Analysis of Acute Hypersensitivity Reactions by Antivenom Type and Geographic Location in the North American Snake Bite Registry (NASBR).

Background: Evidence regarding acute hypersensitivity reactions (AHRs) to the snakebite antivenoms Crotalidae Polyvalent Immune Fab (ovine) (Fab) and Crotalidae Immune F(ab')₂ (equine) (Fab2) supports no differences. However, larger studies may not account for geographic differences. Recent data suggest a correlation with alpha-gal syndrome (AGS). This study investigates the incidence of AHRs in patients receiving Fab2, Fab, or both, with a focus on U.S. states with higher AGS prevalence.

Methods: This is an analysis of native pit viper envenomations reported to the Toxicology Investigators Consortium (ToxIC) North American Snakebite Registry (NASBR) between January 1, 2018, and December 31, 2023. Patients administered Fab2 or Fab on index hospitalization were included. High-AGS and low-AGS regions were defined according to epidemiologic data. The primary outcome was incidence of AHRs after administration of antivenom overall and in high-AGS vs. low-AGS states. Bivariate statistical tests and 95% confidence intervals (CI) for proportions were computed.

Results: A total of 1051 patients were identified. Fab2 was administered in 439 cases, and Fab was administered in 722 cases for a total of 1161 cases. Fifty AHRs were analyzed. AHRs were more common with Fab2 (6.6%; 95% CI: 4.6%, 9.3%) compared to Fab (2.9%; 95% CI: 1.9%, 4.4%) in the overall NASBR population (p = 0.004). In low-AGS states, there were 25/421 (5.9%; 95% CI: 4.1%, 8.6%) Fab2 AHRs vs. 16/569 (2.8%; 95% CI: 1.7%, 4.5%) Fab AHRs (p = 0.02). In high-AGS states, the Fab2 group had 4/18 (22.2%; 95% CI: 9.0%, 45.2%) AHRs vs. 5/153 (3.3%; 95% CI: 1.4%, 7.4%) in the Fab group (p = 0.008).

Conclusion: In this ToxIC NASBR study, administration of Fab2 was associated with a higher incidence of AHRs compared to Fab. The difference was especially notable in states with a higher prevalence of AGS.