Copy number variations in Plasmodium vivax: implications for erythrocyte invasion, malaria transmission, and host-pathogen interactions in Ethiopia and Sudan

Kareen Pestana

doi:10.17918/00010925

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Copy number variations in Plasmodium vivax: implications for erythrocyte invasion, malaria transmission, and host-pathogen interactions in Ethiopia and Sudan

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Copy number variations in Plasmodium vivax: implications for erythrocyte invasion, malaria transmission, and host-pathogen interactions in Ethiopia and Sudan

Kareen Pestana

Doctor of Philosophy (Ph.D.), Drexel University

Mar 2025

DOI:

https://doi.org/10.17918/00010925

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Abstract

Copy number variation

Plasmodium

Ethiopia

Genetics

Malaria

Sudan

Malaria caused by Plasmodium vivax (Pv) is a growing public health concern in Africa, despite the long-held belief that the high prevalence of Duffy-negative individuals would limit its spread. Recent evidence suggests that Pv has evolved alternative invasion mechanisms, allowing it to infect Duffy-negative individuals. However, the genetic factors driving this adaptation remain unclear. This study explores the role of copy number variations (CNVs) in three key invasion genes--Pv Duffy Binding Protein 1 (PvDBP1), Pv Erythrocyte Binding Protein/Duffy Binding Protein 2 (PvEBP/DBP2), and Pv Reticulocyte Binding Protein 2b (PvRBP2b)--to understand how Pv persists in diverse malaria-endemic regions of Ethiopia and Sudan. A total of 740 Pv-infected clinical samples were analyzed using quantitative PCR and transcriptomic profiling to assess CNVs and their potential impact on parasite behavior. The results show that PvDBP1 duplications were significantly more common in Duffy-positive individuals, with copy numbers ranging from 1 to 11, while Duffy-negative individuals had fewer copies (1-3). Both Malagasy- and Cambodian-type PvDBP1 duplications were found across study sites, suggesting multiple evolutionary adaptations. Interestingly, higher PvDBP1 copy numbers were linked to increased reports of chills and shivering, hinting at a possible relationship between gene amplification and immune response. Similarly, multiplications of PvEBP/DBP2 and PvRBP2b were detected in both Duffy-positive and Duffy-negative individuals, reinforcing the idea that these genes may play a role in alternative invasion pathways. These findings provide new insights into how Pv is adapting to different host populations, raising important questions about its potential expansion in Africa. Understanding how CNVs contribute to erythrocyte invasion could have significant implications for malaria control, particularly for vaccine development targeting alternative invasion pathways. Further research is needed to determine whether PvDBP1 duplications give the parasite a survival advantage and how they influence disease severity in Duffy-negative individuals.

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Title: Copy number variations in Plasmodium vivax
Creators: Kareen Pestana
Contributors: Eugenia Lo (Advisor)
Akhil B. Vaidya (Advisor)
Awarding Institution: Drexel University
Degree Awarded: Doctor of Philosophy (Ph.D.)
Publisher: Drexel University; Philadelphia, Pennsylvania
Number of pages: viii, 92 pages
Resource Type: Dissertation
Language: English
Academic Unit: Biochemistry and Molecular Biology; College of Medicine; Drexel University
Other Identifier: 991022052640304721

Copy number variations in Plasmodium vivax: implications for erythrocyte invasion, malaria transmission, and host-pathogen interactions in Ethiopia and Sudan

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