Plasmodium falciparum gametocyte production correlates with genetic markers of parasite replication but is not influenced by experimental exposure to mosquito biting.

Autor:	Blanken SL; Department of Medical Microbiology, Radboud University Medical Centre, Nijmegen, the Netherlands., Barry A; Groupe de Recherche Action en Santé (GRAS), Ouagadougou, Burkina Faso., Lanke K; Department of Medical Microbiology, Radboud University Medical Centre, Nijmegen, the Netherlands., Guelbeogo M; Centre National de Recherche et de Formation sur le Paludisme (CNRFP), Ouagadougou 01, Burkina Faso., Ouedraogo A; Centre National de Recherche et de Formation sur le Paludisme (CNRFP), Ouagadougou 01, Burkina Faso., Soulama I; Centre National de Recherche et de Formation sur le Paludisme (CNRFP), Ouagadougou 01, Burkina Faso., Coulibaly SA; Centre National de Recherche et de Formation sur le Paludisme (CNRFP), Ouagadougou 01, Burkina Faso., Teelen K; Department of Medical Microbiology, Radboud University Medical Centre, Nijmegen, the Netherlands., Graumans W; Department of Medical Microbiology, Radboud University Medical Centre, Nijmegen, the Netherlands., Dumont E; Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, UK., Stone W; Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, UK., Ramjith J; Department of Medical Microbiology, Radboud University Medical Centre, Nijmegen, the Netherlands., Marti M; Wellcome Centre for Integrative Parasitology, Institute of Infection and Immunity, University of Glasgow, Glasgow, Scotland, UK., Andrade CM; Department of Medical Microbiology, Radboud University Medical Centre, Nijmegen, the Netherlands., Drakeley C; MRC International Statistics and Epidemiology Group, London School of Hygiene and Tropical Medicine, London, UK., Collins K; Department of Medical Microbiology, Radboud University Medical Centre, Nijmegen, the Netherlands., Tiono A; Centre National de Recherche et de Formation sur le Paludisme (CNRFP), Ouagadougou 01, Burkina Faso., Bousema T; Department of Medical Microbiology, Radboud University Medical Centre, Nijmegen, the Netherlands; Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, UK. Electronic address: teun.bousema@radboudumc.nl.
Jazyk:	angličtina
Zdroj:	EBioMedicine [EBioMedicine] 2024 Jul; Vol. 105, pp. 105190. Date of Electronic Publication: 2024 Jun 19.
DOI:	10.1016/j.ebiom.2024.105190
Abstrakt:	Background: Plasmodium blood-stage parasites balance asexual multiplication with gametocyte development. Few studies link these dynamics with parasite genetic markers in vivo; even fewer in longitudinally monitored infections. Environmental influences on gametocyte formation, such as mosquito exposure, may influence the parasite's investment in gametocyte production. Methods: We investigated gametocyte production and asexual multiplication in two Plasmodium falciparum infected populations; a controlled human malaria infection (CHMI) study and a 28-day observational study in naturally infected individuals in Burkina Faso with controlled mosquito exposure. We measured gene transcript levels previously related to gametocyte formation (ap2-g, surfin1.2, surfin13.1, gexp-2) or inhibition of asexual multiplication (sir2a) and compared transcript levels to ring-stage parasite and mature gametocyte densities. Findings: Three of the five markers (ap2-g, surfin1.2, surfin13.1) predicted peak gametocytaemia in the CHMI study. An increase in all five markers in natural infections was associated with an increase in mature gametocytes 14 days later; the effect of sir2a on future gametocytes was strongest (fold change = 1.65, IQR = 1.22-2.24, P = 0.004). Mosquito exposure was not associated with markers of gametocyte formation (ap2-g P = 0.277; sir2a P = 0.499) or carriage of mature gametocytes (P = 0.379). Interpretation: All five parasite genetic markers predicted gametocyte formation over a single cycle of gametocyte formation and maturation in vivo; sir2a and ap2-g were most closely associated with gametocyte growth dynamics. We observed no evidence to support the hypothesis that exposure to Anopheles mosquito bites stimulates gametocyte formation. Funding: This work was funded by the Bill & Melinda Gates Foundation (INDIE OPP1173572), the European Research Council fellowship (ERC-CoG 864180) and UKRI Medical Research Council (MR/T016272/1) and Wellcome Center (218676/Z/19/Z). Competing Interests: Declaration of interests We declare no competing interests. (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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