Effects of sublethal exposure of European brown hares to paraoxon on the course of tularemia.

OBJECTIVES: The causative agent of tularemia Francisella tularensis is highly infectious and lagomorphs are important reservoirs and a source of human disease. The aim of the present study was to test the hypothesis that sublethal exposure to pesticides increases the susceptibility of hares to F. tularensis and modulates the course of the infection.

METHODS: Experimental hares were allocated to a) control, b) paraoxon-treated, c) F. tularensis-treated, and d) paraoxon-and-F. tularensis-treated groups of five specimens on a random basis and subcutaneously inoculated with a wild F. tularensis subsp. holarctica strain (a single dose of 9 × 108 CFU pro toto) and/or injected a sublethal dose of paraoxon (100 μg/kg). Group differences were evaluated using survival curves, oxidative stress responses as well as caspase-3 and acetylcholinesterase activities in whole blood samples collected on day 2 post exposure.

RESULTS: The paraoxon-and-F. tularensis-treated group showed a rapid onset of clinical signs and all deaths occurred on days 2 and 3 post exposure. F. tularensis-inoculated hares survived from 3 to 10 days, while only one hare died on day 12 in the paraoxon-treated group. Survival curves in the three exposed groups were significantly different from the control and median survival in F. tularensis-inoculated and paraoxon-and-F. tularensis-treated hares amounted to 7 and 2 days, respectively. Compared with controls, significant responses included an eight- and seven-fold activation of caspase-3 in F. tularensis-inoculated and paraoxon-and-F. tularensis-treated hares, respectively, and a 1.5-fold decrease of blood acetylcholinesterase activities in the paraoxon-treated and paraoxon-and-F. tularensis-treated groups. There was a 1.3- to 1.4-fold decrease of the ferric reducing antioxidant power in blood of F. tularensis-inoculated hares and the paraoxon-and-F. tularensis-treated group, respectively. The blood lipid peroxidation levels were of no differences among the four experimental groups.

CONCLUSIONS: Results of this study can help understand the pathogenesis of tularemia and mortality of hares in agricultural habitats. Use of anticholinesterase agents in agriculture can pose a threat of infectious disease outbreaks and higher mortality in wildlife populations.