ArticleMalaria journal2015
Attenuation of Plasmodium falciparum in vitro drug resistance phenotype following culture adaptation compared to fresh clinical isolates in Cambodia.
Article in Malaria journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Ex vivo piperaquine resistance developed rapidly in Plasmodium falciparum isolates in northern Cambodia compared to Thailand.Malaria journal · 2016Trial
- Methylene blue retains in vitro activity against early ring-stage artemisinin-resistant Plasmodium falciparum.Malaria journal · 2026Article
- Article
- Towards clinically relevant dose ratios for Cabamiquine and Pyronaridine combination using P. falciparum field isolate data.Nature communications · 2024Article
- In vitro activity of rhinacanthin analogues against drug resistant Plasmodium falciparum isolates from Northeast Thailand.Malaria journal · 2023Article
- Short-term cryopreservation and thawing have minimal effects onFrontiers in cellular and infection microbiology · 2022Article
- Efficient Transmission of Mixed Plasmodium falciparum/vivax Infections From Humans to Mosquitoes.The Journal of infectious diseases · 2020Article
- Measuring ex vivo drug susceptibility in Plasmodium vivax isolates from Cambodia.Malaria journal · 2017Article
- Artemisinin resistance without pfkelch13 mutations in Plasmodium falciparum isolates from Cambodia.Malaria journal · 2017Article
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Authors and funding
17 authors.
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Abstract
backgroundThere is currently no standardized approach for assessing in vitro anti-malarial drug susceptibility. Potential alterations in drug susceptibility results between fresh immediate ex vivo (IEV) and cryopreserved culture-adapted (CCA) Plasmodium falciparum isolates, as well as changes in parasite genotype during culture adaptation were investigated.
methodsThe 50 % inhibitory concentration (IC50) of 12 P. falciparum isolates from Cambodia against a panel of commonly used drugs were compared using both IEV and CCA. Results were compared using both histidine-rich protein-2 ELISA (HRP-2) and SYBR-Green I fluorescence methods. Molecular genotyping and amplicon deep sequencing were also used to compare multiplicity of infection and genetic polymophisms in fresh versus culture-adapted isolates.
resultsIC50 for culture-adapted specimens were significantly lower compared to the original fresh isolates for both HRP-2 and SYBR-Green I assays, with greater than a 50 % decline for the majority of drug-assay combinations. There were correlations between IC50s from IEV and CCA for most drugs assays. Infections were nearly all monoclonal, with little or no change in merozoite surface protein 1 (MSP1), MSP2, glutamate-rich protein (GLURP) or apical membrane antigen 1 (AMA1) polymorphisms, nor differences in P. falciparum multidrug resistance 1 gene (PfMDR1) copy number or single nucleotide polymorphisms following culture adaptation.
conclusionsThe overall IC50 reduction combined with the correlation between fresh isolates and culture-adapted drug susceptibility assays suggests the utility of both approaches, as long as there is consistency of method, and remaining mindful of possible attenuation of resistance phenotype occurring in culture. Further study should be done in higher transmission settings where polyclonal infections are prevalent.
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