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1. Polymorphism of Plasmodium falciparum Na+/H+ exchanger is indicative of a low in vitro quinine susceptibility in isolates from Viet Nam

Author

Le Minh Tai, Marc Desbordes, Stéphane Pelleau, Daniel Parzy, Nguyen Thu Huong, Lionel Bertaux, Vu Nhu Huong, Nguyen Xuan Thanh, Christine Latour, Le Hong Quang, Véronique Sinou, and Lai Quang Long

Subjects
Sodium-Hydrogen Exchangers, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, Plasmodium falciparum, Drug Resistance, Locus (genetics), lcsh:Infectious and parasitic diseases, Antimalarials, Gene Frequency, Parasitic Sensitivity Tests, medicine, Humans, Parasite hosting, lcsh:RC109-216, Malaria, Falciparum, Genetics, Quinine, Polymorphism, Genetic, biology, Research, Haplotype, biology.organism_classification, Molecular biology, Infectious Diseases, Haplotypes, Vietnam, Parasitology, Genetic marker, Microsatellite, medicine.drug
Abstract

Background The Plasmodium falciparum NA+/H+ exchanger (pfnhe1, gene PF13_0019) has recently been proposed to influence quinine (QN) susceptibility. However, its contribution to QN resistance seems to vary geographically depending on the genetic background of the parasites. Here, the role of this gene was investigated in in vitro QN susceptibility of isolates from Viet Nam. Method Ninety-eight isolates were obtained from three different regions of the Binh Phuoc and Dak Nong bordering Cambodia provinces during 2006-2008. Among these, 79 were identified as monoclonal infection and were genotyped at the microsatellite pfnhe1 ms4760 locus and in vitro QN sensitivity data were obtained for 51 isolates. Parasite growth was assessed in the field using the HRP2 immunodetection assay. Results Significant associations were found between polymorphisms at pfnhe1 microsatellite ms4760 and susceptibility to QN. Isolates with two or more DNNND exhibited much lower susceptibility to QN than those harbouring zero or one DNNND repeats (median IC50 of 682 nM versus median IC50 of 300 nM; p = 0.0146) while isolates with one NHNDNHNNDDD repeat presented significantly reduced QN susceptibility than those who had two (median IC50 of 704 nM versus median IC50 of 375 nM; p < 0.01). These QNR associated genotype features were mainly due to the over representation of profile 7 among isolates (76.5%). The majority of parasites had pfcrt76T and wild-type pfmdr1 (> 95%) thus preventing analysis of associations with these mutations. Interestingly, area with the highest median QN IC50 showed also the highest percentage of isolates carrying the pfnhe1 haplotype 7. Conclusions The haplotype 7 which is the typical Asian profile is likely well-adapted to high drug pressure in this area and may constitute a good genetic marker to evaluate the dissemination of QNR in this part of the world.

Published
2011

2. Past and new challenges for malaria control and elimination: the role of operational research for innovation in designing interventions

Author

François Nosten, Marc Coosemans, Arjen M. Dondorp, Philippe Guyant, Sébastien Boyer, Véronique Sinou, Philippe J Guerin, Adeline Lautissier, Nicholas J. White, Vincent Corbel, Shunmay Yeung, Partners for Development [Phnom Penh, Cambodia], Partners For Development [Silver Spring, MD] (PFD), Kasetsart University (KU), 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 for Tropical Medicine and Global Health [Oxford, UK], Nuffield Department of Medicine [Oxford, UK] (Big Data Institute), University of Oxford-University of Oxford, WorldWide Antimalarial Resistance Network (WWARN), University of Oxford-Churchill Hospital Oxford Centre for Haematology, Initiative 5%, Expertise France, 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, Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP), University of Antwerp (UA), Institute of Tropical Medicine [Antwerp] (ITM), Mahidol University [Bangkok], 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, London School of Hygiene and Tropical Medicine (LSHTM), 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), The authors would like to thank Expertise France (formerly known as France Expertise Internationale) and the 5% Initiative (indirect contribution of France to the Global Fund to fight AIDS, Tuberculosis and Malaria) for taking the initiative of this meeting, and the government of the Kingdom of Thailand, the French Ministry of Foreign Affairs and International Development, the French Embassy of Thailand and the Roll Back Malaria Partnership for supporting the organization of this event., Institut de Recherche pour le Développement (IRD [France-Sud])-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), University of Oxford [Oxford]-University of Oxford [Oxford], University of Oxford [Oxford]-Churchill Hospital Oxford Centre for Haematology, Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford]-Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford], Service de Santé des Armées-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Institut de Recherche pour le Développement (IRD), and INSB-INSB-Centre National de la Recherche Scientifique (CNRS)

Subjects
Operations Research, Civil society, Operations research, [SDV]Life Sciences [q-bio], 030231 tropical medicine, Population, ARTEMISININ RESISTANCE, Psychological intervention, India, Resistance (psychoanalysis), Meeting Report, Global Health, World Health Organization, Education, Scientific evidence, Insecticide Resistance, 03 medical and health sciences, 0302 clinical medicine, KNOCKDOWN RESISTANCE, ARTEMETHER-LUMEFANTRINE, parasitic diseases, medicine, Global health, Humans, 030212 general & internal medicine, education, SOUTHEAST-ASIA, Health policy, education.field_of_study, Health Policy, CAMBODIA, PLASMODIUM-FALCIPARUM MALARIA, Thailand, medicine.disease, CHLOROQUINE RESISTANCE, ANOPHELES-GAMBIAE, Malaria, 3. Good health, Infectious Diseases, 13. Climate action, DIHYDROARTEMISININ-PIPERAQUINE FAILURE, MEKONG REGION, Africa, Parasitology, Human medicine, Business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

This meeting report presents the outcomes of a workshop held in Bangkok on December 1st 2014, where the following challenges were discussed: the threat of resistance to artemisinin and artemisinin-based combination therapy in the Greater Mekong Sub-region (GMS) and in Africa; access to treatment for most at risk and hard to reach population; insecticide resistance, residual and outdoors transmission. The role of operational research and the interactions between research institutions, National Malaria Control Programmes, Civil Society Organizations, and of financial and technical partners to address those challenges and to accelerate translation of research into policies and programmes were debated. The threat and the emergency of the artemisinin resistance spread and independent emergence in the GMS was intensely debated as it is now close to the border of India. The need for key messages, based on scientific evidence and information available and disseminated without delay, was highlighted as crucial for an effective and urgent response. Electronic supplementary material The online version of this article (doi:10.1186/s12936-015-0802-4) contains supplementary material, which is available to authorized users.

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