Longitudinal profiling of plasma cytokines in melioidosis and their association with mortality: a prospective cohort study

Longitudinal profiling of plasma cytokines in melioidosis and their association with mortality: a prospective cohort study

To characterize plasma cytokine responses in melioidosis and analyse their association with mortality. A prospective longitudinal study was conducted in two hospitals in Northeast Thailand to enrol 161 individuals with melioidosis, plus 13 uninfected healthy individuals and 11 uninfected individuals...

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Published in:Clinical microbiology and infection Vol. 26; no. 6; pp. 783.e1 - 783.e8
Main Authors: Kaewarpai, T., Ekchariyawat, P., Phunpang, R., Wright, S.W., Dulsuk, A., Moonmueangsan, B., Morakot, C., Thiansukhon, E., Day, N.P.J., Lertmemongkolchai, G., West, T.E., Chantratita, N.
Format: Journal Article
Language:English
Published: England Elsevier Ltd 01-06-2020
Subjects:
Bacteremia - immunology
Bacteremia - mortality
Biomarker
Biomarkers - blood
Cohort Studies
Comorbidity
Cytokine
Cytokines - blood
Cytokines - immunology
Diabetes
Female
Humans
Inflammation - mortality
Longitudinal Studies
Male
Melioidosis
Melioidosis - blood
Melioidosis - immunology
Melioidosis - mortality
Middle Aged
Outcome
Prospective Studies
ROC Curve
Severity of Illness Index
Thailand
Thailand
Melioidosis
Biomarker
Diabetes
Outcome
Cytokine
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Summary:To characterize plasma cytokine responses in melioidosis and analyse their association with mortality. A prospective longitudinal study was conducted in two hospitals in Northeast Thailand to enrol 161 individuals with melioidosis, plus 13 uninfected healthy individuals and 11 uninfected individuals with diabetes to act as controls. Blood was obtained from all individuals at enrolment (day 0), and at days 5, 12 and 28 from surviving melioidosis patients. Interferon-γ (IFN-γ), interleukin-1β (IL-1β), IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, IL-23, and tumour necrosis factor-α (TNF-α) were assayed in plasma. The association of each cytokine and its dynamics with 28-day mortality was determined. Of the individuals with melioidosis, 131/161 (81%) were bacteraemic, and 68/161 (42%) died. On enrolment, median levels of IFN-γ, IL-6, IL-8, IL-10, IL-23 and TNF-α were higher in individuals with melioidosis compared with uninfected healthy individuals and all but IFN-γ were positively associated with 28-day mortality. Interleukin-8 provided the best discrimination of mortality (area under the receiver operating characteristic curve 0.78, 95% CI 0.71–0.85). Over time, non-survivors had increasing IL-6, IL-8 and IL-17A levels, in contrast to survivors. In joint modelling, temporal trajectories of IFN-γ, IL-6, IL-8, IL-10 and TNF-α predicted survival. In a severely ill cohort of individuals with melioidosis, specific pro- and anti-inflammatory and T helper type 17 cytokines were associated with survival from melioidosis, at enrolment and over time. Persistent inflammation preceded death. These findings support further evaluation of these mediators as prognostic biomarkers and to guide targeted immunotherapeutic development for severe melioidosis.
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These authors contributed equally to this work.
NC, TEW were involved in the design of the study. TK, PE and AD collected samples and performed experiments. RP, BM, CM, ET and GL recruited patients and collected data. TEW, SWW and TK performed the statistical analysis. NPJ, NC and GL provided facilities. NC and TEW were responsible for supervision of the study. All authors were involved in writing the paper and have approved the final version.
Contributions
ISSN:1198-743X
1469-0691
DOI:10.1016/j.cmi.2019.10.032