylvestre Biligui, Oussama Mouri, Eric Kendjo, Flavie Ader, Marie Nguyen, Camille Roussel, Muriel Vray, Liliane Ciceron, Kasturi Haldar, Martin Danis, François Bricaire, Papa Alioune Ndour, Julien Mayaux, Pierre Buffet, Eric Caumes, and Stéphane Jauréguiberry

Subjects
Hemolytic anemia, medicine.medical_specialty, Quinine, business.industry, Anemia, Immunology, Cmax, Liter, Cell Biology, Hematology, medicine.disease, Biochemistry, Gastroenterology, Hemolysis, chemistry.chemical_compound, chemistry, Artesunate, Internal medicine, medicine, business, Malaria, medicine.drug
Abstract

Patients with severe malaria treated with artesunate sometimes experience a delayed hemolytic episode. Artesunate (AS) induces pitting, a splenic process whereby dead parasites are expelled from their host erythrocytes. These once-infected erythrocytes then return to the circulation. We analyzed hematologic parameters in 123 travelers treated with AS for severe malaria. Among 60 nontransfused patients observed for more than 8 days, 13 (22%) had delayed hemolysis. The peak concentration of circulating once-infected erythrocytes was measured during the first week in 21 patients and was significantly higher in 9 patients with delayed hemolysis than in 12 with other patterns of anemia (0.30 vs 0.07; P = .0001). The threshold of 180 million once-infected erythrocytes per liter discriminated patients with delayed hemolysis with 89% sensitivity and 83% specificity. Once-infected erythrocyte morphology analyzed by using ImageStream in 4 patients showed an 8.9% reduction in their projected area, an alteration likely contributing to their shorter lifespan. Delayed clearance of infected erythrocytes spared by pitting during AS treatment is an original mechanism of hemolytic anemia. Our findings consolidate a disease framework for posttreatment anemia in malaria in which delayed hemolysis is a new entity. The early concentration of once-infected erythrocytes is a solid candidate marker to predict post-AS delayed hemolysis

Published
2014
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5. Whole‐Transcriptome Analysis ofPlasmodium falciparumField Isolates: Identification of New Pathogenicity Factors

Author

Catherine Vaquero, Peter H. David, Patrick Froissard, Nassira Mahmoudi, Emmanuel Bischoff, Odile Ouwe-Missi-Oukem-Boyer, Liliane Ciceron, Dominique Mazier, Ulrick Bisvigou, Anthony Siau, Fousseyni S. Touré, Sylvie Bisser, and Jean-Yves Coppée

Subjects
Erythrocytes, Virulence Factors, Genes, Protozoan, Plasmodium falciparum, Malaria, Cerebral, Apoptosis, Biology, Microbiology, Transcriptome, parasitic diseases, Cell Adhesion, medicine, Animals, Humans, Immunology and Allergy, Parasite hosting, Gene silencing, Gabon, Malaria, Falciparum, Child, Gene, Oligonucleotide Array Sequence Analysis, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling, Brain, Endothelial Cells, DNA, Protozoan, medicine.disease, biology.organism_classification, Virology, Infectious Diseases, Blood-Brain Barrier, Cerebral Malaria, DNA microarray, Malaria
Abstract

Background. Severe malaria and one of its most important pathogenic processes, cerebral malaria, involves the sequestration of parasitized red blood cells (pRBCs) in brain postcapillary veinules. Although the pathogenic mechanisms underlying malaria remain poorly characterized, it has been established that adhesion of pRBCs to endothelial cells (ECs) can result in cell apoptosis, which in turn may lead to disruption of the blood-brain barrier. The nature of the parasite molecules involved in the pathogenesis of severe malaria remains elusive. Methods. Whole-transcriptome profiling of nonapoptogenic versus apoptogenic parasite field isolates obtained from Gabonese children was performed with pan-genomic Plasmodium faldparum DNA microarrays; radiolabeled instead of fluorescent cDNAs were used to improve the sensitivity of signal detection. Results. Our methods allowed the identification of 59 genes putatively associated with the induction of EC apoptosis. Silencing of Plasmodium gene expression with specific double-stranded RNA was performed on 8 selected genes; 5 of these, named "Plasmodium apoptosis-linked pathogenicity factors" (PALPFs), were found to be linked to parasite apoptogenicity. Of these genes, 2 might act via parasite cytoadherence. Conclusion. This is the first attempt to identify genes involved in parasite pathogenic mechanisms against human ECs. The finding of PALPFs illuminates perspectives for novel therapeutic strategies against cerebral complications of malaria.

Published
2007
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6. In Vitro Activities of 25 Quinolones and Fluoroquinolones against Liver and Blood Stage Plasmodium spp

Author

Khemais Farhati, Martin Danis, Robert W. Sauerwein, Francis Derouin, Jean-François Franetich, Dominique Mazier, Wijnand Eling, Liliane Ciceron, Nassira Mahmoudi, and Olivier Silvie

Subjects
Plasmodium, Erythrocytes, Antiparasitic, medicine.drug_class, Plasmodium falciparum, Microbiology, Mice, Anti-Infective Agents, parasitic diseases, medicine, Animals, Pharmacology (medical), Mechanisms of Action: Physiological Effects, Cells, Cultured, Pharmacology, 4-Quinolones, biology, Chemistry, Plasmodium yoelii, biology.organism_classification, Piromidic acid, In vitro, Grepafloxacin, Ciprofloxacin, Trovafloxacin, Infectious Diseases, Liver, Fluoroquinolones, medicine.drug
Abstract

The in vitro activities of 25 quinolones and fluoroquinolones against erythrocytic stages of Plasmodium falciparum and against liver stages of Plasmodium yoelii yoelii and P. falciparum were studied. All compounds were inhibitory for chloroquine-sensitive and chloroquine-resistant P. falciparum grown in red blood cells. This inhibitory effect increased with prolonged incubation and according to the logarithm of the drug concentration. Grepafloxacin, trovafloxacin, and ciprofloxacin were the most effective drugs, with 50% inhibitory concentrations of P. falciparum and P. yoelii yoelii ; this effect combined reductions of the numbers and the sizes of schizonts in treated cultures. Thus, quinolones have a potential for treatment or prevention of malaria through their unique antiparasitic effect against erythrocytic and hepatic stages of Plasmodium .

Published
2003
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7. An Atypical Mitogen-activated Protein Kinase (MAPK) Homologue Expressed in Gametocytes of the Human Malaria Parasite Plasmodium falciparum

Author

Caroline Doerig, Dominique Dorin, Pietro Alano, Irène Boccaccio, Daniel Parzy, Liliane Ciceron, Christian Doerig, and Renan Sulpice

Subjects
MAPK/ERK pathway, biology, Kinase, Autophosphorylation, Plasmodium falciparum, Cell Biology, biology.organism_classification, Biochemistry, law.invention, Cell biology, Open reading frame, law, Complementary DNA, Recombinant DNA, Kinase activity, Molecular Biology
Abstract

The cDNA encoding Pfmap-2, an enzyme of the human malaria parasite Plasmodium falciparum, was cloned, sequenced, and expressed in Escherichia coli. The open reading frame carried by the Pfmap-2 cDNA encodes a 508-amino acid polypeptide of 59.2 kDa with maximal homology to mitogen-activated protein kinases (MAPKs) from various organisms. The purified recombinant enzyme displayed functional characteristics of MAPKs such as (i) ability to undergo autophosphorylation, (ii) ability to phosphorylate myelin basic protein, a classical MAPK substrate, (iii) regulation of kinase activity by a MAPK-specific phosphatase, and (iv) ability to be activated by component(s) present in cell extracts. Mutational analysis of the recombinant protein allowed the identification of residues that are important for enzymatic activity. Northern blot analysis and immunofluorescence assays indicated that Pfmap-2 is expressed specifically in gametocytes, the form that is responsible for transmission of the parasite to the mosquito vector. Gametocyte extracts activated recombinant Pfmap-2 more efficiently than extracts from asexual parasites, which is consistent with this stage specificity. Despite its overall high level of homology to MAPKs, Pfmap-2 presents the peculiarity of not possessing the conserved threonine-X-tyrosine activation motif usually found in enzymes of this family; instead, it has a threonine-serine-histidine at the same location. This atypical feature formed the basis for a detailed analysis of the primary structure of MAPKs, allowing us to define an operational MAPK signature, which is shared by Pfmap-2. The fact that no MAPK from vertebrates diverge in the activation motif suggests that the fine mechanisms of Pfmap-2 regulation may offer an opportunity for antimalarial drug targeting.

Published
1999
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8. Reduced erythrocyte deformability associated with hypoargininemia during Plasmodium falciparum malaria

Author

Geneviève Milon, Odile Mercereau-Puijalon, Juliana Rey, Liliane Ciceron, Innocent Safeukui, Pierre Buffet, Immunologie moléculaire des parasites, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Immunité et Infection, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pasteur [Paris] (IP), HAL UPMC, Gestionnaire, Service de Parasitologie - Mycologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), 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), and Institut Pasteur [Paris]

Subjects
Male, MESH: Erythrocyte Deformability, Erythrocytes, Arginine, Parasitemia, chemistry.chemical_compound, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Erythrocyte deformability, Malaria, Falciparum, MESH: Plasmodium falciparum, media_common, Multidisciplinary, MESH: Middle Aged, biology, Chemistry, Convalescence, MESH: Erythrocytes, MESH: Malaria, Falciparum, Temperature, MESH: Arginine, Middle Aged, MESH: Temperature, 3. Good health, medicine.anatomical_structure, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, Adult, media_common.quotation_subject, Plasmodium falciparum, Nitric Oxide, Article, Nitric oxide, Andrology, Erythrocyte Deformability, medicine, Humans, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Humans, MESH: Adult, medicine.disease, biology.organism_classification, MESH: Male, Red blood cell, MESH: Nitric Oxide, Immunology, MESH: Female, Malaria
Abstract

The mechanisms underlying reduced red blood cell (RBC) deformability during Plasmodium falciparum (Pf) malaria remain poorly understood. Here, we explore the possible involvement of the L-arginine and nitric oxide (NO) pathway on RBC deformability in Pf-infected patients and parasite cultures. RBC deformability was reduced during the acute attack (day0) and returned to normal values upon convalescence (day28). Day0 values correlated with plasma L-arginine levels (r = 0.69; p = 0.01) and weakly with parasitemia (r = −0.38; p = 0.006). In vitro, day0 patient's plasma incubated with ring-stage cultures at 41°C reduced RBC deformability and this effect correlated strongly with plasma L-arginine levels (r = 0.89; p < 0.0001). Moreover, addition of exogenous L-arginine to the cultures increased deformability of both Pf-free and trophozoite-harboring RBCs. NO synthase activity, evidenced in Pf-infected RBCs, induced L-arginine-dependent NO production. These data show that hypoargininemia during P.falciparum malaria may altogether impair NO production and reduce RBC deformability, particularly at febrile temperature.

Published
2014
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9. Metabolic acidosis induced by Plasmodium falciparum intraerythrocytic stages alters blood-brain barrier integrity

Author

Sergine Zougbédé, Philippe Ravassard, Alicia Moreno, Florence Miller, Pierre-Olivier Couraud, Angelita Rebollo, Dominique Mazier, and Liliane Ciceron

Subjects
Erythrocytes, Cell, Plasmodium falciparum, Malaria, Cerebral, Blood–brain barrier, Permeability, Cell Line, Tight Junctions, Transduction, Genetic, medicine, Cell Adhesion, Humans, Trypsin, Annexin A5, Malaria, Falciparum, Cell adhesion, Microscopy, Confocal, biology, Tight junction, L-Lactate Dehydrogenase, Merozoites, Lentivirus, Endothelial Cells, Hydrogen-Ion Concentration, biology.organism_classification, Flow Cytometry, Cell biology, Endothelial stem cell, medicine.anatomical_structure, Neurology, Cerebral Malaria, Blood-Brain Barrier, Paracellular transport, Immunology, RNA Interference, Original Article, Neurology (clinical), Cardiology and Cardiovascular Medicine, Acidosis
Abstract

The pathogenesis of cerebral malaria (CM) remains largely unknown. There is growing evidence that combination of both parasite and host factors could be involved in blood–brain barrier (BBB) breakdown. However, lack of adequate in vitro model of human BBB so far hampered molecular studies. In this article, we propose the use of hCMEC/D3 cells, a well-established human cerebral microvascular endothelial cell (EC) line, to study BBB breakdown induced by Plasmodium falciparum-parasitized red blood cells and environmental conditions. We show that coculture of parasitized erythrocytes with hCMEC/D3 cells induces cell adhesion and paracellular permeability increase, which correlates with disorganization of zonula occludens protein 1 expression pattern. Permeability increase and modification of tight junction proteins distribution are cytoadhesion independent. Finally, we show that permeability of hCMEC/D3 cell monolayers is mediated through parasite induced metabolic acidosis, which in turns correlates with apoptosis of parasitized erythrocytes. This new coculture model represents a very useful tool, which will improve the knowledge of BBB breakdown and the development of adjuvant therapies, together with antiparasitic drugs.

Published
2010

10. ChemInform Abstract: Artemisinin Tricyclic Analogues Bearing a Methyl Group at C-5a: Preparation and Antimalarial Activity

Author

Fatima Zouhiri, Didier Desmaele, Jean d'Angelo, Jacqueline Mahuteau, Claude Riche, Frederick Gay, and Liliane Ciceron

Subjects
chemistry.chemical_classification, Bearing (mechanical), Stereochemistry, Chemistry, General Medicine, law.invention, Terpene, chemistry.chemical_compound, law, medicine, Artemisinin, medicine.drug, Tricyclic, Methyl group
Published
2010
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11. Rho kinase inhibition in severe malaria: thwarting parasite-induced collateral damage to endothelia

Author

Maurel Tefit, Philippe Lechat, Liliane Ciceron, Dominique Mazier, Judith Balvanyos, and Zacharie Taoufiq

Subjects
Erythrocytes, Endothelium, Population, Plasmodium falciparum, Apoptosis, Biology, Models, Biological, 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine, parasitic diseases, medicine, Immunology and Allergy, Animals, Humans, education, Rho-associated protein kinase, Protein Kinase Inhibitors, education.field_of_study, rho-Associated Kinases, Fasudil, NF-kappa B, biology.organism_classification, medicine.disease, Coculture Techniques, Infectious Diseases, medicine.anatomical_structure, Cerebral Malaria, Rho kinase inhibitor, Immunology, Endothelium, Vascular, Malaria
Abstract

Acute clinical manifestations of falciparum malaria, such as multiorgan failure and cerebral malaria, occur unpredictably and lead to coma and death within hours if left untreated. Despite the emergency administration of effective antimalarial drugs, 15%-20% of patients die. Other therapeutic approaches are therefore urgently needed. There is increasing evidence that endothelial changes play a key role in the pathogenesis of severe malaria. We therefore used coculture models to study interactions between infected erythrocytes and endothelium. We found that adhesion of Plasmodium falciparum to endothelial cells in vitro activated the Rho kinase signaling pathway, which is strongly involved in various vascular diseases. When added concomitantly with parasites, the Rho kinase inhibitor fasudil (HA-1077), a drug already in clinical use, decreased both NF-kappaB activation and endothelial cell apoptosis. Fasudil also helped to restore endothelial barrier integrity after P. falciparum adhesion. Rho kinase inhibition thus appears to be a promising adjunctive therapeutic approach to the management of severe human malaria.

Published
2008

12. Effects of hydroxyurea on malaria, parasite growth and adhesion in experimental models

Author

Jean-François Franetich, Paco Pino, R. Krishnamoorthy, M. Brun, Zacharie Taoufiq, Liliane Ciceron, Dominique Mazier, and Maurel Tefit

Subjects
Erythrocytes, Endothelium, Immunology, Plasmodium falciparum, Malaria, Cerebral, Apoptosis, Anemia, Sickle Cell, Mice, Antisickling Agents, parasitic diseases, medicine, Cell Adhesion, Animals, Humans, Hydroxyurea, Malaria, Falciparum, Cell adhesion, ICAM-1, biology, Endothelial Cells, biology.organism_classification, medicine.disease, Intercellular Adhesion Molecule-1, Endothelial stem cell, Mice, Inbred C57BL, medicine.anatomical_structure, Treatment Outcome, Cerebral Malaria, Parasitology, Endothelium, Vascular, Malaria
Abstract

We recently raised concern over using hydroxyurea (HU) in the treatment of sickle cell disease in areas endemic for malaria, becauseit up-regulates the endothelial surface expression of ICAM-1, a major receptor for Plasmodium falciparum-infected erythrocytes in the brain. Using human in vitro models of cerebral malaria, we evaluated the interaction of HU with parasites and demonstrated that HU pretreatment increased the number of infected red blood cells adhering to the endothelium, but did not increase endothelial apoptosis. Moreover, using an experimental cerebral malaria model, HU pretreatment was found to prevent significantly mice from developing neurological syndrome by inhibiting parasite growth, opening potential therapeutic avenues.

Published
2006

13. Identification of new antimalarial drugs by linear discriminant analysis and topological virtual screening

Author

Ramón García-Domenech, Jesus-Vicente de Julián-Ortiz, Martin Danis, Francis Derouin, Nassira Mahmoudi, Liliane Ciceron, Jorge Galvez, and Dominique Mazier

Subjects
Microbiology (medical), Quantitative structure–activity relationship, Plasmodium falciparum, Drug Evaluation, Preclinical, Quantitative Structure-Activity Relationship, Pharmacology, Topology, Hycanthone, Models, Biological, chemistry.chemical_compound, Antimalarials, Inhibitory Concentration 50, medicine, Animals, Pharmacology (medical), Amsacrine, Salinomycin, Virtual screening, biology, Molecular Structure, Discriminant Analysis, Linear discriminant analysis, biology.organism_classification, In vitro, Infectious Diseases, chemistry, Drug Design, Multivariate Analysis, Linear Models, medicine.drug
Abstract

Objectives A quantitative structure-activity relationship study using a database of 395 compounds previously tested against chloroquine-susceptible strains of the blood stages of Plasmodium falciparum to predict new in vitro antimalarial drugs has been developed. Methods Topological indices were used as structural descriptors and were related to antimalarial activity by using linear discriminant analysis (LDA) and multilinear regression (MLR). Two discriminant equations were obtained (FD1 and FD2), which allowed us to carry out successful classification of 90% and 80% of compounds, respectively. The IC50 values of the compounds were introduced to get an MLR equation model suitable to predict their in vitro activities. Results Using this model, a set of 27 drugs against a chloroquine-susceptible clone (3D7) of P. falciparum have been selected and evaluated in vitro. Among these drugs are monensin, nigericin, vincristine, vindesine, ethylhydrocupreine and salinomycin with in vitro IC50s at nanomolar concentrations (0.3, 0.4, 2, 6, 26 and 188 nM, respectively). Other compounds such as hycanthone, amsacrine, aphidicolin, bepridil, amiodarone, ranolazine and triclocarban showed in vitro IC50 values below 5 microM in the mathematical model. Conclusions These results demonstrate the usefulness of the approach for the selection and design of new lead drugs active against P. falciparum.

Published
2006

14. Drug Development Papers in PLoS Medicine: How We Try to Spot a Winner

Author

Robert W. Sauerwein, Akino Jossang, François Frappier, Anthony Siau, Laurent Hannoun, Jean-François Franetich, Georges Snounou, Dominique Mazier, Liliane Ciceron, Philippe Rasoanaivo, Maëlle Carraz, Immunobiologie Cellulaire et Moléculaire des Infections Parasitaires, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de chimie et biochimie des substances naturelles, Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Service de Chirurgie Digestive, Hépato-Bilio-pancréatique et Transplantation Hépatique [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), Department of Medical Microbiology, Radboud University Medical Center [Nijmegen], Laboratoire de Pharmacognosie Appliquée aux Maladies Infectieuses, Institut Malgache de Recherches Appliquées, Parasitologie et modèles expérimentaux, This work was supported in part by grants from the Ministère Délégué à la Recherche et aux Nouvelles Technologies (Programme Pal+) and the Fondation pour la Recherche Médicale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Peduzzi, Jean

Subjects
Morphinan, Primaquine, lcsh:Medicine, Plasmodium, MESH: Hepatocytes, chemistry.chemical_compound, Mice, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Animals, Cells, Cultured, MESH: Plasmodium falciparum, MESH: Plasmodium yoelii, MESH: Inhibitory Concentration 50, 0303 health sciences, biology, Drug discovery, General Medicine, 3. Good health, MESH: Morphinans, Liver, Morphinans, MESH: Phytotherapy, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Plant Bark, MESH: Cell Fractionation, Biological Assay, Lead compound, Infection and autoimmunity [NCMLS 1], Plasmodium yoelii, MESH: Plant Bark, medicine.drug, Research Article, MESH: Cells, Cultured, 030231 tropical medicine, Molecular Sequence Data, Plasmodium falciparum, MESH: Malaria, Cell Fractionation, MESH: Biological Assay, Auto-immunity, transplantation and immunotherapy [N4i 4], Microbiology, 03 medical and health sciences, Antimalarials, Inhibitory Concentration 50, Drugs and Adverse Drug Reactions, parasitic diseases, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Mice, 030304 developmental biology, MESH: Molecular Sequence Data, MESH: Humans, lcsh:R, Poverty-related infectious diseases [N4i 3], medicine.disease, biology.organism_classification, Virology, MESH: Antimalarials, Malaria, chemistry, Immunology, Hepatocytes, Microbial pathogenesis and host defense [UMCN 4.1], Immunity, infection and tissue repair [NCMLS 1], Phytotherapy, MESH: Liver
Abstract

Background The global spread of multidrug–resistant malaria parasites has led to an urgent need for new chemotherapeutic agents. Drug discovery is primarily directed to the asexual blood stages, and few drugs that are effective against the obligatory liver stages, from which the pathogenic blood infection is initiated, have become available since primaquine was deployed in the 1950s. Methods and Findings Using bioassay-guided fractionation based on the parasite's hepatic stage, we have isolated a novel morphinan alkaloid, tazopsine, from a plant traditionally used against malaria in Madagascar. This compound and readily obtained semisynthetic derivatives were tested for inhibitory activity against liver stage development in vitro (P. falciparum and P. yoelii) and in vivo (P. yoelii). Tazopsine fully inhibited the development of P. yoelii (50% inhibitory concentration [IC50] 3.1 μM, therapeutic index [TI] 14) and P. falciparum (IC50 4.2 μM, TI 7) hepatic parasites in cultured primary hepatocytes, with inhibition being most pronounced during the early developmental stages. One derivative, N-cyclopentyl-tazopsine (NCP-tazopsine), with similar inhibitory activity was selected for its lower toxicity (IC50 3.3 μM, TI 46, and IC50 42.4 μM, TI 60, on P. yoelii and P. falciparum hepatic stages in vitro, respectively). Oral administration of NCP-tazopsine completely protected mice from a sporozoite challenge. Unlike the parent molecule, the derivative was uniquely active against Plasmodium hepatic stages. Conclusions A readily obtained semisynthetic derivative of a plant-derived compound, tazopsine, has been shown to be specifically active against the liver stage, but inactive against the blood forms of the malaria parasite. This unique specificity in an antimalarial drug severely restricts the pressure for the selection of drug resistance to a parasite stage limited both in numbers and duration, thus allowing researchers to envisage the incorporation of a true causal prophylactic in malaria control programs., A derivative of a morphinan alkaloid, tazopsine, from a plant used against malaria in Madagascar, is active against the hepatic stages ofPlasmodium species., Editors' Summary Background. The parasite that causes malaria has quickly developed resistance to many of the drugs that are commonly used to treat this disease. As a result, new drugs and drug combinations are needed. In some parts of the world where antimalarial drugs are failing due to resistance, or are not available to everyone, people often turn to traditional herbal remedies instead. These traditional plant remedies can be a useful starting point for development of new drugs, but the process of developing effective new drugs from plant remedies is long and complicated. An important initial step is to isolate and identify the active compounds from plants and then see how well these compounds perform against malaria parasites in laboratory tests. If the tests are successful, such compounds could then progress to experiments in animals and possibly eventually human trials. One plant used widely in Madagascar for treatment of malaria is Strychnopsis thouarsii; the traditional remedy consists of the plant stem bark boiled in water. Why Was This Study Done? The group of researchers doing this study wanted to discover candidates for new malaria drugs. They therefore wanted to find out which molecular compounds in the stem bark of S. thouarsii contained antimalarial activity, and what particular stage of the malaria parasite's life cycle these compounds had an effect on. The researchers suspected that the agents in this plant bark had some activity against the “liver stage” of malaria infection in humans. This is the first stage of infection, after a person has been bitten by a malaria-infected mosquito, and before blood cells are invaded by malaria parasites (which then causes the disease symptoms). Very few drugs currently in existence have an effect on the “liver stage” of infection, but activity at this stage would be tremendously useful because it could mean a drug is better for prevention of malaria than others in existence. What Did the Researchers Do and Find? First, the researchers wanted to take the traditional herbal remedy—of S. thouarsii bark boiled in water—and find out precisely which molecule in that remedy was responsible for the antimalarial activity. They therefore used a method called chromatography to progressively separate the herbal extract into its distinct components. At each stage of separation, the extract was checked for activity against malaria using a laboratory test. Inactive extracts were disregarded, and the active component then taken on to a further separation round. After many rounds of separation and testing, the researchers got down to a single, apparently new, molecule that was active against malaria in the laboratory test, and this molecule was named tazopsine (in the Malagasy language the word Tazo refers to malaria). In order to find out how effective the molecule was at killing malaria parasites, the researchers took human or mouse liver cells cultured in the laboratory, infected them with malaria parasites (either the malaria parasite that normally infects humans, or a related species that infects mice), and then added tazopsine at different concentrations. The compound completely killed the malaria parasites even at very low concentrations, and had activity against malaria infecting either liver cells or red blood cells. Tazopsine was then given to mice injected with a species of the malaria parasite. The compound protected most mice against malaria infection when it was used at a dosage level lower than the toxic dose. The researchers then tried making a series of different variants of tazopsine in the hope that some variants would be less toxic, but equally active as, the original compound. They found one variant, named NCP-tazopsine, that was much less toxic but just as active as tazopsine, but only against the malaria infecting liver cells. What Do These Findings Mean? In these experiments a new molecule, tazopsine, was discovered from a Malagasy plant, and it was found to be active against liver-stage malaria parasites, in laboratory experiments and in mice. This molecule or variants of it could in future become candidate antimalarial drugs in humans. However, much work would need to be done before testing could get to that stage. Different variants of molecules related to tazopsine would need to be tested to find one that has low toxicity, and these variants would need to be fully evaluated in animals to see how they are handled in the body before any trials could begin in humans. Additional Information. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030513 The World Health Organization publishes a minisite containing links to information about all aspects of malaria worldwide, including treatment, prevention, and current programmes for malaria control Medicines for Malaria Venture is a collaboration between public and private organizations (including the pharmaceutical industry) that aims to fund and manage the development of new drugs for treatment and prevention of malaria Wikipedia entries for drug discovery and drug development (note: Wikipedia is an internet encyclopedia that anyone can edit)

Published
2006
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15. Synthesis and antimalarial activity of 2-methoxyprop-2-yl peroxides derivatives

Author

Laure Cointeaux, Olivier Provot, Joëlle Mayrargue, Viviane Peyrou, Martin Danis, Anne Robert, Bernard Meunier, Liliane Ciceron, Jean-François Berrien, Biomolécules : Conception, Isolement, Synthèse (BioCIS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Université de Cergy Pontoise (UCP), Université Paris-Seine-Université Paris-Seine, Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Molécules bioactives, conception, isolement et synthèse (MBCIS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-Université de Cergy Pontoise (UCP), Université Paris-Seine-Université Paris-Seine-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Alkylation, Stereochemistry, Metalloporphyrins, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Plasmodium falciparum, Pharmaceutical Science, 010402 general chemistry, 01 natural sciences, Biochemistry, Chemical synthesis, chemistry.chemical_compound, Antimalarials, Inhibitory Concentration 50, Structure-Activity Relationship, Drug Discovery, parasitic diseases, medicine, Animals, [CHIM]Chemical Sciences, Molecular Biology, Heme, Bicyclic molecule, biology, 010405 organic chemistry, Chemistry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Organic Chemistry, biology.organism_classification, In vitro, Artemisinins, 0104 chemical sciences, Peroxides, Mechanism of action, Molecular Medicine, medicine.symptom, Aliphatic compound, Sesquiterpenes
Abstract

International audience; 2-Methoxyprop-2-yl peroxides were synthesized and evaluated in vitro against Plasmodium falciparum. These acyclic artemisinin-related peroxides revealed moderate to good activity but were devoided of alkylating property towards the synthetic model of haeme Mn II-TPP.

Published
2003
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17. Development of a Plasmodium PCR for monitoring efficacy of antimalarial treatment

Author

Liliane Ciceron, Ginette Jaureguiberry, Frederick Gay, and Martin Danis

Subjects
Microbiology (medical), Plasmodium, Plasmodium falciparum, Dot blot, Polymerase Chain Reaction, Sensitivity and Specificity, law.invention, Apicomplexa, Antimalarials, law, parasitic diseases, medicine, RNA, Ribosomal, 18S, Parasite hosting, Animals, Humans, Malaria, Falciparum, Polymerase chain reaction, Whole blood, biology, Process Assessment, Health Care, DNA, Protozoan, biology.organism_classification, medicine.disease, Virology, Parasitology, Malaria
Abstract

We report in this work a highly sensitive and nonradioactive PCR method for the detection of the four species of parasite causing human malaria. Plasmodium -specific primers corresponding to the small-subunit rRNA genes of the malaria parasite were used, and a 291-bp fragment was amplified. Our results showed a high specificity for the four human Plasmodium species, and we were able to detect one parasite in 50 μl of whole blood. The responses of 12 patients infected with Plasmodium falciparum to antimalarial therapy were monitored by PCR diagnosis and examination of thick blood film for at least 20 min by an experienced microscopist. For one patient this study allowed early diagnosis of therapeutic failure, confirmed 7 days later by examination of the thick blood film. A total of 134 samples were examined; 94 were positive by PCR, and among these 68 were positive by thick blood film examination. The sensitivity of the thick blood film was 72.3% compared to PCR and 60.7% compared to dot blot hybridization.

Published
1998

18. Selective cytotoxicity of dermaseptin S3 toward intraerythrocytic Plasmodium falciparum and the underlying molecular basis

Author

Liliane Ciceron, Philippe Guillaud, Jimut Kanti Ghosh, Irina Kustanovich, Yechiel Shai, Amram Mor, Dominique Mazier, and Dan Shaool

Subjects
Erythrocytes, Molecular Sequence Data, Plasmodium falciparum, Peptide, Biology, Biochemistry, Hemolysis, Amphibian Proteins, chemistry.chemical_compound, Anti-Infective Agents, Phosphatidylcholine, Animals, Humans, Amino Acid Sequence, Cytotoxicity, Molecular Biology, Hypoxanthine, Chromatography, High Pressure Liquid, chemistry.chemical_classification, Dermaseptin, Microscopy, Video, Vesicle, Intracellular parasite, Cell Biology, Phosphatidylserine, Spectrometry, Fluorescence, chemistry, Peptides, Antimicrobial Cationic Peptides
Abstract

The antimicrobial activity of various naturally occurring microbicidal peptides was reported to result from their interaction with microbial membrane. In this study, we investigated the cytotoxicity of the hemolytic peptide dermaseptin S4 (DS4) and the nonhemolytic peptide dermaseptin S3 (DS3) toward human erythrocytes infected by the malaria parasite Plasmodium falciparum. Both DS4 and DS3 inhibited the parasite's ability to incorporate [3H]hypoxanthine. However, while DS4 was toxic toward both the parasite and the host erythrocyte, DS3 was toxic only toward the intraerythrocytic parasite. To gain insight into the mechanism of this selective cytotoxicity, we labeled the peptides with fluorescent probes and investigated their organization in solution and in membranes. In Plasmodium-infected cells, rhodamine-labeled peptides interacted directly with the intracellular parasite, in contrast to noninfected cells, where the peptides remained bound to the erythrocyte plasma membrane. Binding experiments to phospholipid membranes revealed that DS3 and DS4 had similar binding characteristics. Membrane permeation studies indicated that the peptides were equally potent in permeating phosphatidylserine/phosphatidylcholine vesicles, whereas DS4 was more permeative with phosphatidylcholine vesicles. In aqueous solutions, DS4 was found to be in a higher aggregation state. Nevertheless, both DS3 and DS4 spontaneously dissociated to monomers upon interaction with vesicles, albeit with different kinetics. In light of these results, we propose a mechanism by which dermaseptins permeate cells and affect intraerythrocytic parasites.

Published
1998

19. In vitro response of Plasmodium falciparum to atovaquone and correlation with other antimalarials: comparison between African and Asian strains

Author

Frederick Gay, Boubacar Traore, Manivanh Southammavong, Liliane Ciceron, Catherine Jardinel, M. Martin Danis, and Dorina Bustos

Subjects
Asia, Proguanil, Plasmodium falciparum, Biology, Pharmacology, chemistry.chemical_compound, Antimalarials, Halofantrine, Chloroquine, Virology, parasitic diseases, medicine, Animals, Humans, Artemether, Artemisinin, Atovaquone, Mefloquine, Infectious Diseases, chemistry, Artesunate, Africa, Parasitology, medicine.drug, Naphthoquinones
Abstract

Atovaquone (dihydroxynaphthoquinone 566C80) is a broad-spectrum antiprotozoal compound demonstrating potent antimalarial activity against multidrug-resistant malaria. We present the results of in vitro drug sensitivity tests of 142 Plasmodium falciparum isolates, 108 from 14 countries of West and Central Africa, 32 from the Philippines, and one each from Laos and Myanmar. These were tested in vitro against nine drugs: the classic antimalarials chloroquine, quinine, mefloquine and halofantrine, the four qinghaosu derivatives, artemisinin, artemether, artesunate, and arteether, and the new compound atovaquone. Results showed the Asian strains have a higher median 50% inhibitory concentration (IC 50 ) to almost all drugs compared with those from Africa. This was significantly different for chloroquine, halofantrine, and artemisinin. We used three different approaches to estimate the threshold for resistance of atovaquone to be approximately 5-7 nmol/L. The global median of 96 pooled strains is 1.4 nmol/L and the 90th percentile is 5.5 nmol/L for atovaquone. There were no correlations of atovaquone with the eight other antimalarials among African strains, but significant correlations, except for halofantrine, were observed among Asian strains. The absence of a correlation between atovaquone and the other available drugs indicates the potential of atovaquone as an alternative antimalarial in Africa. The correlation observed among Asian strains, however, suggests that atovaquone has to be used cautiously in Asia. Nevertheless, the association with proguanil in recently concluded clinical trials in Europe, South America, Asia, and Africa has demonstrated its antimalarial efficacy.

Published
1997

20. Is airport malaria a transfusion-transmitted malaria risk?

Author

Claude Guiguen, Martin Danis, Fabrice Legros, Liliane Ciceron, Maryvonne Delamaire, Dominique Mazier, Marc Thellier, Daniel Lusina, and Michel Klerlein

Subjects
Transfusion transmitted malaria, medicine.medical_specialty, business.industry, Immunology, Transfusion Reaction, Hematology, Airport malaria, Risk Factors, Emergency medicine, Aerospace Medicine, Humans, Immunology and Allergy, Medicine, Malaria, Falciparum, business
Published
2001
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23. Identification of new antimalarial drugs by linear discriminant analysis and topological virtual screening.

Author

Nassira Mahmoudi, Jesus-Vicente de Julián-Ortiz, Liliane Ciceron, Jorge Gálvez, Dominique Mazier, Martin Danis, Francis Derouin, and Ramón García-Domenech

Abstract

Objectives: A quantitative structure–activity relationship study using a database of 395 compounds previously tested against chloroquine-susceptible strains of the blood stages of Plasmodium falciparum to predict new in vitro antimalarial drugs has been developed.Methods: Topological indices were used as structural descriptors and were related to antimalarial activity by using linear discriminant analysis (LDA) and multilinear regression (MLR). Two discriminant equations were obtained (FD1 and FD2), which allowed us to carry out successful classification of 90% and 80% of compounds, respectively. The IC50 values of the compounds were introduced to get an MLR equation model suitable to predict their in vitro activities.Results: Using this model, a set of 27 drugs against a chloroquine-susceptible clone (3D7) of P. falciparum have been selected and evaluated in vitro. Among these drugs are monensin, nigericin, vincristine, vindesine, ethylhydrocupreine and salinomycin with in vitro IC50s at nanomolar concentrations (0.3, 0.4, 2, 6, 26 and 188 nM, respectively). Other compounds such as hycanthone, amsacrine, aphidicolin, bepridil, amiodarone, ranolazine and triclocarban showed in vitro IC50 values below 5 μM in the mathematical model.Conclusions: These results demonstrate the usefulness of the approach for the selection and design of new lead drugs active against P. falciparum. [ABSTRACT FROM AUTHOR]

Published
2006
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24. 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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