An experimental human blood stage model for studying Plasmodium malariae infection

Woodford, J. et al. (2019) An experimental human blood stage model for studying Plasmodium malariae infection. Journal of Infectious Diseases, 221(6), pp. 948-955. (doi: 10.1093/infdis/jiz102) (PMID:30852586)

Abstract

Background: Plasmodium malariae is considered a ‘minor’ malaria parasite, although its global disease burden is underappreciated. The aim of this study was to develop an induced blood stage malaria (IBSM) model of P. malariae to study parasite biology, diagnostics, and treatment. Methods: This clinical trial involved two healthy subjects who were intravenously inoculated with cryopreserved P. malariae-infected erythrocytes. Subjects were treated with artemether-lumefantrine following development of clinical symptoms. Prior to antimalarial therapy, mosquito feeding assays were performed to investigate transmission, and blood samples were collected for rapid diagnostic testing and parasite transcription profiling. Serial blood samples were collected for biomarker analysis. Results: Both subjects experienced symptoms and signs typical of early malaria. Parasitaemia was detected 7 days post-inoculation and increased until antimalarial treatment was initiated 25 and 21 days post-inoculation for Subject 1 and 2 respectively (peak parasitaemia levels were 174,182 and 50,291 parasites/mL respectively). The parasite clearance half-life following artemether-lumefantrine treatment was 6.7 hours. Mosquito transmission was observed for one subject, while in vivo parasite transcription and biomarkers were successfully profiled. Conclusions: An IBSM model of P. malariae has been successfully developed and may be used to study the biology, diagnostics, and treatment of this neglected malaria species.

• Item Type: Articles
• Additional Information: This study was supported by funds from NHMRC Program Grant 1132975. JSM was supported by a Practitioner Fellowship from the National Health and Medical Research Council and a Government of Queensland Health Research Fellowship.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Otto, Professor Thomas
• Authors: Woodford, J., Collins, K. A., Odedra, A., Wang, C., Kyung, J. I., Domingo, G. J., Watts, R., Marquart, L., Berriman, M., Otto, T. D., and McCarthy, J. S.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Research Centre: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology
• Journal Name: Journal of Infectious Diseases
• Publisher: Oxford University Press
• ISSN: 0022-1899
• ISSN (Online): 1537-6613
• Published Online: 11 March 2019
• Copyright Holders: Copyright © 2019 The Authors
• First Published: First published in Journal of Infectious Diseases 221(6):948-955
• Publisher Policy: Reproduced under a Creative Commons license