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1. Plasmodium falciparum merozoite surface antigen-specific cytophilic IgG and control of malaria infection in a Beninese birth cohort

Author

Gregory Nuel, Paulin Sonon, Adrian J. F. Luty, Gilles Cottrell, Ibrahim Sadissou, André Garcia, Roukiyath Amoussa, Tania d’Almeida, Ambaliou Sanni, Shirley Longacre, D. Courtin, Aziz Bouraima, Florence Migot-Nabias, Rafiou Adamou, Célia Dechavanne, Michael Theisen, Kabirou Moutairou, Edmond J. Remarque, Achille Massougbodji, Jacqueline Milet, Agnès Le Port, Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 216), Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), Laboratoire de Biochimie et de Biologie Moléculaire (Université d'Abomey Calavi, Cotonou, Bénin) (LBBM), Université d’Abomey-Calavi = University of Abomey Calavi (UAC), Universidade de São Paulo = University of São Paulo (USP), Statens Serum Institut [Copenhagen], University of Copenhagen = Københavns Universitet (UCPH), Biomedical Primate Research Centre [Rijswijk] (BPRC), Vaccinologie Parasitaire, Institut Pasteur [Paris] (IP), Laboratoire de Probabilités, Statistique et Modélisation (LPSM (UMR_8001)), Université Paris Diderot - Paris 7 (UPD7)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), This paper describes work undertaken in the context of the PALNOUGENENV, 'Paludisme-Nouvéau-né-Génétique et Environnement', a project supported by Agence Nationale pour la Recherche (projet SEST2006/040/001), Ministère des Affaires Etrangères français (projet REFS No.2006-22) for their financial support. This publication was made possible through the Faculté des Sciences de la Santé (FSS), the Institut des Sciences Biomédicales Appliquées de Cotonou (ISBA), the Programme National de Lutte contre le Paludisme (PNLP) for their institutional support and the Institut de Recherche et de Développment AIRD-ARTS and Ambassade de France à Cotonou (SCAC) for their PhD scholarships to Rafiou ADAMOU and Ibrahim SADISSOU., ANR-06-SEST-0040,PALNOURGENENV,survenue des premières infections palustres chez le noueau-né : déterminants génétiques, biologiques et environnementaux(2006), Mère et enfant face aux infections tropicales (MERIT - UMR_D 216), University of Abomey Calavi (UAC), University of São Paulo (USP), University of Copenhagen = Københavns Universitet (KU), Institut Pasteur [Paris], and Laboratoire de Probabilités, Statistiques et Modélisations (LPSM (UMR_8001))

Subjects
Male, Protozoan Proteins, Antibodies, Protozoan, MESH: Malaria, Falciparum/immunology, 0302 clinical medicine, MESH: Pregnancy, MESH: Antigens, Protozoan/immunology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Pregnancy, Surveys and Questionnaires, Benin, 030212 general & internal medicine, MESH: Plasmodium falciparum/immunology, Longitudinal Studies, Malaria, Falciparum, MESH: Longitudinal Studies, MESH: Antibodies, Protozoan/blood, biology, Malaria vaccine, MESH: Infant, Newborn, MESH: Enzyme-Linked Immunosorbent Assay, MESH: Infant, 3. Good health, Infectious Diseases, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Cytophilic IgG, Female, Merozoite vaccine candidate antigens, Antibody, medicine.symptom, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, 030231 tropical medicine, Plasmodium falciparum, Context (language use), Antigens, Protozoan, Enzyme-Linked Immunosorbent Assay, Asymptomatic, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, MESH: Benin, Antigen, Immunity, parasitic diseases, medicine, Humans, lcsh:RC109-216, MESH: Surveys and Questionnaires, MESH: Humans, business.industry, Research, Infant, Newborn, Infant, biology.organism_classification, medicine.disease, MESH: Protozoan Proteins/immunology, MESH: Male, Malaria, Immunoglobulin G, Immunology, biology.protein, Parasitology, business, MESH: Immunoglobulin G/blood, MESH: Female
Abstract

BACKGROUND: Substantial evidence indicates that cytophilic IgG responses to Plasmodium falciparum merozoite antigens play a role in protection from malaria. The specific targets mediating immunity remain unclear. Evaluating antibody responses in infants naturally-exposed to malaria will allow to better understand the establishment of anti-malarial immunity and to contribute to a vaccine development by identifying the most appropriate merozoite candidate antigens.METHODS: The study was based on parasitological and clinical active follow-up of infants from birth to 18 months of age conducted in the Tori Bossito area of southern Benin. For 399 infants, plasma levels of cytophilic IgG antibodies with specificity for five asexual stage malaria vaccine candidate antigens were determined by ELISA in infants' peripheral blood at 6, 9, 12 and 15 months of age. Multivariate mixed logistic model was used to investigate the association between antibody levels and anti-malarial protection in the trimester following the IgG quantification. Moreover, the concentrations of merozoite antigen-specific IgG were compared between a group of infants apparently able to control asymptomatic malaria infection (CAIG) and a group of infants with no control of malaria infection (Control group (NCIG)). Protective effect of antibodies was also assessed after 15 months of malaria exposure with a Cox regression model adjusted on environmental risk.RESULTS: Cytophilic IgG responses to AMA1, MSP1, MSP2-3D7, MSP2-FC27, MSP3 and GLURP R2 were associated with increasing malarial infection risk in univariate analysis. The multivariate mixed model showed that IgG1 and IgG3 to AMA1 were associated with an increased risk of malarial infection. However infants from CAIG (n = 53) had significantly higher AMA1-, MSP2-FC27-, MSP3-specific IgG1 and AMA1-, MSP1-, MSP2-FC27-, MSP3 and GLURP-R2-specific IgG3 than those from NCIG (n = 183). The latter IgG responses were not associated with protection against clinical malaria in the whole cohort when protective effect is assessed after 15 months of malaria exposition.CONCLUSION: In this cohort, merozoite antigen-specific cytophilic IgG levels represent a marker of malaria exposure in infants from 6 to 18 months of age. However, infants with resolution of asymptomatic infection (CAIG) seem to have acquired naturally immunity against P. falciparum. This observation is encouraging in the context of the development of multitarget P. falciparum vaccines.

Published
2019

2. Plasmepsin II–III copy number accounts for bimodal piperaquine resistance among Cambodian Plasmodium falciparum

Author

Bopp, S, Magistrado, P, Wong, W, Schaffner, S, Mukherjee, A, Lim, P, Dhorda, M, Amaratunga, C, Woodrow, C, Ashley, E, White, N, Dondorp, A, Fairhurst, R, Ariey, F, Menard, D, Wirth, D, Volkman, S, Harvard T.H. Chan School of Public Health, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], National Institutes of Health [Bethesda] (NIH), WWARN Asia Regional Centre [Bangkok, Thailand], Mahidol University [Bangkok], Mahidol Oxford Tropical Medicine Research Unit, University of Oxford-Mahidol University [Bangkok], Myanmar Oxford Clinical Research Unit [Yangon, Myanmar], Centre for Tropical Medicine and Global Health [Oxford, UK], Nuffield Department of Medicine [Oxford, UK] (Big Data Institute), University of Oxford-University of Oxford, Mahidol Oxford Tropical Medicine Research Unit (MORU), University of Oxford-Mahidol University [Bangkok]-Wellcome Trust, 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), 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), Simmons college, This work was supported in part by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health., We thank Courtney Edison for slide reading and subcloning the KH001_053 isolate., The computations in this paper were run on the Odyssey cluster supported by the FAS Division of Science, Research Computing Group at Harvard University. N.J.W., C.J.W. were supported by Bill and Melinda Gates Foundation Global Health Grant Number OPP1040463, which also funded culture adaptation of the parasites described herein. Additional support was provided to DFW by the Bill and Melinda Gates Foundation Global Health Grant Number OPP1053604. This document is an output from a project of the Tracking Resistance to Artemisinin Collaboration funded by the UK Department for International Development (DFID) for the benefit of developing countries. However, the views expressed and information contained in it are not necessarily those of or endorsed by DFID, which can accept no responsibility for such views or for any reliance place on them., University of Oxford [Oxford]-Mahidol University [Bangkok], University of Oxford [Oxford]-University of Oxford [Oxford], Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford], and Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Infectious-disease epidemiology, DNA Copy Number Variations, Whole Genome Sequencing, Cell Survival, Science, Plasmodium falciparum, Drug Resistance, Gene Dosage, Protozoan Proteins, Article, Malaria, Target validation, Isoenzymes, Antimalarials, parasitic diseases, Quinolines, Aspartic Acid Endopeptidases, Humans, lcsh:Q, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, lcsh:Science, Cambodia, Antiparasitic agents
Abstract

Multidrug resistant Plasmodium falciparum in Southeast Asia endangers regional malaria elimination and threatens to spread to other malaria endemic areas. Understanding mechanisms of piperaquine (PPQ) resistance is crucial for tracking its emergence and spread, and to develop effective strategies for overcoming it. Here we analyze a mechanism of PPQ resistance in Cambodian parasites. Isolates exhibit a bimodal dose–response curve when exposed to PPQ, with the area under the curve quantifying their survival in vitro. Increased copy number for plasmepsin II and plasmepsin III appears to explain enhanced survival when exposed to PPQ in most, but not all cases. A panel of isogenic subclones reinforces the importance of plasmepsin II–III copy number to enhanced PPQ survival. We conjecture that factors producing increased parasite survival under PPQ exposure in vitro may drive clinical PPQ failures in the field., Piperaquine (PPQ) resistance of Plasmodium is an increasing problem. Here, Bopp et al. find a bimodal dose−response curve of Cambodian isolates exposed to PPQ, with the area under the curve correlating with in vitro PPQ resistance, and show the importance of Plasmepsin II–III copy number to PPQ resistance.

Published
2018

3. Optimization of a magnetic bead-based assay (MAGPIX®-Luminex) for immune surveillance of exposure to malaria using multiple Plasmodium antigens and sera from different endemic settings

Author

Aissata Basse, Inès Vigan-Womas, Alioune Dieye, Cheikh Loucoubar, Babacar Mbengue, Marie Louise Varela, Ronald Perraut, Aissatou Touré, Institut Pasteur de Dakar, Réseau International des Instituts Pasteur (RIIP), Institut Pasteur de Madagascar, Département Parasites et Insectes vecteurs - Department of Parasites and Insect Vectors, Institut Pasteur [Paris], This study was supported by grants from Institut Pasteur Fondation, from Rotary International, ACIP (Institut Pasteur, N°25_2012) and EDCTP—European & Developing Countries Clinical Trials Partnership., We thank Dr Odile Mercereau-Puijalon and Dr Shirley Longacre for constant support and providing antigens, we are grateful to Dr Shirley Longacre for revising this paper. We thank Drs Marc Jouan and Jérôme Salomon from Division International (Institut Pasteur, Paris) for their help to initiate this work in the very early steps. We are grateful to the villagers of Dielmo and Ndiop for their active participation and continuing collaboration in the project and Pr Bacary Diatta for help providing hospital samples., and Institut Pasteur [Paris] (IP)

Subjects
0301 basic medicine, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, 030231 tropical medicine, Plasmodium falciparum, Protozoan Proteins, Antigens, Protozoan, Plasmodium malariae, Biology, lcsh:Infectious and parasitic diseases, Serology, 03 medical and health sciences, 0302 clinical medicine, Antigen, parasitic diseases, medicine, lcsh:RC109-216, Multiplex, Malaria, Falciparum, IgG response, Immunoassay, medicine.diagnostic_test, Immunomagnetic Separation, Magnetic beads assay, Methodology, medicine.disease, biology.organism_classification, 3. Good health, Malaria, 030104 developmental biology, Infectious Diseases, Immunology, biology.protein, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Parasitology, Antibody, Biomarkers
Abstract

International audience; Background: Serological markers are potentially useful tools for monitoring the progress of malaria control programs , but a better understanding of antibody response dynamics is necessary. The use of a magnetic bead-based immunoassay (MBA) is advantageous compared to ELISA, due to its multiplexing capacity, but limited information is available on the standardization and validation of this assay. Methods: Several parameters for multiplex testing of antibodies to Plasmodium antigens were analysed using a set of 4 antigens and 98 sera from Senegalese rural asymptomatic and urban symptomatic individuals. The 4 antigens included Plasmodium falciparum CSP and PfAMA1 peptides, recombinant P. falciparum MSP4p20 and a Plasmodium malariae CSP (PmCSP) peptide. Comparisons with ELISA were done using MSP4p20 and whole schizont extract (SE) antigens.Results: The use of fewer beads (1000 beads per well instead of 2000) and 5 µg of antigen per 10 6 bead were validated as lower amounts. The use of a carrier protein (BSA) was shown to be critical when using peptides and the effect of a 24 h delayed measures was evaluated (5-25% signal decrease). Analysis of Ab responses showed almost equally high levels and prevalence in all transmission settings. Clear distinctions between rural and urban malaria were noted using PmCSP and SE antigens.Conclusions: This study underlines the importance of further optimization of the MBA technique and highlights the interest of using multistage/multispecies antigens for surveillance of malaria in endemic settings.

Published
2018

4. Single low-dose primaquine for blocking transmission of plasmodium falciparum malaria - a proposed model-derived age-based regimen for sub-Saharan Africa

Author

Muhindo Mavoko, Htee Khu Naw, Estrella Lasry, Nicholas J. White, Sodiomon B. Sirima, Melissa C. Kapulu, Mores Loolpapit, Marie Claire Henry, Thomas N. Williams, Alfred Ngwa Amambua, Claude Rwagacondo, Rick M. Fairhurst, Nicholas P. J. Day, Joseph Okebe, Umberto D'Alessandro, Mahamadou Diakite, Rindra Randremanana, Mavuto Mukaka, James A. Berkley, Jean-Pierre Van Geertruyden, Charles O Obonyo, Malcolm E. Molyneux, Muna Affara, Philipe Brasseur, Peter G. Kremsner, Pascal Lutumba, Endalamaw Gadisa, Abraham Aseffa, Grace Malenga, Caterina I. Fanello, Grant Dorsey, Karen I. Barnes, Zolia Yah, Jane Achan, Patrice Piola, Kathryn Maitland, Chandy C. John, Davis Nwakanma, Joel J. Jones, W. Robert Taylor, Birgit Schramm, Marie A. Onyamboko, Junior Matangila, Philip Bejon, Geneva University Hospital (HUG), Mahidol Oxford Tropical Medicine Research Unit (MORU), Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford], KEMRI-Wellcome Trust Research Programme (KWTRP), Imperial College London, University of Oxford [Oxford], Medical Research Council Unit The Gambia (MRC), University of Antwerp (UA), University of Kinshasa (UNIKIN), 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), Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP), Epicentre [Paris] [Médecins Sans Frontières], Kinshasa Mahidol Oxford Research Unit (KIMORU), Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford]-Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford], Ecole de Santé Publique de Kinshasa (KSPH ou ESP), National Malaria Control Programme, Ministry of Health and Social Welfare, National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Malaria Research and Training Center [Bamako, Mali], Université de Bamako, Queen Elizabeth Hospital, University of Liverpool, Kenya Medical Research Institute (KEMRI), Armauer Hansen Research Institute (AHRI), Amref Health Africa [Kenya], African Medical and Research Foundation (AMREF), Centre de Recherche Entomologique de Cotonou (CREC), Ministère de la Santé, University of California [San Francisco] (UCSF), University of California, Indiana University - Purdue University Indianapolis (IUPUI), Indiana University System, Centre National de Recherche et de Formation sur le Paludisme [Ouagadougou, Burkina Faso] (CNRFP), Groupe de recherche action en santé (GRAS), University of Cape Town, University of Tübingen, TNW is supported by a Fellowship from the Wellcome Trust (202800). The KEMRI–Wellcome Trust Research Programme in Kenya is funded through a Strategic Award from the KEMRI–Wellcome Trust Research Programme (203077). RMF was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, US National Institutes of Health. NJW is a Wellcome Trust Principal Fellow., We acknowledge with gratitude the Demographic Health Survey of USAID for permission to download data from their website. This paper is published with permission from the Director of KEMRI., University of Oxford-Mahidol University [Bangkok]-Wellcome Trust, University of Oxford, 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), University of Oxford-Mahidol University [Bangkok]-Wellcome Trust-University of Oxford-Mahidol University [Bangkok]-Wellcome Trust, University of California [San Francisco] (UC San Francisco), University of California (UC), RANDRIAMANANTSOA, Volatiana Manohisoa, and Wellcome Trust

Subjects
Male, Primaquine, Antimalarials / therapeutic use, lcsh:Medicine, MESH: Dose-Response Relationship, Drug, MESH: Clinical Protocols, MESH: Aged, 80 and over, 0302 clinical medicine, Clinical Protocols, MESH: Child, Epidemiology, 030212 general & internal medicine, Malaria, Falciparum, Child, MESH: Plasmodium falciparum, Aged, 80 and over, MESH: Aged, MESH: Middle Aged, biology, MESH: Malaria, Falciparum, Age Factors, 11 Medical And Health Sciences, General Medicine, Middle Aged, MESH: Primaquine, MESH: Infant, 3. Good health, MESH: Glucosephosphate Dehydrogenase Deficiency, Tolerability, MESH: Young Adult, Child, Preschool, Primaquine / administration & dosage, Female, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Research Article, medicine.drug, Adult, medicine.medical_specialty, Adolescent, Plasmodium falciparum, 030231 tropical medicine, Antimalarials / adverse effects, Antimalarials, Malaria, Falciparum / prevention & control, Young Adult, 03 medical and health sciences, Pharmacokinetics, Age-based dosing, General & Internal Medicine, Internal medicine, parasitic diseases, medicine, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, MESH: Africa South of the Sahara, Dosing, Africa South of the Sahara, ddc:613, Aged, MESH: Adolescent, MESH: Age Factors, MESH: Humans, Dose-Response Relationship, Drug, business.industry, lcsh:R, Malaria, Falciparum / transmission, MESH: Child, Preschool, Infant, MESH: Adult, medicine.disease, biology.organism_classification, MESH: Antimalarials, MESH: Male, Malaria, Regimen, Glucosephosphate Dehydrogenase Deficiency, Primaquine / adverse effects, Primaquine / therapeutic use, Antimalarials / administration & dosage, Malaria, Falciparum / drug therapy, Transmission blocking, Human medicine, business, MESH: Female
Abstract

Background In 2012, the World Health Organization recommended blocking the transmission of Plasmodium falciparum with single low-dose primaquine (SLDPQ, target dose 0.25 mg base/kg body weight), without testing for glucose-6-phosphate dehydrogenase deficiency (G6PDd), when treating patients with uncomplicated falciparum malaria. We sought to develop an age-based SLDPQ regimen that would be suitable for sub-Saharan Africa. Methods Using data on the anti-infectivity efficacy and tolerability of primaquine (PQ), the epidemiology of anaemia, and the risks of PQ-induced acute haemolytic anaemia (AHA) and clinically significant anaemia (CSA), we prospectively defined therapeutic-dose ranges of 0.15–0.4 mg PQ base/kg for children aged 1–5 years and 0.15–0.5 mg PQ base/kg for individuals aged ≥6 years (therapeutic indices 2.7 and 3.3, respectively). We chose 1.25 mg PQ base for infants aged 6–11 months because they have the highest rate of baseline anaemia and the highest risks of AHA and CSA. We modelled an anthropometric database of 661,979 African individuals aged ≥6 months (549,127 healthy individuals, 28,466 malaria patients and 84,386 individuals with other infections/illnesses) by the Box–Cox transformation power exponential and tested PQ doses of 1–15 mg base, selecting dosing groups based on calculated mg/kg PQ doses. Results From the Box–Cox transformation power exponential model, five age categories were selected: (i) 6–11 months (n = 39,886, 6.03%), (ii) 1–5 years (n = 261,036, 45.46%), (iii) 6–9 years (n = 20,770, 3.14%), (iv) 10–14 years (n = 12,155, 1.84%) and (v) ≥15 years (n = 328,132, 49.57%) to receive 1.25, 2.5, 5, 7.5 and 15 mg PQ base for corresponding median (1st and 99th centiles) mg/kg PQ base of: (i) 0.16 (0.12–0.25), (ii) 0.21 (0.13–0.37), (iii) 0.25 (0.16–0.38), (iv) 0.26 (0.15–0.38) and (v) 0.27 (0.17–0.40). The proportions of individuals predicted to receive optimal therapeutic PQ doses were: 73.2 (29,180/39,886), 93.7 (244,537/261,036), 99.6 (20,690/20,770), 99.4 (12,086/12,155) and 99.8% (327,620/328,132), respectively. Conclusions We plan to test the safety of this age-based dosing regimen in a large randomised placebo-controlled trial (ISRCTN11594437) of uncomplicated falciparum malaria in G6PDd African children aged 0.5 − 11 years. If the regimen is safe and demonstrates adequate pharmacokinetics, it should be used to support malaria elimination. Electronic supplementary material The online version of this article (doi:10.1186/s12916-017-0990-6) contains supplementary material, which is available to authorized users.

Published
2018

5. Larval nutritional stress affects vector life history traits and human malaria transmission

Author

Thierry Lefèvre, Amélie Vantaux, Anna Cohuet, Olivier Roux, Benjamin Roche, Kounbobr Roch Dabiré, 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]), Institut de Recherche en Sciences de la Santé (IRSS), CNRST, 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]), Institut de Recherche en Sciences de la Santé (IRSS) / Centre Muraz, Unité de modélisation mathématique et informatique des systèmes complexes [Bondy] (UMMISCO), Université Cadi Ayyad [Marrakech] (UCA)-Université de Yaoundé I-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de la francophonie pour l'informatique-Université Pierre et Marie Curie - Paris 6 (UPMC), Diversity, ecology, evolution & Adaptation of arthropod vectors (MIVEGEC-DEEVA), This study was funded by the ANR grant 11-PDOC-006-01 to TL., We would like to thank all of the children and their parents who participated in this study, as well as the local authorities for their support, and Andrea Yockey-Dejean for proofreading the paper. We are very grateful to the IRSS staff in Burkina Faso for technical assistance., and Institut de Recherche pour le Développement (IRD)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université de Yaoundé I-Institut de la francophonie pour l'informatique-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cadi Ayyad [Marrakech] (UCA)

Subjects
0301 basic medicine, media_common.quotation_subject, [SDV]Life Sciences [q-bio], Plasmodium falciparum, Zoology, Insect, MESH: Insect Vectors, Biology, Article, law.invention, Life history theory, 03 medical and health sciences, MESH: Plasmodium falciparum/growth & development, law, Stress, Physiological, Anopheles, parasitic diseases, medicine, Gametocyte, Animals, Humans, MESH: Animals, MESH: Stress, Physiological, Life History Traits, media_common, Larva, Multidisciplinary, MESH: Humans, MESH: Life History Traits, MESH: Anopheles/parasitology, Ecology, fungi, MESH: Anopheles/growth & development, medicine.disease, Fecundity, 3. Good health, Insect Vectors, Malaria, MESH: Larva/parasitology, MESH: Malaria/transmission, 030104 developmental biology, Transmission (mechanics), MESH: Larva/growth & development, Vector (epidemiology), Female, MESH: Female
Abstract

Exposure to stress during an insect’s larval development can have carry-over effects on adult life history traits and susceptibility to pathogens. We investigated the effects of larval nutritional stress for the first time using field mosquito vectors and malaria parasites. In contrast to previous studies, we show that larval nutritional stress may affect human to mosquito transmission antagonistically: nutritionally deprived larvae showed lower parasite prevalence for only one gametocyte carrier; they also had lower fecundity. However, they had greater survival rates that were even higher when infected. When combining these opposing effects into epidemiological models, we show that larval nutritional stress induced a decrease in malaria transmission at low mosquito densities and an increase in transmission at high mosquito densities, whereas transmission by mosquitoes from well-fed larvae was stable. Our work underscores the importance of including environmental stressors towards understanding host–parasite dynamics to improve disease transmission models and control.

Published
2016

6. Evidence for carry-over effects of predator exposure on pathogen transmission potential

Author

Thierry Lefèvre, Koudraogo B. Yameogo, Kounbobr Roch Dabiré, Frédéric Simard, Olivier Roux, Abdoulaye Diabaté, Benjamin Roche, Amélie Vantaux, Institut de Recherche en Sciences de la Santé (IRSS), CNRST, 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]), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Unité de modélisation mathématique et informatique des systèmes complexes [Bondy] (UMMISCO), Institut de Recherche pour le Développement (IRD [France-Nord])-Institut de la francophonie pour l'informatique-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cadi Ayyad [Marrakech] (UCA)-Université de Yaoundé I-Sorbonne Université (SU), Transmission-Interactions-Adaptations hôtes/vecteurs/pathogènes (MIVEGEC-TRIAD), O.R. received financial support through a post-doctoral fellowship from the IRD. Experimental infections were supported by the ANR grant no. 11-PDOC-006-01., and We thank the Associate Editor Dr Pejman Rohani and two anonymous reviewers for their valuable comments that greatly improved the manuscript. We thank Boubacar Nikiema for the RFLP-PCR, Jean Bazié and Raymond Hien for technical help with dissections and Andrea Yockey-Dejean for proofreading the paper.

Subjects
Male, life history, [SDV]Life Sciences [q-bio], Predation, Food chain, MESH: Malaria, Falciparum/transmission, MESH: Animals, Malaria, Falciparum, Life history, Predator, Pathogen, Research Articles, General Environmental Science, media_common, Ecology, Transmission potential, Longevity, General Medicine, Anopheles coluzzii, 3. Good health, carry-over effects, MESH: Larva/growth & development, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Anopheles/physiology, MESH: Longevity, Larva, Female, General Agricultural and Biological Sciences, Food Chain, media_common.quotation_subject, Plasmodium falciparum, MESH: Insect Vectors, Biology, General Biochemistry, Genetics and Molecular Biology, Competition (biology), MESH: Predatory Behavior, Heteroptera, MESH: Plasmodium falciparum/growth & development, Anopheles, parasitic diseases, Animals, Humans, MESH: Food Chain, host-parasite and predator-prey, MESH: Humans, General Immunology and Microbiology, fungi, MESH: Anopheles/growth & development, MESH: Heteroptera/physiology, MESH: Fertility, interactions, host–parasite and predator–prey interactions, MESH: Male, Insect Vectors, non-consumptive effects, MESH: Larva/physiology, Fertility, Predatory Behavior, MESH: Female
Abstract

Accumulating evidence indicates that species interactions such as competition and predation can indirectly alter interactions with other community members, including parasites. For example, presence of predators can induce behavioural defences in the prey, resulting in a change in susceptibility to parasites. Such predator-induced phenotypic changes may be especially pervasive in prey with discrete larval and adult stages, for which exposure to predators during larval development can have strong carry-over effects on adult phenotypes. To the best of our knowledge, no study to date has examined possible carry-over effects of predator exposure on pathogen transmission. We addressed this question using a natural food web consisting of the human malaria parasite Plasmodium falciparum , the mosquito vector Anopheles coluzzii and a backswimmer, an aquatic predator of mosquito larvae. Although predator exposure did not significantly alter mosquito susceptibility to P. falciparum , it incurred strong fitness costs on other key mosquito life-history traits, including larval development, adult size, fecundity and longevity. Using an epidemiological model, we show that larval predator exposure should overall significantly decrease malaria transmission. These results highlight the importance of taking into account the effect of environmental stressors on disease ecology and epidemiology.

Published
2015

7. Malaria risk in Corsica, former hot spot of malaria in France

Author

Gilbert Le Goff, Céline Toty, Hélène Barré, Daniel Couret, Nil Rahola, Didier Fontenille, Isabelle Larget-Thiery, Caractérisation et contrôle des populations de vecteurs, Institut de Recherche pour le Développement (IRD), Direction de la Solidarité et de la Santé de Corse et de Corse-du-Sud, Sciences pour l'environnement (SPE), Centre National de la Recherche Scientifique (CNRS)-Université Pascal Paoli (UPP), Centre de Production et Infection des Anophèles (plateforme) - Center for the Production and Infection of Anopheles (platform) (CEPIA), Institut Pasteur [Paris], The paper is catalogued by the EDEN Steering Committee as EDEN 232 http://www.eden-fp6project.net/., Université Pascal Paoli (UPP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), and Centre de Production et Infection des Anophèles (Plateforme) (CEPIA)

Subjects
Risk, Entomology, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, 030231 tropical medicine, Plasmodium vivax, Plasmodium falciparum, MESH: Malaria, Zoology, MESH: Insect Vectors, Biology, Plasmodium, Polymerase Chain Reaction, lcsh:Infectious and parasitic diseases, MESH: Anopheles, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Anopheles, parasitic diseases, medicine, Animals, Humans, MESH: Animals, lcsh:RC109-216, MESH: Plasmodium falciparum, 0303 health sciences, MESH: Humans, MESH: Risk, 030306 microbiology, Ecology, Research, Outbreak, MESH: Polymerase Chain Reaction, medicine.disease, biology.organism_classification, 3. Good health, Insect Vectors, Malaria, MESH: Plasmodium vivax, MESH: France, Infectious Diseases, Parasitology, France
Abstract

Background The prevalence of Plasmodium falciparum and Plasmodium vivax malaria was very high in Corsica just before the Second World War. The last outbreak was in 1972 and the most recent indigenous case was in 2006. Results Analysis of historical data shows that anopheline vectors were abundant. Recent surveys demonstrated that potential vectors are still present in Corsica, despite the likely disappearance of Anopheles sacharovi. Moreover, P. falciparum can develop experimentally into these mosquitoes, notably Anopheles labranchiae, which is locally abundant, and parasites are regularly introduced into the island. Discussion, Conclusions The presence of vectors, the introduction of parasites and the conducive climate raise questions about the possibility of malaria re-emerging and becoming re-established in Corsica. Analysis of historic and current parasitological and entomological data shows that the current theoretical risk of indigenous cases or malaria foci is negligible, particularly since there is very little contact between humans and Anopheles mosquitoes, Plasmodium carriers are reliably treated and there is a widespread vector control on the island.

Published
2010