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

Malaria Journal

Research

Lionel Bertaux¹  Véronique Hubert²  Eric Kendjo³  Philippe J Guérin⁴  Jessica E Metcalf⁵  Jacques Le Bras⁶  Myriam Gharbi⁷  Jennifer A Flegg⁸ 

[1] Centre National de Référence du Paludisme, Marseille, France;Unité de Recherche en Physiologie et Pharmacocinétique Parasitaires - UMR-MD3 Relations Hôte-Parasites - Pharmacologie et Thérapeutique, Institut de Recherche Biomédicale des Armées, Marseille, France;Centre National de Référence du Paludisme, Paris, France;Service de Parasitologie Mycologie, CHU Bichat-Claude Bernard, APHP, Paris, France;Centre National de Référence du Paludisme, Paris, France;Service de Parasitologie Mycologie, CHU Pitié-Salpétrière, APHP, Paris, France;EHESP Rennes, Sorbonne, Paris Cité, France;WWARN, Oxford, UK;Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, CCVTM, University of Oxford, Oxford, UK;UMR S 707: Epidemiology, Information Systems, Modelling, INSERM and Université Pierre et Marie-Curie-Paris, Paris, France;Epidemiology and Infectious Diseases, Department of Zoology, University of Oxford, Oxford, UK;Mère et enfant face aux infections tropicales, IRD unité mixte de recherche 216, Université Paris Descartes-Paris V, 4 avenue de l'Observatoire, 75270, Paris Cedex 06, France;PRES Sorbonne Paris Cité, Faculté de Pharmacie, Paris, France;WorldWide Antimalarial Resistance Network (WWARN), Paris, France;Centre National de Référence du Paludisme, Paris, France;Service de Parasitologie Mycologie, CHU Bichat-Claude Bernard, APHP, Paris, France;Mère et enfant face aux infections tropicales, IRD unité mixte de recherche 216, Université Paris Descartes-Paris V, 4 avenue de l'Observatoire, 75270, Paris Cedex 06, France;PRES Sorbonne Paris Cité, Faculté de Pharmacie, Paris, France;WorldWide Antimalarial Resistance Network (WWARN), Paris, France;EHESP Rennes, Sorbonne, Paris Cité, France;WWARN, Oxford, UK;Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, CCVTM, University of Oxford, Oxford, UK;

关键词: Plasmodium falciparum;    Malaria;    Travellers;    Chloroquine;    Resistance;    pfcrt76;    In vitro;    West Africa;    Central Africa;   

DOI  :  10.1186/1475-2875-12-35

 received in 2012-10-11, accepted in 2013-01-19,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundChloroquine (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.MethodsThe 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.ResultsA 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).ConclusionsAn 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.

【 授权许可】

CC BY   
© Gharbi et al.; licensee BioMed Central Ltd. 2013