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The impact of Plasmodium vivax DBP1 copy number variation and duplication type on parasite load and total IgG reactivity through antibody binding to PvDBP-RII in sub-Saharan Africa cases
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The impact of Plasmodium vivax DBP1 copy number variation and duplication type on parasite load and total IgG reactivity through antibody binding to PvDBP-RII in sub-Saharan Africa cases

Victoria Nichole Ruszin
Master of Science (M.S.), Drexel University
Apr 2025
DOI:
https://doi.org/10.17918/00010924
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Abstract

Copy number variation DARC Duffy-negative Plasmodium PvDBP Africa Immunology
The interaction between Plasmodium vivax (P. vivax) Duffy Binding Protein 1 (PvDBP1)and the Duffy antigen receptor for chemokines (DARC) is crucial to human erythrocyte invasion. Vivax malaria cases are increasingly reported in various parts of Africa. P. vivax malaria cases, once considered rare in Duffy-negative Africans, are now increasingly reported in various parts of Africa, suggesting potential alternate invasion mechanisms and parasite adaptability to infecting Duffy-null cells. PvDBP1 was assessed in 92 P. vivax samples isolated from Duffy-negative individuals in three eco-epidemiological sites in Cameroon. The majority (92%) of patients had 2-5 copies of PvDBP1. Of 35 samples, 33 of them had both Malagasy and Cambodian duplication. In Bertoua and Buea, Cambodian duplication was more prevalent (29/29 (100%) and 21/23 (91%) of samples, respectively). Parasite load was significantly higher in samples with both duplication types and those with Cambodian type than in those without duplications. Though no significant difference was observed in PvDBP1 CNV among the three sites, the highest copies were observed in Buea and Bertoua, which are considered regions of high malaria transmission. High PvDBP1 copies (90%) in Duffy-negative infections in Central Africa in contrast to 25% in East Africa from our earlier study suggest different magnitudes of selection pressure among the African populations and possible functional advantages in erythrocyte invasion through an increase in PvDBP1 dosage. Linear regression showed a significant but weak correlation between CNV and log parasite load. To make PvDBP1-RII and see if CNV had an impact on total IgG reactive indexes, PvDBP1-RII's sequence was codon-harmonized, and the protein was successfully expressed and purified for use in indirect ELISAs. Digital PCR of Duffy-positive samples from Jimma, Ethiopia revealed most samples contained multiple copies of PvDBP1. Copy number and reactive index of 20 samples from Jimma, Ethiopia, were analyzed. Most of the samples (16/20 or 80%) were seropositive, and no significant differences were observed between single-copy and multiple-copy PvDBP1 samples.

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