Journal article
Circulating neutrophil extracellular traps and neutrophil activation are increased in proportion to disease severity in human malaria
- Abstract:
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Background: Neutrophil activation results in Plasmodium parasite killing in vitro, but neutrophil products including neutrophil extracellular traps (NETs) mediate host organ damage and may contribute to severe malaria. The role of NETs in the pathogenesis of severe malaria has not been examined.
Methods: In Papua, Indonesia, we enrolled adults with symptomatic Plasmodium falciparum (n = 47 uncomplicated, n = 8 severe), Plasmodium vivax (n = 37), or Plasmodium malariae (n = 14) malaria; asymptomatic P falciparum (n = 19) or P vivax (n = 21) parasitemia; and healthy adults (n = 23) without parasitemia. Neutrophil activation and NETs were quantified by immunoassays and microscopy and correlated with parasite biomass and disease severity.
Results: In patients with symptomatic malaria, neutrophil activation and NET counts were increased in all 3 Plasmodium species. In falciparum malaria, neutrophil activation and NET counts positively correlated with parasite biomass (Spearman rho = 0.41, P = .005 and r2 = 0.26, P = .002, respectively) and were significantly increased in severe disease. In contrast, NETs were inversely associated with parasitemia in adults with asymptomatic P falciparum infection (r2 = 0.24, P = .031) but not asymptomatic P vivax infection.
Conclusions: Although NETs may inhibit parasite growth in asymptomatic P falciparum infection, neutrophil activation and NET release may contribute to pathogenesis in severe falciparum malaria. Agents with potential to attenuate these processes should be evaluated.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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- Files:
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(Preview, Accepted manuscript, pdf, 646.2KB, Terms of use)
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(Preview, Accepted manuscript, pdf, 677.3KB, Terms of use)
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- Publisher copy:
- 10.1093/infdis/jiy661
Authors
- Funding agency for:
- Yeo, TW
- Grant:
- 15nov007
- Grant:
- 1045156
- 1135820
- Funding agency for:
- Anstey, NM
- Funding agency for:
- Poespoprodjo, JR
- Price, RN
- Grant:
- 099875
- 200909/Z/16/Z
- 099875
- Publisher:
- Oxford University Press
- Journal:
- Journal of Infectious Diseases More from this journal
- Volume:
- 219
- Issue:
- 12
- Pages:
- 1994–2004
- Publication date:
- 2018-11-19
- Acceptance date:
- 2018-11-11
- DOI:
- EISSN:
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1537-6613
- ISSN:
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0022-1899
- Pmid:
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30452670
- Language:
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English
- Keywords:
- Pubs id:
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pubs:948871
- UUID:
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uuid:2f0003db-c2fd-482e-9ac6-f8cdf2ccdc05
- Local pid:
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pubs:948871
- Source identifiers:
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948871
- Deposit date:
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2018-12-03
Terms of use
- Copyright holder:
- Kho et al
- Copyright date:
- 2018
- Notes:
- © The Authors 2018. Published by Oxford University Press for the Infectious Diseases Society of America. This is the accepted manuscript version of the article. The final version and supplementary materials are available online from Oxford University Press at: https://doi.org/10.1093/infdis/jiy661 and a correction has been published at: https://doi.org/10.1093/infdis/jiz028
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