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 ◽  
...  

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.

2016 ◽  
Vol 15 (1) ◽  
Author(s):  
Aye A. Win ◽  
Mallika Imwong ◽  
Myat P. Kyaw ◽  
Charles J. Woodrow ◽  
Kesinee Chotivanich ◽  
...  

2015 ◽  
Vol 59 (5) ◽  
pp. 2934-2937 ◽  
Author(s):  
Pharath Lim ◽  
Dalin Dek ◽  
Vorleak Try ◽  
Sokunthea Sreng ◽  
Seila Suon ◽  
...  

ABSTRACTDihydroartemisinin-piperaquine is the current frontline artemisinin combination therapy (ACT) forPlasmodium falciparummalaria in Cambodia but is now failing in several western provinces. To investigate artesunate plus mefloquine (AS+MQ) as a replacement ACT, we measured the prevalence of multiplepfmdr1copies—a molecular marker for MQ resistance—in 844P. falciparumclinical isolates collected in 2008 to 2013. Thepfmdr1copy number is decreasing in Western Cambodia, suggesting thatP. falciparumis regainingin vitrosusceptibility to MQ.


Author(s):  
Chaiyaporn Chaisatit ◽  
Piyaporn Sai-ngam ◽  
Sasikanya Thaloengsok ◽  
Sabaithip Sriwichai ◽  
Krisada Jongsakul ◽  
...  

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.


2016 ◽  
Vol 15 (1) ◽  
Author(s):  
Aye A. Win ◽  
Mallika Imwong ◽  
Myat P. Kyaw ◽  
Charles J. Woodrow ◽  
Kesinee Chotivanich ◽  
...  

2009 ◽  
Vol 8 (1) ◽  
Author(s):  
Pharath Lim ◽  
Alisa P Alker ◽  
Nimol Khim ◽  
Naman K Shah ◽  
Sandra Incardona ◽  
...  

2021 ◽  
Vol 9 (5) ◽  
pp. e001942
Author(s):  
Xu Yang ◽  
Ying Hu ◽  
Keyan Yang ◽  
Dongxu Wang ◽  
Jianzhen Lin ◽  
...  

BackgroundThis study was designed to screen potential biomarkers in plasma cell-free DNA (cfDNA) for predicting the clinical outcome of immune checkpoint inhibitor (ICI)-based therapy in advanced hepatobiliary cancers.MethodsThree cohorts including 187 patients with hepatobiliary cancers were recruited from clinical trials at the Peking Union Medical College Hospital. Forty-three patients received combination therapy of programmed cell death protein 1 (PD-1) inhibitor with lenvatinib (ICI cohort 1), 108 patients received ICI-based therapy (ICI cohort 2) and 36 patients received non-ICI therapy (non-ICI cohort). The plasma cfDNA and blood cell DNA mutation profiles were assessed to identify efficacy biomarkers by a cancer gene-targeted next-generation sequencing panel.ResultsBased on the copy number variations (CNVs) in plasma cfDNA, the CNV risk score model was constructed to predict survival by using the least absolute shrinkage and selection operator Cox regression methods. The results of the two independent ICI-based therapy cohorts showed that patients with lower CNV risk scores had longer overall survival (OS) and progression-free survival (PFS) than those with high CNV risk scores (log-rank p<0.01). In the non-ICI cohort, the CNV risk score was not associated with PFS or OS. Furthermore, the results indicated that 53% of patients with low CNV risk scores achieved durable clinical benefit; in contrast, 88% of patients with high CNV risk scores could not benefit from combination therapy (p<0.05).ConclusionsThe CNVs in plasma cfDNA could predict the clinical outcome of the combination therapy of PD-1 inhibitor with lenvatinib and other ICI-based therapies in hepatobiliary cancers.


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