Abstract
BackgroundFew 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.MethodsFour 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.ResultsIL-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).ConclusionssTREM-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 registrationThe Ubon-sepsis study was registered on ClinicalTrials.gov (NCT02217592), 2014.
Highlights
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
Biomarker concentrations in survivors and non-survivors IL-8, soluble tumor necrosis factor receptor 1 (sTNFR-1), Ang-1, Ang-2, and sTREM-1 concentrations measured in enrollment plasma samples were
In a relatively large cohort of patients with infection admitted to a referral hospital either through the emergency department (ED) or by transfer from an outside facility, a single measurement of sTREM-1 within 24 h of admission is similar to clinical illness score models in predicting 28day mortality
Summary
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. Low- and middle-income countries (LMICs)—where etiologies, host factors, and clinical management may differ from highincome settings—are impacted [1, 2]. Sepsisrelated mortality in tropical Southeast Asia is especially high and related to a heterogenous group of causes [2, 3]. And accurate assessment of the sepsis-related clinical trajectory is imperative, especially in settings with developing emergency transportation infrastructure and limited tertiary healthcare centers [1]. Thailand is an upper middle-income country with a tropical climate [4]. Optimizing prediction of outcomes from sepsis in environments such as this is essential
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