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1. Longitudinal study assessing the return of chloroquine susceptibility of Plasmodium falciparum in isolates from travellers returning from West and Central Africa, 2000-2011.

Author

Gharbi M, Flegg JA, Hubert V, Kendjo E, Metcalf JE, Bertaux L, Guérin PJ, Le Bras J, Aboubaca A, Agnamey P, Angoulvant A, Barbut P, Basset D, Belkadi G, Bellanger AP, Bemba D, Benoit-Vica F, Berry A, Bigel ML, Bonhomme J, Botterel F, Bouchaud O, Bougnoux ME, Bourée P, Bourgeois N, Branger C, Bret L, Buret B, Casalino E, Chevrier S, Conquere de Monbrison F, Cuisenier B, Danis M, Darde ML, De Gentile L, Delarbre JM, Delaunay P, Delaval A, Desoubeaux G, Develoux M, Dunand J, Durand R, Eloy O, Fauchet N, Faugere B, Faye A, Fenneteau O, Flori P, Fontrouge M, Garabedian C, Gayandrieu F, Godineau N, Houzé P, Houzé S, Hurst JP, Ichou H, Lachaud L, Lebuisson A, Lefevre M, LeGuern AS, Le Moal G, Lusina D, Machouart MC, Malvy D, Matheron S, Maubon D, Mechali D, Megarbane B, Menard G, Millon L, Aiach MM, Minodier P, Morelle C, Nevez G, Parola P, Parzy D, Patey O, Patoz P, Penn P, Perignon A, Picot S, Pilo JE, Poilane I, Pons D, Poupart M, Pradines B, Raffenot D, Rapp C, Receveur MC, Sarfati C, Senghor Y, Simon F, Siriez JY, Taudon N, Thellier M, Thouvenin M, and Toubas D

Subjects
Adolescent, Adult, Africa, Central, Africa, Western, Aged, Aged, 80 and over, Child, Child, Preschool, Drug Resistance, Female, Genotype, Humans, Infant, Longitudinal Studies, Male, Middle Aged, Parasitic Sensitivity Tests, Plasmodium falciparum genetics, Plasmodium falciparum isolation & purification, Travel, Young Adult, Antimalarials therapeutic use, Chloroquine therapeutic use, Malaria, Falciparum drug therapy, Plasmodium falciparum drug effects
Abstract

Background: Chloroquine (CQ) was the main malaria therapy worldwide from the 1940s until the 1990s. Following the emergence of CQ-resistant Plasmodium falciparum, most African countries discontinued the use of CQ, and now promote artemisinin-based combination therapy as the first-line treatment. This change was generally initiated during the last decade in West and Central Africa. The aim of this study is to describe the changes in CQ susceptibility in this African region, using travellers returning from this region as a sentinel system., Methods: The study was conducted by the Malaria National Reference Centre, France. The database collated the pfcrtK76T molecular marker for CQ susceptibility and the in vitro response to CQ of parasites from travellers' isolates returning from Senegal, Mali, Ivory Coast or Cameroon. As a proxy of drug pressure, data regarding CQ intake in febrile children were collated for the study period. Logistic regression models were used to detect trends in the proportions of CQ resistant isolates., Results: A total of 2874 parasite isolates were genotyped between 2000-2011. The prevalence of the pfcrt76T mutant genotype significantly decreased for Senegal (from 78% to 47%), Ivory Coast (from 63% to 37%), Cameroon (from 90% to 59%) and remained stable for Mali. The geometric mean of the 50% inhibitory concentration (IC50) of CQ in vitro susceptibility and the proportion of resistant isolates (defining resistance as an IC50 value > 100 nM) significantly decreased for Senegal (from 86 nM (59%) to 39 nM (25%)), Mali (from 84 nM (50%) to 51 nM (31%)), Ivory Coast (from 75 nM (59%) to 29 nM (16%)) and Cameroon (from 181 nM (75%) to 51 nM (37%)). Both analyses (molecular and in vitro susceptibility) were performed for the 2004-2011 period, after the four countries had officially discontinued CQ and showed an accelerated decline of the resistant isolates for the four countries. Meanwhile, CQ use among children significantly deceased in this region (fixed effects slope = -0.3, p < 10-3)., Conclusions: An increase in CQ susceptibility following official withdrawal of the drug was observed in travellers returning from West and Central African countries. The same trends were observed for molecular and in vitro analysis between 2004-2011 and they correlated to the decrease of the drug pressure.

Published
2013
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2. Transfusion-transmitted malaria.

Author

Bruneel F, Thellier M, Eloy O, Mazier D, Boulard G, Danis M, and Bédos JP

Subjects
Aged, Aged, 80 and over, Animals, Coronary Disease complications, Diabetes Mellitus, Type 2 complications, Humans, Male, Plasmodium falciparum isolation & purification, Quinine therapeutic use, Malaria, Falciparum etiology, Transfusion Reaction
Published
2004
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3. [Pediatric imported malaria. Experience of the hospital center of Versailles (1997-2001)].

Author

Eloy O, Bruneel F, Diebold C, Belaid Y, Foucaud P, Charara O, Nathanson S, and Ghnassia JC

Subjects
Adolescent, Child, Child, Preschool, Female, France, Humans, Infant, Male, Malaria, Falciparum diagnosis, Malaria, Falciparum drug therapy, Malaria, Falciparum epidemiology, Travel
Abstract

Unlabelled: Few data are available about pediatric imported malaria, whereas the number of cases seems in constant increase., Patients and Methods: all pediatric malaria cases diagnosed by a positive thin or thick blood film at the Versailles Hospital, from January 1997 to December 2001, were studied retrospectively., Results: sixty cases of pediatric imported malaria were studied. They were 58 cases of uncomplicated malaria and 2 cases of severe malaria; 85% of the children had travelled to sub-Saharan Africa and 15% to Oceania; 90% of the children were of African origin. Plasmodium falciparum was found alone in 84% of the cases. The anti-malarial chemoprophylaxis was inappropriate in 92% of the cases. No child had profited from preventive measures against mosquitos. Fever > 37,5 degrees C was observed in 100% of the cases. The other clinical signs were present in less than 50% of the cases. The median of haemoglobin and platelet was 10.5 g/dL and 141,000/mm(3), respectively. After treatment, the evolution was good in all the cases, without relapse or any consequences., Discussion/conclusion: our study, in agreement with the national data, confirms the increase in the number of case of pediatric imported malaria, and underlines the mediocrity of the prevention, in particular in term of anti-malarial chemo-prophylaxis. These data, in a context of regular increase of international travels to endemic areas, suggest the necessity to improve the information of the general public, and the urgency of a better staff training of health care workers concerning malaria, in order to improve the prevention and the treatment of this potentially fatal disease.

Published
2003

5. Preferential expression of domain cassettes 4, 8 and 13 of Plasmodium falciparum erythrocyte membrane protein 1 in severe malaria imported in France

Author

Argy, S, Bertin, S, Milet, S, Hubert, P., Clain, S., Cojean, S., Houze, S., Tuikue-Ndam, S, Kendjo, P, Deloron, S, Argy, N., Bertin, G., Milet, J., Hubert, V., Clain, J., Houzé, P., Tuikue-Ndam, N., Kendjo, E., Deloron, P., Matheron, S., Casalino, E., Wolff, M., Delaval, A., Agnamey, P., Durand, R., Pilo, E., Rapp, C., Faucher, F., Cuisenier, B., Poilane, I., Bemba, D., Roide, A., Debourgogne, A., Thibault, M., Toubas, D., Patoz, P., De Gentile, L., Pons, D., Hurst, P., Lohmann, C., Bigel, M., Godineau, N., Thouvenin, M., Dunand, J., Ait-Ammar, N., Angoulvant, A., Dahane, N., Lefevre, M., Murat, B., Garnaud, C., Dannaoui, E., Botterel, F., Dutoit, E., Dardé, M., Ichou, H., Branger, C., Penn, P., Angebault, C., Morio, F., Bret, L., Thellier, M., Mouri, O., Cateau, E., Siriez, J.Y., Fenneteau, O., Revest, M., Belaz, S., Belkadi, G., Hamane, S., Bretagne, S., Aboubacar, A., Leloup, G., Develoux, M., Lapillonne, H., Eloy, O., Nevez, G., Raffenot, D., Buret, B., Desoubeaux, G., Goepp, A., Department of Mechanical Engineering [Montréal], McGill University, Laboratoire de Mathématiques Blaise Pascal (LMBP), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS), Services de Maladies Infectieuses et Tropicales [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Alltech France, Mère et enfant face aux infections tropicales (MERIT - UMR_D 216), Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), Space Science Institute [Boulder] (SSI), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM ICMMM), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Parasitology department, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Parasitologie-Mycologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), Paléobiodiversité et paléoenvironnements, Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), EA 2594 LBCM, Université de Bretagne Sud (UBS), CHU Tenon [APHP], Service d'anatomie pathologique [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Thérapeutique Recombinante Expérimentale (TIMC-IMAG-TheREx), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire de Parasitologie et Mycologie (Parasito - Myco - LILLE), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Ecologie et Evolution des Microorganismes (EEM), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), IICiMed - EA 1155, Université de Nantes (UN)-UFR Sciences et Techniques [Université de Nantes], Université de Nantes (UN)-UFR des Sciences Pharmaceutiques [Université de Nantes], Université de Nantes (UN), Service de Microbiologie, Hôpital Avicenne, Laboratoire de Parasitologie-Mycologie, Groupe hospitalier Pitié- Salpêtrière, AP-HP, Service de parasitologie - mycologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Ecologie et biologie des interactions (EBI), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Microbiologie de l'Eau (MDE), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire [Rennes], Anofel Cryptosporidium National Network, Université Paris Diderot - Paris 7 (UPD7), Université de Tours, Institut de veille sanitaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de Référence du Paludisme [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Stress, Immunité, Pathogènes (SIMPA), Université de Lorraine (UL), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, McGill University = Université McGill [Montréal, Canada], Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), Thérapeutique Recombinante Expérimentale [?-2015] (TIMC-TheREx [?-2015]), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 [2011-2015] (TIMC [2011-2015]), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-IMAG-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2007-2019] (Grenoble INP [2007-2019])-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-IMAG-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2007-2019] (Grenoble INP [2007-2019])-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC), and VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2007-2019] (Grenoble INP [2007-2019])-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2007-2019] (Grenoble INP [2007-2019])-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)

Subjects
0301 basic medicine, Microbiology (medical), Adult, Male, Plasmodium falciparum, Protozoan Proteins, DC4, Context (language use), Domain cassette, Real-Time Polymerase Chain Reaction, Group A, Severity of Illness Index, 03 medical and health sciences, Young Adult, Severe malaria, 0302 clinical medicine, DC8, Gene expression, parasitic diseases, medicine, Humans, Imported malaria, Var gene, Malaria, Falciparum, DC13, Gene, Genetics, biology, Gene Expression Profiling, General Medicine, Middle Aged, biology.organism_classification, medicine.disease, Virology, 3. Good health, Erythrocyte membrane, 030104 developmental biology, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, biology.protein, Female, France, Antibody, Malaria, 030215 immunology
Abstract

International audience; Objectives - Severe Plasmodium falciparum malaria (SM) involves cytoadhesion of parasitized red blood cells, mediated by P. falciparum erythrocyte membrane protein 1, which is encoded by var genes. Expression of var gene group A and B or encoding domain cassettes DC4, DC5, DC8 and DC13 has been implicated in SM in African children, but no data exist in the context of imported malaria. The aim of this study was to investigate var gene expression linked to clinical presentation and host factors in SM imported into France. Methods - Expression level of var gene groups A, B, C, var1, var2csa, var3 and var genes encoding DC4, DC5, DC8 and DC13 was measured by quantitative RT-PCR and expressed in transcript units. Seventy SM and 48 uncomplicated malaria (UM) P. falciparum cases were analysed according to disease severity, epidemiological characteristics (migrants or travellers) and anti-P. falciparum antibodies. Cluster analysis was performed to identify gene expression profiles. Results - Var1 and B/C expression were higher in UM than SM (0.66 (0-1.1) and 1.88 (1.3-2.4); p

Published
2017
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6. Longitudinal study assessing the return of chloroquine susceptibility of Plasmodium falciparum in isolates from travellers returning from West and Central Africa, 2000-2011

Author

Gharbi, M, Flegg, JA, Hubert, V, Kendjo, E, Metcalf, JE, Bertaux, L, Guérin, PJ, Le Bras, J, Members of the French National Reference Centre for Imported Malaria Study, Aboubaca, A, Agnamey, P, Angoulvant, A, Barbut, P, Basset, D, Belkadi, G, Bellanger, AP, Bemba, D, Benoit-Vica, F, Berry, A, Bigel, ML, Bonhomme, J, Botterel, F, Bouchaud, O, Bougnoux, ME, Bourée, P, Bourgeois, N, Branger, C, Bret, L, Buret, B, Casalino, E, Chevrier, S, Conquere de Monbrison, F, Cuisenier, B, Danis, M, Darde, ML, De Gentile, L, Delarbre, JM, Delaunay, P, Delaval, A, Desoubeaux, G, Develoux, M, Dunand, J, Durand, R, Eloy, O, Fauchet, N, Faugere, B, Faye, A, Fenneteau, O, Flori, P, Fontrouge, M, Garabedian, C, Gayandrieu, F, Godineau, N, Houzé, P, Houzé, S, Hurst, JP, Ichou, H, Lachaud, L, Lebuisson, A, Lefevre, M, LeGuern, AS, Le Moal, G, Lusina, D, Machouart, MC, Malvy, D, Matheron, S, Maubon, D, Mechali, D, Megarbane, B, Menard, G, Millon, L, Aiach, MM, Minodier, P, Morelle, C, Nevez, G, Parola, P, Parzy, D, Patey, O, Patoz, P, Penn, P, Perignon, A, Picot, S, Pilo, JE, Poilane, I, Pons, D, Poupart, M, Pradines, B, Raffenot, D, Rapp, C, Receveur, MC, Sarfati, C, Senghor, Y, Simon, F, Siriez, JY, Taudon, N, Thellier, M, Thouvenin, M, Toubas, D, Faculté de Pharmacie, PRES Sorbonne Paris Cité, WorldWide Antimalarial Resistance Network, WWARN, École des Hautes Études en Santé Publique [EHESP] ( EHESP ), Mère et enfant face aux infections tropicales ( MERIT - UMR_D 216 ), Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ), Centre for Tropical Medicine, University of Oxford [Oxford], Service de Parasitologie Mycologie [Bichat- Claude Bernard], Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), Centre National de Référence du Paludisme, Consiglio Nazionale delle Ricerche ( CNR ), Service de parasitologie - mycologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Epidemiology and Infectious Diseases, Infections Parasitaires : Transmission, Physiopathologie et Thérapeutiques ( IP-TPT ), Institut de Recherche pour le Développement ( IRD ) -Aix Marseille Université ( AMU ) -Assistance Publique - Hôpitaux de Marseille ( APHM ) -Service de Santé des Armées-Université de Montpellier ( UM ), Epidémiologie des maladies infectieuses et modélisation ( ESIM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), This study was supported in part by a grant for doctoral studies to M Gharbi from the Doctoral Network of the École des Hautes Études en Santé Publique, Rennes, France and a grant for CNRpaludisme from Institut national de Veille Sanitaire, St Maurice, France., Members of the French National Reference Centre for Imported Malaria Study, École des Hautes Études en Santé Publique [EHESP] (EHESP), 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), University of Oxford, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Infections Parasitaires : Transmission, Physiopathologie et Thérapeutiques (IP-TPT), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Service de Santé des Armées, Epidémiologie des maladies infectieuses et modélisation (ESIM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Consiglio Nazionale delle Ricerche (CNR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), BMC, Ed., Service de Parasitologie - Mycologie [CHU Pitié-Salpétrière], 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
Male, Veterinary medicine, Resistance, Drug Resistance, Drug resistance, 0302 clinical medicine, Parasitic Sensitivity Tests, 1108 Medical Microbiology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Chloroquine, Longitudinal Studies, 030212 general & internal medicine, Malaria, Falciparum, Child, Aged, 80 and over, Travel, Central Africa, Mefloquine, pfcrt76, Middle Aged, 3. Good health, Africa, Western, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Infectious Diseases, Child, Preschool, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, In vitro, medicine.drug, Adult, Travellers, medicine.medical_specialty, lcsh:Arctic medicine. Tropical medicine, Adolescent, Genotype, lcsh:RC955-962, 030231 tropical medicine, Plasmodium falciparum, Biology, lcsh:Infectious and parasitic diseases, Antimalarials, Young Adult, 03 medical and health sciences, Tropical Medicine, parasitic diseases, West Africa, medicine, Humans, lcsh:RC109-216, Africa, Central, Aged, Molecular epidemiology, Research, Members of the French National Reference Centre for Imported Malaria Study, Infant, medicine.disease, biology.organism_classification, Virology, Malaria, Parasitology, Tropical medicine
Abstract

Background Chloroquine (CQ) was the main malaria therapy worldwide from the 1940s until the 1990s. Following the emergence of CQ-resistant Plasmodium falciparum, most African countries discontinued the use of CQ, and now promote artemisinin-based combination therapy as the first-line treatment. This change was generally initiated during the last decade in West and Central Africa. The aim of this study is to describe the changes in CQ susceptibility in this African region, using travellers returning from this region as a sentinel system. Methods The study was conducted by the Malaria National Reference Centre, France. The database collated the pfcrtK76T molecular marker for CQ susceptibility and the in vitro response to CQ of parasites from travellers’ isolates returning from Senegal, Mali, Ivory Coast or Cameroon. As a proxy of drug pressure, data regarding CQ intake in febrile children were collated for the study period. Logistic regression models were used to detect trends in the proportions of CQ resistant isolates. Results A total of 2874 parasite isolates were genotyped between 2000–2011. The prevalence of the pfcrt76T mutant genotype significantly decreased for Senegal (from 78% to 47%), Ivory Coast (from 63% to 37%), Cameroon (from 90% to 59%) and remained stable for Mali. The geometric mean of the 50% inhibitory concentration (IC50) of CQ in vitro susceptibility and the proportion of resistant isolates (defining resistance as an IC50 value > 100 nM) significantly decreased for Senegal (from 86 nM (59%) to 39 nM (25%)), Mali (from 84 nM (50%) to 51 nM (31%)), Ivory Coast (from 75 nM (59%) to 29 nM (16%)) and Cameroon (from 181 nM (75%) to 51 nM (37%)). Both analyses (molecular and in vitro susceptibility) were performed for the 2004–2011 period, after the four countries had officially discontinued CQ and showed an accelerated decline of the resistant isolates for the four countries. Meanwhile, CQ use among children significantly deceased in this region (fixed effects slope = −0.3, p -3). Conclusions An increase in CQ susceptibility following official withdrawal of the drug was observed in travellers returning from West and Central African countries. The same trends were observed for molecular and in vitro analysis between 2004-2011and they correlated to the decrease of the drug pressure.

Published
2013
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