Ex vivo susceptibilities of Plasmodium vivax isolates from the China-Myanmar border to antimalarial drugs and association with polymorphisms in Pvmdr1 and Pvcrt-o genes

Li, Jiangyan; Zhang, Jie; Li, Qian; Hu, Yue; Ruan, Yuanyuan; Tao, Zhi‐Yong; Xing, Hui; Qiao, Ji-chen; Li, Meng; Zeng, Weilin; Li, Cuiying; He, Xi; Zhao, Liang; Siddiqui, Faiza Amber; Miao, Jun; Yang, Zhaoqing; Fang, Qiang; Cui, Liwang

doi:10.1371/journal.pntd.0008255

Cited by 22 publications

(41 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nevertheless, this clear-cut association between Y976F change and CQ response ex vivo has not been confirmed in subsequent studies in Southeast Asia ( Shalini et al, 2014 ; Rungsihirunrat et al, 2015 ; Roesch et al, 2020 ; Li et al, 2020 ), East Asia ( Lu et al, 2011 , 2012 ; Li et al, 2020 ), and South America ( Chehuan et al, 2013 ; Aguiar et al, 2014 ). Additionally, pvmdr1 gene polymorphism does not predict CQ treatment failure in clinical trials ( Orjuela-Sánchez et al, 2009 ; Ganguly et al, 2013 ; Shalini et al, 2014 ; Melo et al, 2014 ; Marques et al, 2014 ).…”

Section: Molecular Monitoring Of Chloroquine Resistancementioning

confidence: 89%

“…Additionally, pvmdr1 gene polymorphism does not predict CQ treatment failure in clinical trials ( Orjuela-Sánchez et al, 2009 ; Ganguly et al, 2013 ; Shalini et al, 2014 ; Melo et al, 2014 ; Marques et al, 2014 ). Finally, copy number variation at the pvmdr-1 does not appear to modulate CQ sensitivity ( Suwanarusk et al, 2008 ; Lu et al, 2011 ; Htun et al, 2017 ; Silva et al, 2018 ; Li et al, 2020 ).…”

Section: Molecular Monitoring Of Chloroquine Resistancementioning

confidence: 95%

“…Bar heights are directly proportional to the percentage of parasite samples from each location with two or more pvmdr-1 gene copies (n = 14 studies), ranging between 0 and 59%. Data compiled from: Auburn et al (2016) ; Chaorattanakawee et al (2017) ; Costa et al (2017) ; Htun et al (2017) ; Imwong et al (2008) ; Joy et al (2018) ; Li et al (2020) ; Lo et al (2017) ; Musset et al (2019) ; Roesch et al (2020) ; Silva et al (2018) ; Suwanarusk et al (2007) , and Vargas-Rodríguez et al (2012) . …”

Section: Global Distribution Of Antimalarial Resistance In mentioning

confidence: 99%

“…Copy number variation also occurs in pvcrt-o and has similarly been associated with the CQ resistant phenotype in Brazil ( Silva et al, 2018 ) but not in Cambodia ( Roesch et al, 2020 ). However, no pvcrt-o polymorphism has so far been unequivocally shown to predict CQ treatment failure in vivo or CQ resistance ex vivo in different laboratories across the World ( Suwanarusk et al, 2007 , 2008 ; Barnadas et al, 2008 ; Orjuela-Sánchez et al, 2009 ; Lu et al, 2011 , 2012 ; Ganguly et al, 2013 ; Melo et al, 2014 ; Marques et al, 2014 ; Li et al, 2020 ; Roesch et al, 2020 ). Interestingly, a recent analysis of a genetic cross progeny appears to support upregulated pvcrt-o gene expression as a mechanism of CQ resistance in P. vivax ( Sá et al, 2019 ).…”

Section: Molecular Monitoring Of Chloroquine Resistancementioning

confidence: 99%

See 3 more Smart Citations

Monitoring Plasmodium vivax resistance to antimalarials: Persisting challenges and future directions

Ferreira

Sousa²,

Rangel

et al. 2021

International Journal for Parasitology: Drugs and Drug Resistan

View full text Add to dashboard Cite

Emerging antimalarial drug resistance may undermine current efforts to control and eliminate Plasmodium vivax , the most geographically widespread yet neglected human malaria parasite. Endemic countries are expected to assess regularly the therapeutic efficacy of antimalarial drugs in use in order to adjust their malaria treatment policies, but proper funding and trained human resources are often lacking to execute relatively complex and expensive clinical studies, ideally complemented by ex vivo assays of drug resistance. Here we review the challenges for assessing in vivo P. vivax responses to commonly used antimalarials, especially chloroquine and primaquine, in the presence of confounding factors such as variable drug absorption, metabolism and interaction, and the risk of new infections following successful radical cure. We introduce a simple modeling approach to quantify the relative contribution of relapses and new infections to recurring parasitemias in clinical studies of hypnozoitocides. Finally, we examine recent methodological advances that may render ex vivo assays more practical and widely used to confirm P. vivax drug resistance phenotypes in endemic settings and review current approaches to the development of robust genetic markers for monitoring chloroquine resistance in P. vivax populations.

show abstract

Section: Molecular Monitoring Of Chloroquine Resistancementioning

confidence: 89%

Section: Molecular Monitoring Of Chloroquine Resistancementioning

confidence: 95%

Section: Global Distribution Of Antimalarial Resistance In mentioning

confidence: 99%

Section: Molecular Monitoring Of Chloroquine Resistancementioning

confidence: 99%

See 2 more Smart Citations

Monitoring Plasmodium vivax resistance to antimalarials: Persisting challenges and future directions

Ferreira

Sousa²,

Rangel

et al. 2021

International Journal for Parasitology: Drugs and Drug Resistan

View full text Add to dashboard Cite

show abstract

“…Plasmodium malariae infection rate is generally underestimated and overlooked because it is often asymptomatic and mostly mixed with other Plasmodium species. Drug-resistant P. falciparum and P. vivax have been reported in many regions, including Thailand [9,10] and Myanmar [11,12]. Chloroquine-resistant P. falciparum was first documented in 1957 in Thailand which is now widely spread around the globe [13].…”

mentioning

confidence: 99%

Genetic analysis of the orthologous crt and mdr1 genes in Plasmodium malariae from Thailand and Myanmar

Pimpat

Saralamba

Boonyuen

et al. 2020

Malar J

View full text Add to dashboard Cite

Background: Plasmodium malariae is a widely spread but neglected human malaria parasite, which causes chronic infections. Studies on genetic polymorphisms of anti-malarial drug target genes in P. malariae are limited. Previous reports have shown polymorphisms in the P. malariae dihydrofolate reductase gene associated with pyrimethamine resistance and linked to pyrimethamine drug pressure. This study investigated polymorphisms of the P. malariae homologous genes, chloroquine resistant transporter and multidrug resistant 1, associated with chloroquine and mefloquine resistance in Plasmodium falciparum. Methods: The orthologous P. malariae crt and mdr1 genes were studied in 95 patients with P. malariae infection between 2002 and 2016 from Thailand (N = 51) and Myanmar (N = 44). Gene sequences were analysed using BioEdit, MEGA7, and DnaSP programs. Mutations and gene amplifications were compared with P. falciparum and Plasmodium vivax orthologous genes. Protein topology models derived from the observed pmcrt and pmmdr1 haplotypes were constructed and analysed using Phyre2, SWISS MODEL and Discovery Studio Visualization V 17.2. Results: Two non-synonymous mutations were observed in exon 2 (H53P, 40%) and exon 8 (E278D, 44%) of pmcrt. The topology model indicated that H53P and E278D were located outside of the transmembrane domain and were unlikely to affect protein function. Pmmdr1 was more diverse than pmcrt, with 10 non-synonymous and 3 synonymous mutations observed. Non-synonymous mutations were located in the parasite cytoplasmic site, transmembrane 11 and nucleotide binding domains 1 and 2. Polymorphisms conferring amino acid changes in the transmembrane and nucleotide binding domains were predicted to have some effect on PmMDR1 conformation, but were unlikely to affect protein function. All P. malariae parasites in this study contained a single copy of the mdr1 gene. Conclusions: The observed polymorphisms in pmcrt and pmmdr1 genes are unlikely to affect protein function and unlikely related to chloroquine drug pressure. Similarly, the absence of pmmdr1 copy number variation suggests limited mefloquine drug pressure on the P. malariae parasite population, despite its long time use in Thailand for the treatment of falciparum malaria.

show abstract

Global scenario of Plasmodium vivax occurrence and resistance pattern

2022

View full text Add to dashboard Cite

Malaria caused by Plasmodium vivax is comparatively less virulent than Plasmodium falciparum, which can also lead to severe disease and death. It shows a wide geographical distribution. Chloroquine serves as a drug of choice, with primaquine as a radical cure. However, with the appearance of resistance to chloroquine and treatment has been shifted to artemisinin combination therapy followed by primaquine as a radical cure. Sulphadoxine‐pyrimethamine, mefloquine, and atovaquone‐proguanil are other drugs of choice in chloroquine‐resistant areas, and later resistance was soon reported for these drugs also. The emergence of drug resistance serves as a major hurdle to controlling and eliminating malaria. The discovery of robust molecular markers and regular surveillance for the presence of mutations in malaria‐endemic areas would serve as a helpful tool to combat drug resistance. Here, in this review, we will discuss the endemicity of P. vivax, a historical overview of antimalarial drugs, the appearance of drug resistance and molecular markers with their global distribution along with different measures taken to reduce malaria burden due to P. vivax infection and their resistance.

show abstract

Ex vivo susceptibilities of Plasmodium vivax isolates from the China-Myanmar border to antimalarial drugs and association with polymorphisms in Pvmdr1 and Pvcrt-o genes

Cited by 22 publications

References 73 publications

Monitoring Plasmodium vivax resistance to antimalarials: Persisting challenges and future directions

Monitoring Plasmodium vivax resistance to antimalarials: Persisting challenges and future directions

Genetic analysis of the orthologous crt and mdr1 genes in Plasmodium malariae from Thailand and Myanmar

Global scenario of Plasmodium vivax occurrence and resistance pattern

Contact Info

Product

Resources

About