Molecular monitoring of antimalarial drug resistance among Plasmodium falciparum field isolates from Odisha,India |
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| Affiliation: | 1. Department of Molecular Biology, Regional Medical Research Centre, Bhubaneswar 751023, India;2. Department of Biotechnology, North Orissa University, Baripada, Odisha 757003, India;1. Evolutionary Genomics and Bioinformatics Laboratory, Division of Genomics and Bioinformatics, National Institute of Malaria Research, Sector 8, Dwarka, New Delhi 110077, India;2. Department of Biotechnology, Kumaun University, Nainital 263001, Uttarakhand, India;1. Malaria Research, Infectious Diseases Unit, Department of Medicine Solna, Karolinska University Hospital/Karolinska Institutet, Retzius väg 10, 171 77 Stockholm, Sweden;2. Departamento de Parasitología, Escuela de Microbiología, Facultad de Ciencias, Universidad Nacional Autónoma de Honduras (UNAH), Tegucigalpa, Honduras;3. Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden;4. Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal;5. ICVS/3B’s – PT Government Associate Laboratory, Braga/Guimarães, Portugal;6. Global Health, Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden;7. Malaria and Vector Research Group, Biotechnology Research Center, Pasteur Institute of Iran, Iran;8. Centro Internacional de Entrenamiento e Investigaciones Médicas, Cali, Colombia;9. Shoklo Malaria Research Unit, Mae Sot Tak, Thailand;10. Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;11. Nuffield Department of Clinical Medicine, Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Oxford, United Kingdom;12. School of Biological Sciences, Nanyang Technological University, Singapore;13. Department of Biomedical Sciences and Veterinary Public Health, Section of Virology, Swedish University of Agricultural Sciences, Uppsala, Sweden;1. Department of Molecular Tropical Medicine and Genetics, Mahidol University, Bangkok, Thailand;2. Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;3. Buntharik Hospital, Amphoe Buntharik, Ubon Ratchathani, Thailand;4. Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Vientiane, Laos;5. Faculty of Postgraduate Studies, University of Health Sciences, Vientiane, Laos;6. Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom;7. National Centre for Parasitology, Entomology, and Malaria Control (CNM), Phnom Penh, Cambodia;8. Myanmar Oxford Clinical Research Unit, Yangon, Myanmar;9. Medical Action Myanmar, Yangon, Myanmar;10. Defence Services Medical Research Centre, Naypyitaw, Myanmar;11. Wellcome Trust Sanger Institute, Hinxton, UK;12. Malaria Molecular Epidemiology Unit, Institut Pasteur in Cambodia, Phnom Penh, Cambodia;13. Worldwide Antimalarial Resistance Network (WWARN), Bangkok, Thailand;1. Department of Molecular Parasitology, National Institute of Malaria Research, ICMR, Bengaluru, Karnataka, India E-mail: ghoshnimr@gmail.com |
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| Abstract: | In the absence of definite marker for artemisinin (ART) resistance, molecular monitoring of its partner drug sulfadoxine pyrimethamine (SP) in artemisinin based combination therapy (ACTs) together with chloroquine (CQ) for which ART is negatively correlated, may predict the effectiveness of ACT. We analyzed 201 Plasmodium falciparum field isolates for drug resistance markers for CQ (pfcrt and pfmdr1), pyrimethamine (pfdhfr) and sulfadoxine (pfdhps). Our study reveals high prevalence and non-random association of resistant mutants (K76T and N86Y) of CQ markers (pfcrt and pfmdr1). The predominance of highly resistant pfdhfr genotypes for SP with intragenic and intergenic pair-wise linkage disequilibrium between single nucleotide polymorphisms of resistant mutants of pfdhfr (C59R and S108N) and pfdhps (S436A, A437G, K540E) warn on further inclusion of SP in ACT. These findings suggest the replacement of SP in ACT with alternative partner drug for better efficacy. |
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