ArticleAntimicrobial agents and chemotherapy2015
Splenic retention of Plasmodium falciparum gametocytes to block the transmission of malaria.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- Adaptations in Plasmodium tubulin determine distinct microtubule architectures, mechanics and drug susceptibility.Nature communications · 2026Article
- Article
- Clearance of pathogenic erythrocytes is maintained despite spleen dysfunction in children with sickle cell disease.American journal of hematology · 2024Article
- Safe drugs with high potential to block malaria transmission revealed by a spleen-mimetic screening.Nature communications · 2023Article
- Variable microtubule architecture in the malaria parasite.Nature communications · 2023Article
- Advances in Microfluidics for Single Red Blood Cell Analysis.Biosensors · 2023Review
- The role of cholesterol in invasion and growth of malaria parasites.Frontiers in cellular and infection microbiology · 2022Review
- The Phosphodiesterase Inhibitor Tadalafil Promotes Splenic RetentionFrontiers in cellular and infection microbiology · 2022Article
- Evaluation of splenic accumulation and colocalization of immature reticulocytes and Plasmodium vivax in asymptomatic malaria: A prospective human splenectomy study.PLoS medicine · 2021Article
- Microfluidic electrical impedance assessment of red blood cell-mediated microvascular occlusion.Lab on a chip · 2021Article
- An assessment of racial differences in epidemiological, clinical and psychosocial factors among head and neck cancer patients at the time of surgery.World journal of otorhinolaryngology - head and neck surgery · 2020Article
- Reticulocyte and red blood cell deformation triggers specific phosphorylation events.Blood advances · 2019Article
- Methods to Investigate the Deformability of RBC During Malaria.Frontiers in physiology · 2019Review
- High-throughput microsphiltration to assess red blood cell deformability and screen for malaria transmission-blocking drugs.Nature protocols · 2018Article
- Developing transmission-blocking strategies for malaria control.PLoS pathogens · 2017Review
- Biological characterization of chemically diverse compounds targeting the Plasmodium falciparum coenzyme A synthesis pathway.Parasites & vectors · 2016Article
- Large-scale production of Plasmodium falciparum gametocytes for malaria drug discovery.Nature protocols · 2016Article
- Immune mechanisms targeting malaria transmission: opportunities for vaccine development.Expert review of vaccinesReview
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Plasmodium falciparum is transmitted from humans to Anopheles mosquito vectors via the sexual erythrocytic forms termed gametocytes. Erythrocyte filtration through microsphere layers (microsphiltration) had shown that circulating gametocytes are deformable. Compounds reducing gametocyte deformability would induce their splenic clearance, thus removing them from the blood circulation and blocking malaria transmission. The hand-made, single-sample prototype for microsphiltration was miniaturized to a 96-well microtiter plate format, and gametocyte retention in the microsphere filters was quantified by high-content imaging. The stiffening activity of 40 pharmacological compounds was assessed in microtiter plates, using a small molecule (calyculin) as a positive control. The stiffening activity of calyculin was assessed in spleen-mimetic microfluidic chips and in macrophage-depleted mice. Marked mechanical retention (80% to 90%) of mature gametocytes was obtained in microplates following exposure to calyculin at concentrations with no effect on parasite viability. Of the 40 compounds tested, including 20 antimalarials, only 5 endoperoxides significantly increased gametocyte retention (1.5- to 2.5-fold; 24 h of exposure at 1 μM). Mature gametocytes exposed to calyculin accumulated in microfluidic chips and were cleared from the circulation of macrophage-depleted mice as rapidly as heat-stiffened erythrocytes, thus confirming results obtained using the microsphiltration assay. An automated miniaturized approach to select compounds for their gametocyte-stiffening effect has been established. Stiffening induces gametocyte clearance both in vitro and in vivo. Based on physiologically validated tools, this screening cascade can identify novel compounds and uncover new targets to block malaria transmission. Innovative applications in hematology are also envisioned.
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