Evaluation of plasmodium vivax genotyping markers for molecular monitoring in clinical trials

C Koepfli, Ivo Mueller, Jutta Marfurt, M Goroti, Albert Sie, Olive Oa, Blaise Genton, Hans-Peter Beck, Ingrid Felger

    Research output: Contribution to journalArticleResearchpeer-review

    Abstract

    Background. Many antimalarial interventions are accompanied by molecular monitoring of parasite infections, and a number of molecular typing techniques based on different polymorphic marker genes are used. Here, we describe a genotyping technique that provides a fast and precise approach to study Plasmodium vivax infection dynamics during circumstances in which individual clones must be followed over time. The method was tested with samples from an in vivo drug efficacy study. Methods. The sizes of polymerase chain reaction fragments were evaluated by capillary electrophoresis to determine the extent of size polymorphism for 9 potential genetic markers (5 genes of merozoite surface proteins [msp] and 4 microsatellites) in 93-108 P. vivax-positive blood samples from 3 villages in Papua New Guinea. Results. The microsatellites MS16 and Pv3.27 showed the greatest diversity in the study area, with 66 and 31 different alleles, respectively, followed by 2 fragments of msp1 and 2 other microsatellites. msp3?, msp4, and msp5 revealed limited polymorphism. Conclusions. Even for the most diverse markers, the highest allelic frequencies reached 6% (MS16) or 13% (Pv3.27). To reduce the theoretical probability of superinfection with parasites that have the same haplotype as that detected at baseline, we propose to combine at least 2 markers for genotyping individual P. vivax infections. � 2009 by the Infectious Diseases Society of America.
    Original languageEnglish
    Pages (from-to)1074-1080
    Number of pages7
    JournalJournal of Infectious Diseases
    Volume199
    Issue number7
    Publication statusPublished - 2009

    Fingerprint

    Plasmodium vivax
    Microsatellite Repeats
    Clinical Trials
    Malaria
    Genotyping Techniques
    Papua New Guinea
    Molecular Typing
    Superinfection
    Parasitic Diseases
    Antimalarials
    Capillary Electrophoresis
    Genetic Markers
    Haplotypes
    Genes
    Parasites
    Clone Cells
    Alleles
    Polymerase Chain Reaction
    Pharmaceutical Preparations

    Cite this

    Koepfli, C., Mueller, I., Marfurt, J., Goroti, M., Sie, A., Oa, O., ... Felger, I. (2009). Evaluation of plasmodium vivax genotyping markers for molecular monitoring in clinical trials. Journal of Infectious Diseases, 199(7), 1074-1080.
    Koepfli, C ; Mueller, Ivo ; Marfurt, Jutta ; Goroti, M ; Sie, Albert ; Oa, Olive ; Genton, Blaise ; Beck, Hans-Peter ; Felger, Ingrid. / Evaluation of plasmodium vivax genotyping markers for molecular monitoring in clinical trials. In: Journal of Infectious Diseases. 2009 ; Vol. 199, No. 7. pp. 1074-1080.
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    abstract = "Background. Many antimalarial interventions are accompanied by molecular monitoring of parasite infections, and a number of molecular typing techniques based on different polymorphic marker genes are used. Here, we describe a genotyping technique that provides a fast and precise approach to study Plasmodium vivax infection dynamics during circumstances in which individual clones must be followed over time. The method was tested with samples from an in vivo drug efficacy study. Methods. The sizes of polymerase chain reaction fragments were evaluated by capillary electrophoresis to determine the extent of size polymorphism for 9 potential genetic markers (5 genes of merozoite surface proteins [msp] and 4 microsatellites) in 93-108 P. vivax-positive blood samples from 3 villages in Papua New Guinea. Results. The microsatellites MS16 and Pv3.27 showed the greatest diversity in the study area, with 66 and 31 different alleles, respectively, followed by 2 fragments of msp1 and 2 other microsatellites. msp3?, msp4, and msp5 revealed limited polymorphism. Conclusions. Even for the most diverse markers, the highest allelic frequencies reached 6{\%} (MS16) or 13{\%} (Pv3.27). To reduce the theoretical probability of superinfection with parasites that have the same haplotype as that detected at baseline, we propose to combine at least 2 markers for genotyping individual P. vivax infections. � 2009 by the Infectious Diseases Society of America.",
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    year = "2009",
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    Koepfli, C, Mueller, I, Marfurt, J, Goroti, M, Sie, A, Oa, O, Genton, B, Beck, H-P & Felger, I 2009, 'Evaluation of plasmodium vivax genotyping markers for molecular monitoring in clinical trials', Journal of Infectious Diseases, vol. 199, no. 7, pp. 1074-1080.

    Evaluation of plasmodium vivax genotyping markers for molecular monitoring in clinical trials. / Koepfli, C; Mueller, Ivo; Marfurt, Jutta; Goroti, M; Sie, Albert; Oa, Olive; Genton, Blaise; Beck, Hans-Peter; Felger, Ingrid.

    In: Journal of Infectious Diseases, Vol. 199, No. 7, 2009, p. 1074-1080.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - Evaluation of plasmodium vivax genotyping markers for molecular monitoring in clinical trials

    AU - Koepfli, C

    AU - Mueller, Ivo

    AU - Marfurt, Jutta

    AU - Goroti, M

    AU - Sie, Albert

    AU - Oa, Olive

    AU - Genton, Blaise

    AU - Beck, Hans-Peter

    AU - Felger, Ingrid

    PY - 2009

    Y1 - 2009

    N2 - Background. Many antimalarial interventions are accompanied by molecular monitoring of parasite infections, and a number of molecular typing techniques based on different polymorphic marker genes are used. Here, we describe a genotyping technique that provides a fast and precise approach to study Plasmodium vivax infection dynamics during circumstances in which individual clones must be followed over time. The method was tested with samples from an in vivo drug efficacy study. Methods. The sizes of polymerase chain reaction fragments were evaluated by capillary electrophoresis to determine the extent of size polymorphism for 9 potential genetic markers (5 genes of merozoite surface proteins [msp] and 4 microsatellites) in 93-108 P. vivax-positive blood samples from 3 villages in Papua New Guinea. Results. The microsatellites MS16 and Pv3.27 showed the greatest diversity in the study area, with 66 and 31 different alleles, respectively, followed by 2 fragments of msp1 and 2 other microsatellites. msp3?, msp4, and msp5 revealed limited polymorphism. Conclusions. Even for the most diverse markers, the highest allelic frequencies reached 6% (MS16) or 13% (Pv3.27). To reduce the theoretical probability of superinfection with parasites that have the same haplotype as that detected at baseline, we propose to combine at least 2 markers for genotyping individual P. vivax infections. � 2009 by the Infectious Diseases Society of America.

    AB - Background. Many antimalarial interventions are accompanied by molecular monitoring of parasite infections, and a number of molecular typing techniques based on different polymorphic marker genes are used. Here, we describe a genotyping technique that provides a fast and precise approach to study Plasmodium vivax infection dynamics during circumstances in which individual clones must be followed over time. The method was tested with samples from an in vivo drug efficacy study. Methods. The sizes of polymerase chain reaction fragments were evaluated by capillary electrophoresis to determine the extent of size polymorphism for 9 potential genetic markers (5 genes of merozoite surface proteins [msp] and 4 microsatellites) in 93-108 P. vivax-positive blood samples from 3 villages in Papua New Guinea. Results. The microsatellites MS16 and Pv3.27 showed the greatest diversity in the study area, with 66 and 31 different alleles, respectively, followed by 2 fragments of msp1 and 2 other microsatellites. msp3?, msp4, and msp5 revealed limited polymorphism. Conclusions. Even for the most diverse markers, the highest allelic frequencies reached 6% (MS16) or 13% (Pv3.27). To reduce the theoretical probability of superinfection with parasites that have the same haplotype as that detected at baseline, we propose to combine at least 2 markers for genotyping individual P. vivax infections. � 2009 by the Infectious Diseases Society of America.

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    KW - chloroquine

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    KW - genotype

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    KW - microsatellite marker

    KW - molecular cloning

    KW - Papua New Guinea

    KW - Plasmodium vivax

    KW - Plasmodium vivax malaria

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    KW - priority journal

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    KW - superinfection

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    KW - parasitology

    KW - Alleles

    KW - Animals

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    KW - Drug Resistance

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    KW - Genetic Markers

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