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[Doxycycline in the prevention of experimental plague induced by plague microbe variants]
Abstract:
A comparative study was performed on the efficacy of doxycycline in experimental plague infection induced in albino mice by strain 231 of the plague microbe and its variant 231 Fra- deprived of the ability to produce the fraction I antigen. It was shown that the LD50 for strain 231 during animal treatment with doxycycline was significantly higher than that for variant 231 Fra-. Prophylaxis of the plague infection caused by the Fra- forms of the plague microbe required significantly higher doses of doxycycline (ED50) than that of the infection caused by the Fra+ forms. The use of the daily maximum permissible doses of doxycycline (50 to 100 mg/kg a day) for 10 days in treatment of albino mice infected with the strain Fra- did not provide animal survival at the level higher than 60 to 70 per cent while the survival rate in the animals infected with the strain Fra+ of the plague microbe and treated according to the same scheme amounted to 90-100 per cent. The lower therapeutic efficacy of doxycycline in the treatment of the infection caused by the fractionless variant of the plague microbe should be considered in development of rational schemes for prophylaxis and treatment of plague.
Insights
Doxycycline is less effective against plague strains lacking fraction I antigen. Higher doses are needed for prophylaxis and treatment of these variants, impacting plague management strategies.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Plague is a serious bacterial infection caused by Yersinia pestis.
- Fraction I antigen is a key virulence factor in Yersinia pestis.
- Doxycycline is a common antibiotic used for plague treatment.
Purpose of the Study:
- To compare the efficacy of doxycycline against experimental plague infections caused by Fraction I antigen-positive (Fra+) and Fraction I antigen-negative (Fra-) Yersinia pestis strains.
- To determine the impact of Fraction I antigen on doxycycline's therapeutic and prophylactic effectiveness.
Main Methods:
- Experimental plague infection induced in albino mice using Yersinia pestis strain 231 (Fra+) and its variant 231 Fra- (Fra-).
- Comparative analysis of Lethal Dose 50 (LD50) and Effective Dose 50 (ED50) values for doxycycline in infected mice.
- Evaluation of survival rates in mice treated with maximum permissible doses of doxycycline.
Main Results:
- LD50 for the Fra+ strain was significantly higher than for the Fra- strain during doxycycline treatment.
- Prophylaxis against Fra- strains required significantly higher doxycycline ED50 doses compared to Fra+ strains.
- Doxycycline treatment (50-100 mg/kg/day for 10 days) resulted in 60-70% survival for Fra- infections versus 90-100% for Fra+ infections.
Conclusions:
- Doxycycline exhibits lower therapeutic efficacy against Yersinia pestis strains lacking Fraction I antigen.
- The absence of Fraction I antigen necessitates higher doxycycline doses for effective plague prophylaxis and treatment.
- These findings are crucial for developing optimized doxycycline treatment regimens for plague, considering bacterial antigen expression.