Constant rate of Plasmodium falciparum sexual commitment promotes variable gametocyte proportions as infection progresses over time

Portugal, S.; van Dijk, H.; Ferreira Lima, N.; Kampmann, M.; Gabel, M.; Dabbas, U.; Doumbo, S.; Cisse, H.; Li, S.; Jeninga, M.; Thomson Luque, R.; Doumtabe, D.; Petter, M.; Kayentao, K.; Ongoiba, A.; Bousema, T.; Crompton, P. D.; Traore, B.; Graw, F.

doi:10.1101/2021.11.05.467456

bioRxiv · 10.1101/2021.11.05.467456

Constant rate of Plasmodium falciparum sexual commitment promotes variable gametocyte proportions as infection progresses over time

Portugal, S.·van Dijk, H.·Ferreira Lima, N.·Kampmann, M.·Gabel, M.·Dabbas, U.·Doumbo, S.·Cisse, H.·Li, S.·Jeninga, M.·Thomson Luque, R.·Doumtabe, D.·Petter, M.·Kayentao, K.·Ongoiba, A.·Bousema, T.·Crompton, P. D.·Traore, B.·Graw, F.

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Abstract

Plasmodium falciparum infections persist through long dry seasons at low parasitaemia without causing malaria symptoms and thus remain untreated. In asymptomatic children, increased circulation of infected erythrocytes without adhering to the vascular endothelium is observed during the dry months, compared to febrile malaria in the wet season. However, alterations of parasite sexual commitment and gametocytogenesis have not been investigated. Here, we compared the expression of genes related to sexual commitment and gametocytogenesis, the proportion and density of P. falciparum gametocytes, and the blood concentration of phospholipids in dry season asymptomatic individuals versus symptomatic subjects in the wet season. Additionally, we adapted a within-host mathematical model considering asexual and sexually-committed parasites and gametocytes to understand the dynamics of gametocyte number and proportion as infections progress. Compared to clinical malaria cases, transcripts of late-stage gametocytes were predominantly upregulated in the dry season, associating with increased proportions of mature gametocytes; while transcription of genes related to parasite sexual commitment was unaltered throughout the year. Our data suggest that gametocyte density and proportion diverge as infections progress from recent transmission to chronic carriage, without alterations in the sexual commitment rate over time.

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Portugal, S., van Dijk, H., Ferreira Lima, N., Kampmann, M., Gabel, M., Dabbas, U., Doumbo, S., Cisse, H., Li, S., Jeninga, M., Thomson Luque, R., Doumtabe, D., Petter, M., Kayentao, K., Ongoiba, A., Bousema, T., Crompton, P. D., Traore, B., Graw, F.. 2021-11-06. Constant rate of Plasmodium falciparum sexual commitment promotes variable gametocyte proportions as infection progresses over time. https://doi.org/10.1101/2021.11.05.467456

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