ArticleThe Journal of clinical investigation1994
Resistance to artemisinin of malaria parasites (Plasmodium falciparum) infecting alpha-thalassemic erythrocytes in vitro. Competition in drug accumulation with uninfected erythrocytes.
Article in The Journal of clinical investigation, 1994. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Artemisinin Therapy for Malaria in Hemoglobinopathies: A Systematic Review.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2018Pooled it
- Plasmodium falciparum clearance with artemisinin-based combination therapy (ACT) in patients with glucose-6-phosphate dehydrogenase deficiency in Mali.Malaria journal · 2010Trial
- Disposition of artesunate and dihydroartemisinin after administration of artesunate suppositories in children from Papua New Guinea with uncomplicated malaria.Antimicrobial agents and chemotherapy · 2004Trial
- Article
- Plasmodium falciparum resistance to ACTs: Emergence, mechanisms, and outlook.International journal for parasitology. Drugs and drug resistance · 2021Article
- Prevalence and distribution of glucose-6-phosphate dehydrogenase (G6PD) variants in Thai and Burmese populations in malaria endemic areas of Thailand.Malaria journal · 2011Article
- The presence of leukocytes in ex vivo assays significantly increases the 50-percent inhibitory concentrations of artesunate and chloroquine against Plasmodium vivax and Plasmodium falciparum.Antimicrobial agents and chemotherapy · 2011Article
- Artemisone uptake in Plasmodium falciparum-infected erythrocytes.Antimicrobial agents and chemotherapy · 2011Article
- Resistance to antimalarial drugs: molecular, pharmacologic, and clinical considerations.Pediatric research · 2009Review
- Artemisinin effectiveness in erythrocytes is reduced by heme and heme-containing proteins.Biochemical pharmacology · 2007Article
- Reaction of artemisinin with haemoglobin: implications for antimalarial activity.The Biochemical journal · 2005Article
- Effects of alpha-thalassemia on pharmacokinetics of the antimalarial agent artesunate.Antimicrobial agents and chemotherapy · 1998Article
- Artemisinin and the antimalarial endoperoxides: from herbal remedy to targeted chemotherapy.Microbiological reviews · 1996Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Plasmodium falciparum infecting hemoglobin (Hb)H and/or Hb Constant Spring erythrocytes has higher resistance to artemisinin in vitro than when infecting normal erythrocytes. This is due to low drug accumulation of infected erythrocytes resulting from competition with uninfected variant erythrocytes, which have a higher accumulation capacity than genetically normal cells. Drug accumulation of the parasite was shown to be saturable and dependent on metabolic energy. The 50% inhibitory concentrations (IC50's) for the parasite in HbH/Hb Constant Spring erythrocytes were decreased when normal erythrocytes were added to the infected cells, and correspondingly, the IC50's in normal erythrocytes were increased when HbH/Hb Constant Spring erythrocytes were added to the infected cells. The changes of IC50 corresponded to the variation in drug accumulation of mixtures of normal and variant erythrocytes of different compositions. The IC50's for the parasite in variant erythrocytes were also greatly decreased when the hematocrit of the culture was lowered, while the IC50's in normal erythrocytes were independent of the hematocrit. The increase in IC50 values for the parasites infecting variant erythrocytes was also related to the decrease in parasite accumulation, indicating that drug accumulation capacity of the parasite also has a role in determining drug sensitivity. Artemisinin sensitivity therefore is determined by its accessibility to the parasite, which is decreased in infected variant erythrocytes.
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Registered trials
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