scholarly journals Molecular Detection of Mutations in the Propeller Domain of Kelch 13 and pfmdr1 Copy Number Variation in Plasmodium falciparum Isolates from Thailand Collected from 2002 to 2007

2021 ◽  
Author(s):  
Chaiyaporn Chaisatit ◽  
Piyaporn Sai-ngam ◽  
Sasikanya Thaloengsok ◽  
Sabaithip Sriwichai ◽  
Krisada Jongsakul ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Copy Number ◽  
Molecular Detection ◽  
Background Information ◽  
Southern Thailand ◽  
Geographic Diversity ◽  
Number Variation ◽  
Detection Of Mutations ◽  
Pfmdr1 Copy Number ◽  
Kelch 13

We determined the prevalence of Kelch 13 mutations and pfmdr1 copy number in samples collected from the Thailand–Myanmar border, the Thailand–Cambodia border, and southern Thailand from 2002 to 2007. C580Y was the most prevalent in Trat (Thailand–Cambodia border) and Ranong (Thailand–Myanmar border) at 42% (24/57) and 13% (6/48), respectively. Less predominant mutations were also identified including R539T (7%, 4/57) and Y493H (2%, 1/57) in Trat, P574L (6%, 3/48) and P553L (2%, 1/48) in Ranong, and N537I and D452E (7%, 1/15) in Sangkhlaburi (Thailand–Myanmar border). Samples from Mae sot (33%, 11/33) harbored the highest percentage of multiple pfmdr1 copies, followed by Trat (18%, 10/57), Chiang Dao in 2003 (13%, 4/30), Phang Nga (5%, 2/44), and Chiang Dao in 2002 (4%, 1/26). This retrospective study provides geographic diversity of K13 and pfmdr1 copies and the emergence of these molecular markers in Thailand, an important background information for future surveillance in the region.

scholarly journals Erratum to: K13 mutations and pfmdr1 copy number variation in Plasmodium falciparum malaria in Myanmar

2016 ◽  
Vol 15 (1) ◽  
Author(s):  
Aye A. Win ◽  
Mallika Imwong ◽  
Myat P. Kyaw ◽  
Charles J. Woodrow ◽  
Kesinee Chotivanich ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Copy Number Variation ◽  
Falciparum Malaria ◽  
Copy Number ◽  
Plasmodium Falciparum Malaria ◽  
Number Variation ◽  
Pfmdr1 Copy Number

scholarly journals K13 mutations and pfmdr1 copy number variation in Plasmodium falciparum malaria in Myanmar

2016 ◽  
Vol 15 (1) ◽  
Author(s):  
Aye A. Win ◽  
Mallika Imwong ◽  
Myat P. Kyaw ◽  
Charles J. Woodrow ◽  
Kesinee Chotivanich ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Copy Number Variation ◽  
Falciparum Malaria ◽  
Copy Number ◽  
Plasmodium Falciparum Malaria ◽  
Number Variation ◽  
Pfmdr1 Copy Number

scholarly journals Development of copy number assays for detection and surveillance of piperaquine resistance associated plasmepsin 2/3 copy number variation in Plasmodium falciparum

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Megan R. Ansbro ◽  
Christopher G. Jacob ◽  
Roberto Amato ◽  
Mihir Kekre ◽  
Chanaki Amaratunga ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Copy Number Variation ◽  
Copy Number ◽  
Number Variation

scholarly journals Plasmodium falciparum Isolates with Increased pfmdr1 Copy Number Circulate in West Africa

2010 ◽  
Vol 54 (7) ◽  
pp. 3049-3051 ◽  
Author(s):  
Benoit Witkowski ◽  
Marie-Laure Nicolau ◽  
Patrice Njomnang Soh ◽  
Xavier Iriart ◽  
Sandie Menard ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Combination Therapy ◽  
West Africa ◽  
Copy Number ◽  
Amino Alcohols ◽  
Pfmdr1 Copy Number

ABSTRACT Amplification of pfmdr1 in Plasmodium falciparum is linked to resistance to aryl-amino-alcohols and in reduced susceptibility to artemisinins. We demonstrate here that duplicated pfmdr1 genotypes circulate in West Africa. The monitoring of this prevalence in Africa appears essential for determining the antimalarial policy and to maintain the efficiency of artemisinin-based combination therapy (ACT) for as long as possible.

scholarly journals Baseline Ex Vivo and Molecular Responses of Plasmodium falciparum Isolates to Piperaquine before Implementation of Dihydroartemisinin-Piperaquine in Senegal

2019 ◽  
Vol 63 (5) ◽  
Author(s):  
Marie Gladys Robert ◽  
Francis Foguim Tsombeng ◽  
Mathieu Gendrot ◽  
Silman Diawara ◽  
Marylin Madamet ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Copy Number ◽  
Ex Vivo ◽  
Line Treatment ◽  
First Line ◽  
Molecular Responses ◽  
Content Type ◽  
Number Variation ◽  
Plasmepsin Ii ◽  
First Line Treatment

ABSTRACT Dihydroartemisinin-piperaquine, which was registered in 2017 in Senegal, is not currently used as the first-line treatment against uncomplicated malaria. A total of 6.6% to 17.1% of P. falciparum isolates collected in Dakar in 2013 to 2015 showed ex vivo-reduced susceptibility to piperaquine. Neither the exonuclease E415G mutation nor the copy number variation of the plasmepsin II gene (Pfpm2), associated with piperaquine resistance in Cambodia, was detected in Senegalese parasites.

scholarly journals Atypical molecular basis for drug resistance to mitochondrial function inhibitors in Plasmodium falciparum

2020 ◽  
Author(s):  
Heather J. Painter ◽  
Joanne M. Morrisey ◽  
Michael W. Mather ◽  
Lindsey M. Orchard ◽  
Cuyler Luck ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Copy Number Variation ◽  
Copy Number ◽  
De Novo ◽  
Rapid Development ◽  
Point Mutations ◽  
Parasite Line ◽  
Pyrimidine Synthesis ◽  
Number Variation

AbstractThe continued emergence of drug-resistant Plasmodium falciparum parasites hinders global attempts to eradicate malaria, emphasizing the need to identify new antimalarial drugs. Attractive targets for chemotherapeutic intervention are the cytochrome (cyt) bc1 complex, which is an essential component of the mitochondrial electron transport chain (mtETC) necessary for ubiquinone recycling and mitochondrially localized dihydroorotate dehydrogenase (DHODH) critical for de novo pyrimidine synthesis. Despite the essentiality of this complex, resistance to a novel acridone class of compounds targeting cyt bc1 was readily attained, resulting in a parasite strain (SB1-A6) that was pan-resistant to both mtETC and DHODH inhibitors. Here we describe the molecular mechanism behind the resistance of the SB1-A6 parasite line which lacks the common cyt bc1 point mutations characteristic of resistance to mtETC inhibitors. Using Illumina whole-genome sequencing, we have identified both a copy number variation (∼2x) and a single-nucleotide polymorphism (C276F) associated with pfdhodh in SB1-A6. We have characterized the role of both genetic lesions by mimicking the copy number variation via episomal expression of pfdhodh and introducing the identified SNP using CRISPR/Cas9 and assessed their contributions to drug resistance. Although both of these genetic polymorphisms have been previously identified as contributing to both DSM-1 (1) and atovaquone resistance (2, 3), SB1-A6 represents a unique genotype in which both alterations are present in a single line, suggesting that the combination contributes to the pan-resistant phenotype. This novel mechanism of resistance to mtETC inhibition has critical implications for the development of future drugs targeting the bc1 complex or de novo pyrimidine synthesis that could help guide future anti-malarial combination therapies and reduce the rapid development of drug resistance in the field.

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