sTREM-1 predicts mortality in hospitalized patients with infection in a tropical, middle-income country

Shelton W Wright, Lara Lovelace-Macon, Viriya Hantrakun, Kristina E Rudd, Prapit Teparrukkul, Susanna Kosamo, W Conrad Liles, Direk Limmathurotsakul, T Eoin West, Shelton W Wright, Lara Lovelace-Macon, Viriya Hantrakun, Kristina E Rudd, Prapit Teparrukkul, Susanna Kosamo, W Conrad Liles, Direk Limmathurotsakul, T Eoin West

Abstract

Background: Few studies of biomarkers as predictors of outcome in infection have been performed in tropical, low- and middle-income countries where the burden of sepsis is highest. We evaluated whether selected biomarkers could predict 28-day mortality in infected patients in rural Thailand.

Methods: Four thousand nine hundred eighty-nine adult patients admitted with suspected infection to a referral hospital in northeast Thailand were prospectively enrolled within 24 h of admission. In a secondary analysis of 760 patients, interleukin-8 (IL-8), soluble tumor necrosis factor receptor 1 (sTNFR-1), angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), and soluble triggering receptor expressed by myeloid cells 1 (sTREM-1) were measured in the plasma. Association with 28-day mortality was evaluated using regression; a parsimonious biomarker model was selected using the least absolute shrinkage and selection operator (LASSO) method. Discrimination of mortality was assessed by receiver operating characteristic curve analysis and verified by multiple methods.

Results: IL-8, sTNFR-1, Ang-2, and sTREM-1 concentrations were strongly associated with death. LASSO identified a three-biomarker model of sTREM-1, Ang-2, and IL-8, but sTREM-1 alone provided comparable mortality discrimination (p = 0.07). sTREM-1 alone was comparable to a model of clinical variables (area under receiver operating characteristic curve [AUC] 0.81, 95% confidence interval [CI] 0.77-0.85 vs AUC 0.79, 95% CI 0.74-0.84; p = 0.43). The combination of sTREM-1 and clinical variables yielded greater mortality discrimination than clinical variables alone (AUC 0.83, 95% CI 0.79-0.87; p = 0.004).

Conclusions: sTREM-1 predicts mortality from infection in a tropical, middle-income country comparably to a model derived from clinical variables and, when combined with clinical variables, can further augment mortality prediction.

Trial registration: The Ubon-sepsis study was registered on ClinicalTrials.gov ( NCT02217592 ), 2014.

Keywords: LMIC; Low- and middle-income countries; Sepsis; Soluble triggering receptor expressed by myeloid cells 1; sTREM-1.

Conflict of interest statement

WCL has the following patents: “Biomarkers for early determination of a critical or life threatening response to illness and monitoring response to treatment thereof” (Application CA2769433 A1 – August 27, 2013; WO20131270000 A1 – September 6, 2013), “Biomarkers for malaria” (Application: WO2012016333 A1 – February 9, 2012), “Angiopoietin-1 and -2 biomarkers for infectious diseases that compromise endothelial integrity” (Application: WO2009059404 A1 – May 14, 2009; US20110008804 A1 – January 13, 2011), “Biomarkers for early determination of a critical or life threatening response to illness and/or treatment response” (Application: US14/916,758 – March 4, 2016), and “Biomarkers to identify and predict severe toxicity after adoptive T cell therapy” (Application: US62/456,798 – February 9, 2017). All other authors declared that they have no competing interests. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.

Figures

Fig. 1
Fig. 1
Discrimination of death by sTREM-1 and clinical variable models. Area under the receiver operating characteristic curve (AUC) for the clinical variable model including age, sex, Charlson Comorbidity Index, transfer status, and modified SOFA score; an sTREM-1 model (sTREM-1); and a model combining the clinical variable model and sTREM-1 (Clin. var. + sTREM-1) for 28-day mortality discrimination
Fig. 2
Fig. 2
sTREM-1 and death at 28 days by modified SOFA score. Concentrations of sTREM-1 (pg/ml) and proportion of non-survivors at 28-days (%) are shown by quartile of modified SOFA score

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