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An Experimental Human Blood-Stage Model for Studying Plasmodium malariae Infection.
- Source :
-
The Journal of infectious diseases [J Infect Dis] 2020 Mar 02; Vol. 221 (6), pp. 948-955. - Publication Year :
- 2020
-
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, diagnostic assays, and treatment.<br />Methods: This clinical trial involved 2 healthy subjects who were intravenously inoculated with cryopreserved P. malariae-infected erythrocytes. Subjects were treated with artemether-lumefantrine after 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.<br />Results: Both subjects experienced symptoms and signs typical of early malaria. Parasitemia was detected 7 days after inoculation, and parasite concentrations increased until antimalarial treatment was initiated 25 and 21 days after inoculation for subjects 1 and 2 respectively (peak parasitemia levels, 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 1 subject, while in vivo parasite transcription and biomarkers were successfully profiled.<br />Conclusions: An IBSM model of P. malariae has been successfully developed and may be used to study the biology of, diagnostic testing for, and treatment of this neglected malaria species.<br />Clinical Trials Registration: ACTRN12617000048381.<br /> (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)
- Subjects :
- Adolescent
Animals
Anopheles parasitology
Feeding Behavior
Humans
Malaria pathology
Male
Parasitemia blood
Parasitemia drug therapy
Parasitemia parasitology
Plasmodium malariae physiology
Transcriptome
Young Adult
Antimalarials therapeutic use
Artemether, Lumefantrine Drug Combination therapeutic use
Malaria blood
Malaria parasitology
Plasmodium malariae genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1537-6613
- Volume :
- 221
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- The Journal of infectious diseases
- Publication Type :
- Academic Journal
- Accession number :
- 30852586
- Full Text :
- https://doi.org/10.1093/infdis/jiz102