Descriptor: "MESH: Malaria" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"MESH: Malaria"' showing total 135 results

Start Over Descriptor "MESH: Malaria"

135 results on '"MESH: Malaria"'

1. Genomic variation during culture adaptation of genetically complex Plasmodium falciparum clinical isolates

Author: Antoine Claessens, Lindsay B. Stewart, Eleanor Drury, Ambroise D. Ahouidi, Alfred Amambua-Ngwa, Mahamadou Diakite, Dominic P. Kwiatkowski, Gordon A. Awandare, David J. Conway, Laboratory of Pathogen and Host Immunity [Montpellier] (LPHI), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM), London School of Hygiene and Tropical Medicine (LSHTM), London School of Hygiene and Tropical Medicine [Fajara, Gambia], The Wellcome Trust Sanger Institute [Cambridge], Hôpital Aristide-Le-Dantec, Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD), University of Bamako [Mali], West African Centre for Cell Biology of Infectious Pathogens [Legon, Ghana] (WACCBIP), University of Ghana, and This study was supported by funding from the European Research Council (AdG-2011–294428), the Royal Society (AA110050) and the UK Medical Research Council (MR/S009760/1). Support for A.C. was provided by a joint MRC Gambia-LSHTM fellowship. Genome sequencing was conducted at the Wellcome Sanger Institute, with funding from The Wellcome Trust (grants 098051, 206194, 090770).
Subjects: MESH: Humans, MESH: Genomics, MESH: Malaria, mixed genotypes, adaptation, General Medicine, MESH: Protein Serine-Threonine Kinases, culture, MESH: Genotype, loss-of-function mutants, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Guanine Nucleotide Exchange Factors, genomic relatedness, MESH: Plasmodium falciparum, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Experimental studies on the biology of malaria parasites have mostly been based on laboratory-adapted lines, but there is limited understanding of how these may differ from parasites in natural infections. Loss-of-function mutants have previously been shown to emerge during culture of some Plasmodium falciparum clinical isolates in analyses focusing on single-genotype infections. The present study included a broader array of isolates, mostly representing multiple-genotype infections, which are more typical in areas where malaria is highly endemic. Genome sequence data from multiple time points over several months of culture adaptation of 28 West African isolates were analysed, including previously available sequences along with new genome sequences from additional isolates and time points. Some genetically complex isolates eventually became fixed over time to single surviving genotypes in culture, whereas others retained diversity, although proportions of genotypes varied over time. Drug resistance allele frequencies did not show overall directional changes, suggesting that resistance-associated costs are not the main causes of fitness differences among parasites in culture. Loss-of-function mutants emerged during culture in several of the multiple-genotype isolates, affecting genes (including AP2-HS, EPAC and SRPK1) for which loss-of-function mutants were previously seen to emerge in single-genotype isolates. Parasite clones were derived by limiting dilution from six of the isolates, and sequencing identified de novo variants not detected in the bulk isolate sequences. Interestingly, several of these were nonsense mutants and frameshifts disrupting the coding sequence of EPAC, the gene with the largest number of independent nonsense mutants previously identified in laboratory-adapted lines. Analysis of genomic identity by descent to explore relatedness among clones revealed co-occurring non-identical sibling parasites, illustrative of the natural genetic structure within endemic populations.
Published: 2023

2. Spatio-Temporal Variability of Malaria Incidence in the Health District of Kati, Mali, 2015-2019

Author: Abdoulaye Katile, Issaka Sagara, Mady Cissoko, Cedric Stephane Bationo, Mathias Dolo, Ismaila Thera, Siriman Traore, Mamady Kone, Pascal Dembele, Djoouro Bocoum, Ibrahima Sidibe, Ismael Simaga, Mahamadou Soumana Sissoko, Jordi Landier, Jean Gaudart, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des sciences de la santé publique [Marseille] (ISSPAM), Malaria Research and Training Center [Bamako, Mali] (MRTC), Université de Bamako, Programme National de la Lutte contre le Paludisme [Bamako, Mali] (PNLP Mali), Direction Nationale de l’Hydraulique, Bamako, and Centre de Santé de Référence du District Sanitaire de Kati [Mali] (CSRDSK)
Subjects: MESH: Humans, Health, Toxicology and Mutagenesis, [SDV]Life Sciences [q-bio], Incidence, MESH: Malaria, Public Health, Environmental and Occupational Health, Temperature, MESH: Mali, spatio-temporal dynamics, Mali, MESH: Temperature, Malaria, geoepidemiology, MESH: Spatio-Temporal Analysis, Spatio-Temporal Analysis, environmental factors, Humans, hotspot, MESH: Incidence, Seasons, MESH: Seasons, malaria
Abstract: Introduction: Despite the implementation of control strategies at the national scale, the malaria burden remains high in Mali, with more than 2.8 million cases reported in 2019. In this context, a new approach is needed, which accounts for the spatio-temporal variability of malaria transmission at the local scale. This study aimed to describe the spatio-temporal variability of malaria incidence and the associated meteorological and environmental factors in the health district of Kati, Mali. Methods: Daily malaria cases were collected from the consultation records of the 35 health areas of Kati’s health district, for the period 2015–2019. Data on rainfall, relative humidity, temperature, wind speed, the normalized difference vegetation index, air pressure, and land use–land cover were extracted from open-access remote sensing sources, while data on the Niger River’s height and flow were obtained from the National Department of Hydraulics. To reduce the dimension and account for collinearity, strongly correlated meteorological and environmental variables were combined into synthetic indicators (SI), using a principal component analysis. A generalized additive model was built to determine the lag and the relationship between the main SIs and malaria incidence. The transmission periods were determined using a change-point analysis. High-risk clusters (hotspots) were detected using the SatScan method and were ranked according to risk level, using a classification and regression tree analysis. Results: The peak of the malaria incidence generally occurred in October. Peak incidence decreased from 60 cases per 1000 person–weeks in 2015, to 27 cases per 1000 person–weeks in 2019. The relationship between the first SI (river flow and height, relative humidity, and rainfall) and malaria incidence was positive and almost linear. A non-linear relationship was found between the second SI (air pressure and temperature) and malaria incidence. Two transmission periods were determined per year: a low transmission period from January to July—corresponding to a persisting transmission during the dry season—and a high transmission period from July to December. The spatial distribution of malaria hotspots varied according to the transmission period. Discussion: Our study confirmed the important variability of malaria incidence and found malaria transmission to be associated with several meteorological and environmental factors in the Kati district. The persistence of malaria during the dry season and the spatio-temporal variability of malaria hotspots reinforce the need for innovative and targeted strategies.
Published: 2022

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

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

4. Ecological plasticity to ions concentration determines genetic response and dominance of Anopheles coluzzii larvae in urban coastal habitats of Central Africa

Author: Neil M, Longo-Pendy, Billy, Tene-Fossog, Robert E, Tawedi, Ousman, Akone-Ella, Celine, Toty, Nil, Rahola, Jean-Jacques, Braun, Nicolas, Berthet, Pierre, Kengne, Carlo, Costantini, Diego, Ayala, Centre International de Recherches Médicales de Franceville (CIRMF), Institut de Recherches Géologiques et Minières (IRGM), 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]), Géosciences Environnement Toulouse (GET), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), Université de Yaoundé I, Institut de Recherche pour le Développement (IRD), Environnement et Risques infectieux - Environment and Infectious Risks (ERI), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Funds were provided by the Agence Universitaire de la Francophonie (AUF, ‘Salt-Adapt’ Project), the Institut de Recherche pour le Développement (IRD, ‘URBANO’ Project), and the Centre International de Recherches Médicales de Franceville (CIRMF). N. L-P was funded by AUF and CIRMF scholarships., Institut national des sciences de l'Univers (INSU - CNRS)-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-Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD), and Institut Pasteur [Paris]
Subjects: Insecticides, Mosquito Control, MESH: Ions, Chemical Phenomena, Evolution, [SDV]Life Sciences [q-bio], Science, MESH: Malaria, Diseases, Mosquito Vectors, Article, Insecticide Resistance, MESH: Anopheles, Osmoregulation, Anopheles, parasitic diseases, MESH: Osmoregulation, Animals, MESH: Insecticide Resistance, Africa, Central, MESH: Animals, MESH: Ecosystem, Ecosystem, MESH: Mosquito Control, Ions, Ecology, fungi, MESH: Chemical Phenomena, Malaria, MESH: Insecticides, MESH: Africa, Central, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Larva, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Medicine, MESH: Mosquito Vectors, MESH: Larva
Abstract: International audience; In Central Africa, the malaria vector Anopheles coluzzii is predominant in urban and coastal habitats. However, little is known about the environmental factors that may be involved in this process. Here, we performed an analysis of 28 physicochemical characteristics of 59 breeding sites across 5 urban and rural sites in coastal areas of Central Africa. We then modelled the relative frequency of An. coluzzii larvae to these physicochemical parameters in order to investigate environmental patterns. Then, we assessed the expression variation of 10 candidate genes in An. coluzzii , previously incriminated with insecticide resistance and osmoregulation in urban settings. Our results confirmed the ecological plasticity of An. coluzzii larvae to breed in a large range of aquatic conditions and its predominance in breeding sites rich in ions. Gene expression patterns were comparable between urban and rural habitats, suggesting a broad response to ions concentrations of whatever origin. Altogether, An. coluzzii exhibits a plastic response to occupy both coastal and urban habitats. This entails important consequences for malaria control in the context of the rapid urban expansion in Africa in the coming years.
Published: 2021

5. Surveillance to achieve malaria elimination in eastern Myanmar: a 7-year observational study

Author: Rae, JD, Nosten, S, Kajeechiwa, L, Wiladphaingern, J, Parker, DM, Landier, J, Thu, AM, Dah, H, Be, A, Cho, WC, Paw, KN, Paw, ES, Shee, PB, Poe, C, Nu, C, Nyaw, B, Simpson, JA, Devine, A, Maude, RJ, Moo, KL, Min, MC, Thwin, MM, Tun, SW, Nosten, FH, Mahidol Oxford Tropical Medicine Research Unit (MORU), University of Oxford-Mahidol University [Bangkok]-Wellcome Trust, Nuffield Department of Clinical Medicine [Oxford], University of Oxford, University of California [Irvine] (UC Irvine), University of California (UC), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des sciences de la santé publique [Marseille] (ISSPAM), University of Melbourne, Charles Darwin University [Australia], The Open University [Milton Keynes] (OU), Harvard T.H. Chan School of Public Health, and Nuffield Department of Medicine [Oxford, UK] (Big Data Institute)
Subjects: MESH: Humans, [SDV]Life Sciences [q-bio], MESH: Malaria, COVID-19, MESH: Retrospective Studies, Myanmar, MESH: Myanmar, MESH: Antimalarials, Microbiology, Malaria, Vector-Borne Diseases, Antimalarials, Infectious Diseases, Rare Diseases, Good Health and Well Being, Medical Microbiology, Tropical Medicine, Public Health and Health Services, MESH: COVID-19, Humans, Parasitology, Infection, Retrospective Studies
Abstract: Background The collection and utilization of surveillance data is essential in monitoring progress towards achieving malaria elimination, in the timely response to increases in malaria case numbers and in the assessment of programme functioning. This paper describes the surveillance activities used by the malaria elimination task force (METF) programme which operates in eastern Myanmar, and provides an analysis of data collected from weekly surveillance, case investigations, and monitoring and evaluation of programme performance. Methods This retrospective analysis was conducted using data collected from a network of 1250 malaria posts operational between 2014 and 2021. To investigate changes in data completeness, malaria post performance, malaria case numbers, and the demographic details of malaria cases, summary statistics were used to compare data collected over space and time. Results In the first 3 years of the METF programme, improvements in data transmission routes resulted in a 18.9% reduction in late reporting, allowing for near real-time analysis of data collected at the malaria posts. In 2020, travel restrictions were in place across Karen State in response to COVID-19, and from February 2021 the military coup in Myanmar resulted in widescale population displacement. However, over that period there has been no decline in malaria post attendance, and the majority of consultations continue to occur within 48 h of fever onset. Case investigations found that 43.8% of cases travelled away from their resident village in the 3 weeks prior to diagnosis and 36.3% reported never using a bed net whilst sleeping in their resident village, which increased to 72.2% when sleeping away from their resident village. Malaria post assessments performed in 82.3% of the METF malaria posts found malaria posts generally performed to a high standard. Conclusions Surveillance data collected by the METF programme demonstrate that despite significant changes in the context in which the programme operates, malaria posts have remained accessible and continue to provide early diagnosis and treatment contributing to an 89.3% decrease in Plasmodium falciparum incidence between 2014 and 2021.
Published: 2022

6. Linking microbiota composition with antimalarial antibody response

Author: Liliana Mancio-Silva, Mathilde Gendrin, Ottavia Romoli, Microbiote des insectes vecteurs / Microbiota of Insect Vectors [Cayenne, Guyane française], Vectopôle Amazonien Emile Abonnenc [Cayenne, Guyane française], Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Biologie des Interactions Hôte-Parasite - Biology of Host-Parasite Interactions, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département Parasites et Insectes vecteurs - Department of Parasites and Insect Vectors, Institut Pasteur [Paris] (IP), This work is funded by the French Government’s Investissement d’Avenir program, Laboratoire d’Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (grant no. ANR-10-LABX-62-IBEID) and by ANR JCJC MosMi to M.G. (grant no. ANR-18-CE15-0007)., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), and ANR-18-CE15-0007,MosMi,Remodelage du microbiote de moustique pour étudier son impact sur la transmission du paludisme(2018)
Subjects: 0106 biological sciences, Plasmodium, MESH: Parasitemia, 2019-20 coronavirus outbreak, MESH: Malaria, malaria, severity, Spleen, Parasitemia, Biology, digestive system, 010603 evolutionary biology, 01 natural sciences, 03 medical and health sciences, fluids and secretions, parasitic diseases, microbiota, medicine, MESH: Microbiota, MESH: Animals, MESH: Mice, 030304 developmental biology, 0303 health sciences, Germinal center, medicine.disease, biology.organism_classification, MESH: Antimalarials, Virology, MESH: Antibody Formation, 3. Good health, stomatognathic diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious Diseases, medicine.anatomical_structure, Antibody response, Parasitology, Malaria, Microbiota composition
Abstract: International audience; Microbiota composition recently arose as a factor correlating with malaria infection. Mandal et al. showed, via cecal transplant and antibacterial treatment, that the mouse microbiota modulates parasitemia by affecting spleen germinal centers where B cells are matured. They further identified correlations between microbiota composition and malaria severity in Ugandan children.
Published: 2021

7. Discrimination of 15 Amazonian Anopheline Mosquito Species by Polymerase Chain Reaction—Restriction Fragment Length Polymorphism

Author: S B Vezenegho, J Issaly, R Carinci, P Gaborit, R Girod, Isabelle Dusfour, S Briolant, Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM), Département de Santé Globale - Department Global Health, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Institut de Recherche Biomédicale des Armées [Antenne Marseille] (IRBA), Financial support was made available by the French Army (Grant LR607e) for which we are grateful. This work has benefited from an ‘Investissement d’Avenir’ grant managed by Agence Nationale de la Recherche (CEBA, ref. ANR-10-LABX-25-01). This study received a European commission ‘REGPOT-CT-2011-285837-STRonGer’ Grant within the FP7., ANR-10-LABX-0025,CEBA,CEnter of the study of Biodiversity in Amazonia(2010), and European Project: 285837,EC:FP7:REGPOT,FP7-REGPOT-2011-1,STRONGER(2011)
Subjects: MESH: Malaria, molecular identification, Mosquito Vectors, Polymerase Chain Reaction, MESH: Anopheles, malaria vector, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, DNA, Ribosomal Spacer, parasitic diseases, Anopheles, Animals, MESH: Animals, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, MESH: DNA, Ribosomal Spacer, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, General Veterinary, MESH: Polymorphism, Restriction Fragment Length, MESH: Polymerase Chain Reaction, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Malaria, French Guiana, Infectious Diseases, Insect Science, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Parasitology, MESH: Mosquito Vectors, Polymorphism, Restriction Fragment Length
Abstract: Precise identification of anopheline species is paramount for incrimination of malaria vectors and implementation of a sustainable control program. Anopheline mosquitoes are routinely identified morphologically, a technique that is time-consuming, needs high level of expertise, and prone to misidentifications especially when considering Amazonian species. The aim of this study was therefore to develop a DNA-based identification technique to supplement traditional morphological identification methods for the discrimination of anopheline mosquitoes collected in French Guiana. The internal transcribed spacer 2 (ITS2) region of ribosomal DNA (rDNA) for anopheline species was amplified by polymerase chain reaction (PCR), and digested with AluI/MspI restriction enzymes. PCR-restriction fragments length polymorphism (RFLP) assay was compared to sequencing of the ITS2 region for validation. Fifteen Anopheles species have shown distinct PCR-RFLP profiles. A concordance of 100% was obtained when identification by PCR-RFLP was compared to sequencing of ITS2. A high throughput, fast, and cost-effective PCR-RFLP assay has been developed for unambiguous discrimination of fifteen anopheline mosquito species from French Guiana including primary and suspected secondary malaria vectors.
Published: 2022

8. Clinical and In Vitro Resistance of Plasmodium falciparum to Artesunate-Amodiaquine in Cambodia

Author: Saorin Kim, Chhayleang Kauy, Maria Dorina Bustos, Nimol Kloeung, Rotha Eam, Nimol Khim, Denis Mey Bouth, Sopheakvatey Ke, Brigitte Izac, Benoit Witkowski, Rithea Leang, Melissa Mairet-Khedim, Pascal Ringwald, Frédéric Ariey, Camille Marmai, Sophy Chy, Malaria Molecular Epidemiology, Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Malaria Translational Research Unit (MTRU), Institut Pasteur [Paris]-Institut Pasteur du Cambodge, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), National Center for Parasitology, Entomology and Malaria Control [Phnom Penh, Cambodia] (CNM), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Service de parasitologie-mycologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), World Health Organization [Phnom Penh] (WHO), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), World Health Organization (WHO), country office for Thailand, This work was supported by the Bill & Melinda Gates Foundation and United State Agency for International development-President’s Malaria Initiative through the World Health Organization. M. M.-K. and B. W. were supported by 5% initiative (MIVS-ACT, grant number 15SANIN211)., Malaria Molecular Epidemiology (MMEU), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Subjects: 0301 basic medicine, Primaquine, Artesunate, Drug resistance, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, MESH: Child, Prospective Studies, Malaria, Falciparum, Artemisinin, Child, MESH: Plasmodium falciparum, biology, MESH: Asia, MESH: Malaria, Falciparum, Artesunate/amodiaquine, Artemisinins, 3. Good health, AcademicSubjects/MED00290, Infectious Diseases, Cambodia, medicine.drug, Adult, Microbiology (medical), medicine.medical_specialty, Asia, Plasmodium falciparum, MESH: Malaria, 030231 tropical medicine, Amodiaquine, Antimalarials, 03 medical and health sciences, Internal medicine, MESH: Artemisinins, parasitic diseases, medicine, Humans, MESH: Amodiaquine, artesunate-amodiaquine, drug resistance, MESH: Humans, business.industry, MESH: Cambodia, MESH: Adult, MESH: Artesunate, biology.organism_classification, medicine.disease, MESH: Antimalarials, MESH: Prospective Studies, Malaria, Major Articles and Commentaries, 030104 developmental biology, artemisinin, chemistry, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background Artesunate-amodiaquine is a potential therapy for uncomplicated malaria in Cambodia. Methods Between September 2016 and January 2017, artesunate-amodiaquine efficacy and safety were evaluated in a prospective, open-label, single-arm observational study at health centers in Mondulkiri, Pursat, and Siem Reap Provinces, Cambodia. Adults and children with microscopically confirmed Plasmodium falciparum malaria received oral artesunate-amodiaquine once daily for 3 days plus single-dose primaquine, with follow-up on days 7, 14, 21, and 28. The primary outcome was day-28 polymerase chain reaction (PCR)-adjusted adequate clinical and parasitological response (ACPR). An amodiaquine parasite survival assay (AQSA) was developed and applied to whole genome sequencing results to evaluate potential amodiaquine resistance molecular markers. Results In 63 patients, day-28 PCR-adjusted ACPR was 81.0% (95% confidence interval [CI], 68.9–88.7). Day 3 parasite positivity rate was 44.4% (28/63; 95% CI, 31.9–57.5). All 63 isolates had the K13(C580Y) marker for artemisinin resistance; 79.4% (50/63) had Pfpm2 amplification. The AQSA resistance phenotype (≥45% parasite survival) was expressed in 36.5% (23/63) of isolates and was significantly associated with treatment failure (P = .0020). Pfmdr1 mutant haplotypes were N86/184F/D1246, and Pfcrt was CVIET or CVIDT at positions 72–76. Additional Pfcrt mutations were not associated with amodiaquine resistance, but the G353V mutant allele was associated with ACPR compared to Pfmdr1 haplotypes harboring F1068L or S784L/R945P mutations (P = .030 and P = .0004, respectively). Conclusions For uncomplicated falciparum malaria in Cambodia, artesunate-amodiaquine had inadequate efficacy owing to amodiaquine-resistant P. falciparum. Amodiaquine resistance was not associated with previously identified molecular markers., Artesunate-amodiaquine has inadequate efficacy in Cambodian patients with uncomplicated falciparum malaria. Amodiaquine resistance is present in Cambodia and not associated with molecular markers reported in Africa and South America.
Published: 2020

9. Sub-national tailoring of seasonal malaria chemoprevention in Mali based on malaria surveillance and rainfall data

Author: Cissoko, Mady, Sagara, Issaka, Landier, Jordi, Guindo, Abdoulaye, Sanogo, Vincent, Coulibaly, Oumou, Dembélé, Pascal, Dieng, Sokhna, Bationo, Cedric, Diarra, Issa, Magassa, Mahamadou, Berthé, Ibrahima, Katilé, Abdoulaye, Traoré, Diahara, Dessay, Nadine, Gaudart, Jean, Université des Sciences, des Techniques et des Technologies de Bamako (USTTB), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des sciences de la santé publique [Marseille] (ISSPAM), Direction Régionale de la Santé de Tombouctou [Tombouctou, Mali], Programme National de la Lutte contre le Paludisme [Bamako, Mali] (PNLP Mali), Direction Générale de la Santé et Hygiène Publique [Bamako, Mali] (DGSHP), UMR 228 Espace-Dev, Espace pour le développement, Institut de Recherche pour le Développement (IRD)-Université de Perpignan Via Domitia (UPVD)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Guyane (UG)-Université des Antilles (UA)-Université de Montpellier (UM), Biostatistique et technologies de l'information et de la communication (BioSTIC) - [Hôpital de la Timone - APHM] (BiosTIC ), and Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)
Subjects: Rainfall, MESH: Chemoprevention, MESH: Humans, Tailoring, [SDV]Life Sciences [q-bio], MESH: Child, Preschool, MESH: Malaria, Infant, High transmission season, Sub-national, MESH: Mali, Mali, MESH: Antimalarials, MESH: Infant, Chemoprevention, Malaria, Antimalarials, MESH: Child, Child, Preschool, Humans, Seasons, Child, MESH: Seasons
Abstract: International audience; Background: In malaria endemic countries, seasonal malaria chemoprevention (SMC) interventions are performed during the high malaria transmission in accordance with epidemiological surveillance data. In this study we propose a predictive approach for tailoring the timing and number of cycles of SMC in all health districts of Mali based on sub-national epidemiological surveillance and rainfall data. Our primary objective was to select the best of two approaches for predicting the onset of the high transmission season at the operational scale. Our secondary objective was to evaluate the number of malaria cases, hospitalisations and deaths in children under 5 years of age that would be prevented annually and the additional cost that would be incurred using the best approach.Methods: For each of the 75 health districts of Mali over the study period (2014-2019), we determined (1) the onset of the rainy season period based on weekly rainfall data; (ii) the onset and duration of the high transmission season using change point analysis of weekly incidence data; and (iii) the lag between the onset of the rainy season and the onset of the high transmission. Two approaches for predicting the onset of the high transmission season in 2019 were evaluated.Results: In the study period (2014-2019), the onset of the rainy season ranged from week (W) 17 (W17; April) to W34 (August). The onset of the high transmission season ranged from W25 (June) to W40 (September). The lag between these two events ranged from 5 to 12 weeks. The duration of the high transmission season ranged from 3 to 6 months. The best of the two approaches predicted the onset of the high transmission season in 2019 to be in June in two districts, in July in 46 districts, in August in 21 districts and in September in six districts. Using our proposed approach would prevent 43,819 cases, 1943 hospitalisations and 70 deaths in children under 5 years of age annually for a minimal additional cost. Our analysis shows that the number of cycles of SMC should be changed in 36 health districts.Conclusion: Adapting the timing of SMC interventions using our proposed approach could improve the prevention of malaria cases and decrease hospitalisations and deaths. Future studies should be conducted to validate this approach.
Published: 2022

10. Calcium in the Backstage of Malaria Parasite Biology

Author: Lucas Silva de Oliveira, Marcos Rodrigo Alborghetti, Renata Garcia Carneiro, Izabela Marques Dourado Bastos, Rogerio Amino, Philippe Grellier, Sébastien Charneau, Universidade de Brasilia [Brasília] (UnB), Molécules de Communication et Adaptation des Micro-organismes (MCAM), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Centro Nacional de Pesquisa em Energia e Materiais = Brazilian Center for Research in Energy and Materials (CNPEM), Infection et Immunité paludéennes - Malaria Infection and Immunity, and Institut Pasteur [Paris] (IP)
Subjects: Microbiology (medical), Plasmodium, Erythrocytes, [SDV]Life Sciences [q-bio], Plasmodium falciparum, MESH: Malaria, Immunology, Ca 2+ signaling, Review, Mitochondrion, Biology, MESH: Calcium Signaling, Microbiology, 03 medical and health sciences, Cellular and Infection Microbiology, 0302 clinical medicine, MESH: Biology, homeostasis, Food vacuole, Animals, Parasites, MESH: Animals, Calcium Signaling, Ca2+ signaling, MESH: Parasites, Gene, intracellular messenger, MESH: Plasmodium falciparum, 030304 developmental biology, 0303 health sciences, Kinase, MESH: Erythrocytes, Endoplasmic reticulum, invasion, biology.organism_classification, QR1-502, Malaria, egress, Cell biology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious Diseases, MESH: Calcium, Second messenger system, Calcium, 030217 neurology & neurosurgery, Intracellular
Abstract: The calcium ion (Ca2+) is a ubiquitous second messenger involved in key biological processes in prokaryotes and eukaryotes. In Plasmodium species, Ca2+ signaling plays a central role in the parasite life cycle. It has been associated with parasite development, fertilization, locomotion, and host cell infection. Despite the lack of a canonical inositol-1,4,5-triphosphate receptor gene in the Plasmodium genome, pharmacological evidence indicates that inositol-1,4,5-triphosphate triggers Ca2+ mobilization from the endoplasmic reticulum. Other structures such as acidocalcisomes, food vacuole and mitochondria are proposed to act as supplementary intracellular Ca2+ reservoirs. Several Ca2+-binding proteins (CaBPs) trigger downstream signaling. Other proteins with no EF-hand motifs, but apparently involved with CaBPs, are depicted as playing an important role in the erythrocyte invasion and egress. It is also proposed that a cross-talk among kinases, which are not members of the family of Ca2+-dependent protein kinases, such as protein kinases G, A and B, play additional roles mediated indirectly by Ca2+ regulation. This statement may be extended for proteins directly related to invasion or egress, such as SUB1, ERC, IMC1I, IMC1g, GAP45 and EBA175. In this review, we update our understanding of aspects of Ca2+-mediated signaling correlated to the developmental stages of the malaria parasite life cycle.
Published: 2021

11. Chloroquine Potentiates Primaquine Activity against Active and Latent Hepatic Plasmodia Ex Vivo: Potentials and Pitfalls

Author: Nadia Amanzougaghene, J. Kevin Baird, Georges Snounou, Shahin Tajeri, Roger Le Grand, Teun Bousema, Jean-François Franetich, Geert-Jan van Gemert, Laurent Dembélé, Dominique Mazier, Valérie Soulard, Nathalie Dereuddre-Bosquet, Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université des sciences, des techniques et des technologies de Bamako, Université des sciences, des techniques et des technologies de Bamako (USTTB), Faculté de Médecine, de pharmacie et d’Odonto-Stomatologie [Bamako, Mali] (FMPOS), Université de Bamako, Radboud University Medical Center [Nijmegen], Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Infectious Diseases Models for Innovative Therapies (IDMIT), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Nuffield Department of Medicine [Oxford, UK] (Big Data Institute), University of Oxford [Oxford], Centre d'Immunologie et des Maladies Infectieuses (CIMI), Université des Sciences, des Techniques et des Technologies de Bamako (USTTB), University of Oxford, ANR-17-CE13-0025,IMHyp,Recherches sur l'Hypnozoïte du Paludisme(2017), and Gestionnaire, Hal Sorbonne Université
Subjects: Plasmodium, latent infection, Primaquine, primaquine, [SDV]Life Sciences [q-bio], 030231 tropical medicine, MESH: Malaria, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], malaria, Pharmacology, chemotherapy, chloroquine, Antimalarials, 03 medical and health sciences, 0302 clinical medicine, All institutes and research themes of the Radboud University Medical Center, Chloroquine, parasitic diseases, medicine, Animals, Humans, Experimental Therapeutics, Pharmacology (medical), Plasmodium berghei, MESH: Animals, 0303 health sciences, potentiation, MESH: Humans, biology, 030306 microbiology, Chemistry, MESH: Plasmodium, Plasmodium falciparum, MESH: Chloroquine, MESH: Primaquine, biology.organism_classification, medicine.disease, MESH: Antimalarials, 3. Good health, [SDV] Life Sciences [q-bio], Infectious Diseases, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], hepatic parasites, Plasmodium yoelii, Ex vivo, Malaria, Atovaquone, medicine.drug
Abstract: For a long while, 8-aminoquinoline compounds have been the only therapeutic agents against latent hepatic malaria parasites. These have poor activity against the blood-stage plasmodia causing acute malaria and must be used in conjunction with partner blood schizontocidal agents. We examined the impacts of one such agent, chloroquine, upon the activity of primaquine, an 8-aminoquinoline, against hepatic stages of Plasmodium cynomolgi, Plasmodium yoelii, Plasmodium berghei, and Plasmodium falciparum within several ex vivo systems—primary hepatocytes of Macaca fascicularis, primary human hepatocytes, and stably transformed human hepatocarcinoma cell line HepG2., For a long while, 8-aminoquinoline compounds have been the only therapeutic agents against latent hepatic malaria parasites. These have poor activity against the blood-stage plasmodia causing acute malaria and must be used in conjunction with partner blood schizontocidal agents. We examined the impacts of one such agent, chloroquine, upon the activity of primaquine, an 8-aminoquinoline, against hepatic stages of Plasmodium cynomolgi, Plasmodium yoelii, Plasmodium berghei, and Plasmodium falciparum within several ex vivo systems—primary hepatocytes of Macaca fascicularis, primary human hepatocytes, and stably transformed human hepatocarcinoma cell line HepG2. Primaquine exposures to formed hepatic schizonts and hypnozoites of P. cynomolgi in primary simian hepatocytes exhibited similar 50% inhibitory concentration (IC50) values near 0.4 μM, whereas chloroquine in the same system exhibited no inhibitory activities. Combining chloroquine and primaquine in this system decreased the observed primaquine IC50 for all parasite forms in a chloroquine dose-dependent manner by an average of 18-fold. Chloroquine also decreased the primaquine IC50 against hepatic P. falciparum in primary human hepatocytes, P. berghei in simian primary hepatocytes, and P. yoelii in primary human hepatocytes. Chloroquine had no impact on primaquine IC50 against P. yoelii in HepG2 cells and, likewise, had no impact on the IC50 of atovaquone (hepatic schizontocide) against P. falciparum in human hepatocytes. We describe important sources of variability in the potentiation of primaquine activity by chloroquine in these systems. Chloroquine potentiated primaquine activity against hepatic forms of several plasmodia. We conclude that chloroquine specifically potentiated 8-aminoquinoline activities against active and dormant hepatic-stage plasmodia in normal primary hepatocytes but not in a hepatocarcinoma cell line.
Published: 2020

12. Choosing interventions to eliminate forest malaria: preliminary results of two operational research studies inside Cambodian forests

Author: Mark Debackere, Amber Kunkel, Jean-Olivier Guintran, Sarun Im, Sophea, Jean Popovici, Dom Peov, Saorin Kim, Patrice Piola, Sreynet Srun, Amélie Vantaux, Chea Nguon, Srean Chhim, Phanith Kong, Nimol Khim, Benoit Witkowski, Unité d'Épidémiologie et de Santé Publique [Phnom Penh], Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), National Center for Parasitology, Entomology and Malaria Control [Phnom Penh, Cambodia] (CNM), Malaria Molecular Epidemiology (MMEU), Partners for Development [Phnom Penh, Cambodia], Partners For Development [Silver Spring, MD] (PFD), Malaria Consortium [Phnom Penh, Cambodge], World Health Organization [Phnom Penh] (WHO), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), These studies were funded by the French Initiative 5%: 'Blocking Malaria Transmission in Forest Vulnerable Populations through Forest Malaria Workers: A Key for Malaria Elimination in Cambodia'. Grant Code: 17SANIN205 and the Regional Artemisinin-resistance Initiative—Regional Component Package 2—Operational Research: Effectiveness of forest-based malaria control interventions in large forests of Cambodia. Grant code: QSE-M-UNOPS. AK was supported by the Pasteur Foundation (US)., Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Malaria Molecular Epidemiology, Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), and HESAM Université (HESAM)-HESAM Université (HESAM)
Subjects: MESH: Disease Eradication, Plasmodium vivax, Rapid diagnostic test, Forests, Greater mekong subregion, 0302 clinical medicine, MESH: Risk Factors, Risk Factors, Prevalence, Mass Screening, MESH: Animals, 030212 general & internal medicine, Malaria, Falciparum, Forestgoers, education.field_of_study, MESH: Operations Research, biology, MESH: Malaria, Falciparum, MESH: Forests, 3. Good health, Infectious Diseases, MESH: Mosquito Vectors, Female, Mass screening and treatment, Cambodia, medicine.medical_specialty, Operations Research, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, MESH: Malaria, 030231 tropical medicine, Population, Plasmodium falciparum, Mosquito Vectors, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, Forest-goers, Asian People, Environmental health, parasitic diseases, medicine, Malaria, Vivax, Animals, Humans, lcsh:RC109-216, MESH: Mass Screening, Forest, Disease Eradication, education, MESH: Prevalence, Mass screening, MESH: Humans, business.industry, MESH: Cambodia, Public health, Research, MESH: Malaria, Vivax, 15. Life on land, medicine.disease, biology.organism_classification, Malaria, Culicidae, Tropical medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Parasitology, MESH: Asians, MESH: Culicidae, business, MESH: Female
Abstract: Background Rapid elimination of Plasmodium falciparum malaria in Cambodia is a goal with both national and international significance. Transmission of malaria in Cambodia is limited to forest environments, and the main population at risk consists of forest-goers who rely on forest products for income or sustenance. The ideal interventions to eliminate malaria from this population are unknown. Methods In two forested regions of Cambodia, forest-goers were trained to become forest malaria workers (FMWs). In one region, FMWs performed mass screening and treatment, focal screening and treatment, and passive case detection inside the forest. In the other region, FMWs played an observational role for the first year, to inform the choice of intervention for the second year. In both forests, FMWs collected blood samples and questionnaire data from all forest-goers they encountered. Mosquito collections were performed in each forest. Results Malaria prevalence by PCR was high in the forest, with 2.3–5.0% positive for P. falciparum and 14.6–25.0% positive for Plasmodium vivax among forest-goers in each study site. In vectors, malaria prevalence ranged from 2.1% to 9.6%, but no P. falciparum was observed. Results showed poor performance of mass screening and treatment, with sensitivity of rapid diagnostic tests equal to 9.1% (95% CI 1.1%, 29.2%) for P. falciparum and 4.4% (95% CI 1.6%, 9.2%) for P. vivax. Malaria infections were observed in all demographics and throughout the studied forests, with no clear risk factors emerging. Conclusions Malaria prevalence remains high among Cambodian forest-goers, but performance of rapid diagnostic tests is poor. More adapted strategies to this population, such as intermittent preventive treatment of forest goers, should be considered.
Published: 2020

13. Effect of mass dihydroartemisinin-piperaquine administration in southern Mozambique on the carriage of molecular markers of antimalarial resistance

Author: Himanshu Gupta, Beatriz Galatas, Didier Menard, Wilson Simone, Silvie Huijben, Lidia Nhamussua, Quique Bassat, Pedro Aide, Francisco Saute, Pau Cisteró, Pascal Ringwald, Arlindo Chidimatembue, Alfredo Mayor, Pedro L. Alonso, Gloria Matambisso, N. Regina Rabinovich, Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Universitat de Barcelona (UB), Centro de Investigação em Saúde de Manhiça [Maputo, Mozambique] (CISM), Institució Catalana de Recerca i Estudis Avançats (ICREA), CIBER de Epidemiología y Salud Pública (CIBERESP), Hospital Sant Joan de Déu [Barcelona], Biologie des Interactions Hôte-Parasite - Biology of Host-Parasite Interactions, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), World Health Organisation (WHO), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Harvard T.H. Chan School of Public Health, National Institute of Health Mozambique, Ministry of Health [Mozambique], We would like to thank La Caixa and Bill and Melinda Gates Foundations for providing the funds for this study (grant number INV-008483 / OPP1115265). A.M. is supported by the Departament d’Universitats i Recerca de la Generalitat de Catalunya, Agència de Gestió d’Ajuts Universitaris i de Recerca (2017SGR664). HG was supported (January 2017-January 2019) by the Science and Engineering Research Board (SERB), Department of Science & Technology, Government of India (Overseas Postdoctoral Fellowship, SB/OS/PDF043/201516). We acknowledge support from the Spanish Ministry of Science and Innovation through the 'Centro de Excelencia Severo Ochoa 2019-2023' Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. The Centro de Investigaçao em Saude de Manhica (CISM) is supported by the Government of Mozambique and the Spanish Agency for International Development Cooperation (AECID). This research is part of ISGlobal’s Program on the Molecular Mechanisms of Malaria, which is partially supported by the Fundación Ramón Areces., and Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: Plasmodium, Drug Resistance, Protozoan Proteins, Drug resistance, 0302 clinical medicine, Medical Conditions, Dihydroartemisinin/piperaquine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine and Health Sciences, 030212 general & internal medicine, Artemisinin, MESH: Protozoan Proteins, Mozambique, MESH: Plasmodium falciparum, Protozoans, Multidisciplinary, biology, Pharmaceutics, Malarial Parasites, Eukaryota, Drugs, Artemisinins, 3. Good health, Drug Combinations, Medicaments antipalúdics, Quinolines, MESH: Drug Resistance, Medicine, MESH: Quinolines, medicine.drug, Research Article, Drug Administration, Science, MESH: Mozambique, 030231 tropical medicine, MESH: Malaria, Plasmodium falciparum, Microbiology, 03 medical and health sciences, Antimalarials, Antibiotic resistance, Drug Therapy, Piperaquine, Microbial Control, Parasite Groups, MESH: Artemisinins, MESH: Polymorphism, Genetic, parasitic diseases, medicine, Parasitic Diseases, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Mass drug administration, Resistència als medicaments, Pharmacology, MESH: Drug Combinations, Polymorphism, Genetic, Organisms, Biology and Life Sciences, medicine.disease, biology.organism_classification, Tropical Diseases, Virology, MESH: Antimalarials, Parasitic Protozoans, Malaria, Parasitology, Antimicrobial Resistance, Apicomplexa
Abstract: Background Mass drug administration (MDA) can rapidly reduce the burden of Plasmodium falciparum (Pf). However, concerns remain about its contribution to select for antimalarial drug resistance. Methods We used Sanger sequencing and real-time PCR to determine the proportion of molecular markers associated with antimalarial resistance (k13, pfpm2, pfmdr1 and pfcrt) in Pf isolates collected before (n = 99) and after (n = 112) the implementation of two monthly MDA rounds with dihydroartemisinin–piperaquine (DHAp) for two consecutive years in Magude district of Southern Mozambique. Results None of the k13 polymorphisms associated with artemisinin resistance were observed in the Pf isolates analyzed. The proportion of Pf isolates with multiple copies of pfpm2, an amplification associated with piperaquine resistance, was similar in pre- (4.9%) and post-MDA groups (3.4%; p = 1.000). No statistically significant differences were observed between pre- and post-MDA groups in the proportion of Pf isolates neither with mutations in pfcrt and pfmdr1 genes, nor with the carriage of pfmdr1 multiple copies (p>0.05). Conclusions This study does not show any evidence of increased frequency of molecular makers of antimalarial resistance after MDA with DHAp in southern Mozambique where markers of antimalarial resistance were absent or low at the beginning of the intervention.
Published: 2020

14. Two-Year Scale-Up of Seasonal Malaria Chemoprevention Reduced Malaria Morbidity among Children in the Health District of Koutiala, Mali

Author: Moussa Djimde, Ogobara K. Doumbo, Amadou Bamadio, Boubou Sangare, Abdoulaye Djimde, Estrella Lasry, Alassane Dicko, Jean Gaudart, Hamma Maiga, Samba Coumare, Djibril Traore, Issaka Sagara, Aly Tembely, Yeyia Dicko, Modibo Diarra, Institut National de Recherche en Santé Publique [Bamako] (INRSP), Malaria Research and Training Center [Bamako, Mali], Université de Bamako, Université des Sciences, des Techniques et des Technologies de Bamako (USTTB), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biostatistique et technologies de l'information et de la communication (BioSTIC) - [Hôpital de la Timone - APHM] (BiosTIC ), Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Médecins Sans Frontières - Doctors Without Borders [New York] (MSF-USA), Université des sciences, des techniques et des technologies de Bamako (USTTB), Service Biostatistique et Technologies de l’Information et de la Communication [AP-HM Hôpital de la Timone] (BioSTIC), Hôpital de la Timone [CHU - APHM] (TIMONE), and Dupuis, Christine
Subjects: MESH: Chemoprevention, Health, Toxicology and Mutagenesis, [SDV]Life Sciences [q-bio], lcsh:Medicine, morbidity, Controlled studies, Mali, 0302 clinical medicine, MESH: Child, Child, 0303 health sciences, musculoskeletal system, MESH: Infant, 3. Good health, seasonal malaria chemoprevention, [SDV] Life Sciences [q-bio], Drug Combinations, Pyrimethamine, Child, Preschool, cardiovascular system, Female, Seasons, medicine.drug, medicine.medical_specialty, Anemia, MESH: Pyrimethamine, 030231 tropical medicine, MESH: Malaria, malaria, Malaria morbidity, Amodiaquine, Chemoprevention, Article, Antimalarials, 03 medical and health sciences, MESH: Cross-Sectional Studies, Internal medicine, Sulfadoxine, parasitic diseases, medicine, Humans, MESH: Drug Combinations, MESH: Humans, 030306 microbiology, business.industry, lcsh:R, MESH: Child, Preschool, Public Health, Environmental and Occupational Health, Infant, MESH: Mali, medicine.disease, MESH: Antimalarials, Cross-Sectional Studies, MESH: Morbidity, Propensity score matching, business, MESH: Female, MESH: Seasons, Malaria, MESH: Sulfadoxine
Abstract: Background: Previous controlled studies demonstrated seasonal malaria chemoprevention (SMC) reduces malaria morbidity by &gt, 80% in children aged 3&ndash, 59 months. Here, we assessed malaria morbidity after large-scale SMC implementation during a pilot campaign in the health district of Koutiala, Mali. Methods: Starting in August 2012, children received three rounds of SMC with sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ). From July 2013 onward, children received four rounds of SMC. Prevalence of malaria infection, clinical malaria and anemia were assessed during two cross-sectional surveys conducted in August 2012 and June 2014. Investigations involved 20 randomly selected clusters in 2012 against 10 clusters in 2014. Results: Overall, 662 children were included in 2012, and 670 in 2014. Children in 2014 versus those surveyed in 2012 showed reduced proportions of malaria infection (12.4% in 2014 versus 28.7% in 2012 (p = 0.001)), clinical malaria (0.3% versus 4.2%, respectively (p &lt, 0.001)), and anemia (50.1% versus 67.4%, respectively (p = 0.001)). A propensity score approach that accounts for environmental differences showed that SMC conveyed a significant protective effect against malaria infection (IR = 0.01, 95% CI (0.0001, 0.09), clinical malaria (OR = 0.25, 95% CI (0.06, 0.85)), and hemoglobin concentration (&beta, = 1.3, 95% CI (0.69, 1.96)) in 2012 and 2014, respectively. Conclusion: SMC significantly reduced frequency of malaria infection, clinical malaria and anemia two years after SMC scale-up in Koutiala.
Published: 2020

15. Variation in Anopheles distribution and predictors of malaria infection risk across regions of Madagascar

Author: Marcia C. Castro, Gauthier N. Emile, Romain Girod, Christopher D. Golden, Benjamin L. Rice, Hervet J. Randriamady, Nicholas J. Arisco, Luciano Michaël Tantely, Harvard T.H. Chan School of Public Health, Harvard University [Cambridge], Unité d'Entomologie Médicale [Antananarivo, Madagascar] (IPM), Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Madagascar Health and Environmental Research [Maroantsetra, Madagascar] (MAHERY), and We are grateful for the support from the United States Agency for International Development (Grant AID-FFP-A-14-00,008) implemented by Catholic Relief Services (CRS) in consortium with four local implementing partners in Madagascar. The views and opinions expressed in this paper are those of the authors and not necessarily the views and opinions of the United States Agency for International Development. GeoStore funds provided by Airbus Defense & Space (Grant AH08211501).
Subjects: Male, Environmental change, Range (biology), [SDV]Life Sciences [q-bio], Distribution (economics), MESH: Madagascar, 0302 clinical medicine, MESH: Aged, 80 and over, Risk Factors, Planetary health, MESH: Demography, MESH: Risk Factors, MESH: Child, Disease ecology, MESH: Animals, MESH: Ecosystem, 030212 general & internal medicine, Child, Land use change, Aged, 80 and over, MESH: Aged, 2. Zero hunger, MESH: Middle Aged, biology, Multilevel model, Anopheles, Middle Aged, MESH: Infant, Infectious Diseases, Geography, MESH: Young Adult, Child, Preschool, Female, MESH: Mosquito Vectors, Adult, MESH: Socioeconomic Factors, lcsh:Arctic medicine. Tropical medicine, Adolescent, lcsh:RC955-962, 030231 tropical medicine, MESH: Malaria, Mosquito Vectors, lcsh:Infectious and parasitic diseases, MESH: Anopheles, 03 medical and health sciences, Young Adult, MESH: Cross-Sectional Studies, Deforestation, Environmental health, Vector-borne disease, parasitic diseases, medicine, Madagascar, Animals, Humans, lcsh:RC109-216, Socioeconomic status, Ecosystem, Aged, Demography, MESH: Adolescent, MESH: Humans, business.industry, Research, MESH: Child, Preschool, MESH: Animal Distribution, Infant, MESH: Adult, 15. Life on land, medicine.disease, biology.organism_classification, MESH: Male, Malaria, Cross-Sectional Studies, Socioeconomic Factors, Parasitology, business, Animal Distribution, MESH: Female
Abstract: Background Deforestation and land use change is widespread in Madagascar, altering local ecosystems and creating opportunities for disease vectors, such as the Anopheles mosquito, to proliferate and more easily reach vulnerable, rural populations. Knowledge of risk factors associated with malaria infections is growing globally, but these associations remain understudied across Madagascar’s diverse ecosystems experiencing rapid environmental change. This study aims to uncover socioeconomic, demographic, and ecological risk factors for malaria infection across regions through analysis of a large, cross-sectional dataset. Methods The objectives were to assess (1) the ecological correlates of malaria vector breeding through larval surveys, and (2) the socioeconomic, demographic, and ecological risk factors for malaria infection in four ecologically distinct regions of rural Madagascar. Risk factors were determined using multilevel models for the four regions included in the study. Results The presence of aquatic agriculture (both within and surrounding communities) is the strongest predictive factor of habitats containing Anopheles larvae across all regions. Ecological and socioeconomic risk factors for malaria infection vary dramatically across study regions and range in their complexity. Conclusions Risk factors for malaria transmission differ dramatically across regions of Madagascar. These results may help stratifying current malaria control efforts in Madagascar beyond the scope of existing interventions.
Published: 2020

16. Current vector research challenges in the greater Mekong subregion for dengue, Malaria, and Other Vector-Borne Diseases: A report from a multisectoral workshop March 2019

Author: Stephen S. Whitehead, Jessica E. Manning, Sazaly AbuBakar, Jesus G. Valenzuela, Jeffrey Hii, Kobporn Boonnak, Bruce A. Wilcox, Daniel M. Parker, Rekol Huy, Rebecca C. Christofferson, Vu Sinh Nam, Thomas E. Wellems, Hans J. Overgaard, Tho Sochantha, Leang Rithea, Gregor J. Devine, Sébastien Boyer, Louisiana State University (LSU), University of California [Irvine] (UCI), University of California, Norwegian University of Life Sciences (NMBU), PMI VectorLink Project [Cambodia], PMI VectorLink Project, U.S. President's Malaria Initiative [Atlanta, GA,]-U.S. President's Malaria Initiative [Atlanta, GA,], QIMR Berghofer Medical Research Institute, Mahidol University [Bangkok], National Institute of Hygiene and Epidemiology [Hanoi, Vietnam] (NIHE), Réseau International des Instituts Pasteur (RIIP), Tropical Infectious Diseases Research & Education Centre [Kuala Lumpur] (TIDREC), University of Malaya [Kuala Lumpur, Malaisie], Institut Pasteur du Cambodge, National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), National Center for Parasitology, Entomology and Malaria Control [Phnom Penh, Cambodia] (CNM), National Institute of Allergy and Infectious Diseases [Phnom Penh, Cambodia] (NIAID), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), and Dinglasan, Rhoel Ramos
Subjects: 0301 basic medicine, History, [SDV]Life Sciences [q-bio], RC955-962, MESH: Dengue, Disease Vectors, Pathology and Laboratory Medicine, Mosquitoes, Medical and Health Sciences, Dengue, 0302 clinical medicine, Arctic medicine. Tropical medicine, Dengue transmission, Medicine and Health Sciences, Public and Occupational Health, MESH: Animals, Malaria epidemiology, ComputingMilieux_MISCELLANEOUS, Vaccines, Eukaryota, Biological Sciences, Vaccination and Immunization, 3. Good health, Insects, Infectious Diseases, MESH: Health Priorities, MESH: Mekong Valley, Public aspects of medicine, RA1-1270, Pathogens, Mekong Valley, Infectious Disease Control, Arthropoda, 030231 tropical medicine, Immunology, MESH: Malaria, MESH: Insect Vectors, 03 medical and health sciences, Malaria transmission, Tropical Medicine, Vaccine Development, medicine, Parasitic Diseases, Animals, Humans, Symposium, MESH: Humans, Extramural, Health Priorities, Public Health, Environmental and Occupational Health, Organisms, Biology and Life Sciences, Congresses as Topic, medicine.disease, Tropical Diseases, Invertebrates, Malaria, Insect Vectors, Vector-Borne Diseases, MESH: Vaccines, Species Interactions, 030104 developmental biology, Good Health and Well Being, Vector (epidemiology), Current vector, Preventive Medicine, Humanities, MESH: Congresses as Topic
Abstract: Author(s): Christofferson, Rebecca C; Parker, Daniel M; Overgaard, Hans J; Hii, Jeffrey; Devine, Gregor; Wilcox, Bruce A; Nam, Vu Sinh; Abubakar, Sazaly; Boyer, Sebastien; Boonnak, Kobporn; Whitehead, Stephen S; Huy, Rekol; Rithea, Leang; Sochantha, Tho; Wellems, Thomas E; Valenzuela, Jesus G; Manning, Jessica E
Published: 2020

17. Evolution of abiotic cubane chemistries in a nucleic acid aptamer allows selective recognition of a malaria biomarker

Author: Marcel Hollenstein, Patrick Weber, Ariel E. Mechaly, Ahmed Haouz, Pascal Röthlisberger, Fabienne Levi-Acobas, G. Paul Savage, Young Lo, Alvin W C Wong, Julian A. Tanner, Yee-Wai Cheung, AB Kinghorn, The University of Hong Kong (HKU), Chimie bioorganique des acides nucléiques - Bioorganic chemistry of nucleic acids, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Cristallographie (Plateforme) - Crystallography (Platform), Division of Manufacturing Science and Technology (CSIRO), Commonwealth Scientific and Industrial Research Organisation [Canberra] (CSIRO), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: M.H, Plasmodium vivax, MESH: Aptamers, Nucleotide, Protozoan Proteins, MESH: Molecular Diagnostic Techniques, 01 natural sciences, malaria diagnosis, Nucleotide, MESH: Molecular Dynamics Simulation, MESH: Protozoan Proteins, chemistry.chemical_classification, modified aptamer, 0303 health sciences, Multidisciplinary, biology, Hydrogen bond, SELEX, Y.W.C. and P.R. were responsible, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Aptamers, Nucleotide, 3. Good health, MESH: Plasmodium vivax, Molecular Diagnostic Techniques, Physical Sciences, Protein Binding, MESH: L-Lactate Dehydrogenase, Aptamer, MESH: Malaria, Computational biology, Molecular Dynamics Simulation, 010402 general chemistry, 03 medical and health sciences, cubane, parasitic diseases, MESH: Protein Binding, [CHIM]Chemical Sciences, Humans, MESH: Hydrogen Bonding, 030304 developmental biology, X-ray crystallography, MESH: Humans, L-Lactate Dehydrogenase, Mechanism (biology), Plasmodium falciparum, Hydrogen Bonding, biology.organism_classification, 0104 chemical sciences, Malaria, chemistry, Nucleic acid, MESH: Biomarkers, malaria diagnosis Author Contributions J.A.T, Systematic evolution of ligands by exponential enrichment, Biomarkers
Abstract: We thank the Shirley Boyde Trust for their generous support through a Shirley Boyde Foundation Grant to J.A.T. and acknowledge Institut Pasteur funding to M.H., A.H., P.R., and F.L.-A.. J.A.T. acknowledges The University of Hong Kong Outstanding Young Researcher Award 2015-16, The University of Hong Kong Outstanding Research Student Supervisor Award 2016-2017, and The University of Hong Kong Seed Fund for Basic Research grants 201711159185 and 201611159269. We thank the staff of the platform for production and purification of recombinant proteins of Institut Pasteur for technical assistance during the expression and purification of the proteins steps and the staff of the crystallography platform at Institut Pasteur for carrying out robot-driven crystallization screening. We acknowledge synchrotron SOLEIL (Saint-Aubin, France) for granting access to their facility and the staff of Proxima1 for helpful assistance during the data collection.; International audience; for the overall study design and data interpretation. Y.W.C. performed all cubamer selections, characterized the cubamers and oversaw all application experiments. A.W.C.W., Y.L., and A.B.K. were involved in aspects of cubamer characterization and in assay design. F.L.-A. expressed and purified the proteins and performed the biochemical characterization of the triphosphate. P.R. performed all chemical syntheses and was involved in aspects of experimental design of cubamer structural analysis. P.R. was also significantly involved in all data interpretation. G.P.S. was involved in steps of synthesis relating to cubanes and advised on study design.
Published: 2020

18. Malaria and Dengue Mosquito Vectors from Lao PDR Show a Lack of the rdl Mutant Allele Responsible for Cyclodiene Insecticide Resistance

Author: Susannah Lechmere, Omobolanle H Abdullateef, Phoutmany Thammavong, Natalie M Portwood, Safina Khadam, Chloé Boer, Somsanith Chonephetsarath, Rosie Longstreeth, Paul T. Brey, Anna E Jacob, Nursu C Kuyucu, Wlaa Ali, Phonesavanh Luangamath, Jordan Forward, Andrew K. Jones, Santi Maithaviphet, Sébastien Marcombe, Somphat Nilaxay, Zuhal Rahmani, Simone Nambanya, Hayato Kakinuma, Natasha Brown, Joseph Hawkins, Penelope J Saverton, Madeleine Smee, Khaitong Lakeomany, Gabriela Stieger, Nothasin Phommavanh, Institut Pasteur du Laos, Réseau International des Instituts Pasteur (RIIP), Oxford Brookes University, Ministry of Health [Laos], and The mosquito collections, rearing and identification work was carried out within the framework of the MALVEC research project funded by the 5% initiative from the French Ministry of Foreign Affairs and International Development. For extraction and amplification of DNA from mosquitoes, funding was provided by Oxford Brookes University.
Subjects: Insecticides, MESH: Dengue, medicine.disease_cause, Dengue fever, Dengue, chemistry.chemical_compound, 0302 clinical medicine, Aedes, MESH: Insect Proteins, MESH: Animals, 0303 health sciences, Mutation, biology, Anopheles, dieldrin, insecticide resistance, MESH: Aedes, 3. Good health, Infectious Diseases, Laos, Insect Proteins, MESH: Mosquito Vectors, Aedes albopictus, MESH: Mutation, 030231 tropical medicine, MESH: Malaria, mosquito, Aedes aegypti, Mosquito Vectors, MESH: Anopheles, 03 medical and health sciences, Dieldrin, GABA receptor, parasitic diseases, medicine, Animals, MESH: Insecticide Resistance, Alleles, 030304 developmental biology, General Veterinary, MESH: Alleles, fungi, medicine.disease, biology.organism_classification, Virology, Malaria, MESH: Insecticides, [SDV.BA.ZI]Life Sciences [q-bio]/Animal biology/Invertebrate Zoology, chemistry, MESH: Laos, Insect Science, MESH: Dieldrin, Parasitology
Abstract: The gamma-aminobutyric acid (GABA) receptor, RDL, plays important roles in neuronal signaling and is the target of highly effective insecticides. A mutation in RDL, commonly A296S, underlies resistance to several insecticides such as cyclodienes. Even though the use of cyclodienes has been banned, the occurrence of mutations substituting A296 is notably high in mosquitoes from several countries. Here, we report a survey investigating the prevalence of the Rdl mutant allele in mosquitoes from Laos, a country where mosquito-borne diseases such as malaria and dengue fever are health concerns. Anopheles and Aedes mosquitoes were collected from 12 provinces in Laos. Adult bioassays on Aedes aegypti (Linnaeus) (Diptera: Culicidae) and Aedes albopictus (Skuse) (Diptera: Culicidae) showed that all the populations tested were susceptible to dieldrin (4%) following WHO protocols. Exon 7 from a total of 791 mosquitoes was sequenced to identify the amino acid encoded for at 296 of RDL. Only one of these mosquitoes, Anopheles maculatus rampae Harbach and Somboon (Diptera: Culicidae) from Attapeu, carried the mutant allele being heterozygous for A296S. We therefore found a general lack of the Rdl mutant allele indicating that mosquitoes from Laos are not exposed to insecticides that act on the GABA receptor compared to mosquitoes in several other countries. Identifying the prevalence of the Rdl mutation may help inform the potential use of alternative insecticides that act on the GABA receptor should there be a need to replace pyrethroids in order to prevent/manage resistance.
Published: 2020

19. Keep the quality high: the benefits of lot testing for the quality control of malaria rapid diagnostic tests

Author: Ana Campillo, Thierry Fandeur, Jane Cunningham, Jennifer Luchavez, Didier Menard, Xavier C. Ding, Sandra Incardona, Zachary Katz, Christian Anthony Luna, Sabine Dittrich, Benoit Witkowski, Frédéric Ariey, Derek Bell, Sina Nhem, Johanna Beulah Sornillo, Foundation for Innovative New Diagnostics (FIND), World Health Organisation (WHO), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Service de parasitologie-mycologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Direction Internationale de l'Institut Pasteur, Institut Pasteur [Paris] (IP), Research Institute for Tropical Medicine [Muntinlupa City, Philippines], Génétique du paludisme et résistance - Malaria Genetics and Resistance, National Center for Parasitology, Entomology and Malaria Control [Phnom Penh, Cambodia] (CNM), Malaria Molecular Epidemiology (MMEU), Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), University of Oxford, Our work on malaria and specifically RDT quality systems was enabled by grants from the Bill and Melinda Gates Foundation, the Global Fund to fight AIDS, Tuberculosis and Malaria, the United States President’s Malaria Initiative (via the United States Agency for International Development) and UNITAID, as well as funding from the Department of Foreign Affairs and Trade of the Australian government. Publication of this article was funded by FIND., Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut Pasteur [Paris], Malaria Molecular Epidemiology, and University of Oxford [Oxford]
Subjects: Quality Control, Post-market surveillance, medicine.medical_specialty, Opinion, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, media_common.quotation_subject, 030231 tropical medicine, Control (management), MESH: Malaria, MESH: Quality Control, Postmarketing surveillance, Rapid diagnostic test, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, parasitic diseases, medicine, Operations management, Quality (business), lcsh:RC109-216, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, 030212 general & internal medicine, Diagnostics, MESH: Diagnostic Tests, Routine, health care economics and organizations, media_common, Receipt, Diagnostic Tests, Routine, Public health, Reproducibility of Results, Lot testing, medicine.disease, 3. Good health, Malaria, MESH: Reproducibility of Results, Infectious Diseases, Quality management system, Parasitology, Business
Abstract: Background The production and use of malaria rapid diagnostic tests (RDTs) has risen dramatically over the past 20 years. In view of weak or non-existing in vitro diagnostics (IVD) regulations and post-marketing surveillance (PMS) systems in malaria endemic countries, the World Health Organization, later joined by the Foundation for Innovative New Diagnostics, established an independent, centralized performance evaluation and Lot Testing (LT) programme to safeguard against poor quality of RDTs being distributed through the public health sector of malaria endemic countries. RDT performances and manufacturer quality management systems have evolved over the past decade raising questions about the future need for a centralized LT programme. Results Between 2007 and 2017, 6056 lots have been evaluated, representing approximately 1.6 Billion RDTs. A total of 69 lots (1.1%) failed the quality control. Of these failures, 26 were detected at receipt of the RDT lot in the LT laboratory, representing an estimated 7.9 million poor quality RDTs, and LT requesters were advised that RDTs were not of sufficient quality for use in patient management. Forty-three were detected after long-term storage in the laboratory, of which 24 (56%) were found to be due to a major issue with insufficient buffer volume in single use buffer vials, others predominantly showing loss of sensitivity. The annual cost of running the programme, based on expenses recorded in years 2014–2016, an estimated volume of 700 lots per year and including replenishment of quality control samples, was estimated at US$ 178,500 ($US 255 per lot tested). Conclusions Despite the clear benefits of the centralized LT programme and its low cost compared with the potential costs of each country establishing its own PMS system for RDTs, funding concerns have made its future beyond 2020 uncertain. In order to manage the risks of misdiagnosis due to low quality RDTs, and to ensure the continued safety and reliability of malaria case management, there is a need to ensure that an effective and implementable approach to RDT quality control continues to be available to programmes in endemic countries.
Published: 2020

20. Gene copy number and function of the APL1 immune factor changed during Anopheles evolution

Author: Abbasali Raz, Christian Mitri, Emma Brito-Fravallo, Kenneth D. Vernick, Emmanuel Bischoff, Constentin Dieme, Inge Holm, Sedigheh Zakeri, Michelle M. Riehle, Karin Eiglmeier, Mahdokht I. K. Nejad, Navid Dinparast Djadid, Génétique et Génomique des Insectes Vecteurs, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Génétique des Génomes Bactériens, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Malaria and Vector Research Group (MVRG), Institut Pasteur d'Iran, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Medical College of Wisconsin [Milwaukee] (MCW), This study received financial support to KDV from the European Commission, Horizon 2020 Infrastructures #731060 Infravec2, European Research Council, Support for frontier research, Advanced Grant #323173 AnoPath, Agence Nationale de la Recherche, #ANR-19-CE35-0004 ArboVec, and French Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' #ANR-10-LABX-62-IBEID and to MMR from National Institutes of Health, NIAID #AI121587. Funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 731060,INFRAVEC2(2017), European Project: 323173,EC:FP7:ERC,ERC-2012-ADG_20120314,ANOPATH(2013), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Anopheles gambiae, [SDV]Life Sciences [q-bio], Gene Dosage, MESH: Gene Dosage, 0302 clinical medicine, Mosquito, MESH: Insect Proteins, MESH: Animals, Copy-number variation, MESH: Peptide Fragments, MESH: Phylogeny, Phylogeny, Gene essentiality, MESH: Evolution, Molecular, Genetics, Gene neofunctionalization, MESH: Immunologic Factors, Anopheles, 3. Good health, Infectious Diseases, MESH: Longevity, Insect immunity, Insect Proteins, 030231 tropical medicine, Longevity, MESH: Malaria, Locus (genetics), MESH: Insect Vectors, Biology, lcsh:Infectious and parasitic diseases, Evolution, Molecular, MESH: Anopheles, 03 medical and health sciences, parasitic diseases, Gene silencing, Gene family, Animals, Immunologic Factors, lcsh:RC109-216, Gene, Anopheles stephensi, [SDV.GEN]Life Sciences [q-bio]/Genetics, Research, fungi, Chaperonin 60, biology.organism_classification, Peptide Fragments, Insect Vectors, Malaria, 030104 developmental biology, MESH: Chaperonin 60, Parasitology
Abstract: Background The recent reference genome assembly and annotation of the Asian malaria vector Anopheles stephensi detected only one gene encoding the leucine-rich repeat immune factor APL1, while in the Anopheles gambiae and sibling Anopheles coluzzii, APL1 factors are encoded by a family of three paralogs. The phylogeny and biological function of the unique APL1 gene in An. stephensi have not yet been specifically examined. Methods The APL1 locus was manually annotated to confirm the computationally predicted single APL1 gene in An. stephensi. APL1 evolution within Anopheles was explored by phylogenomic analysis. The single or paralogous APL1 genes were silenced in An. stephensi and An. coluzzii, respectively, followed by mosquito survival analysis, experimental infection with Plasmodium and expression analysis. Results APL1 is present as a single ancestral gene in most Anopheles including An. stephensi but has expanded to three paralogs in an African lineage that includes only the Anopheles gambiae species complex and Anopheles christyi. Silencing of the unique APL1 copy in An. stephensi results in significant mosquito mortality. Elevated mortality of APL1-depleted An. stephensi is rescued by antibiotic treatment, suggesting that pathology due to bacteria is the cause of mortality, and indicating that the unique APL1 gene is essential for host survival. Successful Plasmodium development in An. stephensi depends upon APL1 activity for protection from high host mortality due to bacteria. In contrast, silencing of all three APL1 paralogs in An. coluzzii does not result in elevated mortality, either with or without Plasmodium infection. Expression of the single An. stephensi APL1 gene is regulated by both the Imd and Toll immune pathways, while the two signaling pathways regulate different APL1 paralogs in the expanded APL1 locus. Conclusions APL1 underwent loss and gain of functions concomitant with expansion from a single ancestral gene to three paralogs in one lineage of African Anopheles. We infer that activity of the unique APL1 gene promotes longevity in An. stephensi by conferring protection from or tolerance to an effect of bacterial pathology. The evolution of an expanded APL1 gene family could be a factor contributing to the exceptional levels of malaria transmission mediated by human-feeding members of the An. gambiae species complex in Africa.
Published: 2020

21. Towards harmonization of microscopy methods for malaria clinical research studies

Author: Jane Carter, J. Kevin Baird, Ric N. Price, Piero Olliaro, John C. Reeder, Michelle L. Gatton, Peter Obare, Philippe J Guerin, El Hadji Ba, Stephane Proux, Derek Bell, Cheikh Sokhna, Andrew Ramsay, Arjen M. Dondorp, Mehul Dhorda, Ken Lilley, François Nosten, Didier Menard, Kamolrat Silamut, Lenny L Ekawati, Iveth J González, John W. Barnwell, Bernhards Ogutu, Sandra Incardona, WorldWide Antimalarial Resistance Network [Bangkok] (WWARN), WorldWide Antimalarial Resistance Network (WWARN), University of Washington [Seattle]-University of Washington [Seattle], University of Oxford, Mahidol University [Bangkok], Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD), Eijkman Institute for Molecular Biology [Jakarta], Centers for Disease Control and Prevention [Atlanta] (CDC), Centers for Disease Control and Prevention, Amref Health Africa [Kenya], African Medical and Research Foundation (AMREF), Queensland University of Technology [Brisbane] (QUT), Terre des hommes [Lausanne], WorldWide Antimalarial Resistance Network, WWARN, Foundation for Innovative New Diagnostics (FIND), Australian Defence Force Malaria and Infectious Disease Institute [Enoggera] (ADFMIDI), Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Shoklo Malaria Research Unit [Mae Sot, Thailand] (SMRU), Mahidol Oxford Tropical Medicine Research Unit (MORU), University of Oxford-Mahidol University [Bangkok]-Wellcome Trust-University of Oxford-Mahidol University [Bangkok]-Wellcome Trust, Kenya Medical Research Institute (KEMRI), Menzies School of Health Research [Australia], Charles Darwin University [Australia], University of Saint Andrews, UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR), UNICEF Headquarters-World Bank Group-United Nations Development Programme (UNDP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Université de Washington Seattle-Université de Washington Seattle, University of Oxford [Oxford], Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), University of Oxford [Oxford]-Mahidol University [Bangkok]-Wellcome Trust-University of Oxford [Oxford]-Mahidol University [Bangkok]-Wellcome Trust, Charles Darwin University, Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO)-UNICEF Headquarters-World Bank Group-United Nations Development Programme (UNDP), and University of St Andrews. School of Medicine
Subjects: Laboratory Proficiency Testing, MESH: Quality Control, Review, MESH: Laboratory Proficiency Testing, Clinical research, 0302 clinical medicine, RA0421, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, RA0421 Public health. Hygiene. Preventive Medicine, Microscopy, 030212 general & internal medicine, Reliability (statistics), Standard, 3. Good health, MESH: Reproducibility of Results, MESH: Staining and Labeling, Infectious Diseases, T-DAS, Quality Control, medicine.medical_specialty, lcsh:Arctic medicine. Tropical medicine, MESH: Microscopy, lcsh:RC955-962, 030231 tropical medicine, MESH: Malaria, Harmonization, Sensitivity and Specificity, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, SDG 3 - Good Health and Well-being, parasitic diseases, medicine, Humans, lcsh:RC109-216, Medical physics, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Diagnostic, MESH: Diagnostic Tests, Routine, MESH: Humans, Staining and Labeling, Diagnostic Tests, Routine, business.industry, Reproducibility of Results, medicine.disease, MESH: Sensitivity and Specificity, Malaria, Clinical trial, Quality management system, Parasitology, business, Quality assurance
Abstract: Microscopy performed on stained films of peripheral blood for detection, identification and quantification of malaria parasites is an essential reference standard for clinical trials of drugs, vaccines and diagnostic tests for malaria. The value of data from such research is greatly enhanced if this reference standard is consistent across time and geography. Adherence to common standards and practices is a prerequisite to achieve this. The rationale for proposed research standards and procedures for the preparation, staining and microscopic examination of blood films for malaria parasites is presented here with the aim of improving the consistency and reliability of malaria microscopy performed in such studies. These standards constitute the core of a quality management system for clinical research studies employing microscopy as a reference standard. They can be used as the basis for the design of training and proficiency testing programmes as well as for procedures and quality assurance of malaria microscopy in clinical research.
Published: 2020

22. A Potent Anti-Malarial Human Monoclonal Antibody Targets Circumsporozoite Protein Minor Repeats and Neutralizes Sporozoites in the Liver

Author: Annie S. P. Yang, Carolina Barillas-Mury, Marlon Dillon, Rachel Vistein, Nicole Cavett, David Baker, Arne Schön, Monica W. Gerber, Robert W. Sauerwein, Reid B. Ballard, James O’Connor, Barbara J. Flynn, Alvaro Molina-Cruz, Jorgen Nelson, Fidel Zavala, Lawrence T. Wang, Robert A. Seder, Neville K. Kisalu, Amanda Fabra-García, Joseph R. Francica, Lais Pereira, Rogerio Amino, Bryan T. Mayer, Ian A. Cockburn, Neil P. King, Marie Pancera, Rosemarie D. Mason, Yevel Flores-Garcia, Raphael Gottardo, Azza H. Idris, Nicholas K. Hurlburt, National Institutes of Health [Bethesda] (NIH), Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Australian National University (ANU), Medical School [Australian National University - ANU], Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Radboud University Medical Center [Nijmegen], University of Washington [Seattle], Infection et Immunité paludéennes - Malaria Infection and Immunity, Institut Pasteur [Paris] (IP), This work was supported by the National Institute of Allergy and Infectious Diseases, the National Cancer Institute (HHSN261200800001E to A.S.), the Dutch Research Council (NWO) talent program veni (VI.Veni.192.171 to A.S.P.Y.), the Bill & Melinda Gates Foundation for N.K.H and M.P. (OPP1156262) and Y.F.-G. and F.Z., who also thank the Bloomberg Philanthropies for continued support., and Institut Pasteur [Paris]
Subjects: Male, 0301 basic medicine, sporozoites, [SDV]Life Sciences [q-bio], Protozoan Proteins, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Antibodies, Protozoan, MESH: Sporozoites, Neutralization, MESH: Antibodies, Monoclonal, MESH: Antibodies, Neutralizing, MESH: Hepatocytes, Epitopes, Mice, 0302 clinical medicine, Immunology and Allergy, MESH: Animals, MESH: Protozoan Proteins, MESH: Plasmodium falciparum, MESH: Middle Aged, biology, Antibodies, Monoclonal, Translation (biology), NVDP minor repeats, MESH: Malaria Vaccines, Middle Aged, 3. Good health, Circumsporozoite protein, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Liver, MESH: Young Adult, 030220 oncology & carcinogenesis, MESH: HEK293 Cells, malaria vaccines, Female, Antibody, circumsporozoite protein, Adult, Subdominant, MESH: Cell Line, Tumor, MESH: Epitopes, Adolescent, medicine.drug_class, Immunology, Plasmodium falciparum, MESH: Malaria, Monoclonal antibody, Cell Line, Antimalarials, Young Adult, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, MESH: Mice, Inbred C57BL, Cell Line, Tumor, medicine, Animals, Humans, MESH: Antibodies, Protozoan, MESH: Mice, MESH: Adolescent, passive transfer, MESH: Humans, Isothermal titration calorimetry, MESH: Adult, biology.organism_classification, Antibodies, Neutralizing, Virology, MESH: Antimalarials, MESH: Male, Malaria, MESH: Cell Line, Mice, Inbred C57BL, HEK293 Cells, 030104 developmental biology, Hepatocytes, biology.protein, Monoclonal antibodies, MESH: Female, MESH: Liver
Abstract: International audience; Discovering potent human monoclonal antibodies (mAbs) targeting the Plasmodium falciparum circumsporozoite protein (PfCSP) on sporozoites (SPZ) and elucidating their mechanisms of neutralization will facilitate translation for passive prophylaxis and aid next-generation vaccine development. Here, we isolated a neutralizing human mAb, L9 that preferentially bound NVDP minor repeats of PfCSP with high affinity while cross-reacting with NANP major repeats. L9 was more potent than six published neutralizing human PfCSP mAbs at mediating protection against mosquito bite challenge in mice. Isothermal titration calorimetry and multiphoton microscopy showed that L9 and the other most protective mAbs bound PfCSP with two binding events and mediated protection by killing SPZ in the liver and by preventing their egress from sinusoids and traversal of hepatocytes. This study defines the subdominant PfCSP minor repeats as neutralizing epitopes, identifies an in vitro biophysical correlate of SPZ neutralization, and demonstrates that the liver is an important site for antibodies to prevent malaria.
Published: 2020

23. 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

24. Sustained Malaria Control Over an 8-Year Period in Papua New Guinea: The Challenge of Low-Density Asymptomatic Plasmodium Infections

Author: Maria Ome-Kaius, Cristian Koepfli, James W. Kazura, Shadrach Jally, Lincoln Timinao, Jason Ginny, Johanna H Kattenberg, Ivo Mueller, Michael T. White, Patricia Rarau, Nicolas Senn, Alyssa E. Barry, Elisheba Malau, Samuel Maripal, Thomas Obadia, Leanne J. Robinson, The Walter and Eliza Hall Institute of Medical Research (WEHI), University of Melbourne, University of California [Irvine] (UCI), University of California, Papua New Guinea Institute of Medical Research (PNG-IMR), Malaria : parasites et hôtes - Malaria : parasites and hosts, Institut Pasteur [Paris], Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Imperial College London, Swiss Tropical and Public Health Institute [Basel], Case Western Reserve University [Cleveland], Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Burnet Institute [Melbourne, Victoria], This work was supported by the International Centers of Excellence for Malaria Research (grant U19 AI089686), the TransEPI consortium, funded by the Bill and Melinda Gates Foundation, the NHMRC (grant 1021544, early career fellowship 1016443 to L. J. R.), the Victorian State Government, through operational infrastructure support, the Australian Government NHMRC IRIISS, the Swiss National Science Foundation (fellowship P2BSP3_151880 to C. K.), the Medical Research Council (population health scientist fellowship to M. W.), and the NHMRC (senior research fellowship to I.M.)., University of California [Irvine] (UC Irvine), University of California (UC), Institut Pasteur [Paris] (IP), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, MESH: Parasitemia, Plasmodium, MESH: Topography, Medical, temporal trend, Plasmodium vivax, Geographic Mapping, Parasitemia, MESH: Infection Control, 0302 clinical medicine, MESH: Child, Prevalence, Immunology and Allergy, Malaria, Falciparum, MESH: Geographic Mapping, Child, Asymptomatic Infections, MESH: Plasmodium falciparum, education.field_of_study, biology, MESH: Real-Time Polymerase Chain Reaction, Incidence (epidemiology), MESH: Malaria, Falciparum, MESH: Genome, Protozoan, 3. Good health, MESH: Plasmodium vivax, Infectious Diseases, Blood, Topography, Medical, medicine.symptom, Malaria control, 030231 tropical medicine, Population, MESH: Malaria, Plasmodium falciparum, MESH: Asymptomatic Infections, MESH: DNA, Protozoan, Real-Time Polymerase Chain Reaction, Asymptomatic, 03 medical and health sciences, Major Articles and Brief Reports, Papua New Guinea, MESH: Cross-Sectional Studies, submicroscopic, parasitic diseases, medicine, Gametocyte, MESH: Blood, Malaria, Vivax, asymptomatic, Humans, Parasites, education, MESH: Papua New Guinea, MESH: Life Cycle Stages, MESH: Prevalence, Infection Control, Life Cycle Stages, MESH: Humans, business.industry, MESH: Plasmodium, MESH: Malaria, Vivax, DNA, Protozoan, medicine.disease, biology.organism_classification, Malaria, 030104 developmental biology, Cross-Sectional Studies, gametocyte, Immunology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Genome, Protozoan
Abstract: Continuous malaria control in Papua New Guinea has resulted in a marked decline of Plasmodium falciparum and P. vivax prevalence. Yet, an increasing proportion of submicroscopic infections, many of them carrying gametocytes, demands for novel strategies to target residual transmission., Background The scale-up of effective malaria control in the last decade has resulted in a substantial decline in the incidence of clinical malaria in many countries. The effects on the proportions of asymptomatic and submicroscopic infections and on transmission potential are yet poorly understood. Methods In Papua New Guinea, vector control has been intensified since 2008, and improved diagnosis and treatment was introduced in 2012. Cross-sectional surveys were conducted in Madang Province in 2006 (with 1280 survey participants), 2010 (with 2117 participants), and 2014 (with 2516 participants). Infections were quantified by highly sensitive quantitative polymerase chain reaction (PCR) analysis, and gametocytes were quantified by reverse-transcription qPCR analysis. Results Plasmodium falciparum prevalence determined by qPCR decreased from 42% in 2006 to 9% in 2014. The P. vivax prevalence decreased from 42% in 2006 to 13% in 2010 but then increased to 20% in 2014. Parasite densities decreased 5-fold from 2006 to 2010; 72% of P. falciparum and 87% of P. vivax infections were submicroscopic in 2014. Gametocyte density and positivity correlated closely with parasitemia, and population gametocyte prevalence decreased 3-fold for P. falciparum and 29% for P. vivax from 2010 to 2014. Conclusions Sustained control has resulted in reduced malaria transmission potential, but an increasing proportion of gametocyte carriers are asymptomatic and submicroscopic and represent a challenge to malaria control.
Published: 2017

25. Whole genome sequencing of amplified Plasmodium knowlesi DNA from unprocessed blood reveals genetic exchange events between Malaysian Peninsular and Borneo subpopulations

Author: Nicholas M. Anstey, Robert W. Moon, Lau Yee Ling, Arnab Pain, Jeremy Ryan De Silva, Paola Florez de Sessions, James Charleston, Sarah Auburn, Timothy William, Abhinay Ramaprasad, Taane G. Clark, Bridget E. Barber, Ernest Diez Benavente, Harriet Walker, Matthew J. Grigg, Ana Rita Gomes, Susana Campino, Tsin W. Yeo, Amy Ibrahim, Martin L. Hibberd, Université de Montpellier (UM), Centre National de la Recherche Scientifique (CNRS), and London School of Hygiene and Tropical Medicine (LSHTM)
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], Protozoan Proteins, lcsh:Medicine, Macaque, Genome, Genetic analysis, MESH: Genotype, Genomic analysis, 0302 clinical medicine, Borneo, Genotype, MESH: Animals, MESH: Genetic Variation, lcsh:Science, MESH: Protozoan Proteins, MESH: Borneo, Whole Genome Amplification, Multidisciplinary, biology, Genomics, 3. Good health, MESH: Malaysia, Plasmodium knowlesi, MESH: Whole Genome Sequencing, Bioinformatics, MESH: Malaria, MESH: DNA, Protozoan, Article, 03 medical and health sciences, MESH: Plasmodium knowlesi, biology.animal, parasitic diseases, Animals, Humans, Gene, Whole genome sequencing, MESH: Humans, Whole Genome Sequencing, lcsh:R, Malaysia, Genetic Variation, MESH: Haplotypes, DNA, Protozoan, biology.organism_classification, Malaria, Macaca fascicularis, 030104 developmental biology, MESH: Macaca fascicularis, Haplotypes, Evolutionary biology, lcsh:Q, 030217 neurology & neurosurgery
Abstract: The zoonotic Plasmodium knowlesi parasite is the most common cause of human malaria in Malaysia. Genetic analysis has shown that the parasites are divided into three subpopulations according to their geographic origin (Peninsular or Borneo) and, in Borneo, their macaque host (Macaca fascicularis or M. nemestrina). Whilst evidence suggests that genetic exchange events have occurred between the two Borneo subpopulations, the picture is unclear in less studied Peninsular strains. One difficulty is that P. knowlesi infected individuals tend to present with low parasitaemia leading to samples with insufficient DNA for whole genome sequencing. Here, using a parasite selective whole genome amplification approach on unprocessed blood samples, we were able to analyse recent genomes sourced from both Peninsular Malaysia and Borneo. The analysis provides evidence that recombination events are present in the Peninsular Malaysia parasite subpopulation, which have acquired fragments of the M. nemestrina associated subpopulation genotype, including the DBPβ and NBPXa erythrocyte invasion genes. The NBPXb invasion gene has also been exchanged within the macaque host-associated subpopulations of Malaysian Borneo. Our work provides strong evidence that exchange events are far more ubiquitous than expected and should be taken into consideration when studying the highly complex P. knowlesi population structure.
Published: 2019

26. Comment on 'A. annua and A. afra infusions vs. Artesunate-amodiaquine (ASAQ) in treating Plasmodium falciparum malaria in a large scale, double blind, randomized clinical trial' Munyangi et al., 2019

Author: Landier Jordi, Caumes Eric, Argemi Xavier, Gillibert André, Gaudart Jean, Jauréguiberry Stéphane, Hansmann Yves, Unité de biostatistiques [CHU Rouen], Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU), GILLIBERT, André, CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Virulence Bactérienne Précoce : fonctions cellulaires et contrôle de l'infection aigüe et subaigüe, Université de Strasbourg (UNISTRA), Service des Maladies Infectieuses et Tropicales [CHU Strasbourg], CHU Strasbourg, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U912 INSERM - Aix Marseille Univ - IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biostatistique et technologies de l'information et de la communication (BioSTIC) - [Hôpital de la Timone - APHM] (BiosTIC ), and Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)
Subjects: Pharmaceutical Science, MESH: artemisia, Artesunate-amodiaquine, law.invention, 0302 clinical medicine, Randomized controlled trial, law, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Drug Discovery, éthique, Response rate (survey), MESH: comment, 0303 health sciences, artemisia, [STAT.ME] Statistics [stat]/Methodology [stat.ME], biology, Artesunate/amodiaquine, MESH: methods, methodology, méthodologie, 3. Good health, MESH: malaria, MESH: ethics, research, 030220 oncology & carcinogenesis, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Molecular Medicine, [STAT.ME]Statistics [stat]/Methodology [stat.ME], medicine.drug, essai clinique randomisé, medicine.medical_specialty, Randomization, malaria, 03 medical and health sciences, Internal medicine, medicine, Adverse effect, 030304 developmental biology, Pharmacology, business.industry, Plasmodium falciparum, medicine.disease, biology.organism_classification, ethics, Clinical trial, Complementary and alternative medicine, paludisme, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, randomized controlled trial, MESH: amodiaquine, artesunate drug combination, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Malaria
Abstract: We read with great interest the article entitled “A. annua and A. afra infusions vs. Artesunate-amodiaquine (ASAQ) in treating Plasmodium falciparum malaria in a large scale, double blind, randomized clinical trial“We have noticed some issues and inconsistencies in the background, methods and results, and would like to provide a critical analysis of this study. The scientific validity of the results is affected as well as the ethical integrity given the lethal risk of malaria for infected patients.Critic of Ethics: A large-scale randomized controlled trial for Artemisia (phase III) should not have been conducted without prior evidence of efficacy in smaller randomized trials. The ethics committee authorization number seems to be shared with another clinical trial and seems to have been obtained in 2016, after the clinical trial was conducted.Critic of Methods: Unclear or unadequate randomization. The primary outcome was not mentioned in methods and there is no hypothesis test on any efficacy outcome. No PCR adjustment for reinfection.Critic of Results: Many inconsistencies in sample sizes and efficacy results. Major imbalance of randomized group sizes in some centers. Response rate of ASAQ (34%) far lower than anything described in this region (> 90%). Efficacy varying from 0% to 100% from center to center. Frequencies of adverse effects are almost all multiples of five, which can hardly be explained by random fluctuations (p, Nous avons lu avec grand intérêt l’article intitulé «A. annua and A. afra infusions vs. Artesunate-amodiaquine (ASAQ) in treating Plasmodium falciparum malaria in a large scale, double blind, randomized clinical trial»Nous avons constaté des problèmes et des incohérences dans le contexte, les méthodes et les résultats, et nous souhaitons fournir une analyse critique de cette étude. La validité scientifique des résultats est affectée ainsi que l'intégrité éthique étant donné le risque mortel de paludisme pour les patients infectés.Critique de l’aspect éthique: Un essai contrôlé randomisé à grande échelle sur Artemisia (phase III) n'aurait pas dû être mené sans preuve préalable d'efficacité dans le cadre d'essais randomisés de plus petite envergure. Le numéro d'autorisation du comité d'éthique semble être identique à celui d’un autre essai clinique et semble avoir été obtenu en 2016, après la réalisation de l’essai.Critique des méthodes: randomisation obscure ou inadéquate. Le critère principal d'évaluation n'a pas été mentionné dans les méthodes et il n'y a aucun test d'hypothèse sur les critères d'efficacité. Aucun ajustement PCR pour réinfection.Critique des résultats: nombreuses incohérences dans la taille des échantillons et les résultats d'efficacité. Déséquilibre majeur des effectifs entre les groupes randomisés dans certains centres. Le taux de réponse de l'ASAQ (34%) est bien inférieur à celui décrit dans cette région (> 90%). Efficacité variant de 0% à 100% d'un centre à l'autre. Les fréquences des effets indésirables sont presque toutes des multiples de cinq, ce qui peut difficilement être expliqué par des fluctuations aléatoires (p
Published: 2019

27. [Epidemiology of importedmalaria to France]

Author: Pradines, Bruno, Thellier, Marc, Kendjo, Eric, Houzé, Sandrine, Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), Service d'Immunologie [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), Service de parasitologie - mycologie [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), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Travel, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, MESH: Humans, MESH: Malaria, malaria, MESH: Antimalarials, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: France, Antimalarials, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Humans, epidemiology, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, France, imported malaria, MESH: Travel, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2019

28. Sampling adult populations of anopheles mosquitoes

Author: Alexandra Hiscox, Julie-Anne A. Tangena, Paul T. Brey, Institut Pasteur du Laos, Réseau International des Instituts Pasteur (RIIP), Wageningen University and Research [Wageningen] (WUR), International Centre of Insect Physiology and Ecology (ICIPE), ICIPE, and This work was supported by the Yersin project, funded by the Michelin Corporate Foundation. AH was supported by a grant from the Innovative Vector Control Consortium.
Subjects: Peripheral net collection, MESH: Malaria, 030231 tropical medicine, Optimal deployment, MESH: Disease Vectors, Human-baited net trap, Pyrethrum collection, Resting shelter, Trapping methods, Biogents Suna trap, MESH: Anopheles, Trap (computing), 03 medical and health sciences, 0302 clinical medicine, Anopheles, MESH: Animals, 030212 general & internal medicine, Laboratory of Entomology, Animal-baited net trap, MESH: Mosquito Control, MESH: Humans, biology, Sampling (statistics), MESH: Adult, Animal landing catch, CDC miniature light trap, biology.organism_classification, Laboratorium voor Entomologie, 3. Good health, [SDV.BA.ZI]Life Sciences [q-bio]/Animal biology/Invertebrate Zoology, Fishery, Vector (epidemiology), Mosquito traps, Local environment, Environmental science, MESH: Mosquito Vectors, Human landing catch, Exit-entry trap
Abstract: International audience; For the control and elimination of malaria, information on the local vector dynamics is essential. This information provides guidance on appropriate and timely deployment of vector control tools and their subsequent success. The data on the dynamics of local mosquito populations can be collected using many different Anopheles sampling methods. Dependent on the objectives, resources, time, and local environment, different traps and methods can be chosen. This chapter describes the sampling of adult populations, focusing on the important preparatory stages and some of the widely used sampling methods. The trapping methods discussed in this chapter are the human landing catch, human-baited net trap, animal landing catch, animal-baited net trap, CDC miniature light trap, Biogents Suna trap, peripheral net collection, pyrethrum collection, exit/entry trap, and resting shelter. For optimal deployment in the field, a step-by-step description of the sampling methods is given.
Published: 2019

29. Complex Endosymbioses II: The Nonphotosynthetic Plastid of Apicomplexa Parasites (The Apicoplast) and Its Integrated Metabolism

Author: Cyrille Y, Botté, Yoshiki, Yamaryo-Botté, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), and Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])
Subjects: MESH: Protein Transport, MESH: Malaria, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Apicoplasts, Drug Development, Secondary endosymbiosis, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Apicoplast, parasitic diseases, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, MESH: Genome, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Plastids, Photosynthesis, Symbiosis, MESH: Apicoplasts, MESH: Photosynthesis, MESH: Antiparasitic Agents, MESH: Drug Development, Genome, MESH: Symbiosis, Antiparasitic Agents, MESH: Energy Metabolism, food and beverages, MESH: Plastids, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Malaria, Protein Transport, MESH: Metabolic Networks and Pathways, Energy Metabolism, Apicomplexa, Metabolic Networks and Pathways, Toxoplasmosis
Abstract: International audience; Chloroplasts are essential organelles that are responsible for photosynthesis in a wide range of organisms that have colonized all biotopes on Earth such as plants and unicellular algae. Interestingly, a secondary endosymbiotic event of a red algal ancestor gave rise to a group of organisms that have adopted an obligate parasitic lifestyle named Apicomplexa parasites. Apicomplexa parasites are some of the most widespread and poorly controlled pathogens in the world. These infectious agents are responsible for major human diseases such as toxoplasmosis, caused by Toxoplasma gondii, and malaria caused by Plasmodium spp. Most of these parasites harbor this relict plastid named the apicoplast, which is essential for parasite survival. The apicoplast has lost photosynthetic capacities but are metabolically similar to plant and algal chloroplasts. The apicoplast is considered a novel and important drug target against Apicomplexa parasites. This chapter focuses on the apicoplast of apicomplexa parasites, its maintenance, and its metabolic pathways.
Published: 2018

30. The tripartite interactions between the mosquito, its microbiota and Plasmodium

Author: Ottavia Romoli, Mathilde Gendrin, Microbiote des insectes vecteurs / Microbiota of Insect Vectors [Cayenne, Guyane française], Vectopôle Amazonien Emile Abonnenc [Cayenne, Guyane française], Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Département Parasites et Insectes vecteurs - Department of Parasites and Insect Vectors, Institut Pasteur [Paris], This work is funded by the French Government’s Investissement d’Avenir program, Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (grant no. ANR-10-LABX-62-IBEID)., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), and Institut Pasteur [Paris] (IP)
Subjects: 0301 basic medicine, Plasmodium, Entomology, [SDV]Life Sciences [q-bio], MESH: Malaria, 030106 microbiology, Mosquito Vectors, Review, Colonisation resistance, MESH: Host-Parasite Interactions, digestive system, Host-Parasite Interactions, lcsh:Infectious and parasitic diseases, MESH: Anopheles, 03 medical and health sciences, MESH: Mosquito vectors, Malaria transmission, Anopheles, parasitic diseases, medicine, Animals, Humans, MESH: Microbiota, MESH: Animals, lcsh:RC109-216, Functional studies, MESH: Humans, biology, MESH: Plasmodium, [SDV.BA]Life Sciences [q-bio]/Animal biology, Microbiota, fungi, medicine.disease, biology.organism_classification, Malaria, 3. Good health, [SDV.BA.ZI]Life Sciences [q-bio]/Animal biology/Invertebrate Zoology, Vectorial transmission, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, 030104 developmental biology, Infectious Diseases, Parasitology, Evolutionary biology, Experimental models
Abstract: International audience; The microbiota of Anopheles mosquitoes interferes with mosquito infection by Plasmodium and influences mosquito fitness, therefore affecting vectorial capacity. This natural barrier to malaria transmission has been regarded with growing interest in the last 20 years, as it may be a source of new transmission-blocking strategies. The last decade has seen tremendous progress in the functional characterisation of the tripartite interactions between the mosquito, its microbiota and Plasmodium parasites. In this review, we provide insights into the effects of the mosquito microbiota on Plasmodium infection and on mosquito physiology, and on how these aspects together influence vectorial capacity. We also discuss three current challenges in the field, namely the need for a more relevant microbiota composition in experimental mosquitoes involved in vector biology studies, for a better characterisation of the non-bacterial microbiota, and for further functional studies of the microbiota present outside the gut.
Published: 2018

31. Successes and failures of sixty years of vector control in French Guiana: what is the next step?

Author: Yanouk Epelboin, Nausicaa Habchi-Hanriot, Amandine Guidez, Stanislas Talaga, Lanjiao Wang, Sarah C Chaney, Isabelle Dusfour, Vectopôle Amazonien Emile Abonnenc [Cayenne, Guyane française], Institut Pasteur de la Guyane, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)
Subjects: Insecticides, Mosquito Control, lcsh:QR1-502, Review, MESH: Chikungunya Fever, MESH: Dengue, medicine.disease_cause, lcsh:Microbiology, Dengue fever, Dengue, MESH: Health Education, 0302 clinical medicine, Aedes aegypti, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Animals, Anopheles darlingi, 030212 general & internal medicine, Chikungunya, Socioeconomics, Health Education, MESH: Yellow Fever, MESH: Mosquito Control, Vector control, biology, Zika Virus Infection, Yellow fever, insecticide resistance, 3. Good health, French Guiana, Geography, MESH: Mosquito Vectors, Microbiology (medical), lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, 030231 tropical medicine, MESH: Malaria, vector control, Mosquito Vectors, 03 medical and health sciences, MESH: Zika Virus Infection, Yellow Fever, MESH: French Guiana, parasitic diseases, medicine, Animals, Humans, MESH: Humans, medicine.disease, biology.organism_classification, Malaria, MESH: Insecticides, Culicidae, Insecticide resistance, Chikungunya Fever, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Culicidae
Abstract: International audience; Since the 1940s, French Guiana has implemented vector control to contain or eliminate malaria, yellow fever, and, recently, dengue, chikungunya, and Zika. Over time, strategies have evolved depending on the location, efficacy of the methods, development of insecticide resistance, and advances in vector control techniques. This review summarises the history of vector control in French Guiana by reporting the records found in the private archives of the Institute Pasteur in French Guiana and those accessible in libraries worldwide. This publication highlights successes and failures in vector control and identifies the constraints and expectations for vector control in this French overseas territory in the Americas.
Published: 2018

32. Multidrug-resistant Plasmodium falciparum malaria in the Greater Mekong subregion

Author: Frédéric Ariey, Jérôme Clain, Didier Menard, Biologie des Interactions Hôte-Parasite - Biology of Host-Parasite Interactions, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Menard, Didier, Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 216), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Université de Paris (UP), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)
Subjects: 0301 basic medicine, 030106 microbiology, education, MESH: Asia, Southeastern, MESH: Malaria, Biology, complex mixtures, Article, Disease Outbreaks, Southeast asia, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, mental disorders, parasitic diseases, medicine, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, 030212 general & internal medicine, Malaria, Falciparum, MESH: Disease Outbreaks, Asia, Southeastern, Retrospective Studies, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, MESH: Humans, MESH: Malaria, Falciparum, Outbreak, Plasmodium falciparum, MESH: Retrospective Studies, medicine.disease, biology.organism_classification, Virology, humanities, Malaria, 3. Good health, body regions, Multiple drug resistance, Infectious Diseases, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology
Abstract: Summary Background Antimalarial resistance is rapidly spreading across parts of southeast Asia where dihydroartemisinin–piperaquine is used as first-line treatment for Plasmodium falciparum malaria. The first published reports about resistance to antimalarial drugs came from western Cambodia in 2013. Here, we analyse genetic changes in the P falciparum population of western Cambodia in the 6 years before those reports. Methods We analysed genome sequence data on 1492 P falciparum samples from 11 locations across southeast Asia, including 464 samples collected in western Cambodia between 2007 and 2013. Different epidemiological origins of resistance were identified by haplotypic analysis of the kelch13 artemisinin resistance locus and the plasmepsin 2–3 piperaquine resistance locus. Findings We identified more than 30 independent origins of artemisinin resistance, of which the KEL1 lineage accounted for 140 (91%) of 154 parasites resistant to dihydroartemisinin–piperaquine. In 2008, KEL1 combined with PLA1, the major lineage associated with piperaquine resistance. By 2013, the KEL1/PLA1 co-lineage had reached a frequency of 63% (24/38) in western Cambodia and had spread to northern Cambodia. Interpretation The KEL1/PLA1 co-lineage emerged in the same year that dihydroartemisinin–piperaquine became the first-line antimalarial drug in western Cambodia and spread rapidly thereafter, displacing other artemisinin-resistant parasite lineages. These findings have important implications for management of the global health risk associated with the current outbreak of multidrug-resistant malaria in southeast Asia. Funding Wellcome Trust, Bill & Melinda Gates Foundation, Medical Research Council, UK Department for International Development, and the Intramural Research Program of the National Institute of Allergy and Infectious Diseases.
Published: 2018

33. Identification and characterization of areas of high and low risk for asymptomatic malaria infections at sub-village level in Ratanakiri, Cambodia

Author: Vanna Mean, Saorin Kim, Marc Coosemans, Lies Durnez, Vincent Sluydts, Myrthe Pareyn, Nimol Khim, Didier Menard, Tho Sochantha, Institute of Tropical Medicine [Antwerp] (ITM), University of Antwerp (UA), National Center for Parasitology, Entomology and Malaria Control [Phnom Penh, Cambodia] (CNM), Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), and Funding obtained through the Department of Economy, Science and Innovation of the Flemish government.
Subjects: Male, Plasmodium, Plasmodium vivax, Plasmodium malariae, MESH: Aged, 80 and over, 0302 clinical medicine, MESH: Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Risk Factors, MESH: Child, Prevalence, Cluster Analysis, 030212 general & internal medicine, Child, Asymptomatic Infections, MESH: Aged, Aged, 80 and over, education.field_of_study, MESH: Middle Aged, biology, Coinfection, Pharmacology. Therapy, MESH: Infant, Newborn, Middle Aged, MESH: Infant, 3. Good health, Infectious Diseases, MESH: Young Adult, Child, Preschool, Female, medicine.symptom, Cambodia, Adult, medicine.medical_specialty, lcsh:Arctic medicine. Tropical medicine, Adolescent, lcsh:RC955-962, MESH: Malaria, 030231 tropical medicine, Population, MESH: Asymptomatic Infections, Asymptomatic, lcsh:Infectious and parasitic diseases, Clusters, Young Adult, 03 medical and health sciences, MESH: Spatio-Temporal Analysis, MESH: Cross-Sectional Studies, Spatio-Temporal Analysis, Environmental health, parasitic diseases, medicine, Humans, lcsh:RC109-216, education, Biology, MESH: Prevalence, Aged, MESH: Adolescent, MESH: Humans, MESH: Plasmodium, MESH: Cambodia, Research, MESH: Child, Preschool, Infant, Newborn, Infant, MESH: Adult, Plasmodium falciparum, medicine.disease, biology.organism_classification, MESH: Cluster Analysis, MESH: Male, MESH: Coinfection, Malaria, Cross-Sectional Studies, Tropical medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Hotspots, Parasitology, Human medicine, Asymptomatic carriers, MESH: Female, Asymptomatic carrier
Abstract: Background Malaria elimination needs a concentration of activities towards identification of residual transmission foci and intensification of efforts to eliminate the last few infections, located in so-called ‘malaria hotspots’. Previous work on characterizing malaria transmission hotspots has mainly focused on falciparum malaria and especially on symptomatic cases, while the malaria reservoir is expected to be mainly concentrated in the asymptomatic human population when transmission is low. For Plasmodium vivax, there has been less effort in identifying transmission hotspots. The main aim of this study was to uncover micro-epidemiological mechanisms of clustering of malaria infections at a sub-village level, based on geographical or behavioural features. Methods A cross-sectional survey was performed in three villages within the highest malaria endemic province of Cambodia. The survey took place in the dry season, when the malaria reservoir is expected to be low and residing in the asymptomatic part of the population. Village and field locations of households were georeferenced, blood samples were taken from as many residents as possible and a short questionnaire probing for individual risk factors was taken. Asymptomatic malaria carriers were detected by PCR, and geographical clustering analysis (SaTScan) as well as risk factor analysis were performed. Results A total of 1540 out of 1792 (86%) individuals were sampled. Plasmodial DNA was detected in 129 individuals (8.4%). P. vivax was most prevalent (5.5%) followed by Plasmodium malariae (2.1%) and Plasmodium falciparum (1.6%). Mixed infection occurred in 12 individuals. In two out of three villages geographical clustering of high and low malaria infection risk was clearly present. Cluster location and risk factors associated with the infection differed between the parasite species. Age was an important risk factor for the combined Plasmodium infections, while watching television at evenings was associated with increased odds of P. vivax infections [OR (CI): 1.86 (0.95–3.64)] and bed net use was associated with reduced odds of P. falciparum infections [OR (CI): 0.25 (0.077–0.80)]. Conclusions Clusters of malaria carriers were malaria species specific and often located remotely, outside village centres. As such, at micro-epidemiological level, malaria is not a single disease. Further unravelling the micro-epidemiology of malaria can enable programme managers to define the interventions likely to contribute to halt transmission in a particular hotspot location. Electronic supplementary material The online version of this article (10.1186/s12936-017-2169-1) contains supplementary material, which is available to authorized users.
Published: 2018

34. Étude descriptive du paludisme d’importation pour une approche diagnostique adaptée à l’enfant en médecine générale. A propos de 282 cas à l’Hôpital Robert Debré (75)

Author: Lix, Maelenn, Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), and Jean-Yves Siriez
Subjects: Paludisme chez l’enfant, Pédiatrie, Médecine générale, MESH: Child, MESH: General Practice, MESH: Malaria, MESH: Pediatrics, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Introduction: General Practitioners (GPs) are at the front line in the management of unwell children returning from abroad. Among the diseases affecting these children, imported malaria, and its potentially severe forms, represents a real diagnostic challenge due to its infrequency and the atypical clinical signs. Objective: to evaluate diagnostic and therapeutic attitude of GPs who reviewed children with imported malaria prior to hospital attendance, and analysis of the underlying reasons for misdiagnoses. Methods: retrospective single-center survey conducted at Robert Debré Hospital (Paris, France) between 2007 and 2016. 282 children were included with proven imported malaria AND a prior consultation with a GP were included, with descriptive analysis of the data. Results: among these children, 128 (45.6%) were reviewed by a GP without a diagnosis of malaria being made, resulting in delayed management (mean delay between onset of symptoms and diagnosis: 7.2 days). Imported malaria’s varied and atypical clinical signs make it very difficult to reach the right diagnosis in a primary care setting. Among the 152 children (54%) with a correct diagnosis of malaria by their GP, the mean delay from symptoms to diagnosis was 3.7 days when these children were sent directly to a tertiary reference hospital. The mean delay was greater for children with community-based laboratory test requested by GP’s (6 days), and even longer for those with negative initial laboratory test results (11.2 days). Conclusion: national guidelines including a list of referral hospitals and laboratory centers approved for analysis of thick and thin blood films, homogeneous guidelines, specific medical training program and continuing medical education on traveler’s health management, especially for GP’s working in areas with high density of migrants, could all potentially improve diagnostic reliability for imported malaria and tend to reduce delays to medical management of children with imported malaria.; Introduction : le médecin généraliste est en première ligne dans la prise en charge des enfants au retour d’un voyage. Parmi les pathologies que ces enfants peuvent présenter, le paludisme d’importation, dont l’évolution est potentiellement grave, peut constituer, du fait de sa rareté et de sa clinique atypique, un problème diagnostique. Objectif : évaluer l’attitude diagnostique et thérapeutique des médecins généralistes qui ont examiné les enfants avec un paludisme d’importation avant la consultation hospitalière et analyser les raisons de la non évocation du diagnostic par le généraliste. Méthode : étude rétrospective monocentrique à l’hôpital Robert Debré entre 2007 et 2016. 282 enfants avec un paludisme d’importation ET ayant au préalable consulté un médecin généraliste ont été analysés de manière descriptive. Résultats : parmi ces enfants, 128 (45,4%) ont été examinés en médecine de ville sans que le diagnostic de paludisme soit évoqué, avec pour conséquence une prise en charge retardée (délai moyen entre l’apparition des symptômes et le diagnostic : 7,2 jours). La présentation clinique atypique et variée du paludisme d’importation de l’enfant ne facilite pas le travail des médecins de ville. Parmi les 152 enfants (54%) pour qui le diagnostic a été évoqué, le délai de prise en charge le plus court (3,7 jours) concerne les enfants adressés directement à une structure de référence. Ce délai est plus long pour ceux qui ont eu un diagnostic parasitologique réalisé en laboratoire de ville (6 jours), a fortiori lorsque le résultat initial du frottis/goutte épaisse était négatif (11,2 jours). Conclusion : des recommandations nationales précisant les structures de référence et les laboratoires agréés pour la lecture de frottis/goutte épaisse, une homogénéisation des recommandations, ainsi qu’une formation médicale initiale et continue renforcée sur le thème de la santé des voyageur, contribueraient probablement -pour les médecins généralistes exerçant dans les zones à forte densité de population migrante - à l’amélioration du diagnostic du paludisme d’importation et à la réduction du délai de prise en charge de ces enfants.
Published: 2017

35. Chromosome inversions and ecological plasticity in the main African malaria mosquitoes

Author: Ayala, Diego, Acevedo, P., Pombi, M., Dia, I., Boccolini, D., Costantini, Carlo, Simard, Frédéric, Fontenille, Didier, Centre International de Recherches Médicales de Franceville (CIRMF), Diversity, ecology, evolution & Adaptation of arthropod vectors (MIVEGEC-DEEVA), Evolution des Systèmes Vectoriels (ESV), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Instituto de Investigación en Recursos Cinegéticos (IREC), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Institut Pasteur de Dakar, Réseau International des Instituts Pasteur (RIIP), Istituto Superiore di Sanita [Rome], Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Fieldwork was supported by the Institut de Recherche pour le Développement and the National Institutes of Health grant R01‐AI063508 awarded to Nora J. Besansky. PA is funded by a MINECO and Universidad de Castilla‐La Mancha (UCLM) through 'Ramon y Cajal' contract (RYC‐2012‐11970)., We thank M. Kirkpatrick, P. Nosil, and F. Rousset for their insightful comments, which helped us to improve the article. We thank D. Couret for preliminary GIS assistance, and A. L. Márquez for assistance with chorotype detection. We specially thank R. Gaab for his continuous support and advice., National Institutes of Health (US), Ministerio de Economía y Competitividad (España), and Universidad de Castilla La Mancha
Subjects: parallel evolution, Local adaptation, Karyotype, MESH: Malaria, Mosquito Vectors, MESH: Mosquito Vectors/genetics, Environment, anopheles, chromosome inversions, ecological divergence, local adaptation, ecology, evolution, behavior and systematics, genetics, agricultural and biological sciences (all), Article, Evolution, Molecular, MESH: Polymorphism, Genetic, MESH: Africa, Western, MESH: Chromosome Inversion, evolution, Anopheles, Chromosome inversions, Animals, Africa, Central, MESH: Animals, MESH: Models, Genetic, Ecological divergence, MESH: Environment, MESH: Evolution, Molecular, Polymorphism, Genetic, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], Models, Genetic, Parallel evolution, MESH: Karyotype, behavior and systematics, Malaria, MESH: Africa, Central, Africa, Western, MESH: Anopheles/genetics, Chromosome Inversion, Female, ecology, MESH: Female
Abstract: Chromosome inversions have fascinated the scientific community, mainly because of their role in the rapid adaption of different taxa to changing environments. However, the ecological traits linked to chromosome inversions have been poorly studied. Here, we investigated the roles played by 23 chromosome inversions in the adaptation of the four major African malaria mosquitoes to local environments in Africa. We studied their distribution patterns by using spatially explicit modeling and characterized the ecogeographical determinants of each inversion range. We then performed hierarchical clustering and constrained ordination analyses to assess the spatial and ecological similarities among inversions. Our results show that most inversions are environmentally structured, suggesting that they are actively involved in processes of local adaptation. Some inversions exhibited similar geographical patterns and ecological requirements among the four mosquito species, providing evidence for parallel evolution. Conversely, common inversion polymorphisms between sibling species displayed divergent ecological patterns, suggesting that they might have a different adaptive role in each species. These results are in agreement with the finding that chromosomal inversions play a role in Anopheles ecotypic adaptation. This study establishes a strong ecological basis for future genome-based analyses to elucidate the genetic mechanisms of local adaptation in these four mosquitoes., Fieldwork was supported by the Institut de Recherche pour le Développement and the National Institutes of Health grant R01-AI063508 awarded to Nora J. Besansky. P. Acevedo is funded by a MINECO and Universidad de Castilla-La Mancha (UCLM) through “Ramon y Cajal” contract (RYC-2012-11970).
Published: 2017

36. Analysing trends and forecasting malaria epidemics in Madagascar using a sentinel surveillance network: a web‑based application

Author: Florian Girond, Vincent Herbreteau, Sixte Zigiumugabe, Fanjasoa Rakotomanana, Judith Hedje, Lea Randriamampionona, Patrice Piola, Laurence Randrianasolo, Télesphore Yao Brou, Morgan Mangeas, Christophe Rogier, Maherisoa Ratsitorahina, Milijaona Randrianarivelojosia, Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP), UMR 228 Espace-Dev, Espace pour le développement, Université de Guyane (UG)-Université des Antilles (UA)-Institut de Recherche pour le Développement (IRD)-Université de Perpignan Via Domitia (UPVD)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM), Polytechnic of Namibia [Windhoek], Ministère de la Santé Publique [Antananarivo, Madagascar], U.S. President’s Malaria Initiative [Antananarivo] (PMI), U.S. President's Malaria Initiative [Atlanta, GA,], Centers for Disease Control and Prevention [Atlanta] (CDC), Centers for Disease Control and Prevention, 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), Institute for Biomedical Research of the French Armed Forces (IRBA), This research was supported by the USAID (Grant No. AID-687-G-13-00003). We thank administration authorities and health authorities from the Ministry of Health, the National Malaria Control Program and the President’s Malaria Initiative. We especially thank all the sentinel surveillance team of the Institut Pasteur de Madagascar., Institut de Recherche pour le Développement (IRD)-Université de Perpignan Via Domitia (UPVD)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Université de Guyane (UG)-Université des Antilles (UA), Ministère de la Santé Publique - Ministry of Public Health [Antananarivo, Madagascar], 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), Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Solofoharivelo, Marie Chrystine, and Institut de Recherche Biomédicale des Armées (IRBA)
Subjects: Male, Veterinary medicine, MESH: Text Messaging, Indoor residual spraying, MESH: Madagascar, 0302 clinical medicine, MESH: Aged, 80 and over, MESH: Child, Medicine, Prospective Studies, 030212 general & internal medicine, Child, Aged, 80 and over, MESH: Aged, MESH: Middle Aged, MESH: Infant, Newborn, Middle Aged, MESH: Infant, 3. Good health, Infectious Diseases, MESH: Internet, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Young Adult, Child, Preschool, MESH: Sentinel Surveillance, Female, Adult, MESH: Forecasting, medicine.medical_specialty, Short Message Service, Adolescent, 030231 tropical medicine, MESH: Malaria, Young Adult, 03 medical and health sciences, MESH: Software, parasitic diseases, Madagascar, Humans, Web application, Epidemics, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Epidemics, Aged, Retrospective Studies, MESH: Adolescent, Internet, Text Messaging, MESH: Humans, business.industry, Research, Public health, MESH: Child, Preschool, Infant, Newborn, Infant, Outbreak, MESH: Adult, MESH: Retrospective Studies, medicine.disease, Data science, MESH: Male, MESH: Prospective Studies, Malaria, Mews, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Early warning system, Parasitology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Sentinel Surveillance, MESH: Female, Software, Forecasting
Abstract: Background : The use of a malaria early warning system (MEWS) to trigger prompt public health interventions is a key step in adding value to the epidemiological data routinely collected by sentinel surveillance systems. Methods : This study describes a system using various epidemic thresholds and a forecasting component with the support of new technologies to improve the performance of a sentinel MEWS. Malaria-related data from 21 sentinel sites collected by Short Message Service are automatically analysed to detect malaria trends and malaria outbreak alerts with automated feedback reports. Results : Roll Back Malaria partners can, through a user-friendly web-based tool, visualize potential outbreaks and generate a forecasting model. The system already demonstrated its ability to detect malaria outbreaks in Madagascar in 2014. Conclusion : This approach aims to maximize the usefulness of a sentinel surveillance system to predict and detect epidemics in limited-resource environments.
Published: 2017

37. Optimizing Direct Membrane and Direct Skin Feeding Assays for Plasmodium falciparum Transmission-Blocking Vaccine Trials in Bancoumana, Mali

Author: Ibrahima Baber, Ogobara K. Doumbo, Jen C. C. Hume, Sara A. Healy, Mamadou B. Coulibaly, Patrick E. Duffy, Youssouf Sinaba, Lakamy Sylla, Issaka Sagara, Boubacar Coulibaly, Mahamadoun Hamady Assadou, Daman Sylla, Sekou F. Traore, Yimin Wu, Adama Sacko, Erin E. Gabriel, Lissalde, Claire, National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Washington District of Columbia (United States), Département d'Epidémiologie des Affections parasitaires, Malaria Research and training center Université de Bamako, Mali, Université de Bamako, and Malaria Research and Training Center [Bamako, Mali]
Subjects: 0301 basic medicine, MESH: Malaria transmission, 030231 tropical medicine, MESH: Malaria, Biology, Serum antibody, 03 medical and health sciences, 0302 clinical medicine, Negatively associated, Virology, parasitic diseases, medicine, Parasite transmission, Plasmodium falciparum, biology.organism_classification, medicine.disease, Transmission blocking, Vaccination, MESH: TBV, 030104 developmental biology, Infectious Diseases, Blood smear, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Immunology, Parasitology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Malaria
Abstract: International audience; Malaria transmission-blocking vaccines (TBV) have been evaluated in field trials in Mali since 2013. However, the assays currently used to measure serum antibody TB activity (TBA) after vaccination are highly variable, in part due to the lack of optimization and standardization for field assays in which mosquitoes feed on gametocytemic blood. Herein, we report a study conducted in Bancoumana village, Mali, where we identify and optimize the parameters that contribute to successful mosquito feeding outcomes in both direct skin feeds (DSFs) and direct membrane feeding assays (DMFA). These parameters include: 1) mosquito age, 2) duration of mosquito starvation prior to feeding, 3) membrane selection for DMFA, 4) anatomical location of DSF feeding (arm, calf, and ankle), and 5) time of day for DSF (dawn or dusk). We found that younger mosquitoes were significantly associated with higher feeding, survival, and infection rates. Longer starvation times were positively, but not significantly, associated with higher infection rates, but were negatively associated with feeding and survival. Membrane type and body location did not affect infection outcome significantly. Although dusk was found to be associated with higher infection rates, this may be confounded by the time from positive blood smear. Based on these findings, we make specific recommendations for optimal feeding parameters in the different assay types to maximize the chance of detecting parasite transmission in a standardized manner.
Published: 2017

38. Anopheles fauna of coastal Cayenne, French Guiana: modelling and mapping of species presence using remotely sensed land cover data

Author: Sébastien Briolant, Romain Girod, Emmanuel Roux, Antoine Adde, Isabelle Dusfour, Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP), UMR 228 Espace-Dev, Espace pour le développement, Institut de Recherche pour le Développement (IRD)-Université de Perpignan Via Domitia (UPVD)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Université de Guyane (UG)-Université des Antilles (UA), Direction Interarmées du Service de Santé en Guyane, Hôpital d'Instruction des Armées Laveran, Service de Santé des Armées, Hôpital de la Timone [CHU - APHM] (TIMONE), CNES-DGA-MRIS scholarship and a French army (Grant LR607e). This work has benefited from an investissement d’Avenir grant managed by the Agence Nationale de la Recherche (CEBA, ref. ANR-10-LABX-25-01). This study received a European commission REGPOTCT-2011-285837-STRonGer grant within the FP7., European Project: 285837,EC:FP7:REGPOT,FP7-REGPOT-2011-1,STRONGER(2011), Réseau International des Instituts Pasteur ( RIIP ), Université des Antilles ( UA ) -Université de Guyane ( UG ) -Université de Montpellier ( UM ) -Université de la Réunion ( UR ) -Université d'Avignon et des Pays de Vaucluse ( UAPV ) -Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Université de Perpignan Via Domitia ( UPVD ) -Institut de Recherche pour le Développement ( IRD ), Hôpital de la Timone [CHU - APHM] ( TIMONE ), European Project : 285837,EC:FP7:REGPOT,FP7-REGPOT-2011-1,STRONGER ( 2011 ), and Université de Guyane (UG)-Université des Antilles (UA)-Institut de Recherche pour le Développement (IRD)-Université de Perpignan Via Domitia (UPVD)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)
Subjects: Satellite Imagery, Marsh, Fauna, lcsh:QR1-502, Distribution (economics), MESH : Malaria, lcsh:Microbiology, 0302 clinical medicine, MESH: Satellite Imagery, [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH : Insect Vectors, [ INFO.INFO-TI ] Computer Science [cs]/Image Processing, Satellite imagery, MESH: Animals, 030212 general & internal medicine, Malaria vector, computer.programming_language, [SDV.EE]Life Sciences [q-bio]/Ecology, environment, [STAT.AP]Statistics [stat]/Applications [stat.AP], geography.geographical_feature_category, biology, Ecology, Anopheles, MESH : Spatio-Temporal Analysis, Articles, remote sensing technology, French Guiana, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH : Anopheles, [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], Seasons, Cartography, Microbiology (medical), MESH : French Guiana, [ INFO.INFO-MO ] Computer Science [cs]/Modeling and Simulation, lcsh:Arctic medicine. Tropical medicine, Cayenne, [ INFO.INFO-TS ] Computer Science [cs]/Signal and Image Processing, lcsh:RC955-962, MESH: Population Density, 030231 tropical medicine, MESH: Malaria, malaria, Land cover, MESH: Insect Vectors, [ SDV.EE ] Life Sciences [q-bio]/Ecology, environment, MESH: Anopheles, 03 medical and health sciences, Spatio-Temporal Analysis, MESH: Spatio-Temporal Analysis, MESH: French Guiana, Animals, 14. Life underwater, MESH : Population Density, MESH : Satellite Imagery, Population Density, geography, MESH : Seasons, business.industry, [ STAT.AP ] Statistics [stat]/Applications [stat.AP], 15. Life on land, biology.organism_classification, [SDE.ES]Environmental Sciences/Environmental and Society, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, Insect Vectors, MESH : Animals, business, computer, MESH: Seasons, [ SDE.ES ] Environmental Sciences/Environmental and Society
Abstract: International audience; Little is known about the Anopheles species of the coastal areas of French Guiana, or their spatiotemporal distribution or environmental determinants. The present study aimed to (1) document the distribution of Anopheles fauna in the coastal area around Cayenne, and (2) investigate the use of remotely sensed land cover data as proxies of Anopheles presence. To characterise the Anopheles fauna, we combined the findings of two entomological surveys that were conducted during the period 2007-2009 and in 2014 at 37 sites. Satellite imagery data were processed to extract land cover variables potentially related to Anopheles ecology. Based on these data, a methodology was formed to estimate a statistical predictive model of the spatial-seasonal variations in the presence of Anopheles in the Cayenne region. Two Anopheles species, known as main malaria vectors in South America, were identified, including the more dominant An. aquasalis near town and rural sites, and An. darlingi only found in inland sites. Furthermore, a cross-validated model of An. aquasalis presence that integrated marsh and forest surface area was extrapolated to generate predictive maps. The present study supports the use of satellite imagery by health authorities for the surveillance of malaria vectors and planning of control strategies.
Published: 2016

39. National Malaria Prevalence in Cambodia: Microscopy Versus Polymerase Chain Reaction Estimates

Author: Didier Menard, Jan Bruce, Jean Popovici, Duong Socheat, Seshu Babu Vinjamuri, William O. Rogers, Walter R. J. Taylor, Sylvia Meek, Frédéric Ariey, Dysoley Lek, National Center for Parasitology, Entomology and Malaria Control [Phnom Penh, Cambodia] (CNM), National Institute of Public Health [Phnom Penh, Cambodge], Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Département Parasites et Insectes vecteurs - Department of Parasites and Insect Vectors, Institut Pasteur [Paris], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de parasitologie-mycologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), World Health Organization Lao People's Democratic Republic Office [Vientiane, Laos], Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), London School of Hygiene and Tropical Medicine (LSHTM), Hôpitaux Universitaires de Genève (HUG), Mahidol Oxford Tropical Medicine Research Unit (MORU), University of Oxford [Oxford]-Mahidol University [Bangkok]-Wellcome Trust, US Naval Medical Research Unit n°2, We are grateful to the study participants and for the support of the National Institute of Health Research and Development of Indonesia, and of the Eijkman Institute., Institut Pasteur [Paris] (IP), University of Oxford-Mahidol University [Bangkok]-Wellcome Trust, and Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford]
Subjects: Male, Plasmodium vivax, Prevalence, Plasmodium malariae, Polymerase Chain Reaction, law.invention, 0302 clinical medicine, law, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Child, 030212 general & internal medicine, Malaria, Falciparum, Child, Dried blood, Polymerase chain reaction, MESH: Plasmodium falciparum, MESH: Plasmodium malariae, Microscopy, biology, MESH: Malaria, Falciparum, MESH: Infant, Newborn, Articles, MESH: Infant, 3. Good health, MESH: Plasmodium vivax, Infectious Diseases, MESH: Young Adult, Child, Preschool, Female, Cambodia, medicine.medical_specialty, MESH: Microscopy, Adolescent, Plasmodium falciparum, 030231 tropical medicine, MESH: Malaria, Young Adult, 03 medical and health sciences, Virology, Internal medicine, parasitic diseases, Malaria, Vivax, medicine, Humans, MESH: Prevalence, MESH: Adolescent, MESH: Humans, MESH: Cambodia, MESH: Child, Preschool, Infant, Newborn, Infant, MESH: Malaria, Vivax, MESH: Polymerase Chain Reaction, medicine.disease, biology.organism_classification, Confidence interval, MESH: Male, Malaria, Parasitology, MESH: Female
Abstract: International audience; Accurate information regarding malaria prevalence at national level is required to design and assess malaria control/elimination efforts. Although many comparisons of microscopy and polymerase chain reaction (PCR)-based methods have been conducted, there is little published literature covering such comparisons in southeast Asia especially at the national level. Both microscopic examination and PCR detection were performed on blood films and dried blood spots samples collected from 8,067 individuals enrolled in a nationwide, stratified, multistage, cluster sampling malaria prevalence survey conducted in Cambodia in 2007. The overall malaria prevalence and prevalence rates of Plasmodium falciparum, Plasmodium vivax, and Plasmodium malariae infections estimated by microscopy (N = 8,067) were 2.74% (95% confidence interval [CI]: 2.39-3.12%), 1.81% (95% CI: 1.53-2.13%), 1.14% (95% CI: 0.92-1.40%), and 0.01% (95% CI: 0.003-0.07%), respectively. The overall malaria prevalence based on PCR detection (N = 7,718) was almost 2.5-fold higher (6.31%, 95% CI: 5.76-6.89%, P < 0.00001). This difference was significantly more pronounced for P. falciparum (4.40%, 95% CI: 3.95-4.90%, P < 0.00001) compared with P. vivax (1.89%, 95% CI: 1.60-2.22%, P < 0.001) and P. malariae infections (0.22%, 95% CI: 0.13-0.35%, P < 0.0001). The significant proportion of microscopy-negative but PCR-positive individuals (289/7,491, 3.85%) suggest microscopic examination frequently underestimated malaria infections and that active case detection based on microscopy may miss a significant reservoir of infection, especially in low-transmission settings.
Published: 2016

40. Effectiveness of insecticidal nets on uncomplicated clinical malaria: a case–control study for operational evaluation

Author: Armel Djènontin, Christophe Rogier, Georgia Damien, Marie‑Claire Henry, Franck Remoue, Papa M. Drame, Sandra Yamadjako, Evelyne Chaffa, Emmanuel Elanga Ndille, Vincent Corbel, 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]), Centre de Recherche Entomologique de Cotonou (CREC), Ministère de la Santé, Université d’Abomey-Calavi = University of Abomey Calavi (UAC), Programme National de Lutte contre le Paludisme (PNLP), National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Vector Control Group (MIVEGEC-VCG), Evolution des Systèmes Vectoriels (ESV), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP), Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), 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), Funding received from the World Bank via Booster Programme for Malaria Control in Africa and Malaria National Control Program of Benin (Reference No. 555/MS/DC/SGM/DNPS/PNLP/PALP/DNP du 30/12/2010)., Génétique et évolution des maladies infectieuses (GEMI), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Génétique et évolution des maladies infectieuses (GEMI), Institut de Recherche Biomédicale des Armées (IRBA), RANDRIAMANANTSOA, Volatiana Manohisoa, University of Abomey Calavi (UAC), and INSB-INSB-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Pediatrics, Mosquito Control, Effectiveness, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Medicine, Benin, 030212 general & internal medicine, LLIN, Evaluation, MESH: Mosquito Control, Rapid diagnostic test, MESH: Infant, Newborn, Case-control study, MESH: Infant, MESH: Case-Control Studies, 3. Good health, Infectious Diseases, MESH: Young Adult, Child, Preschool, Female, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Cohort study, Adult, medicine.medical_specialty, MESH: Insecticide-Treated Bednets, Case–control study, 030231 tropical medicine, MESH: Malaria, Context (language use), 03 medical and health sciences, Young Adult, MESH: Benin, Environmental health, parasitic diseases, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Insecticide-Treated Bednets, MESH: Humans, business.industry, Public health, Research, MESH: Child, Preschool, Infant, Newborn, Infant, MESH: Adult, medicine.disease, MESH: Male, Malaria, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Case-Control Studies, Tropical medicine, Parasitology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Female
Abstract: International audience; BACKGROUND:In a context of large-scale implementation of malaria vector control tools, such as the distribution of long-lasting insecticide nets (LLIN), it is necessary to regularly assess whether strategies are progressing as expected and then evaluate their effectiveness. The present study used the case-control approach to evaluate the effectiveness of LLIN 42 months after national wide distribution. This study design offers an alternative to cohort study and randomized control trial as it permits to avoid many ethical issues inherent to them.METHODS:From April to August 2011, a case-control study was conducted in two health districts in Benin; Ouidah-Kpomasse-Tori (OKT) in the south and Djougou-Copargo-Ouake (DCO) in the north. Children aged 0-60 months randomly selected from community were included. Cases were children with a high axillary temperature (≥37.5 °C) or a reported history of fever during the last 48 h with a positive rapid diagnostic test (RDT). Controls were children with neither fever nor signs suggesting malaria with a negative RDT. The necessary sample size was at least 396 cases and 1188 controls from each site. The main exposure variable was "sleeping every night under an LLIN for the 2 weeks before the survey" (SL). The protective effectiveness (PE) of LLIN was calculated as PE = 1 - odds ratio.RESULTS:The declared SL range was low, with 17.0 and 27.5 % in cases and controls in the OKT area, and 44.9 and 56.5 % in cases and controls, in the DCO area, respectively. The declared SL conferred 40.5 % (95 % CI 22.2-54.5 %) and 55.5 % (95 % CI 28.2-72.4 %) protection against uncomplicated malaria in the OKT and the DCO areas, respectively. Significant differences in PE were observed according to the mother's education level.CONCLUSION:In the context of a mass distribution of LLIN, their use still conferred protection in up to 55 % against the occurrence of clinical malaria cases in children. Social factors, the poor use and the poor condition of an LLIN can be in disfavour with its effectiveness. In areas, where LLIN coverage is assumed to be universal or targeted at high-risk populations, case-control studies should be regularly conducted to monitor the effectiveness of LLIN. The findings will help National Malaria Control Programme and their partners to improve the quality of malaria control according to the particularity of each area or region as far as possible
Published: 2016

41. Genetic Characterization of Plasmodium Putative Pantothenate Kinase Genes Reveals Their Essential Role in Malaria Parasite Transmission to the Mosquito

Author: Choukri Ben Mamoun, Emmanuel Cornillot, Robert J. Hart, Amanah Abraham, Emily Molina, Ahmed S. I. Aly, Catherine S. Nation, Department of Tropical Medicine [New Orleans, LA, USA], Tulane University, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Biologie Computationnelle (IBC), Institut National de la Recherche Agronomique (INRA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Section of Infectious Diseases [New Haven, CT, USA] (Department of Internal Medicine), Yale University School of Medicine, AA is supported by funds provided by Tulane University School of Public Health and Tropical Medicine and by NIH-NIAID grant (1R21AI111058-01A1). CBM is supported by NIH grants (AI097218, GM110506, AI09486 and AI112938) and the Bill and Melinda Gates Foundation (ID#: 1021571)., CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Montpellier (UM)-Institut National de la Recherche Agronomique (INRA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS), ALY, AHMED SAYED IBRAHıM, Herrada, Anthony, and Yale School of Medicine [New Haven, Connecticut] (YSM)
Subjects: 0301 basic medicine, MESH: Sequence Analysis, DNA, Plasmodium, Erythrocytes, Transcription, Genetic, Genes, Protozoan, Protozoan Proteins, MESH: Amino Acid Sequence, MESH: Sporozoites, chemistry.chemical_compound, MESH: Animals, MESH: Phylogeny, MESH: Protozoan Proteins, Conserved Sequence, Phylogeny, Genetics, Regulation of gene expression, Mice, Inbred BALB C, Multidisciplinary, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, MESH: Conserved Sequence, biology, MESH: Erythrocytes, Anopheles, MESH: Gene Expression Regulation, 3. Good health, Phosphotransferases (Alcohol Group Acceptor), MESH: Genes, Protozoan, Sporozoites, Pantothenate kinase, MESH: Biosynthetic Pathways, Female, MESH: Oocysts, Coenzyme A, MESH: Malaria, MESH: Mice, Inbred BALB C, Models, Biological, Article, MESH: Anopheles, 03 medical and health sciences, parasitic diseases, medicine, Animals, Parasites, Amino Acid Sequence, Gene, MESH: Life Cycle Stages, MESH: Parasites, Life Cycle Stages, 030102 biochemistry & molecular biology, MESH: Plasmodium, MESH: Transcription, Genetic, MESH: Models, Biological, Oocysts, Plasmodium falciparum, Sequence Analysis, DNA, biology.organism_classification, PANK2, medicine.disease, MESH: Coenzyme A, MESH: Phosphotransferases (Alcohol Group Acceptor), Biosynthetic Pathways, Malaria, 030104 developmental biology, chemistry, Gene Expression Regulation, MESH: Gene Deletion, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Gene Deletion
Abstract: The metabolic machinery for the biosynthesis of Coenzyme A (CoA) from exogenous pantothenic acid (Vitamin B5) has long been considered as an excellent target for the development of selective antimicrobials. Earlier studies in the human malaria parasite Plasmodium falciparum have shown that pantothenate analogs interfere with pantothenate phosphorylation and block asexual blood stage development. Although two eukaryotic-type putative pantothenate kinase genes (PanK1 and PanK2) have been identified in all malaria parasite species, their role in the development of Plasmodium life cycle stages remains unknown. Here we report on the genetic characterization of PanK1 and PanK2 in P. yoelii. We show that P. yoelii parasites lacking either PanK1 or PanK2 undergo normal asexual stages development and sexual stages differentiation, however they are severely deficient in ookinete, oocyst and sporozoite formation inside the mosquito vector. Quantitative transcriptional analyses in wild-type and knockout parasites demonstrate an important role for these genes in the regulation of expression of other CoA biosynthesis genes. Together, our data provide the first genetic evidence for the importance of the early steps of pantothenate utilization in the regulation of CoA biosynthesis and malaria parasite transmission to Anopheles mosquitoes.
Published: 2016

42. An Evolution-Based Screen for Genetic Differentiation between Anopheles Sister Taxa Enriches for Detection of Functional Immune Factors

Author: N’Fale Sagnon, Christian Mitri, Marni Williams, Awa Gneme, Wamdaogo M. Guelbeogo, Eizo Takashima, Richard H. G. Baxter, Adrien Pain, Inge Holm, Karin Eiglmeier, Kenneth D. Vernick, Emmanuel Bischoff, Michelle M. Riehle, Catherine Lavazec, Emma Brito-Fravallo, Génétique et Génomique des Insectes vecteurs, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Department of Chemistry and Molecular Biophysics & Biochemistry, Yale University [New Haven], Centre National de Recherche et de Formation sur le Paludisme [Ouagadougou, Burkina Faso] (CNRFP), Department of Microbiology, University of Minnesota [Twin Cities] (UMN), University of Minnesota System-University of Minnesota System, ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 228421,EC:FP7:INFRA,FP7-INFRASTRUCTURES-2008-1,INFRAVEC(2009), European Project: 323173,EC:FP7:ERC,ERC-2012-ADG_20120314,ANOPATH(2013), Bos, Mireille, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Research capacity for the implementation of genetic control of mosquitoes - INFRAVEC - - EC:FP7:INFRA2009-09-01 - 2014-02-28 - 228421 - VALID, Genetics of mosquito resistance to pathogens. - ANOPATH - - EC:FP7:ERC2013-03-01 - 2018-02-28 - 323173 - VALID, and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: Candidate gene, Anopheles gambiae, Genes, Insect, MESH: Genes, Insect, MESH: Base Sequence, Polymerase Chain Reaction, Mice, MESH: Insect Proteins, MESH: Animals, MESH: Genetic Variation, lcsh:QH301-705.5, MESH: Evolution, Molecular, Genetics, education.field_of_study, Natural selection, Anopheles, Phenotype, 3. Good health, Insect Proteins, Research Article, lcsh:Immunologic diseases. Allergy, Molecular Sequence Data, Immunology, Population, MESH: Malaria, MESH: Insect Vectors, Biology, Microbiology, Evolution, Molecular, MESH: Anopheles, Virology, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, education, Molecular Biology, MESH: Mice, MESH: Molecular Sequence Data, Base Sequence, Genetic Variation, Correction, MESH: Polymerase Chain Reaction, biology.organism_classification, Insect Vectors, Malaria, lcsh:Biology (General), Parasitology, lcsh:RC581-607, Selective sweep, Genetic screen
Abstract: Nucleotide variation patterns across species are shaped by the processes of natural selection, including exposure to environmental pathogens. We examined patterns of genetic variation in two sister species, Anopheles gambiae and Anopheles coluzzii, both efficient natural vectors of human malaria in West Africa. We used the differentiation signature displayed by a known coordinate selective sweep of immune genes APL1 and TEP1 in A. coluzzii to design a population genetic screen trained on the sweep, classified a panel of 26 potential immune genes for concordance with the signature, and functionally tested their immune phenotypes. The screen results were strongly predictive for genes with protective immune phenotypes: genes meeting the screen criteria were significantly more likely to display a functional phenotype against malaria infection than genes not meeting the criteria (p = 0.0005). Thus, an evolution-based screen can efficiently prioritize candidate genes for labor-intensive downstream functional testing, and safely allow the elimination of genes not meeting the screen criteria. The suite of immune genes with characteristics similar to the APL1-TEP1 selective sweep appears to be more widespread in the A. coluzzii genome than previously recognized. The immune gene differentiation may be a consequence of adaptation of A. coluzzii to new pathogens encountered in its niche expansion during the separation from A. gambiae, although the role, if any of natural selection by Plasmodium is unknown. Application of the screen allowed identification of new functional immune factors, and assignment of new functions to known factors. We describe biochemical binding interactions between immune proteins that underlie functional activity for malaria infection, which highlights the interplay between pathogen specificity and the structure of immune complexes. We also find that most malaria-protective immune factors display phenotypes for either human or rodent malaria, with broad specificity a rarity., Author Summary Anopheles gambiae and Anopheles coluzzii are the primary mosquito vectors of human malaria in West Africa. Both of these closely related species efficiently transmit the disease, although they display ecological differences. Previous work showed that A. coluzzii displays distinct genetic patterns in genes important for mosquito immunity. Here, we use this genetic pattern as a filter to examine a panel of potential immune genes, and show that the genetic pattern is strongly predictive for genes that play a functional role in immunity when tested with malaria parasites.
Published: 2015

43. The Fatty Acid Biosynthesis Enzyme FabI Plays a Key Role in the Development of Liver-Stage Malarial Parasites

Author: Juan Carlos Valderramos, Brie Falkard, Celeste D. Li, Mark J. Siedner, Guy A. Schiehser, David A. Fidock, Photini Sinnis, Brendan J Kelly, Pedro A. Moura, Viswanathan Lakshmanan, Arba L. Ager, James C. Sacchettini, Catherine Vilchèze, Min Yu, William R. Jacobs, Chris J. Janse, Joel S. Freundlich, David P. Jacobus, Andrew P. Waters, Lisa A. Purcell, Alida Coppi, Jennifer H.C. Tsai, Volker Heussler, Laurent Kremer, Louis J. Nkrumah, T. R. Santha Kumar, Paul Gratraud, Amar Bir Singh Sidhu, Silke Retzlaff, University College of the Fraser Valley (UCFV), University College of the Fraser Valley (UFV), Courant Institute of Mathematical Sciences [New York] (CIMS), New York University [New York] (NYU), NYU System (NYU)-NYU System (NYU), Institute of Vertebrate Paleontology and Paleoanthropology, Institut Européen des membranes (IEM), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM), Department of Biochemistry and Biophysics, Texas A&M University [College Station], Laboratory of Molecular Neurochemistry, The Research Building, Rom W222, Washington, Laboratory of Molecular Neurochemistry, Department of Pediatrics, Georgetown University, Institut de Neurobiologie Alfred Fessard (INAF), Centre National de la Recherche Scientifique (CNRS), Dynamique des interactions membranaires normales et pathologiques (DIMNP), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1), Dpt of Parasitology [Leiden], Leiden University Medical Center (LUMC), and Howard Hughes Medical Institute (HHMI)
Subjects: Cancer Research, MESH: Parasitemia, MICROBIO, Plasmodium berghei, Protozoan Proteins, Parasitemia, MESH: Triclosan, Plasmodium, Mice, chemistry.chemical_compound, MESH: Animals, MESH: Protozoan Proteins, MESH: Plasmodium falciparum, chemistry.chemical_classification, 0303 health sciences, biology, Transfection, 3. Good health, Liver, Biochemistry, Plasmodium falciparum, MESH: Malaria, Microbiology, Antimalarials, 03 medical and health sciences, MESH: Mice, Inbred C57BL, Immunology and Microbiology(all), Virology, parasitic diseases, Animals, MESH: Plasmodium berghei, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, MESH: Mice, Fatty acid synthesis, 030304 developmental biology, Apicoplast, 030306 microbiology, biology.organism_classification, MESH: Antimalarials, Triclosan, In vitro, Malaria, Mice, Inbred C57BL, Mutagenesis, Insertional, CHEMBIO, Enzyme, MESH: Mutagenesis, Insertional, chemistry, MESH: Gene Deletion, Parasitology, Gene Deletion, MESH: Liver
Abstract: International audience; The fatty acid synthesis type II pathway has received considerable interest as a candidate therapeutic target in Plasmodium falciparum asexual blood-stage infections. This apicoplast-resident pathway, distinct from the mammalian type I process, includes FabI. Here, we report synthetic chemistry and transfection studies concluding that Plasmodium FabI is not the target of the antimalarial activity of triclosan, an inhibitor of bacterial FabI. Disruption of fabI in P. falciparum or the rodent parasite P. berghei does not impede blood-stage growth. In contrast, mosquito-derived, FabI-deficient P. berghei sporozoites are markedly less infective for mice and typically fail to complete liver-stage development in vitro. This defect is characterized by an inability to form intrahepatic merosomes that normally initiate blood-stage infections. These data illuminate key differences between liver- and blood-stage parasites in their requirements for host versus de novo synthesized fatty acids, and create new prospects for stage-specific antimalarial interventions.
Published: 2008

44. A retrospective study of 230 consecutive patients hospitalized for presumed travel-related illness (2000–2006)

Author: Jean-Marc Chapplain, Christian Michelet, Claude Guiguen, H. Leroy, Jérémie Biziragusenyuka, Cédric Arvieux, Pierre Tattevin, Service des maladies infectieuses et réanimation médicale [Rennes] = Infectious Disease and Intensive Care [Rennes], CHU Pontchaillou [Rennes], Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), and Université de Rennes (UR)
Subjects: Male, Pediatrics, HIV Infections, MESH: Hospitalization, Severe Acute Respiratory Syndrome, 0302 clinical medicine, Interquartile range, Epidemiology, Travel medicine, MESH: Incidence, 030212 general & internal medicine, MESH: Travel, Travel, MESH: Middle Aged, Incidence, MESH: HIV Infections, General Medicine, Middle Aged, Concise Article, 3. Good health, Hospitalization, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious Diseases, MESH: Hemorrhagic Fever, Crimean, Salmonella Infections, Chemoprophylaxis, MESH: Communicable Diseases, Female, France, Viral hepatitis, Human Immunodeficiency Virus, Adult, Microbiology (medical), medicine.medical_specialty, Tuberculosis, Hepatitis, Viral, Human, MESH: Malaria, 030231 tropical medicine, Communicable Diseases, Typhoid fever, Pulmonary Tuberculosis, 03 medical and health sciences, MESH: Severe Acute Respiratory Syndrome, medicine, Humans, MESH: Africa South of the Sahara, MESH: Typhoid Fever, Typhoid Fever, Tuberculosis, Pulmonary, MESH: Hepatitis, Viral, Human, Africa South of the Sahara, Retrospective Studies, MESH: Tuberculosis, Pulmonary, MESH: Salmonella Infections, MESH: Humans, business.industry, MESH: Adult, MESH: Retrospective Studies, Retrospective cohort study, medicine.disease, MESH: Male, Malaria, MESH: France, Immunology, Hemorrhagic Fever, Crimean, business, MESH: Female
Abstract: International audience; A good knowledge of morbidity profiles among ill-returned travelers is necessary in order to guide their management. We reviewed the medical charts of 230 patients hospitalized in one infectious diseases department in France for presumed travel-related illnesses. The male-to-female ratio was 1.6 and the median age was 33 years (interquartile range [IQR], 25-50). Most patients (70.9%) were returning from sub-Saharan Africa. The median duration of travel was 28 days (IQR, 15-60) and the median time from return of travel to hospitalization was 13 days (IQR, 7-21). Malaria was the most frequent diagnosis (49.1%), which was especially encountered in patients returning from sub-Saharan Africa (95.6%), without adequate chemoprophylaxis (78.2%). Imported diseases at risk of secondary transmission were also diagnosed, including pulmonary tuberculosis (n = 8), viral hepatitis (n = 8), typhoid fever (n = 6), human immunodeficiency virus (HIV) (six new diagnosis), non-typhoid salmonellosis (n = 5), severe acute respiratory syndrome, and Crimean-Congo hemorrhagic fever. This study underlines the need to maintain tropical expertise for infectious diseases physicians, even in Europe.
Published: 2008

45. Toward a unifying model of malaria-induced channel activity

Author: Guillaume Bouyer, Serge Thomas, Stéphane Egée, Mer et santé (MS), Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Erythrocytes, Plasmodium falciparum, MESH: Malaria, MESH: Electric Conductivity, Models, Biological, Ion Channels, Cell membrane, 03 medical and health sciences, 0302 clinical medicine, Chloride Channels, medicine, Animals, Humans, MESH: Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Membrane conductance, Cells, Cultured, MESH: Plasmodium falciparum, Ion channel, 030304 developmental biology, 0303 health sciences, MESH: Electrophysiology, MESH: Humans, Multidisciplinary, biology, MESH: Erythrocytes, Cell Membrane, MESH: Chloride Channels, Electric Conductivity, MESH: Models, Biological, Conductance, Biological Sciences, biology.organism_classification, Malaria, 3. Good health, Electrophysiology, Membrane, medicine.anatomical_structure, Biochemistry, MESH: Ion Channels, Chloride channel, Biophysics, 030217 neurology & neurosurgery, MESH: Cell Membrane, MESH: Cells, Cultured
Abstract: Infection of RBC by the malaria parasite Plasmodium falciparum activates, at the trophozoite stage, a membrane current 100- to 150-fold larger than in uninfected RBC. This current is carried by small anion channels initially described in supraphysiological ion concentrations (1.115 M Cl − ) and named plasmodial surface anion channels (PSAC), suggesting their plasmodial origin. Our results obtained with physiological ion concentrations (0.145 M Cl − ) support the notion that the parasite-induced channels represent enhanced activity versions of anion channels already present in uninfected RBCs. Among them, an 18-pS inwardly rectifying anion channel (IRC) and a 4- to 5-pS small conductance anion channel (SCC) were present in most single-channel recordings of infected membranes. The aim of this study was to clarify disparities in the reported electrophysiological data and to investigate possible technical reasons why these discrepancies have arisen. We demonstrate that PSAC is the supraphysiological correlate of the SCC and is inhibited by Zn 2+ , suggesting that it is a ClC-2 channel. We show that in physiological solutions 80% of the membrane conductance in infected cells can be accounted for by IRC and 20% can be accounted for by SCC whereas in supraphysiological conditions the membrane conductance is almost exclusively carried by SCC (PSAC) because the IRC is functionally turned off.
Published: 2007

46. Antimalarial drug discovery: targeting protein kinases

Author: Laurent Meijer, Christian Doerig, Controle de la Proliferation Cellulaire Chez Plasmodium Falciparum, Institut National de la Santé et de la Recherche Médicale (INSERM), Molécules et cibles thérapeutiques (MCT), Station biologique de Roscoff [Roscoff] (SBR), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Plasmodium falciparum, MESH: Malaria, Clinical Biochemistry, Computational biology, MESH: Drug Design, Biology, Plasmodium, Antimalarials, 03 medical and health sciences, parasitic diseases, Drug Discovery, polycyclic compounds, medicine, Animals, Humans, MESH: Protein Kinase Inhibitors, MESH: Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Kinome, Vector (molecular biology), MESH: Phylogeny, Protein kinase A, Protein Kinase Inhibitors, MESH: Protein Kinases, Phylogeny, MESH: Plasmodium falciparum, 030304 developmental biology, Pharmacology, 0303 health sciences, MESH: Humans, Drug discovery, Kinase, 030302 biochemistry & molecular biology, medicine.disease, biology.organism_classification, MESH: Antimalarials, Virology, Malaria, 3. Good health, Drug Design, Molecular Medicine, Protein Kinases
Abstract: Protein kinases (PKs) are prime targets for drug discovery in a variety of diseases, including cancer and neurodegenerative pathologies. The characterisation of the kinome of the human malaria parasite Plasmodium falciparum has revealed profound divergences, at several levels, between PKs of the parasite and those of its host. Here, the authors review the major issues and recent advances regarding the development of Plasmodium-selective PK inhibitors, with emphasis on target identification and validation, and on structure-based design. The authors also discuss the possibility of interfering with: i) Plasmodium PKs regulating transmission to the mosquito vector; and ii) host PKs that may be required for parasite survival.
Published: 2007

47. Différenciation morphologique et génétique des populations de douroucoulis (Aotus infulatus, Primates, Platyrhiniens, Cebidae) provenant des rives droite et gauche du rio Tocantins (Brésil)

Author: Sébastien Couette, Biogéosciences [UMR 6282] [Dijon] (BGS), Centre National de la Recherche Scientifique (CNRS)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Biogéosciences [Dijon] ( BGS ), and AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne ( UB ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: 0106 biological sciences, Ajustement Procrustes, Population genetics, MESH : Rivers, MESH : Malaria, [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, 01 natural sciences, Cebidae, MESH : Female, Différenciation intraspécifique, MESH: Animals, Morphométrie géométrique crânienne, MESH : Aotidae, biology, Night monkey, 05 social sciences, General Medicine, MESH: Cephalometry, MESH : Aotus trivirgatus, Taxonomy (biology), General Agricultural and Biological Sciences, Aotus infulatus, Primates, Barrière géographique, MESH : Cephalometry, MESH : Male, MESH: Malaria, MESH: Disease Susceptibility, Zoology, [SDV.BID]Life Sciences [q-bio]/Biodiversity, 010603 evolutionary biology, General Biochemistry, Genetics and Molecular Biology, MESH: Rivers, Aotus azarae, MESH : Disease Susceptibility, Taxinomie, parasitic diseases, Aotus trivirgatus, MESH : Species Specificity, MESH : Brazil, MESH: Species Specificity, 0501 psychology and cognitive sciences, 050102 behavioral science & comparative psychology, [ SDV.BID ] Life Sciences [q-bio]/Biodiversity, Morphometrics, General Immunology and Microbiology, MESH: Aotus trivirgatus, fungi, biology.organism_classification, MESH: Male, MESH: Aotidae, MESH : Animals, MESH: Brazil, MESH: Female, [ SDV.BID.SPT ] Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy
Abstract: 11 pages; La morphologie crânienne de 28 spécimens de douroucoulis (genre Aotus), provenant du Bassin amazonien, a été étudiée à l'aide de méthodes de morphométrie géométrique en trois dimensions. De nouveaux résultats concernant la distinction morphologique de populations de l'espèce Aotus infulatus, réparties de part et d'autre du rio Tocantins, sont proposés. Ces résultats morphologiques concordent avec la distinction génétique de ces populations publiée par Schneider – et Sampaio –, et indiquent probablement de récents et rapides changements évolutifs au sein de cette espèce. Les résultats de cette étude ont une application taxinomique, mais pourraient également ouvrir de nouvelles perspectives médicales, puisque la sensibilité des douroucoulis à la malaria semble varier selon les espèces.
Published: 2007

48. Glucose-6-phosphate dehydrogenase deficiency and the risk of malaria and other diseases in children in Kenya: a case-control and a cohort study

Author: Magnus Manske, Taane Clark, Deus Ishengoma, Valentina D Mangano, Kerrin Small, Issa Nebie, Dushyanth Jyothi, Catherine Moyes, Katja Kivinen, George Mtove, Dominic Kwiatkowski, Jacques Simporé, Behzad Nadjm, Adebola Orimadegun, Kalifa Bojang, Panos Deloukas, Nadira Karunaweera, Kimberly J Johnson, Mahamadou A Thera, Gareth Maslen, Nuno Sepúlveda, Daniel Mead, Sophie Uyoga, Tobias Apinjoh, John Reeder, Lee Hart, Climent Casals-Pascual, Sarah Auburn, Sharon Cox, KEMRI-Wellcome Trust Research Programme (KWTRP), The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford [Oxford], National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Imperial College London, Institut Pasteur [Paris], TNW is funded by the Wellcome Trust (091758) and DPK receives support from the UK Medical Research Council (G19/9). SS is supported by the Medical Scientist Training Program at the US National Institutes of Health and received travel funds from Wolfson College, Oxford, and from the Oxford University Exploration Club. This research received funding from the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement 242095 and from the UK Medical Research Council (G0600718). The MalariaGEN Project is supported by the Wellcome Trust (077383) and by the Foundation for the National Institutes of Health (566) as part of the Bill & Melinda Gates Grand Challenges in Global Health Initiative and through a Wellcome Trust Strategic Award (090770). The Wellcome Trust provides core support to The KEMRI–Wellcome Trust Research Programme in Kilifi (084535) and the Wellcome Trust Centre for Human Genetics (090532), Oxford, UK., the MalariaGEN Consortium: members listed at http://www.malariagen.net/projects/host/consortium-members, European Project: 242095,EC:FP7:HEALTH,FP7-HEALTH-2009-single-stage,EVIMALAR(2009), University of Oxford, and Institut Pasteur [Paris] (IP)
Subjects: Male, Pediatrics, Rate ratio, Cohort Studies, Risk Factors, MESH: Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Child, Child, MESH: Cohort Studies, media_common, MESH: Heterozygote, 2. Zero hunger, hematology, Incidence (epidemiology), 1. No poverty, Articles, glucosephosphate dehydrogenase deficiency, glucosephosphate dehydrogenase, glucose-6-phosphate dehydrogenase, MESH: Case-Control Studies, MESH: Infant, 3. Good health, MESH: Glucosephosphate Dehydrogenase Deficiency, Child, Preschool, Female, Cohort study, Heterozygote, medicine.medical_specialty, Adolescent, MESH: Kenya, MESH: Malaria, parasitic diseases, medicine, MESH: United States, Humans, media_common.cataloged_instance, European union, MESH: Adolescent, Polymorphism, Genetic, MESH: Humans, business.industry, MESH: Child, Preschool, Case-control study, Infant, Odds ratio, medicine.disease, Kenya, United States, MESH: Male, Malaria, Case-Control Studies, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Female, Glucose-6-phosphate dehydrogenase deficiency
Abstract: Summary Background The global prevalence of X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency is thought to be a result of selection by malaria, but epidemiological studies have yielded confusing results. We investigated the relationships between G6PD deficiency and both malaria and non-malarial illnesses among children in Kenya. Methods We did this study in Kilifi County, Kenya, where the G6PD c.202T allele is the only significant cause of G6PD deficiency. We tested the associations between G6PD deficiency and severe and complicated Plasmodium falciparum malaria through a case-control study of 2220 case and 3940 control children. Cases were children aged younger than 14 years, who visited the high dependency ward of Kilifi County Hospital with severe malaria between March 1, 1998, and Feb 28, 2010. Controls were children aged between 3–12 months who were born within the same study area between August 2006, and September 2010. We assessed the association between G6PD deficiency and both uncomplicated malaria and other common diseases of childhood in a cohort study of 752 children aged younger than 10 years. Participants of this study were recruited from a representative sample of households within the Ngerenya and Chonyi areas of Kilifi County between Aug 1, 1998, and July 31, 2001. The primary outcome measure for the case-control study was the odds ratio for hospital admission with severe malaria (computed by logistic regression) while for the cohort study it was the incidence rate ratio for uncomplicated malaria and non-malaria illnesses (computed by Poisson regression), by G6PD deficiency category. Findings 2863 (73%) children in the control group versus 1643 (74%) in the case group had the G6PD normal genotype, 639 (16%) versus 306 (14%) were girls heterozygous for G6PD c.202T, and 438 (11%) versus 271 (12%) children were either homozygous girls or hemizygous boys. Compared with boys and girls without G6PD deficiency, we found significant protection from severe malaria (odds ratio [OR] 0·82, 95% CI 0·70–0·97; p=0·020) among G6PD c.202T heterozygous girls but no evidence for protection among G6PD c.202T hemizygous boys and homozygous girls (OR 1·18, 0·99–1·40; p=0·056). Median follow-up for the mild disease cohort study was 2·24 years (IQR 2·22–2·85). G6PD c.202T had no effect on other common diseases of childhood in heterozygous girls (incidence rate ratio 0·98, 95% CI 0·86–1·11; p=0·82) or homozygous girls or hemizygous boys (0·93, 0·82–1·04; p=0·25), with the sole exception of a marginally significant increase in the incidence of helminth infections among heterozygous girls. Interpretation Heterozygous girls might be the driving force for the positive selection of G6PD deficiency alleles. Further studies are needed to definitively establish the mechanisms by which G6PD deficiency confers an advantage against malaria in heterozygous individuals. Such studies could lead to the development of new treatments. Funding Wellcome Trust, UK Medical Research Council, European Union, and Foundation for the National Institutes of Health (as part of the Bill & Melinda Gates Grand Challenges in Global Health Initiative).
Published: 2015

49. Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author: Shelton, Jennifer MG, Corran, Patrick, Risley, Paul, Silva, Nilupa, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Clark, Taane G, Band, Gavin, Clarke, Geraldine M, Spencer, Christopher CA, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Ly, Alioune Badara, Mercereau-Puijalon, Odile, Sakuntabhai, Anavaj, Djimdé, Abdoulaye, Maiga, Boubacar, Touré, Ousmane, Doumbo, Ogobara K, Dolo, Amagana, Troye-Blomberg, Marita, Mangano, Valentina D, Verra, Frederica, Modiano, David, Bougouma, Edith, Sirima, Sodiomon B, Ibrahim, Muntaser, Hussain, Ayman, Eid, Nahid, Elzein, Abier, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas N, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Manjurano, Alphaxard, Reyburn, Hugh, Lemnge, Martha, Ishengoma, Deus, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Dewasurendra, Rajika, Drakeley, Christopher J, Riley, Eleanor M, Kwiatkowski, Dominic P, Rockett, Kirk A, MalariaGEN Consortium, The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford [Oxford], London School of Hygiene and Tropical Medicine (LSHTM), National Institute for Biological Standards and Control (NIBSC), Medicines and Healthcare Products Regulatory Agency (MHRA), Nuffield Department of Population Health [Oxford], The Wellcome Trust Sanger Institute [Cambridge], Unité d'Epidémiologie des Maladies Infectieuses, Institut Pasteur de Dakar, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Immunologie Moléculaire des Parasites, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Génétique fonctionnelle des Maladies infectieuses - Functional Genetics of Infectious Diseases, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Malaria Research and Training Center [Bamako, Mali], Université de Bamako, Stockholm University, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Centre National de Recherche et de Formation sur le Paludisme [Ouagadougou, Burkina Faso] (CNRFP), University of Khartoum, KEMRI-Wellcome Trust Research Programme (KWTRP), Tumaini University Makumira, National Institute for Medical Research [Tanzania] (NIMR), University of Edinburgh, University of Colombo [Sri Lanka], MalariaGEN is supported by the Wellcome Trust (077383/Z/05/Z) and by the Foundation for the National Institutes of Health (566) as part of the Bill & Melinda Gates Grand Challenges in Global Health Initiative. The Resource Centre for Genomic Epidemiology of Malaria is supported by the Wellcome Trust (090770/Z/09/Z). Support was also provided by the Medical Research Council (G0600718). DPK receives support from the Medical Research Council (G19/9). CCAS was supported by a Wellcome Trust Career Development Fellowship (097364/Z/11/Z). The Wellcome Trust also provides core awards to The Wellcome Trust Centre for Human Genetics (075491/Z/04, 090532/Z/09/Z) and the Wellcome Trust Sanger Institute (077012/Z/05/Z). MTB and BM received funding through the EU Network of Excellence EviMalar. VDM was funded by a Biomalpar (European Community’s Sixth Framework Programme) PhD fellowship. FV was funded by the Italian Malaria Network, sponsored by Compagnia di San Paolo, Turin, Italy. TNW is supported by a Senior Research Fellowship from the Wellcome Trust (091758/Z/10/Z). This study was conducted as part of the Joint Malaria Programme, a collaboration between the National Institute for Medical Research (NIMR), Kilimanjaro Christian Medical College (KCMC), the London School of Hygiene and Tropical Medicine (LSHTM) and the Centre for Medical Parasitology, University of Copenhagen (CMP) with funding from the UK Medical Research Council (GG9901439) and the Danish International Development Agency. CJD is supported by the Wellcome Trust (091924). RD is supported by the University of Colombo Research Grants 2011 (AP/3/2011/PG/15)., European Project: 26843,BIOMALPAR, University of Oxford, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA)
Subjects: Male, Hemoglobin, Sickle, Antibodies, Protozoan, Sickle, MESH: Linear Models, MESH: Child, Child, HbAS, MESH: Infant, Newborn, Antibody, CD36, Genotype, Malaria, Sickle cell trait, Adolescent, Adult, Africa South of the Sahara, Child, Preschool, Female, Humans, Infant, Infant, Newborn, Linear Models, Sri Lanka, Young Adult, Infectious Diseases, Parasitology, MESH: Infant, MESH: Young Adult, Protozoan, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Malaria, Antibodies, parasitic diseases, MESH: Antibodies, Protozoan, Hemoglobin, MESH: Africa South of the Sahara, Preschool, MESH: Sri Lanka, MESH: Adolescent, MESH: Humans, Research, MESH: Child, Preschool, MESH: Adult, Newborn, MESH: Hemoglobin, Sickle, MESH: Male, antibody, cd36, genotype, hbas, malaria, sickle cell trait, infectious diseases, parasitology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Female
Abstract: Background Many studies report associations between human genetic factors and immunity to malaria but few have been reliably replicated. These studies are usually country-specific, use small sample sizes and are not directly comparable due to differences in methodologies. This study brings together samples and data collected from multiple sites across Africa and Asia to use standardized methods to look for consistent genetic effects on anti-malarial antibody levels. Methods Sera, DNA samples and clinical data were collected from 13,299 individuals from ten sites in Senegal, Mali, Burkina Faso, Sudan, Kenya, Tanzania, and Sri Lanka using standardized methods. DNA was extracted and typed for 202 Single Nucleotide Polymorphisms with known associations to malaria or antibody production, and antibody levels to four clinical grade malarial antigens [AMA1, MSP1, MSP2, and (NANP)4] plus total IgE were measured by ELISA techniques. Regression models were used to investigate the associations of clinical and genetic factors with antibody levels. Results Malaria infection increased levels of antibodies to malaria antigens and, as expected, stable predictors of anti-malarial antibody levels included age, seasonality, location, and ethnicity. Correlations between antibodies to blood-stage antigens AMA1, MSP1 and MSP2 were higher between themselves than with antibodies to the (NANP)4 epitope of the pre-erythrocytic circumsporozoite protein, while there was little or no correlation with total IgE levels. Individuals with sickle cell trait had significantly lower antibody levels to all blood-stage antigens, and recessive homozygotes for CD36 (rs321198) had significantly lower anti-malarial antibody levels to MSP2. Conclusion Although the most significant finding with a consistent effect across sites was for sickle cell trait, its effect is likely to be via reducing a microscopically positive parasitaemia rather than directly on antibody levels. However, this study does demonstrate a framework for the feasibility of combining data from sites with heterogeneous malaria transmission levels across Africa and Asia with which to explore genetic effects on anti-malarial immunity. Electronic supplementary material The online version of this article (doi:10.1186/s12936-015-0833-x) contains supplementary material, which is available to authorized users.
Published: 2015

50. Low levels of polymorphisms and no evidence for diversifying selection on the Plasmodium knowlesi Apical Membrane Antigen 1 gene

Author: Clemens H. M. Kocken, Frederick Saul, Khamisah Abdul Kadir, Roberto Rodriguez-Garcia, Graham A. Bentley, Edmond J. Remarque, Bart W. Faber, Balbir Singh, Brigitte Vulliez Le Normand, Department of Parasitology, Biomedical Primate Research Centre [Rijswijk] (BPRC), Malaria Research Centre, Immunologie structurale, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), European Commission EUROMALVAC2 (contract QLK2-CT- 2002-01197), The Centre National de la Recherche Scientifique, The Universiti Malaysia Sarawak (grant number 01(TD03)/1003/2013(01)), European Commission EMVDA grant LSHP-CT-2007-037506, E(M)VI, The European (Malaria) Vaccine Initiative, and Universiti of Sarawak: Grant E14054/F05/54/PKI/09/2012(01), European Project: 40221,EMVDA, European Project, and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: Molecular Sequence Data, Protozoan Proteins, malaria, lcsh:Medicine, Antigens, Protozoan, Balancing selection, plasmodium knowlesi, polymorphism, parasitic diseases, medicine, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Amino Acid Sequence, Selection, Genetic, Allele, Apical membrane antigen 1, lcsh:Science, Gene, Genetics, MESH: plasmodium knowlesi, Polymorphism, Genetic, Multidisciplinary, Sequence Homology, Amino Acid, biology, Malaria vaccine, Haplotype, lcsh:R, Membrane Proteins, Sequence Analysis, DNA, biology.organism_classification, medicine.disease, Virology, 3. Good health, MESH: malaria, MESH: polymorphism, Haplotypes, apical membrane antigen 1, Plasmodium knowlesi, Mutation, lcsh:Q, MESH: apical membrane antigen 1, Malaria, Research Article
Abstract: International audience; Infection with Plasmodium knowlesi, a zoonotic primate malaria, is a growing human health problem in Southeast Asia. P. knowlesi is being used in malaria vaccine studies, and a number of proteins are being considered as candidate malaria vaccine antigens, including the Apical Membrane Antigen 1 (AMA1). In order to determine genetic diversity of the ama1 gene and to identify epitopes of AMA1 under strongest immune selection, the ama1 gene of 52 P. knowlesi isolates derived from human infections was sequenced. Sequence analysis of isolates from two geographically isolated regions in Sarawak showed that polymorphism in the protein is low compared to that of AMA1 of the major human malaria parasites, P. falciparum and P. vivax. Although the number of haplotypes was 27, the frequency of mutations at the majority of the polymorphic positions was low, and only six positions had a variance frequency higher than 10%. Only two positions had more than one alternative amino acid. Interestingly, three of the high-frequency polymorphic sites correspond to invariant sites in PfAMA1 or PvAMA1. Statistically significant differences in the quantity of three of the six high frequency mutations were observed between the two regions. These analyses suggest that the pkama1 gene is not under balancing selection, as observed for pfama1 and pvama1, and that the PkAMA1 protein is not a primary target for protective humoral immune responses in their reservoir macaque hosts, unlike PfAMA1 and PvAMA1 in humans. The low level of polymorphism justifies the development of a single allele PkAMA1-based vaccine.
Published: 2015

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Journal

Database

Publisher

135 results on '"MESH: Malaria"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources