Advancing complement inhibition for the treatment of malarial anemia: a translational roadmap

Ronald P. Taylor; D. Gray Heppner; John D. Lambris; Margaret A. Lindorfer; Dimitrios C. Mastellos; Rosario Notaro; Alexander V. Pichugin; Antonio M. Risitano; Christoph Q. Schmidt; Richard J. H. Smith; José A. Stoute; John N. Waitumbi; Yuzhou Zhang

doi:10.1186/s12936-026-06120-7

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Advancing complement inhibition for the treatment of malarial anemia: a translational roadmap

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Advancing complement inhibition for the treatment of malarial anemia: a translational roadmap

Ronald P. Taylor, D. Gray Heppner, John D. Lambris, Margaret A. Lindorfer, Dimitrios C. Mastellos, Rosario Notaro, Alexander V. Pichugin, Antonio M. Risitano, Christoph Q. Schmidt, Richard J. H. Smith, …

Malaria journal

08/25/2026

DOI: 10.1186/s12936-026-06120-7

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Abstract

Severe anemia is responsible for hundreds of thousands of deaths in children with malaria. For every Plasmodium-infected erythrocyte that is lysed, considerably more than 10 uninfected erythrocytes are cleared by extravascular hemolysis, thus leading to anemia. Compelling evidence indicates that breakdown products released from infected erythrocytes in the bloodstream activate complement and promote “innocent bystander” deposition of C3 activation fragments on the uninfected erythrocytes, thereby sensitizing them for elimination. We propose a series of in vitro experiments with blood cultures of malaria parasites to test the hypothesis that use of inhibitors that block complement at the C3 activation step can preserve and protect uninfected erythrocytes from C3 deposition. Successful demonstration of in vitro protection will set the stage for clinical trials based on the limited and focused use of complement inhibitors to prevent severe anemia in malaria.

Details

Title: Subtitle: Advancing complement inhibition for the treatment of malarial anemia: a translational roadmap
Creators: Ronald P. Taylor - University of Virginia
D. Gray Heppner - ClearMotion (United States)
John D. Lambris - University of Pennsylvania
Margaret A. Lindorfer - University of Virginia
Dimitrios C. Mastellos - National Centre of Scientific Research "Demokritos"
Rosario Notaro - Istituto per lo Studio e la Prevenzione Oncologica
Alexander V. Pichugin - Walter Reed Army Institute of Research
Antonio M. Risitano - Azienda Ospedaliera S.Giuseppe Moscati
Christoph Q. Schmidt - Universität Ulm
Richard J. H. Smith - University of Iowa
José A. Stoute - Jackson Memorial Hospital
John N. Waitumbi - United States Army Medical Research Directorate - Africa
Yuzhou Zhang - University of Iowa
Resource Type: Journal article
Publication Details: Malaria journal
DOI: 10.1186/s12936-026-06120-7
ISSN: 1475-2875
eISSN: 1475-2875
Publisher: Springer Nature
Language: English
Electronic publication date: 08/25/2026
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Otolaryngology; Internal Medicine
Record Identifier: 9985220286602771

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