Plasmodium falciparum gametocyte production correlates with genetic markers of parasite replication but is not influenced by experimental exposure to mosquito bitingResearch in context
Sara Lynn Blanken,
Aissata Barry,
Kjerstin Lanke,
Moussa Guelbeogo,
Alphonse Ouedraogo,
Issiaka Soulama,
Sam Aboubacar Coulibaly,
Karina Teelen,
Wouter Graumans,
Elin Dumont,
Will Stone,
Jordache Ramjith,
Matthias Marti,
Carolina M. Andrade,
Chris Drakeley,
Katharine Collins,
Alfred Tiono,
Teun Bousema
Affiliations
Sara Lynn Blanken
Department of Medical Microbiology, Radboud University Medical Centre, Nijmegen, the Netherlands
Aissata Barry
Groupe de Recherche Action en Santé (GRAS), Ouagadougou, Burkina Faso
Kjerstin Lanke
Department of Medical Microbiology, Radboud University Medical Centre, Nijmegen, the Netherlands
Moussa Guelbeogo
Centre National de Recherche et de Formation sur le Paludisme (CNRFP), Ouagadougou 01, Burkina Faso
Alphonse Ouedraogo
Centre National de Recherche et de Formation sur le Paludisme (CNRFP), Ouagadougou 01, Burkina Faso
Issiaka Soulama
Centre National de Recherche et de Formation sur le Paludisme (CNRFP), Ouagadougou 01, Burkina Faso
Sam Aboubacar Coulibaly
Centre National de Recherche et de Formation sur le Paludisme (CNRFP), Ouagadougou 01, Burkina Faso
Karina Teelen
Department of Medical Microbiology, Radboud University Medical Centre, Nijmegen, the Netherlands
Wouter Graumans
Department of Medical Microbiology, Radboud University Medical Centre, Nijmegen, the Netherlands
Elin Dumont
Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, UK
Will Stone
Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, UK
Jordache Ramjith
Department of Medical Microbiology, Radboud University Medical Centre, Nijmegen, the Netherlands
Matthias Marti
Wellcome Centre for Integrative Parasitology, Institute of Infection and Immunity, University of Glasgow, Glasgow, Scotland, UK
Carolina M. Andrade
Department of Medical Microbiology, Radboud University Medical Centre, Nijmegen, the Netherlands
Chris Drakeley
MRC International Statistics and Epidemiology Group, London School of Hygiene and Tropical Medicine, London, UK
Katharine Collins
Department of Medical Microbiology, Radboud University Medical Centre, Nijmegen, the Netherlands
Alfred Tiono
Centre National de Recherche et de Formation sur le Paludisme (CNRFP), Ouagadougou 01, Burkina Faso
Teun Bousema
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; Corresponding author. Radboud University Medical Centre, Geert Grooteplein Zuid 28, 6525GA, Nijmegen, Netherlands.
Summary: 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).
