Stable Plasmodium falciparum merozoite surface protein-1 allelic diversity despite decreasing parasitaemia in children with multiple malaria infections
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Author(s)
Yaa, Reuben M
Kimenyi, Kelvin M
Palasciano, Henry Antonio
Obiero, George
Ochola-Oyier, L Isabella
Type
Journal Article
Abstract
Background:
Individuals experiencing recurrent malaria infections encounter a variety of alleles with each new infection. This ongoing allelic diversity influences the development of naturally acquired immunity and it can inform vaccine efficacy. To investigate the diversity and infection variability, Plasmodium falciparum merozoite surface protein 1 (PfMSP1), a crucial protein for parasite invasion and immune response, was assessed in parasites isolated from children in the Junju cohort, Kilifi County, who experienced at least 10 febrile malaria episodes over a span of 5 years.
Methods:
Pfmsp1 C-terminal region (Pfmsp119) was genotyped using PCR followed by capillary sequencing in blood samples collected from the children. Sequenced reads were trimmed and aligned to the P. falciparum 3D7 reference genome. Single nucleotide polymorphisms in the Pfmsp119 region were identified from the alignment and grouped to distinct microhaplotypes whose changing frequency over time were examined across the multiple infection episodes. In addition, the variability of infections in the population was assessed using nucleotide and haplotype diversity indices.
Results:
A total of eleven microhaplotypes were observed across all malaria episodes. There were 3 prevalent microhaplotypes, E-KSNG-L, Q-KSNG-L, and Q-KSNG-F in the population. Conversely, microhaplotypes such as Q-KNNG-L, E-KSSR-L, E-KNNG-L, E-KSSG-L, E-TSSR-L (3D7), Q-TSSR-L, E-TSSG-L, and E-KSNG-F were rare and maintained at low frequencies. High allelic replacements were observed, however some individuals experienced consecutive re-infections with the same microhaplotype. Notably, PfMSP119 allelic diversity as measured by haplotype diversity was stable, while nucleotide diversity decreased over time with decreasing parasitemia. Parasite PfMSP119 allelic diversity remained stable over the multiple malaria episodes, despite declining parasitaemia levels. In addition, there are reveal dynamic PfMSP119 allelic replacements across parasite infection episodes.
Conclusions:
Allelic diversity was stable over time in individuals, based on this limited polymorphic region and small sample size, suggesting that there are no significant shifts in allele frequencies or replacements due to alleles being maintained under balancing selection. The dominant alleles in the population are those frequently observed in these children with multiple malaria episodes, further suggesting that early exposure to dominant alleles does not shift their frequency in the population or prevent repeat infection with the same alleles in subsequent infections. However, a blood stage merozoite vaccine is likely to require a multi-allelic formulation.
Individuals experiencing recurrent malaria infections encounter a variety of alleles with each new infection. This ongoing allelic diversity influences the development of naturally acquired immunity and it can inform vaccine efficacy. To investigate the diversity and infection variability, Plasmodium falciparum merozoite surface protein 1 (PfMSP1), a crucial protein for parasite invasion and immune response, was assessed in parasites isolated from children in the Junju cohort, Kilifi County, who experienced at least 10 febrile malaria episodes over a span of 5 years.
Methods:
Pfmsp1 C-terminal region (Pfmsp119) was genotyped using PCR followed by capillary sequencing in blood samples collected from the children. Sequenced reads were trimmed and aligned to the P. falciparum 3D7 reference genome. Single nucleotide polymorphisms in the Pfmsp119 region were identified from the alignment and grouped to distinct microhaplotypes whose changing frequency over time were examined across the multiple infection episodes. In addition, the variability of infections in the population was assessed using nucleotide and haplotype diversity indices.
Results:
A total of eleven microhaplotypes were observed across all malaria episodes. There were 3 prevalent microhaplotypes, E-KSNG-L, Q-KSNG-L, and Q-KSNG-F in the population. Conversely, microhaplotypes such as Q-KNNG-L, E-KSSR-L, E-KNNG-L, E-KSSG-L, E-TSSR-L (3D7), Q-TSSR-L, E-TSSG-L, and E-KSNG-F were rare and maintained at low frequencies. High allelic replacements were observed, however some individuals experienced consecutive re-infections with the same microhaplotype. Notably, PfMSP119 allelic diversity as measured by haplotype diversity was stable, while nucleotide diversity decreased over time with decreasing parasitemia. Parasite PfMSP119 allelic diversity remained stable over the multiple malaria episodes, despite declining parasitaemia levels. In addition, there are reveal dynamic PfMSP119 allelic replacements across parasite infection episodes.
Conclusions:
Allelic diversity was stable over time in individuals, based on this limited polymorphic region and small sample size, suggesting that there are no significant shifts in allele frequencies or replacements due to alleles being maintained under balancing selection. The dominant alleles in the population are those frequently observed in these children with multiple malaria episodes, further suggesting that early exposure to dominant alleles does not shift their frequency in the population or prevent repeat infection with the same alleles in subsequent infections. However, a blood stage merozoite vaccine is likely to require a multi-allelic formulation.
Date Issued
2025-04-28
Date Acceptance
2025-04-18
Citation
Malaria Journal, 2025, 24 (1)
ISSN
1475-2875
Publisher
BMC
Journal / Book Title
Malaria Journal
Volume
24
Issue
1
Copyright Statement
© The Author(s) 2025. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
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Publication Status
Published
Article Number
136
Date Publish Online
2025-04-28