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"dihydrofolate reductase"

Original Article

Molecular Markers for Sulfadoxine/Pyrimethamine and Chloroquine Resistance in Plasmodium falciparum in Thailand
Jiraporn Kuesap, Nutnicha Suphakhonchuwong, Lertluk Kalawong, Natthaya Khumchum
Korean J Parasitol 2022;60(2):109-116.
Published online April 20, 2022
DOI: https://doi.org/10.3347/kjp.2022.60.2.109
Drug resistance is an important problem hindering malaria elimination in tropical areas. Point mutations in Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) genes confer resistance to antifolate drug, sulfadoxine-pyrimethamine (SP) while P. falciparum chloroquine-resistant transporter (Pfcrt) genes caused resistance to chloroquine (CQ). Decline in Pfdhfr/Pfdhps and Pfcrt mutations after withdrawal of SP and CQ has been reported. The aim of present study was to investigate the prevalence of Pfdhfr, Pfdhps, and Pfcrt mutation from 2 endemic areas of Thailand. All of 200 blood samples collected from western area (Thai-Myanmar) and southern area (Thai-Malaysian) contained multiple mutations in Pfdhfr and Pfdhps genes. The most prevalent haplotypes for Pfdhfr and Pfdhps were quadruple and double mutations, respectively. The quadruple and triple mutations of Pfdhfr and Pfdhps were common in western samples, whereas low frequency of triple and double mutations was found in southern samples, respectively. The Pfcrt 76T mutation was present in all samples examined. Malaria isolated from 2 different endemic regions of Thailand had high mutation rates in the Pfdhfr, Pfdhps, and Pfcrt genes. These findings highlighted the fixation of mutant alleles causing resistance of SP and CQ in this area. It is necessary to monitor the re-emergence of SP and CQ sensitive parasites in this area.

Citations

Citations to this article as recorded by  Crossref logo
  • Assessing fitness costs in malaria parasites: a comprehensive review and implications for drug resistance management
    Xyonane Segovia, Bhavya Srivastava, Sergio Serrato-Arroyo, Ashley Guerrero, Silvie Huijben
    Malaria Journal.2025;[Epub]     CrossRef
  • Plasmodium falciparum dhps and dhfr markers of resistance to sulfadoxine–pyrimethamine five years (2016–2020) after the implementation of seasonal malaria chemoprevention in Cameroon
    Pacome V. K. Tchuenkam, Lesley N. Ngum, Innocent M. Ali, Jean Paul K. Chedjou, Akindeh M. Nji, Palmer M. Netongo, Randolph Ngwafor, Peter Thelma N. Niba, Calvino F. Tah, William D. Nana, Germaine Ekoyol, Jude D. Bigoga, Dorothy F. Ashu, Christopher B. Tum
    Wellcome Open Research.2024; 9: 323.     CrossRef
  • Exploring the Recent Pioneering Developments of Small Molecules in Antimalarial Drug Armamentarium: A Chemistry Prospective Appraisal
    Tameika Bagratee, Ritika Prawlall, Thabani Ndlovu, Sinqobile Sibisi, Sisa Ndadane, Baji Baba Shaik, Mahesh B. Palkar, Raghavachary Gampa, Rajshekhar Karpoormath
    Chemistry & Biodiversity.2024;[Epub]     CrossRef
  • In vitro efficacy of next-generation dihydrotriazines and biguanides against babesiosis and malaria parasites
    Pratap Vydyam, Meenal Chand, Shalev Gihaz, Isaline Renard, Gavin D. Heffernan, Laura R. Jacobus, David P. Jacobus, Kurt W. Saionz, Raju Shah, Hong-Ming Shieh, Jacek Terpinski, Wenyi Zhao, Emmanuel Cornillot, Choukri Ben Mamoun, Audrey Odom John
    Antimicrobial Agents and Chemotherapy.2024;[Epub]     CrossRef
  • Antimalarial drug sulfadoxine induces gametocytogenesis in Plasmodium berghei
    Wihda Aisarul Azmi, Andita Fitri Mutiara Rizki, Achmad Shidiq, Yenny Djuardi, I Made Artika, Josephine Elizabeth Siregar
    Malaria Journal.2024;[Epub]     CrossRef
  • Prevalence of molecular markers of sulfadoxine-pyrimethamine resistance in Plasmodium falciparum isolates from West Africa during 2012–2022
    Ruimin Zhou, Suhua Li, Penghui Ji, Shucheng Ruan, Ying Liu, Chengyun Yang, Dan Qian, Zhiquan He, Dan Wang, Deling Lu, Hongwei Zhang, Yan Deng
    Scientific Reports.2024;[Epub]     CrossRef
  • A snapshot of the prevalence of dihydropteroate synthase-431V mutation and other sulfadoxine-pyrimethamine resistance markers in Plasmodium falciparum isolates in Nigeria
    Adebanjo J. Adegbola, Omotade A. Ijarotimi, Akaninyene E. Ubom, Bukola A. Adesoji, Olajide E. Babalola, Emma F. Hocke, Helle Hansson, Andria Mousa, Oluseye O. Bolaji, Michael Alifrangis, Cally Roper
    Malaria Journal.2023;[Epub]     CrossRef
  • Current development of 1,2,3-triazole derived potential antimalarial scaffolds: Structure- activity relationship (SAR) and bioactive compounds
    S. Maheen Abdul Rahman, Jasvinder Singh Bhatti, Suresh Thareja, Vikramdeep Monga
    European Journal of Medicinal Chemistry.2023; 259: 115699.     CrossRef
  • 4,149 View
  • 217 Download
  • 8 Web of Science
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Brief Communication

Genetic Polymorphisms in Plasmodium vivax Dihydrofolate Reductase and Dihydropteroate Synthase in Isolates from the Philippines, Bangladesh, and Nepal
Pimwan Thongdee, Jiraporn Kuesap, Kanchana Rungsihirunrat, Shyam Prakash Dumre, Effie Espino, Harald Noedl, Kesara Na-Bangchang
Korean J Parasitol 2015;53(2):227-232.
Published online April 22, 2015
DOI: https://doi.org/10.3347/kjp.2015.53.2.227
Genetic polymorphisms of pvdhfr and pvdhps genes of Plasmodium vivax were investigated in 83 blood samples collected from patients in the Philippines, Bangladesh, and Nepal. The SNP-haplotypes of the pvdhfr gene at the amino acid positions 13, 33, 57, 58, 61, 117, and 173, and that of the pvdhps gene at the positions 383 and 553 were analyzed by nested PCR-RFLP. Results suggest diverse polymorphic patterns of pvdhfr alone as well as the combination patterns with pvdhps mutant alleles in P. vivax isolates collected from the 3 endemic countries in Asia. All samples carried mutant combination alleles of pvdhfr and pvdhps. The most prevalent combination alleles found in samples from the Philippines and Bangladesh were triple mutant pvdhfr combined with single mutant pvdhps allele and triple mutant pvdhfr combined with double wild-type pvdhps alleles, respectively. Those collected from Nepal were quadruple mutant pvdhfr combined with double wild-type pvdhps alleles. New alternative antifolate drugs which are effective against sulfadoxine-pyrimethamine (SP)-resistant P. vivax are required.

Citations

Citations to this article as recorded by  Crossref logo
  • Molecular surveillance of antifolate drug resistance markers in Plasmodium vivax from Khyber Pakhtunkhwa province, northwest Pakistan
    Thu Hằng Nguyễn, Hương Giang Lê, Tuấn Cường Võ, Đăng Thùy Dương Nguyễn, Kim Oanh Nguyễn, Minkyoung Cho, Youn-Kyoung Goo, Sahib Gul Afridi, Byoung-Kuk Na
    Acta Tropica.2025; 264: 107583.     CrossRef
  • Genetic Diversity of Plasmodium vivax Merozoite Surface Protein-3 Alpha and Beta from Diverse Geographic Areas of Thailand
    Jiraporn Kuesap, Kanchana Rungsihirunrat, Wanna Chaijaroenkul, Mathirut Mungthin
    Japanese Journal of Infectious Diseases.2022; 75(3): 241.     CrossRef
  • Geographical spread and structural basis of sulfadoxine-pyrimethamine drug-resistant malaria parasites
    Rini Chaturvedi, Jyoti Chhibber-Goel, Ishika Verma, Sreehari Gopinathan, Suhel Parvez, Amit Sharma
    International Journal for Parasitology.2021; 51(7): 505.     CrossRef
  • Molecular monitoring of dihydrofolatereductase (dhfr) and dihydropteroatesynthetase (dhps) associated with sulfadoxine-pyrimethamine resistance in Plasmodium vivax isolates of Palawan, Philippines
    Alison Paolo Bareng, Fe Esperanza Espino, Wanna Chaijaroenkul, Kesara Na-Bangchang
    Acta Tropica.2018; 180: 81.     CrossRef
  • Mutations of pvdhfr and pvdhps genes in vivax endemic-malaria areas in Kota Marudu and Kalabakan, Sabah
    Umi Rubiah Sastu, Noor Rain Abdullah, Nor Azrina Norahmad, Muhammad Nor Farhan Saat, Prem Kumar Muniandy, Jenarun Jelip, Moizin Tikuson, Norsalleh Yusof, Hasidah Mohd Sidek
    Malaria Journal.2016;[Epub]     CrossRef
  • Geographic distribution of amino acid mutations in DHFR and DHPS in Plasmodium vivax isolates from Lao PDR, India and Colombia
    Naowarat Saralamba, Supatchara Nakeesathit, Mayfong Mayxay, Paul N. Newton, Lyda Osorio, Jung-Ryong Kim, Nicholas J. White, Nicholas P. J. Day, Arjen M. Dondorp, Mallika Imwong
    Malaria Journal.2016;[Epub]     CrossRef
  • 9,186 View
  • 111 Download
  • 6 Web of Science
  • Crossref
Original Article
Plasmodium vivax dhfr Mutations among Isolates from Malarious Areas of Iran
Jalal Zaman, Abbas Shahbazi, Mohammad Asgharzadeh
Korean J Parasitol 2011;49(2):125-131.
Published online June 14, 2011
DOI: https://doi.org/10.3347/kjp.2011.49.2.125

The use of sulfadoxine and pyrimethamine (SP) for treatment of vivax malaria is uncommon in most malarious areas, but Plasmodium vivax isolates are exposed to SP because of mixed infections with other Plasmodium species. As P. vivax is the most prevalent species of human malaria parasites in Iran, monitoring of resistance of the parasite against the drug is necessary. In the present study, 50 blood samples of symptomatic patients were collected from 4 separated geographical regions of south-east Iran. Point mutations at residues 57, 58, 61, and 117 were detected by the PCR-RFLP method. Polymorphism at positions 58R, 117N, and 117T of P. vivax dihydrofolate reductase (Pvdhfr) gene has been found in 12%, 34%, and 2% of isolates, respectively. Mutation at residues F57 and T61 was not detected. Five distinct haplotypes of the Pvdhfr gene were demonstrated. The 2 most prevalent haplotypes were F57S58T61S117 (62%) and F57S58T61N117 (24%). Haplotypes with 3 and 4 point mutations were not found. The present study suggested that P. vivax in Iran is under the pressure of SP and the sensitivity level of the parasite to SP is diminishing and this fact must be considered in development of malaria control programs.

Citations

Citations to this article as recorded by  Crossref logo
  • Molecular evaluation of pvdhfr and pvmdr-1 mutants in Plasmodium vivax isolates after treatment with sulfadoxine/pyrimethamine and chloroquine in Iran during 2001–2016
    Mahdi Parsaei, Ahmad Raeisi, Adel Spotin, Abbas Shahbazi, Mahmoud Mahami-Oskouei, Teimour Hazratian, Alireza Salimi Khorashad, Jalal Zaman, Ahad Bazmani, Sedighe Sarafraz
    Infection, Genetics and Evolution.2018; 64: 70.     CrossRef
  • Mutational Analysis of Plasmodium vivax dhfr Gene Among Cases in South East of Iran
    Hadi Mirahmadi, Maryam Rafee, Jalal Zaman, Ahmad Mehravaran, Reza Shafiei
    Jundishapur Journal of Microbiology.2017;[Epub]     CrossRef
  • MOLECULAR SURVEILLANCE OF Plasmodium vivax AND Plasmodium falciparum DHFR MUTATIONS IN ISOLATES FROM SOUTHERN IRAN
    Khojasteh SHARIFI-SARASIABI, Ali HAGHIGHI, Bahram KAZEMI, Niloofar TAGHIPOUR, Ehsan Nazemalhosseini MOJARAD, Latif GACHKAR
    Revista do Instituto de Medicina Tropical de São Paulo.2016;[Epub]     CrossRef
  • 7,767 View
  • 58 Download
  • Crossref