Sensitivity of Plasmodium vivax to chloroquine, mefloquine, artemisinin and atovaquone in north-western Thailand

Treiber, Moritz; Wernsdorfer, Gunther; Wiedermann, Ursula; Congpuong, Kanungnit; Sirichaisinthop, Jeeraphat; Wernsdorfer, Walther H.

doi:10.1007/s00508-011-0044-6

Cited by 9 publications

(7 citation statements)

References 29 publications

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“…Researchers have also evaluated drugs 4 , 23 , and 25 on other human malaria species such as P. vivax , and these compounds exhibited IC 50 values of 0.60 nM, 4.90 nM, and 17.0 nM, respectively. It has been previously reported that drug molecules active against both P. falciparum and P. vivax show good correlation and have great clinical value . This investigation provides the first systematic evaluation of current and future malaria treatments against various life stages of three Plasmodium species, P. falciparum , P. vivax , and P. yoelii .…”

Section: Chemical Compounds Effective Against Various Life Stagesmentioning

confidence: 83%

Multistage inhibitors of the malaria parasite: Emerging hope for chemoprotection and malaria eradication

Poonam

Gupta

et al. 2018

Medicinal Research Reviews

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Over time, several exciting advances have been made in the treatment and prevention of malaria; however, this devastating disease continues to be a major global health problem and affects millions of people every year. Notably, the paucity of new efficient drug molecules and the inevitable drug resistance of the malaria parasite, Plasmodium falciparum, against frontline therapeutics are the foremost struggles facing malaria eradication initiatives. According to the malaria eradication agenda, the discovery of new chemical entities that can destroy the parasite at the liver stage, the asexual blood stage, the gametocyte stage, and the insect ookinete stage of the parasite life cycle (i.e., compounds exhibiting multistage activity) are in high demand, preferably with novel and multiple modes of action. Phenotypic screening of chemical libraries against the malaria parasite is certainly a crucial step toward overcoming these crises. In the last few years, various research groups, including industrial research laboratories, have performed large-scale phenotypic screenings that have identified a wealth of chemical entities active against multiple life stages of the malaria parasite. Vital scientific and technological developments have led to the discovery of multistage inhibitors of the malaria parasite; these compounds, considered highly valuable starting points for subsequent drug discovery and eradication of malaria, are reviewed.

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Section: Chemical Compounds Effective Against Various Life Stagesmentioning

confidence: 83%

Multistage inhibitors of the malaria parasite: Emerging hope for chemoprotection and malaria eradication

Poonam

Gupta

et al. 2018

Medicinal Research Reviews

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“…Having established that all -HA-IND alleles expressed proteins of the expected size and in expected locations, where such locations could be predicted, we then assessed whether overexpression of either the -HA-IND or -CMB alleles of these P. vivax proteins had any impact on P. knowlesi sensitivity to common antimalarials. To do so, we adapted the method of van Schalkwyk et al [62] and focused on chloroquine and mefloquine responses, as these comprise the majority of drug resistance reported in the field [13, 27, 29, 36]. As an initial control, we used this drug assay protocol to measure the IC 50 of all the lines to pyrimethamine.…”

Section: Resultsmentioning

confidence: 99%

“…Despite the spread of resistance, chloroquine remains the first-line antimalarial in Latin America and the majority of Asia [22]. In addition, P. vivax antifolate resistance has been described for more than 50 years [23–27], and more recently mefloquine resistance has also been described in South America and Southeast Asia [18, 28, 29] even though these drugs were never recommended as first-line treatment for P. vivax [22].…”

Section: Introductionmentioning

confidence: 99%

Plasmodium knowlesi as a model system for characterising Plasmodium vivax drug resistance candidate genes

et al. 2019

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Plasmodium vivax causes the majority of malaria outside Africa, but is poorly understood at a cellular level partly due to technical difficulties in maintaining it in in vitro culture conditions. In the past decades, drug resistant P. vivax parasites have emerged, mainly in Southeast Asia, but while some molecular markers of resistance have been identified, none have so far been confirmed experimentally, which limits interpretation of the markers, and hence our ability to monitor and control the spread of resistance. Some of these potential markers have been identified through P. vivax genome-wide population genetic analyses, which highlighted genes under recent evolutionary selection in Southeast Asia, where chloroquine resistance is most prevalent. These genes could be involved in drug resistance, but no experimental proof currently exists to support this hypothesis. In this study, we used Plasmodium knowlesi , the most closely related species to P. vivax that can be cultured in human erythrocytes, as a model system to express P. vivax genes and test for their role in drug resistance. We adopted a strategy of episomal expression, and were able to express fourteen P. vivax genes, including two allelic variants of several hypothetical resistance genes. Their expression level and localisation were assessed, confirming cellular locations conjectured from orthologous species, and suggesting locations for several previously unlocalised proteins, including an apical location for PVX_101445. These findings establish P. knowlesi as a suitable model for P. vivax protein expression. We performed chloroquine and mefloquine drug assays, finding no significant differences in drug sensitivity: these results could be due to technical issues, or could indicate that these genes are not actually involved in drug resistance, despite being under positive selection pressure in Southeast Asia. These data confirm that in vitro P. knowlesi is a useful tool for studying P. vivax biology. Its close evolutionary relationship to P. vivax , high transfection efficiency, and the availability of markers for colocalisation, all make it a powerful model system. Our study is the first of its kind using P. knowlesi to study unknown P. vivax proteins and investigate drug resistance mechanisms.

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“…Importantly, it will be associated with the IC 50s in vitro of antimalarials in P. vivax and their tendency to increase toward an eventual therapeutic failure. It is also important to search for specific mutations in genetic markers as has been reported in Asia (10,20,21,37,39,(43)(44)(45).…”

Section: Discussionmentioning

confidence: 99%

In Vitro Susceptibility of Plasmodium vivax to Antimalarials in Colombia

Fernández

Segura

Arboleda

et al. 2014

Antimicrob Agents Chemother

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, and 10% of the isolates showed lower susceptibilities to one of the antimalarial drugs, 13.3% to two antimalarial drugs, and 3.3% to more than three antimalarial drugs. It should be highlighted that despite the extensive use of chloroquine in Colombia, P. vivax continues to be susceptible to antimalarials. This is the first report, to our knowledge, showing in vitro susceptibilities of P. vivax isolates to antimalarials in Colombia.

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Sensitivity of Plasmodium vivax to chloroquine, mefloquine, artemisinin and atovaquone in north-western Thailand

Cited by 9 publications

References 29 publications

Multistage inhibitors of the malaria parasite: Emerging hope for chemoprotection and malaria eradication

Multistage inhibitors of the malaria parasite: Emerging hope for chemoprotection and malaria eradication

Plasmodium knowlesi as a model system for characterising Plasmodium vivax drug resistance candidate genes

In Vitro Susceptibility of Plasmodium vivax to Antimalarials in Colombia

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