The complexity and dynamics of Plasmodium vivax infections in Papua New Guinean children

Plasmodium vivax is the most geographically widespread of the human malaria species and presents a serious public health challenge in South America, Central America, Asia and the southwest Pacific. In Papua New Guinea (PNG), malaria is the second leading cause of death. In this study, we have explor...

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Main Author Cole-Tobian, Jennifer L
Format Dissertation
LanguageEnglish
Published ProQuest Dissertations & Theses 01.01.2007
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Abstract Plasmodium vivax is the most geographically widespread of the human malaria species and presents a serious public health challenge in South America, Central America, Asia and the southwest Pacific. In Papua New Guinea (PNG), malaria is the second leading cause of death. In this study, we have explored the complexity and dynamics of P. vivax infections. We have shown that P. vivax infections are extremely complex consisting of up to 23 unique parasites in Papua New Guinean children---2- to 4-fold higher than previously reported. We have developed a technique to identify the most abundant vivax clone in the infection based on the highly polymorphic P. vivax Duffy binding protein region II ( PvdbpII). Using this technique, we have genotyped the PvdbpII in P. vivax positive samples collected biweekly from 206 Papua New Guinean children for 6 months after treatment to clear blood stage infections. Since the PvDBPII is the only known ligand for the Duffy antigen (DARC) which is essential for merozoite invasion into erythrocytes, we hypothesized that children with strong antibody responses to a specific PvDBPII allelic variant would have longer times to re-infection with that same allele. We found no evidence to support strain-specific immunity to PvDBPII, though the functional significance of the antibodies measured is unclear. We further hypothesized that certain PvDBPII alleles could influence P. vivax parasitemia---some alleles might bind more strongly to the DARC on the surface of the erythrocyte and influence invasion to occur more quickly and/or other alleles might be less immunogenic and be able to avoid the host immune response. We found no evidence that the PvDBPII allele had any significant affect on P. vivax parasitemia. Therefore, P. vivax infections are complex and re-infections occur quickly after treatment in holoendemic areas such as PNG; a better understanding, though, of the dynamics of mixed Plasmodium infections is needed before embarking on a vaccine for P. vivax.
AbstractList Plasmodium vivax is the most geographically widespread of the human malaria species and presents a serious public health challenge in South America, Central America, Asia and the southwest Pacific. In Papua New Guinea (PNG), malaria is the second leading cause of death. In this study, we have explored the complexity and dynamics of P. vivax infections. We have shown that P. vivax infections are extremely complex consisting of up to 23 unique parasites in Papua New Guinean children---2- to 4-fold higher than previously reported. We have developed a technique to identify the most abundant vivax clone in the infection based on the highly polymorphic P. vivax Duffy binding protein region II ( PvdbpII). Using this technique, we have genotyped the PvdbpII in P. vivax positive samples collected biweekly from 206 Papua New Guinean children for 6 months after treatment to clear blood stage infections. Since the PvDBPII is the only known ligand for the Duffy antigen (DARC) which is essential for merozoite invasion into erythrocytes, we hypothesized that children with strong antibody responses to a specific PvDBPII allelic variant would have longer times to re-infection with that same allele. We found no evidence to support strain-specific immunity to PvDBPII, though the functional significance of the antibodies measured is unclear. We further hypothesized that certain PvDBPII alleles could influence P. vivax parasitemia---some alleles might bind more strongly to the DARC on the surface of the erythrocyte and influence invasion to occur more quickly and/or other alleles might be less immunogenic and be able to avoid the host immune response. We found no evidence that the PvDBPII allele had any significant affect on P. vivax parasitemia. Therefore, P. vivax infections are complex and re-infections occur quickly after treatment in holoendemic areas such as PNG; a better understanding, though, of the dynamics of mixed Plasmodium infections is needed before embarking on a vaccine for P. vivax.
Author Cole-Tobian, Jennifer L
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Parasitology
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Title The complexity and dynamics of Plasmodium vivax infections in Papua New Guinean children
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