Sequence variation does not confound the measurement of plasma PfHRP2 concentration in African children presenting with severe malaria

T Ramutton, Ilse Hendriksen, Juliet Mwanga-Amumpaire, George Mtove, Rasaq Olaosebikan, Antoinette K Tshefu, Marie A Onyamboko, Corine Karema, Kathryn Maitland, Ermelinda Gomes, Samwel Gesase, Hugh Reyburn, Kamolrat Silamut, Kesinee Chotivanich, K Promnares, Caterina Fanello, Lorenz Von Seidlein, Nicholas Day, Arjen Dondorp, Mallika Imwong & 1 others Charles Woodrow

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    Abstract

    Background: Plasmodium falciparum histidine-rich protein PFHRP2 measurement is used widely for diagnosis, and more recently for severity assessment in falciparum malaria. The Pfhrp2 gene is highly polymorphic, with deletion of the entire gene reported in both laboratory and field isolates. These issues potentially confound the interpretation of PFHRP2 measurements. 

    Methods: Studies designed to detect deletion of Pfhrp2 and its paralog Pfhrp3 were undertaken with samples from patients in seven countries contributing to the largest hospital-based severe malaria trial (AQUAMAT). The quantitative relationship between sequence polymorphism and PFHRP2 plasma concentration was examined in samples from selected sites in Mozambique and Tanzania. 

    Results: There was no evidence for deletion of either Pfhrp2 or Pfhrp3 in the 77 samples with lowest PFHRP2 plasma concentrations across the seven countries. Pfhrp2 sequence diversity was very high with no haplotypes shared among 66 samples sequenced. There was no correlation between Pfhrp2 sequence length or repeat type and PFHRP2 plasma concentration. 

    Conclusions: 
    These findings indicate that sequence polymorphism is not a significant cause of variation in PFHRP2 concentration in plasma samples from African children. This justifies the further development of plasma PFHRP2 concentration as a method for assessing African children who may have severe falciparum malaria. The data also add to the existing evidence base supporting the use of rapid diagnostic tests based on PFHRP2 detection. 
    Original languageEnglish
    Article number276
    Pages (from-to)1-7
    Number of pages7
    JournalMalaria Journal
    Volume11
    DOIs
    Publication statusPublished - 2012

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    Malaria
    Falciparum Malaria
    Mozambique
    Tanzania
    Gene Deletion
    Plasmodium falciparum
    Routine Diagnostic Tests
    Haplotypes
    Genes

    Cite this

    Ramutton, T., Hendriksen, I., Mwanga-Amumpaire, J., Mtove, G., Olaosebikan, R., Tshefu, A. K., ... Woodrow, C. (2012). Sequence variation does not confound the measurement of plasma PfHRP2 concentration in African children presenting with severe malaria. Malaria Journal, 11, 1-7. [276]. https://doi.org/10.1186/1475-2875-11-276
    Ramutton, T ; Hendriksen, Ilse ; Mwanga-Amumpaire, Juliet ; Mtove, George ; Olaosebikan, Rasaq ; Tshefu, Antoinette K ; Onyamboko, Marie A ; Karema, Corine ; Maitland, Kathryn ; Gomes, Ermelinda ; Gesase, Samwel ; Reyburn, Hugh ; Silamut, Kamolrat ; Chotivanich, Kesinee ; Promnares, K ; Fanello, Caterina ; Von Seidlein, Lorenz ; Day, Nicholas ; Dondorp, Arjen ; Imwong, Mallika ; Woodrow, Charles. / Sequence variation does not confound the measurement of plasma PfHRP2 concentration in African children presenting with severe malaria. In: Malaria Journal. 2012 ; Vol. 11. pp. 1-7.
    @article{fddbabfbdd764960a68ba545aa619bab,
    title = "Sequence variation does not confound the measurement of plasma PfHRP2 concentration in African children presenting with severe malaria",
    abstract = "Background: Plasmodium falciparum histidine-rich protein PFHRP2 measurement is used widely for diagnosis, and more recently for severity assessment in falciparum malaria. The Pfhrp2 gene is highly polymorphic, with deletion of the entire gene reported in both laboratory and field isolates. These issues potentially confound the interpretation of PFHRP2 measurements. Methods: Studies designed to detect deletion of Pfhrp2 and its paralog Pfhrp3 were undertaken with samples from patients in seven countries contributing to the largest hospital-based severe malaria trial (AQUAMAT). The quantitative relationship between sequence polymorphism and PFHRP2 plasma concentration was examined in samples from selected sites in Mozambique and Tanzania. Results: There was no evidence for deletion of either Pfhrp2 or Pfhrp3 in the 77 samples with lowest PFHRP2 plasma concentrations across the seven countries. Pfhrp2 sequence diversity was very high with no haplotypes shared among 66 samples sequenced. There was no correlation between Pfhrp2 sequence length or repeat type and PFHRP2 plasma concentration. Conclusions: These findings indicate that sequence polymorphism is not a significant cause of variation in PFHRP2 concentration in plasma samples from African children. This justifies the further development of plasma PFHRP2 concentration as a method for assessing African children who may have severe falciparum malaria. The data also add to the existing evidence base supporting the use of rapid diagnostic tests based on PFHRP2 detection. ",
    keywords = "Plasmodium falciparum histidine rich protein 2, protozoal protein, unclassified drug, article, correlation analysis, gene deletion, gene sequence, genetic polymorphism, genetic variability, haplotype, human, malaria falciparum, Mozambique, protein blood level, quantitative analysis, Tanzania, Antigens, Protozoan, Child, Clinical Laboratory Techniques, Humans, Malaria, Falciparum, Parasitemia, Polymorphism, Genetic, Protozoan Proteins, Sensitivity and Specificity, Sequence Deletion",
    author = "T Ramutton and Ilse Hendriksen and Juliet Mwanga-Amumpaire and George Mtove and Rasaq Olaosebikan and Tshefu, {Antoinette K} and Onyamboko, {Marie A} and Corine Karema and Kathryn Maitland and Ermelinda Gomes and Samwel Gesase and Hugh Reyburn and Kamolrat Silamut and Kesinee Chotivanich and K Promnares and Caterina Fanello and {Von Seidlein}, Lorenz and Nicholas Day and Arjen Dondorp and Mallika Imwong and Charles Woodrow",
    year = "2012",
    doi = "10.1186/1475-2875-11-276",
    language = "English",
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    pages = "1--7",
    journal = "Malaria Journal",
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    publisher = "BioMed Central",

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    Ramutton, T, Hendriksen, I, Mwanga-Amumpaire, J, Mtove, G, Olaosebikan, R, Tshefu, AK, Onyamboko, MA, Karema, C, Maitland, K, Gomes, E, Gesase, S, Reyburn, H, Silamut, K, Chotivanich, K, Promnares, K, Fanello, C, Von Seidlein, L, Day, N, Dondorp, A, Imwong, M & Woodrow, C 2012, 'Sequence variation does not confound the measurement of plasma PfHRP2 concentration in African children presenting with severe malaria', Malaria Journal, vol. 11, 276, pp. 1-7. https://doi.org/10.1186/1475-2875-11-276

    Sequence variation does not confound the measurement of plasma PfHRP2 concentration in African children presenting with severe malaria. / Ramutton, T; Hendriksen, Ilse; Mwanga-Amumpaire, Juliet; Mtove, George; Olaosebikan, Rasaq; Tshefu, Antoinette K; Onyamboko, Marie A; Karema, Corine; Maitland, Kathryn; Gomes, Ermelinda; Gesase, Samwel; Reyburn, Hugh; Silamut, Kamolrat; Chotivanich, Kesinee; Promnares, K; Fanello, Caterina; Von Seidlein, Lorenz; Day, Nicholas; Dondorp, Arjen; Imwong, Mallika; Woodrow, Charles.

    In: Malaria Journal, Vol. 11, 276, 2012, p. 1-7.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - Sequence variation does not confound the measurement of plasma PfHRP2 concentration in African children presenting with severe malaria

    AU - Ramutton, T

    AU - Hendriksen, Ilse

    AU - Mwanga-Amumpaire, Juliet

    AU - Mtove, George

    AU - Olaosebikan, Rasaq

    AU - Tshefu, Antoinette K

    AU - Onyamboko, Marie A

    AU - Karema, Corine

    AU - Maitland, Kathryn

    AU - Gomes, Ermelinda

    AU - Gesase, Samwel

    AU - Reyburn, Hugh

    AU - Silamut, Kamolrat

    AU - Chotivanich, Kesinee

    AU - Promnares, K

    AU - Fanello, Caterina

    AU - Von Seidlein, Lorenz

    AU - Day, Nicholas

    AU - Dondorp, Arjen

    AU - Imwong, Mallika

    AU - Woodrow, Charles

    PY - 2012

    Y1 - 2012

    N2 - Background: Plasmodium falciparum histidine-rich protein PFHRP2 measurement is used widely for diagnosis, and more recently for severity assessment in falciparum malaria. The Pfhrp2 gene is highly polymorphic, with deletion of the entire gene reported in both laboratory and field isolates. These issues potentially confound the interpretation of PFHRP2 measurements. Methods: Studies designed to detect deletion of Pfhrp2 and its paralog Pfhrp3 were undertaken with samples from patients in seven countries contributing to the largest hospital-based severe malaria trial (AQUAMAT). The quantitative relationship between sequence polymorphism and PFHRP2 plasma concentration was examined in samples from selected sites in Mozambique and Tanzania. Results: There was no evidence for deletion of either Pfhrp2 or Pfhrp3 in the 77 samples with lowest PFHRP2 plasma concentrations across the seven countries. Pfhrp2 sequence diversity was very high with no haplotypes shared among 66 samples sequenced. There was no correlation between Pfhrp2 sequence length or repeat type and PFHRP2 plasma concentration. Conclusions: These findings indicate that sequence polymorphism is not a significant cause of variation in PFHRP2 concentration in plasma samples from African children. This justifies the further development of plasma PFHRP2 concentration as a method for assessing African children who may have severe falciparum malaria. The data also add to the existing evidence base supporting the use of rapid diagnostic tests based on PFHRP2 detection. 

    AB - Background: Plasmodium falciparum histidine-rich protein PFHRP2 measurement is used widely for diagnosis, and more recently for severity assessment in falciparum malaria. The Pfhrp2 gene is highly polymorphic, with deletion of the entire gene reported in both laboratory and field isolates. These issues potentially confound the interpretation of PFHRP2 measurements. Methods: Studies designed to detect deletion of Pfhrp2 and its paralog Pfhrp3 were undertaken with samples from patients in seven countries contributing to the largest hospital-based severe malaria trial (AQUAMAT). The quantitative relationship between sequence polymorphism and PFHRP2 plasma concentration was examined in samples from selected sites in Mozambique and Tanzania. Results: There was no evidence for deletion of either Pfhrp2 or Pfhrp3 in the 77 samples with lowest PFHRP2 plasma concentrations across the seven countries. Pfhrp2 sequence diversity was very high with no haplotypes shared among 66 samples sequenced. There was no correlation between Pfhrp2 sequence length or repeat type and PFHRP2 plasma concentration. Conclusions: These findings indicate that sequence polymorphism is not a significant cause of variation in PFHRP2 concentration in plasma samples from African children. This justifies the further development of plasma PFHRP2 concentration as a method for assessing African children who may have severe falciparum malaria. The data also add to the existing evidence base supporting the use of rapid diagnostic tests based on PFHRP2 detection. 

    KW - Plasmodium falciparum histidine rich protein 2

    KW - protozoal protein

    KW - unclassified drug

    KW - article

    KW - correlation analysis

    KW - gene deletion

    KW - gene sequence

    KW - genetic polymorphism

    KW - genetic variability

    KW - haplotype

    KW - human

    KW - malaria falciparum

    KW - Mozambique

    KW - protein blood level

    KW - quantitative analysis

    KW - Tanzania

    KW - Antigens, Protozoan

    KW - Child

    KW - Clinical Laboratory Techniques

    KW - Humans

    KW - Malaria, Falciparum

    KW - Parasitemia

    KW - Polymorphism, Genetic

    KW - Protozoan Proteins

    KW - Sensitivity and Specificity

    KW - Sequence Deletion

    U2 - 10.1186/1475-2875-11-276

    DO - 10.1186/1475-2875-11-276

    M3 - Article

    VL - 11

    SP - 1

    EP - 7

    JO - Malaria Journal

    JF - Malaria Journal

    SN - 1475-2875

    M1 - 276

    ER -