Neutrophil activation, acute lung injury and disease severity in Plasmodium knowlesi malaria.

Autor: Tan AF; Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Australia.; Infectious Diseases Society Kota Kinabalu Sabah - Menzies School of Health Research Clinical Research Unit, Kota Kinabalu, Malaysia.; QIMR Berghofer Medical Research Institute, Brisbane, Australia., Sakam SSB; Infectious Diseases Society Kota Kinabalu Sabah - Menzies School of Health Research Clinical Research Unit, Kota Kinabalu, Malaysia., Piera K; Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Australia., Rajahram GS; Infectious Diseases Society Kota Kinabalu Sabah - Menzies School of Health Research Clinical Research Unit, Kota Kinabalu, Malaysia.; Clinical Research Centre, Queen Elizabeth Hospital, Kota Kinabalu, Malaysia.; Queen Elizabeth Hospital II, Ministry of Health Malaysia, Kota Kinabalu, Malaysia.; School of Medicine and Health Sciences, Monash University Malaysia, Kuala Lumpur, Malaysia., William T; Infectious Diseases Society Kota Kinabalu Sabah - Menzies School of Health Research Clinical Research Unit, Kota Kinabalu, Malaysia.; Clinical Research Centre, Queen Elizabeth Hospital, Kota Kinabalu, Malaysia., Barber BE; Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Australia.; QIMR Berghofer Medical Research Institute, Brisbane, Australia., Anstey NM; Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Australia.; Infectious Diseases Society Kota Kinabalu Sabah - Menzies School of Health Research Clinical Research Unit, Kota Kinabalu, Malaysia., Grigg MJ; Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Australia.; Infectious Diseases Society Kota Kinabalu Sabah - Menzies School of Health Research Clinical Research Unit, Kota Kinabalu, Malaysia., Kho S; Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Australia.
Jazyk: angličtina
Zdroj: PLoS neglected tropical diseases [PLoS Negl Trop Dis] 2024 Aug 16; Vol. 18 (8), pp. e0012424. Date of Electronic Publication: 2024 Aug 16 (Print Publication: 2024).
DOI: 10.1371/journal.pntd.0012424
Abstrakt: The risk of severe malaria from the zoonotic parasite Plasmodium knowlesi approximates that from P. falciparum. In severe falciparum malaria, neutrophil activation contributes to inflammatory pathogenesis, including acute lung injury (ALI). The role of neutrophil activation in the pathogenesis of severe knowlesi malaria has not been examined. We evaluated 213 patients with P. knowlesi mono-infection (138 non-severe, 75 severe) and 49 Plasmodium-negative controls from Malaysia. Markers of neutrophil activation (soluble neutrophil elastase [NE], citrullinated histone [CitH3] and circulating neutrophil extracellular traps [NETs]) were quantified in peripheral blood by microscopy and immunoassays. Findings were correlated with malaria severity, ALI clinical criteria, biomarkers of parasite biomass, haemolysis, and endothelial activation. Neutrophil activation increased with disease severity, with median levels higher in severe than non-severe malaria and controls for NE (380[IQR:210-930]ng/mL, 236[139-448]ng/mL, 218[134-307]ng/mL, respectively) and CitH3 (8.72[IQR:3.0-23.1]ng/mL, 4.29[1.46-9.49]ng/mL, 1.53[0.6-2.59]ng/mL, respectively)[all p<0.01]. NETs were higher in severe malaria compared to controls (126/μL[IQR:49-323] vs 51[20-75]/μL, p<0.001). In non-severe malaria, neutrophil activation fell significantly upon discharge from hospital (p<0.03). In severe disease, NETs, NE, and CitH3 were correlated with parasitaemia, cell-free haemoglobin and angiopoietin-2 (all Pearson's r>0.24, p<0.05). Plasma NE and angiopoietin-2 were higher in knowlesi patients with ALI than those without (p<0.008); neutrophilia was associated with an increased risk of ALI (aOR 3.27, p<0.01). In conclusion, neutrophil activation is increased in ALI and in proportion to disease severity in knowlesi malaria, is associated with endothelial activation, and may contribute to disease pathogenesis. Trials of adjunctive therapies to regulate neutrophil activation are warranted in severe knowlesi malaria.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Tan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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