title: Crotalidae polyvalent immune Fab (ovine) antivenom is effective in the neutralization of South American viperidae venoms in a murine model.
abstract: OBJECTIVE
  Crotalidae polyvalent immune Fab (ovine) (CroFab; FabAV) is used in the treatment of symptomatic crotaline envenomations in North America. Unlike Antivenin (Crotalidae) Polyvalent, which is approved for treatment of crotaline envenomation in North and South America, FabAV is manufactured using only venoms from crotaline snakes native to the United States. This study was designed to evaluate the efficacy of FabAV in the neutralization of venom from 2 South American crotaline snakes: Crotalus durissus terrificus (tropical rattlesnake) and Bothrops atrox (fer-de-lance).
  
  
  METHODS
  A randomized, blinded, placebo-controlled murine model of intraperitoneal venom injection was used. Venom potency was determined in preliminary median lethal dose (LD 50) dosing studies. Study animals were then divided into 7 groups: (1) C durissus terrificus venom (Sigma-Aldrich Co.)+FabAV, (2) C durissus terrificus venom (Sigma-Aldrich Co.)+0.9% normal saline solution, (3) C durissus terrificus venom (Biotoxins Inc.)+FabAV, (4) C durissus terrificus venom (Biotoxins Inc.)+normal saline solution, (5) B atrox venom+FabAV, (6) B atrox venom+normal saline solution, and (7) FabAV+normal saline solution. Twice the estimated LD 50 was the chosen venom dose, and the amount of FabAV injected was 10 times the amount needed for venom neutralization. Statistical analysis included Fisher's exact test and log-rank testing to compare survival rates and times.
  
  
  RESULTS
  The venom LD 50 was found in preliminary studies to be 0.9 mg/kg and 1.35 mg/kg for the C durissus terrificus venom obtained from Sigma-Aldrich Co. and Biotoxins Inc., respectively. The LD 50 for B atrox venom was 5.0 mg/kg. All animals receiving venom only and saline solution died. Animals receiving FabAV together with either venom survived to the end of the 24-hour observation period ( P <.001). Comparison of survival times between groups demonstrated a significant difference in time to death between venom-only control groups and the FabAV+venom groups (P <.001). All animals in the FabAV+normal saline solution group survived to the conclusion of the study.
  
  
  CONCLUSIONS
  FabAV, when premixed with venom, decreases lethality in a murine model of intraperitoneal venom injection of the South American pit vipers, C durissus terrificus and B atrox .
authors.affiliation: Department of Emergency Medicine, Palmetto Richland Memorial Hospital, Palmetto Poison Center, College of Pharmacy, University of South Carolina, Columbia, SC 29208, USA. whrichardson@sc.rr.com
authors.forename: William H
authors.initials: WH
authors.lastname: Richardson
authors.forename: David A
authors.initials: DA
authors.lastname: Tanen
authors.forename: Tri C
authors.initials: TC
authors.lastname: Tong
authors.forename: David P
authors.initials: DP
authors.lastname: Betten
authors.forename: Shaun D
authors.initials: SD
authors.lastname: Carstairs
authors.forename: Saralyn R
authors.initials: SR
authors.lastname: Williams
authors.forename: Frank L
authors.initials: FL
authors.lastname: Cantrell
authors.forename: Richard F
authors.initials: RF
authors.lastname: Clark
mesh_terms: D000818:Animals; D000997:Antivenins / Q000627:therapeutic use*; D003429:Cross Reactions; D003435:Crotalid Venoms / Q000633:toxicity; D004195:Disease Models, Animal; D007140:Immunoglobulin Fab Fragments; D007128:Immunoglobulin Fragments / Q000627:therapeutic use*; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D011897:Random Allocation; D012909:Snake Bites / Q000628:therapy*; D015996:Survival Rate; D017819:Viperidae
chemical_list: D000997:Antivenins; D003435:Crotalid Venoms; C431183:Crotalidae Polyvalent immune Fab; D007140:Immunoglobulin Fab Fragments; D007128:Immunoglobulin Fragments