Organophosphorus (OP) pesticides
poison more than 3,000,000 people every year in the developing world, mostly through intentional self-
poisoning. Advances in medical
therapy for OP
poisoning have lagged, and current treatment is not highly effective with mortality of up to 40% in even the most advanced Western medical facilities. Administration of a broadly active bacterial OP
hydrolase to patients in order to hydrolyze OPs in circulation might allow current
therapies to be more effective. The objective of this work was to evaluate the efficacy of a new recombinant bacterial OP
hydrolase (
OpdA), cloned from Agrobacterium radiobacter, in rat models of two chemically distinct but highly toxic and rapidly acting OP pesticides:
dichlorvos and
parathion. Without
OpdA treatment, median time to death in rats poisoned with 3x LD(50) of
dichlorvos or
parathion was 6 min and 25.5 min, respectively. Administration of a single dose of
OpdA immediately after
dichlorvos resulted in 100% survival at 24h, with no additional antidotal
therapy. After
parathion poisoning,
OpdA alone caused only a delay to death. However, an additional two doses of
OpdA resulted in 62.5% survival at 24 h after
parathion poisoning. In combination with
pralidoxime therapy, a single dose of
OpdA increased survival to 75% after
parathion poisoning. Our results demonstrate that
OpdA is able to improve survival after
poisoning by two chemically distinct and highly toxic OP pesticides.