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

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.

Host-Based Prognostic Biomarkers to Improve Risk Stratification and Outcome of Febrile Children in Low- and Middle-Income Countries

“…Levels of Ang-1, Ang-2, and sTie-2 have also been examined in other causes of sepsis. Results are mostly comparable to the malaria studies, as elevated Ang-2 and reduced Ang-1 levels have been associated with disease severity, intensive care unit (ICU) admission, shock, organ dysfunction, and death ( 54 , 61 , 79 , 96 – 99 ).…”

“…Another study conducted in rural Thailand in hospitalized patients with suspected infection also reported sTREM-1 to have strong prognostic 28-day mortality (AUC = 0.81 [95% CI: 0.77-0.85]) (61). Moreover, in these two studies, models combining sTREM-1 levels and validated clinical scoring systems (e.g., quick Sequential Organ Failure Assessment [qSOFA] and systemic Inflammatory Response Syndrome [SIRS]) had better prognostic accuracy than the clinical scoring systems alone (54,61).…”

“…Increased TNF levels are also associated with neurological deficits and longer coma duration in children with cerebral malaria ( 53 ). Similarly, several studies have reported that individuals with severe disease and/or non-survivors have higher levels of soluble TNF receptor 1 (sTNFR1) ( 30 , 47 , 48 , 54 – 61 ). Likewise, interleukins (ILs) are key components of the immune system and circulating concentrations of IL-6, IL-8, and IL-10 have been extensively studied in disease severity and progression.…”

“…Several clinical studies show that increased sTREM-1 levels are correlated with disease severity, longer clinical recovery times, multi-organ dysfunction, and mortality in both children and adults ( 54 , 61 , 73 , 74 , 83 – 86 ). It is speculated that these adverse outcomes are reflective of an imbalance in TREM-1 signaling, resulting in excess immune effector cells death and immunosuppression ( 54 ).…”

COVID-19 risk stratification algorithms based on sTREM-1 and IL-6 in emergency department

“…As previously shown, sTREM-1 has a prognostic value in septic shock and other infectious states but has never been studied in the context of COVID-19. [20][21][22] Furthermore, endothelial cell infection and dysfunction might explain systemic impaired microcirculatory and multiorgan dysfunction with onset of…”