Single-cell analyses of polyclonal Plasmodium vivax infections and their consequences on parasite transmission

Brittany Hazzard, Juliana M. Sá, Haikel N. Bogale, Tales V. Pascini, Angela C. Ellis, Shuchi Amin, Jennifer S. Armistead, John H. Adams, Thomas E. Wellems and David Serre ()
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Brittany Hazzard: University of Maryland School of Medicine
Juliana M. Sá: National Institutes of Health
Haikel N. Bogale: University of Maryland School of Medicine
Tales V. Pascini: National Institutes of Health
Angela C. Ellis: National Institutes of Health
Shuchi Amin: National Institutes of Health
Jennifer S. Armistead: National Institutes of Health
John H. Adams: University of South Florida
Thomas E. Wellems: National Institutes of Health
David Serre: University of Maryland School of Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-11

Abstract: Abstract Most Plasmodium vivax infections contain genetically distinct parasites, but the consequences of this polyclonality on the development of asexual parasites, their sexual differentiation, and their transmission remain unknown. We describe infections of Saimiri monkeys with two strains of P. vivax and the analyses of 80,024 parasites characterized by single cell RNA sequencing and individually genotyped. In our model, consecutive inoculations fail to establish polyclonal infections. By contrast, simultaneous inoculations of two strains lead to sustained polyclonal infections, although without detectable differences in parasite regulation or sexual commitment. Analyses of sporozoites dissected from mosquitoes fed on coinfected monkeys show that all genotypes are successfully transmitted to mosquitoes. However, after sporozoite inoculation, not all genotypes contribute to the subsequent blood infections, highlighting an important bottleneck during pre-erythrocytic development. Overall, these studies provide new insights on the mechanisms regulating the establishment of polyclonal P. vivax infections and their consequences for disease transmission.

Date: 2024
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DOI: 10.1038/s41467-024-51949-8

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