High prevalence of sulfadoxine/pyrimethamine resistance alleles in Plasmodium falciparum parasites from Bangladesh |
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| Authors: | Aung Swi Prue Marma Toshihiro Mita Hideaki Eto Takahiro Tsukahara Sumon Sarker Hiroyoshi Endo |
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| Institution: | 1. Department of International Affairs and Tropical Medicine, Faculty of Medicine, Tokyo Women''s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan;2. Bandarban Sadar Hospital, Bandarban, Bangladesh;1. College of Public Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand;2. Mae Sot General Hospital, Tak Province 63110, Thailand;3. Drug Discovery and Development Center, Thammasat University, Bangkok 12121, Thailand;4. Thammasat University Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Chulabhorn International College of Medicine, Thammasat University, Bangkok 12121, Thailand;1. Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine London, WC1E 7HT, UK;2. Centre for Medical Parasitology, Department of International Health, Immunology and Microbiology, University of Copenhagen, Denmark;3. Department of Infectious Disease, Copenhagen University Hospital, Denmark;4. Institut Pasteur, Genetics and Genomics of Insect Vectors Unit, Paris, France;5. Parasitology and Mycology Department, Paris, France;6. Malaria Public Health Department, University of Oxford-KEMRI-Wellcome Trust Programme, Nairobi, Kenya;7. Malaria Molecular Epidemiology Unit, Institut Pasteur in Cambodia, Phnom Penh, Cambodia;8. Drug Resistance and Containment, Global malaria Programme, World Health Organization, Geneva, Switzerland;1. Department of Molecular Biology, Regional Medical Research Centre, Bhubaneswar 751023, India;2. Department of Biotechnology, North Orissa University, Baripada, Odisha 757003, India;1. Immunology and Microbiology Laboratory, Department of Human Physiology with Community Health, Vidyasagar University, Midnapore 721 102, West Bengal, India;2. Former Director, Head of the Department of Medical Entomology and Chairman, Division of Parasitology, Calcutta School of Tropical Medicine, Kolkata 700 073, West Bengal, India;1. Department of Parasitology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia;2. Tropical Disease Research Center, University of Science and Technology, Sana’a, Yemen;3. Department of Parasitology, Faculty of Medicine, Sana’a University, Yemen;1. Program in Public Health, University of California, Irvine, CA, USA;2. Department of Medicine, Division of Infectious Diseases, University of California, Irvine, CA, USA;3. Department of Pathogen Biology and Immunology, Kunming Medical University, Kunming, China;4. Department of Entomology, Pennsylvania State University, University Park, PA, USA |
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| Abstract: | In Bangladesh, despite the official introduction of artemisinin combination therapy in 2004, chloroquine+sulfadoxine/pyrimethamine has been used for the treatment of uncomplicated malaria. To assess the distribution of pfcrt, pfmdr1, dhfr, and dhps genotypes in Plasmodium falciparum, we conducted hospital- and community-based surveys in Bandarban, Bangladesh (near the border with Myanmar) in 2007 and 2008. Using nested PCR followed by digestion, 139 P. falciparum isolates were genotyped. We found fixation of a mutation at position 76 in pfcrt and low prevalence of a mutation at position 86 in pfmdr1. In dhfr, the highest pyrimethamine resistant genotype quadruple mutant was found in 19% of isolates, which is significantly higher prevalence than reported in a previous study in Khagrachari (1%) in 2002. Microsatellite haplotypes flanking dhfr of the quadruple mutants in Bangladesh were identical or very similar to those found in Thailand and Cambodia, indicating a common origin for the mutant in these countries. These observations suggest that the higher prevalence of the dhfr quadruple mutant in Bandarban is because of parasite migration from Myanmar. However, continuous use of sulfadoxine/pyrimethamine would have also played a role through selection for the dhfr quadruple mutant. These results indicate an urgent need to collect molecular epidemiological information regarding dhfr and dhps genes, and a review of current sulfadoxine/pyrimethamine usage with the aim of avoiding the widespread distribution of high levels of resistant parasites in Bangladesh. |
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