The continuous Plasmodium falciparum kelch13 (PfK13) genetic alterations conferring resistance to artemisinin-based combination therapies and partner drugs pose a significant threat to effective treatment and control of P. falciparum infection in developing countries. This review evaluates the emergence and epidemiology of the PfK13 mutation associated with artemisinin resistance in the sub-Saharan Africa (SSA) population. Despite empirical control and artemisinin combination therapy, the PfK13 gene mutation, previously described in Southeast Asia, has been reported in the SSA. Eight of these validated markers, including P553L, M476I, C580Y, A675V, P574L, R561H, R622I, and F446I, were reported among the SSA population. Novel and unvalidated markers, such as P615S, M472I, F434S, A578S, P570L, Y558C, K563R, A569T, I684N, M472I, and C473F spread among the population with low frequency. We provide insight into the emergence and spread of validated and unvalidated PfK13 mutations among the SSA population, which could lead to high artemisinin resistance. Investigating the verified PfK13 mutations will improve prophylactic strategies, prognostic diagnosis and guide effective population-based surveillance for effective P. falciparum malaria control in SSA.
Citations
Citations to this article as recorded by
Emergence of chloroquine-sensitive
Plasmodium falciparum
and rising resistance to first-line artemisinin partner drugs in Malawi
Ernest Mazigo, Hojong Jun, Wang-Jong Lee, Johnsy Mary Louis, Jadidan Hada Syahada, Fadhila Fitriana, Fauzi Muh, Md Atique Ahmed, Feng Lu, Joon-Hee Han, Tae-Hyung Kwon, Se Jin Lee, Sunghun Na, Wanjoo Chun, Won Sun Park, Eun-Taek Han, Winifrida Kidima, Jin- Emerging Microbes & Infections.2025;[Epub] CrossRef
A scoping review of antimalarial drug resistance markers in Kenya (1987–2022): toward a National Surveillance Framework and Data Repository Kevin Wamae, John Magudha, Emmanuel Asiimwe, Kariuki Kimani, Regina Kandie, Kibor Keitany, Robert W. Snow, L. Isabella Ochola-Oyier Malaria Journal.2025;[Epub] CrossRef
Artemisinin resistance (ART) has been confirmed in Greater Mekong Sub-region countries. Currently, C580Y mutation on Pfkelch13 gene is known as the molecular marker for the detection of ART. Rapid and accurate detection of ART in field study is essential to guide malaria containment and elimination interventions. A simple method for collection of malaria-infected blood is to spot the blood on filter paper and is fast and easy for transportation and storage in the field study. This study aims to evaluate LAMP-SNP assay for C580Y mutation detection by introducing an extra mismatched nucleotide at the 3’ end of the FIP primer. The LAMP-SNP assay was performed in a water bath held at a temperature of 56°C for 45 min. LAMP-SNP products were interpreted by both gel-electrophoresis and HNB-visualized changes in color. The method was then tested with 120 P. falciparum DNA from dried blood spot samples. In comparing the LAMP-SNP assay results with those from DNA sequencing of the clinical samples, the 2 results fully agreed to detect C580Y. The sensitivity and specificity of the LAMP-SNP assay showed 100%. There were no cross-reactions with other Plasmodium species and other Pfkelch13 mutations. The LAMP-SNP assay performed in this study was rapid, reliable, and useful in detecting artemisinin resistance in the field study.
Citations
Citations to this article as recorded by
Colorimetric loop-mediated isothermal amplification (cLAMP) assay for the genotyping of a thrombophilia genetic risk factor, MTHFR (C677T) Reham Altwayan, Huseyin Tombuloglu, Moneerah Alsaeed, Abdulrahman Alhusil Analytical Methods.2025; 17(21): 4432. CrossRef
Advancing artemisinin resistance monitoring using a high sensitivity ddPCR assay for Pfkelch13 mutation detection in Asia Suttipat Srisutham, Aungkana Saejeng, Nardlada Khantikul, Rungniran Sugaram, Raweewan Sangsri, Arjen M. Dondorp, Nicholas P. J. Day, Mallika Imwong Scientific Reports.2025;[Epub] CrossRef
Loop-mediated isothermal amplification (LAMP): A promising tool for rapid, point-of-care diagnosis of parasitic diseases in low-income countries Kevin Polpitiya, Madhavi Hewadikaram Molecular and Biochemical Parasitology.2025; 264: 111704. CrossRef
A Biotinylated cpFIT-PNA Platform for the Facile Detection of Drug Resistance to Artemisinin in Plasmodium falciparum Odelia Tepper, Daniel H. Appella, Hongchao Zheng, Ron Dzikowski, Eylon Yavin ACS Sensors.2024; 9(3): 1458. CrossRef
Super-assembly of integrated gold magnetic assay with loop-mediated isothermal amplification for point-of-care testing Jianping Liang, Jie Zeng, Xiaojuan Huang, Tengteng Zhu, Yonglong Gong, Chen Dong, Xiangrong Wang, Lingzhi Zhao, Lei Xie, Kang Liang, Qiongxiang Tan, Yali Cui, Biao Kong, Wenli Hui Nano Research.2023; 16(1): 1242. CrossRef
Engineered Biosensors for Diagnosing Multidrug Resistance in Microbial and Malignant Cells Niharika G. Jha, Daphika S. Dkhar, Sumit K. Singh, Shweta J. Malode, Nagaraj P. Shetti, Pranjal Chandra Biosensors.2023; 13(2): 235. CrossRef
Application of loop-mediated isothermal amplification combined with lateral flow assay visualization of Plasmodium falciparum kelch 13 C580Y mutation for artemisinin resistance detection in clinical samples Wannida Sanmoung, Nongyao Sawangjaroen, Suwannee Jitueakul, Hansuk Buncherd, Aung Win Tun, Supinya Thanapongpichat, Mallika Imwong Acta Tropica.2023; 246: 106998. CrossRef
Visual single nucleotide polymorphism (SNP) detection for ALDH2 genotyping based on multiplex ligation probe amplification (MLPA) and lateral flow assay Dan Yin, Xiaolan Li, Li Mai, Ruxin Wang, Sitian Tang, Liyi Hu Microchemical Journal.2023; 194: 109329. CrossRef
Application of multiple binding sites for LAMP primers across P. falciparum genome improves detection of the parasite from whole blood samples Cavin Mgawe, Clement Shilluli, Steven Nyanjom, Eddy Odari, Jacqueline C. Linnes, Bernard N. Kanoi, Jesse Gitaka, Lucy Ochola Frontiers in Malaria.2023;[Epub] CrossRef
Single nucleotide polymorphism genotyping of ALDH2 gene based on asymmetric PCR and fluorescent probe-mediated melting curves Limei Zhang, Dan Liu, Baolin Li, Jingling Xie, Jinbo Liu, Zhang Zhang Analytical Biochemistry.2022; 642: 114509. CrossRef
Prevalence of Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency among Malaria Patients in Southern Thailand: 8 Years Retrospective Study Thunchanok Khammanee, Nongyao Sawangjaroen, Hansuk Buncherd, Aung Win Tun, Supinya Thanapongpichat The Korean Journal of Parasitology.2022; 60(1): 15. CrossRef
Current Epidemiological Characteristics of Imported Malaria, Vector Control Status and Malaria Elimination Prospects in the Gulf Cooperation Council (GCC) Countries Jamshaid Iqbal, Suhail Ahmad, Ali Sher, Mohammad Al-Awadhi Microorganisms.2021; 9(7): 1431. CrossRef
Artemisinin-based combination therapy (ACT) resistance is widespread throughout the Greater Mekong Subregion. This raises concern over the antimalarial treatment in Thailand since it shares borders with Cambodia, Laos, and Myanmar where high ACT failure rates were reported. It is crucial to have information about the spread of ACT resistance for efficient planning and treatment. This study was to identify the molecular markers for antimalarial drug resistance: Pfkelch13 and Pfmdr1 mutations from 5 provinces of southern Thailand, from 2012 to 2017, of which 2 provinces on the Thai- Myanmar border (Chumphon and Ranong), one on Thai-Malaysia border (Yala) and 2 from non-border provinces (Phang Nga and Surat Thani). The results showed that C580Y mutation of Pfkelch13 was found mainly in the province on the Thai-Myanmar border. No mutations in the PfKelch13 gene were found in Surat Thani and Yala. The Pfmdr1 gene isolated from the Thai-Malaysia border was a different pattern from those found in other areas (100% N86Y) whereas wild type strain was present in Phang Nga. Our study indicated that the molecular markers of artemisinin resistance were spread in the provinces bordering along the Thai-Myanmar, and the pattern of Pfmdr1 mutations from the areas along the international border of Thailand differed from those of the non-border provinces. The information of the molecular markers from this study highlighted the recent spread of artemisinin resistant parasites from the endemic area, and the data will be useful for optimizing antimalarial treatment based on regional differences.
Citations
Citations to this article as recorded by
Advancing artemisinin resistance monitoring using a high sensitivity ddPCR assay for Pfkelch13 mutation detection in Asia Suttipat Srisutham, Aungkana Saejeng, Nardlada Khantikul, Rungniran Sugaram, Raweewan Sangsri, Arjen M. Dondorp, Nicholas P. J. Day, Mallika Imwong Scientific Reports.2025;[Epub] CrossRef
Tracking Drug Resistance in Plasmodium falciparum: Genetic Diversity of Key Resistance Markers in Brazilian Malaria Hotspots Rebecca de Abreu-Fernandes, Lucas Tavares de Queiroz, Natália Ketrin Almeida-de-Oliveira, Aline Rosa de Lavigne Mello, Jacqueline de Aguiar Barros, Lilian Rose Pratt-Riccio, Gisely Cardoso de Melo, Patrícia Brasil, Cláudio Tadeu Daniel-Ribeiro, Didier Men International Journal of Molecular Sciences.2025; 26(13): 5977. CrossRef
Antimalarial Mechanisms and Resistance Status of Artemisinin and Its Derivatives Dan Zheng, Tingting Liu, Shasha Yu, Zhilong Liu, Jing Wang, Ying Wang Tropical Medicine and Infectious Disease.2024; 9(9): 223. CrossRef
Molecular insights into artemisinin resistance in Plasmodium falciparum: An updated review Wihda Aisarul Azmi, Andita Fitri Mutiara Rizki, Yenny Djuardi, I. Made Artika, Josephine Elizabeth Siregar Infection, Genetics and Evolution.2023; 112: 105460. CrossRef
Application of loop-mediated isothermal amplification combined with lateral flow assay visualization of Plasmodium falciparum kelch 13 C580Y mutation for artemisinin resistance detection in clinical samples Wannida Sanmoung, Nongyao Sawangjaroen, Suwannee Jitueakul, Hansuk Buncherd, Aung Win Tun, Supinya Thanapongpichat, Mallika Imwong Acta Tropica.2023; 246: 106998. CrossRef
Prevalence of Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency among Malaria Patients in Southern Thailand: 8 Years Retrospective Study Thunchanok Khammanee, Nongyao Sawangjaroen, Hansuk Buncherd, Aung Win Tun, Supinya Thanapongpichat The Korean Journal of Parasitology.2022; 60(1): 15. CrossRef
An insight into the recent development of the clinical candidates for the treatment of malaria and their target proteins Hari Madhav, Nasimul Hoda European Journal of Medicinal Chemistry.2021; 210: 112955. CrossRef
Diagnosing the drug resistance signature in Plasmodium falciparum: a review from contemporary methods to novel approaches Laxman Kumar Murmu, Arpita Arsmika Sahu, Tapan Kumar Barik Journal of Parasitic Diseases.2021; 45(3): 869. CrossRef
A resistant mutant of Plasmodium falciparum purine nucleoside phosphorylase uses wild-type neighbors to maintain parasite survival Yacoba V.T. Minnow, Rajesh K. Harijan, Vern L. Schramm Journal of Biological Chemistry.2021; 296: 100342. CrossRef
A LAMP-SNP Assay Detecting C580Y Mutation in Pfkelch13 Gene from Clinically Dried Blood Spot Samples Thunchanok Khammanee, Nongyao Sawangjaroen, Hansuk Buncherd, Aung Win Tun, Supinya Thanapongpichat The Korean Journal of Parasitology.2021; 59(1): 15. CrossRef
New insights into the spread of resistance to artemisinin and its analogues Noreen Noreen, Asad Ullah, Syed Muhammad Salman, Yahia Mabkhot, Abdulrhman Alsayari, Syed Lal Badshah Journal of Global Antimicrobial Resistance.2021; 27: 142. CrossRef
Efficacy and safety of artemether-lumefantrine and dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria and prevalence of molecular markers associated with artemisinin and partner drug resistance in Uganda Chris Ebong, Asadu Sserwanga, Jane Frances Namuganga, James Kapisi, Arthur Mpimbaza, Samuel Gonahasa, Victor Asua, Sam Gudoi, Ruth Kigozi, James Tibenderana, John Bosco Bwanika, Agaba Bosco, Denis Rubahika, Daniel Kyabayinze, Jimmy Opigo, Damian Rutazana, Malaria Journal.2021;[Epub] CrossRef
First
Prev
