Effects of Aging on Parasite Biomass, Inflammation, Endothelial Activation, Microvascular Dysfunction and Disease Severity in Plasmodium knowlesi and Plasmodium falciparum Malaria

Bridget E. Barber, Matthew J. Grigg, Timothy WILLIAM, Kim A. Piera, Michelle J. Boyle, Tsin W. Yeo, Nicholas M. Anstey

    Research output: Contribution to journalArticleResearchpeer-review

    Abstract

    Background: In populations pauci-immune to malaria, risk of severe malaria increases with age. This is particularly apparent in Plasmodium knowlesi malaria. However, pathophysiological mechanisms underlying knowlesi malaria, and of the age-related increase in risk of severe malaria in general, are poorly understood. 

    Methods: In Malaysian patients aged ≥12 years with severe (n = 47) and nonsevere (n = 99) knowlesi malaria, severe (n = 21) and nonsevere (n = 109) falciparum malaria, and healthy controls (n = 50), we measured parasite biomass, systemic inflammation (interleukin 6 [IL-6]), endothelial activation (angiopoietin-2), and microvascular function, and evaluated the effects of age. 

    Results: Plasmodium knowlesi parasitemia correlated with age (Spearman's correlation coefficient [r s ] = 0.36; P <.0001). In knowlesi malaria, IL-6, angiopoietin-2, and microvascular dysfunction were increased in severe compared to nonsevere disease, and all correlated with age, independent of parasitemia. In falciparum malaria, angiopoietin-2 increased with age, independent of parasite biomass (histidine-rich protein 2 [HRP2]). Independent risk factors for severe malaria included parasitemia and angiopoietin-2 in knowlesi malaria, and HRP2, angiopoietin-2, and microvascular dysfunction in falciparum malaria. 

    Conclusions: Parasite biomass, endothelial activation, and microvascular dysfunction are associated with severe disease in knowlesi malaria and likely contribute to pathogenesis. The association of each of these processes with aging may account for the greater severity of malaria observed in older adults in low-endemic regions.

    Original languageEnglish
    Pages (from-to)1908-1917
    Number of pages10
    JournalJournal of Infectious Diseases
    Volume215
    Issue number12
    DOIs
    Publication statusPublished - 15 Jun 2017

    Fingerprint

    Plasmodium knowlesi
    Falciparum Malaria
    Biomass
    Malaria
    Parasites
    Angiopoietin-2
    Inflammation
    Parasitemia
    Interleukin-6
    Plasmodium malariae

    Cite this

    @article{ca7ca3cbd2d8402282d5b767aa6727a7,
    title = "Effects of Aging on Parasite Biomass, Inflammation, Endothelial Activation, Microvascular Dysfunction and Disease Severity in Plasmodium knowlesi and Plasmodium falciparum Malaria",
    abstract = "Background: In populations pauci-immune to malaria, risk of severe malaria increases with age. This is particularly apparent in Plasmodium knowlesi malaria. However, pathophysiological mechanisms underlying knowlesi malaria, and of the age-related increase in risk of severe malaria in general, are poorly understood. Methods: In Malaysian patients aged ≥12 years with severe (n = 47) and nonsevere (n = 99) knowlesi malaria, severe (n = 21) and nonsevere (n = 109) falciparum malaria, and healthy controls (n = 50), we measured parasite biomass, systemic inflammation (interleukin 6 [IL-6]), endothelial activation (angiopoietin-2), and microvascular function, and evaluated the effects of age. Results: Plasmodium knowlesi parasitemia correlated with age (Spearman's correlation coefficient [r s ] = 0.36; P <.0001). In knowlesi malaria, IL-6, angiopoietin-2, and microvascular dysfunction were increased in severe compared to nonsevere disease, and all correlated with age, independent of parasitemia. In falciparum malaria, angiopoietin-2 increased with age, independent of parasite biomass (histidine-rich protein 2 [HRP2]). Independent risk factors for severe malaria included parasitemia and angiopoietin-2 in knowlesi malaria, and HRP2, angiopoietin-2, and microvascular dysfunction in falciparum malaria. Conclusions: Parasite biomass, endothelial activation, and microvascular dysfunction are associated with severe disease in knowlesi malaria and likely contribute to pathogenesis. The association of each of these processes with aging may account for the greater severity of malaria observed in older adults in low-endemic regions.",
    keywords = "aging, endothelial activation, malaria, pathogenesis, Plasmodium knowlesi",
    author = "Barber, {Bridget E.} and Grigg, {Matthew J.} and Timothy WILLIAM and Piera, {Kim A.} and Boyle, {Michelle J.} and Yeo, {Tsin W.} and Anstey, {Nicholas M.}",
    year = "2017",
    month = "6",
    day = "15",
    doi = "10.1093/infdis/jix193",
    language = "English",
    volume = "215",
    pages = "1908--1917",
    journal = "Journal of Infectious Diseases",
    issn = "0022-1899",
    publisher = "Oxford University Press",
    number = "12",

    }

    Effects of Aging on Parasite Biomass, Inflammation, Endothelial Activation, Microvascular Dysfunction and Disease Severity in Plasmodium knowlesi and Plasmodium falciparum Malaria. / Barber, Bridget E.; Grigg, Matthew J.; WILLIAM, Timothy; Piera, Kim A.; Boyle, Michelle J.; Yeo, Tsin W.; Anstey, Nicholas M.

    In: Journal of Infectious Diseases, Vol. 215, No. 12, 15.06.2017, p. 1908-1917.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - Effects of Aging on Parasite Biomass, Inflammation, Endothelial Activation, Microvascular Dysfunction and Disease Severity in Plasmodium knowlesi and Plasmodium falciparum Malaria

    AU - Barber, Bridget E.

    AU - Grigg, Matthew J.

    AU - WILLIAM, Timothy

    AU - Piera, Kim A.

    AU - Boyle, Michelle J.

    AU - Yeo, Tsin W.

    AU - Anstey, Nicholas M.

    PY - 2017/6/15

    Y1 - 2017/6/15

    N2 - Background: In populations pauci-immune to malaria, risk of severe malaria increases with age. This is particularly apparent in Plasmodium knowlesi malaria. However, pathophysiological mechanisms underlying knowlesi malaria, and of the age-related increase in risk of severe malaria in general, are poorly understood. Methods: In Malaysian patients aged ≥12 years with severe (n = 47) and nonsevere (n = 99) knowlesi malaria, severe (n = 21) and nonsevere (n = 109) falciparum malaria, and healthy controls (n = 50), we measured parasite biomass, systemic inflammation (interleukin 6 [IL-6]), endothelial activation (angiopoietin-2), and microvascular function, and evaluated the effects of age. Results: Plasmodium knowlesi parasitemia correlated with age (Spearman's correlation coefficient [r s ] = 0.36; P <.0001). In knowlesi malaria, IL-6, angiopoietin-2, and microvascular dysfunction were increased in severe compared to nonsevere disease, and all correlated with age, independent of parasitemia. In falciparum malaria, angiopoietin-2 increased with age, independent of parasite biomass (histidine-rich protein 2 [HRP2]). Independent risk factors for severe malaria included parasitemia and angiopoietin-2 in knowlesi malaria, and HRP2, angiopoietin-2, and microvascular dysfunction in falciparum malaria. Conclusions: Parasite biomass, endothelial activation, and microvascular dysfunction are associated with severe disease in knowlesi malaria and likely contribute to pathogenesis. The association of each of these processes with aging may account for the greater severity of malaria observed in older adults in low-endemic regions.

    AB - Background: In populations pauci-immune to malaria, risk of severe malaria increases with age. This is particularly apparent in Plasmodium knowlesi malaria. However, pathophysiological mechanisms underlying knowlesi malaria, and of the age-related increase in risk of severe malaria in general, are poorly understood. Methods: In Malaysian patients aged ≥12 years with severe (n = 47) and nonsevere (n = 99) knowlesi malaria, severe (n = 21) and nonsevere (n = 109) falciparum malaria, and healthy controls (n = 50), we measured parasite biomass, systemic inflammation (interleukin 6 [IL-6]), endothelial activation (angiopoietin-2), and microvascular function, and evaluated the effects of age. Results: Plasmodium knowlesi parasitemia correlated with age (Spearman's correlation coefficient [r s ] = 0.36; P <.0001). In knowlesi malaria, IL-6, angiopoietin-2, and microvascular dysfunction were increased in severe compared to nonsevere disease, and all correlated with age, independent of parasitemia. In falciparum malaria, angiopoietin-2 increased with age, independent of parasite biomass (histidine-rich protein 2 [HRP2]). Independent risk factors for severe malaria included parasitemia and angiopoietin-2 in knowlesi malaria, and HRP2, angiopoietin-2, and microvascular dysfunction in falciparum malaria. Conclusions: Parasite biomass, endothelial activation, and microvascular dysfunction are associated with severe disease in knowlesi malaria and likely contribute to pathogenesis. The association of each of these processes with aging may account for the greater severity of malaria observed in older adults in low-endemic regions.

    KW - aging

    KW - endothelial activation

    KW - malaria

    KW - pathogenesis

    KW - Plasmodium knowlesi

    UR - http://www.scopus.com/inward/record.url?scp=85022340393&partnerID=8YFLogxK

    U2 - 10.1093/infdis/jix193

    DO - 10.1093/infdis/jix193

    M3 - Article

    VL - 215

    SP - 1908

    EP - 1917

    JO - Journal of Infectious Diseases

    JF - Journal of Infectious Diseases

    SN - 0022-1899

    IS - 12

    ER -