Utility of Three Serum Biomarkers for Early Detection of Systemic Envenoming Following Viper Bites in Sri Lanka.

Abstract

Early detection of systemic envenoming is critical for early antivenom therapy to minimize morbidity and mortality from snakebite. We assessed the diagnostic utility of 3 serum biomarkers in the early detection of systemic envenoming in viper bites in rural Sri Lanka. All confirmed snakebite patients admitted to Teaching Hospital Anuradhapura from July 2020 to June 2021 were included. On admission, blood was collected for venom concentrations, prothrombin time/international normalized ratio, fibrinogen concentration, serum creatinine concentration, and 3 serum biomarkers, namely secretory phospholipase A₂ (sPLA₂) activity, neutrophil gelatinase-associated lipocalin (sNGAL) concentration, and clusterin (sClu) concentration. Systemic envenoming was defined by the presence of venom-induced consumption coagulopathy, neurotoxicity, acute kidney injury, or the presence of nonspecific clinical effects. A total of 237 confirmed snakebite patients (Russell's viper, 72; hump-nosed viper, 80; nonvenomous snakes, 31; and unidentified bites, 54) with sufficient preantivenom serum samples were recruited [median age: 42 years (interquartile range [IQR] 29 to 53 years); 173 men (73%)]. Systemic envenoming occurred in 68 (94%) Russell's viper bites, 48 (60%) hump-nosed viper bites, and 45 (83%) unidentified bites. The median sPLA₂ activity was 72 nmol/mL/min (IQR 30 to 164) for Russell's viper envenoming, 12 nmol/mL/min (IQR 9 to 16) for hump-nosed viper envenoming, and 11 nmol/mL/min (IQR 9 to 14) for nonvenomous bites. There was no difference in sNGAL and sCLu concentrations among the 3 groups. The median sPLA₂ activity of patients with systemic envenoming was 16 nmol/min/mL (IQR 11 to 59) compared to 11 nmol/min/mL (IQR 9 to 14) in patients without systemic envenoming; the difference between medians was 5 nmol/min/mL (95% confidence interval [CI] 4 to 12). The area under the receiver operator characteristic curve (AUC-ROC) of admission sPLA₂ activity was the best predictor of systemic envenoming in all snakebites (AUC-ROC 0.72, 95% CI 0.66 to 0.79), whereas sNGAL and sClu concentrations were poor predictors. sPLA₂ activity was a better predictor of systemic envenoming in Russell's viper bites (AUC-ROC 0.90, 95% CI 0.76 to 1.00) and in those presenting within 2 hours of a bite. A sPLA₂ activity more than 23.5 nmol/min/mL had a sensitivity of 41% (95% CI 34% to 49%), and a specificity of 97% (95% CI 91% to 99.5%) in predicting systemic envenoming. A sPLA₂ activity of more than 46 nmol/min/mL on admission had a sensitivity of 67% (95% CI 55% to 77%) and a specificity of 100% (95% CI 51% to 100%) in predicting systemic envenoming in Russell's viper bites. sPLA₂ activity is an early predictor of systemic envenoming following snakebite, particularly in Russell's viper bites and in those who present early.