EMERGENCY PROPHYLAXIS OF EXPERIMENTAL MELIOIDOSIS USING SYNTHETIC IMMUNOMODULATORS AND HETEROLOGOUS VACCINES

Cover Page

Cite item

Abstract

Melioidosis is a particularly dangerous infection caused by Burkholderia pseudomallei , against which a vaccine has not yet been created. In this regard, the development of effective treatment regimens and emergency prevention of melioidosis is very relevant. To improve the effectiveness of emergency prophylaxis of melioidosis, synthetic peptides (bestim, imunofan) and thiopoietin preparation glutoxim were used when combined with the antibiotic doxycycline. In addition, in experiments on white mice, the ability of heterologous vaccines (plague and tularemia), used in the emergency prevention mode, to increase the resistance of animals to melioidosis infection was assessed. It was shown that the most effective was imunofan, which, when combined with doxycycline, increased by 20% the survival rate of 5LD50 Burkholderia pseudomallei infection and significantly increased the average life span of mice infected with 5-12 LD50 (p < 0.05). The efficiency of use for stimulation of non-specific resistance to melioidosis of a heterologous plague vaccine EV, once administered 1 day prior to infection, protected 90% of mice from 6 LD50 Burkholderia pseudomallei and 60% - with an increase in the infectious dose of the pathogen of melioidosis up to 15 LD50. The same level of protection from melioidosis was provided by a 3 day course of antibiotic therapy with doxycycline. It was concluded that the tularemia vaccine is not suitable for immunostimulation in melioidosis due to its high residual virulence and reactogenicity.

About the authors

I A Khabarova

Volgograd Research Institute for Plague Control

Author for correspondence.
Email: svetlana25.01@yandex.ru

S I Zhukova

Volgograd Research Institute for Plague Control

Email: svetlana25.01@yandex.ru

K A Rotov

Volgograd Research Institute for Plague Control

Email: svetlana25.01@yandex.ru

E A Snatenkov

Volgograd Research Institute for Plague Control

Email: svetlana25.01@yandex.ru

A V Toporkov

Volgograd Research Institute for Plague Control

Email: svetlana25.01@yandex.ru

D V Viktorov

Volgograd Research Institute for Plague Control

Email: svetlana25.01@yandex.ru

References

  1. Ilyukhin V.I., Senina T.V., Trushkina M.N., Shubnikova E.V., Antonov Yu. V., Andronova N.V. Problems of the correspondence of antibiotic susceptibility in vitro and the effectiveness of chemotherapy of infections caused by pathogenic burkholderia. Antibiotics and chemotherapy. 2009. No. 7—8. P. 19—23.
  2. Emergency prevention and treatment of dangerous infectious diseases. (Under the general editorship of academic RAMS Maleev V.V.) Methodical recommendations. М., 2009. 128 с.
  3. David Dance. Treatment and prophylaxis of melioidosis. Int J Antimicrob Agents. 2014. No. 43 (4). P. 310—318.
  4. Batmanov V.P., Ilyukhin V.I., Lozovaya N.A., Alekseev V.V. Emergency prevention of diseases caused by probable bacterial agents of bioterrorism. Sanitary protection of the territories of the CIS member states: problems of biosafety and counteracting bioterrorism in modern conditions: Mater. IV interstate scientific-practical. Conf. of the CIS member states. Volgograd, 2005. P. 202—203.
  5. Zhukova S.I., Antonov V.A., Demyanova O.B., Abdrakhmanova R.O. The problem of emergency prophylaxis of infectious diseases (review). Volgograd scientific-medical journal. 2015. No. 1 (45). P. 24—31.
  6. Sentsova T.B. Modern immunomodulators. Handbook of a polyclinic. 2004. No. 5. P. 27.
  7. Bondareva T.A., Poyarkov A.Yu., Vakhnov E.Yu. The use of polyoxidonium in the complex treatment of generalized forms of experimental plague. Problems of especially dangerous infections. 2009. No. 99. P. 67—69.
  8. Kogotkova O.I., Buravtseva N.P., Yurkevich Yu.V., Andronova Т.М. A method for emergency prevention of anthrax infection in laboratory animals. Patent No. 2050857. 1995.
  9. Kanatbaev S.G., Ten V.B., Tuyashev E.K., Nysanov E.S. The use of immunomodulators in animal brusellosis. Veterinary Today. 2013. № 3. P. 45—48.
  10. Bezpalko O.R., Ziganshin I.I., Dolgushin V.L., Ryshkov A.A., Kolobov A.A., Simbirtsev A.S. Bestim and betaleukin in complex therapy of chronic gonococcal infection of the urogenital organs in a woman. Cytokines and inflammation. 2008. T. 7. № 4. P. 58—62.
  11. Kuznik B.I., Tsybikov M.N., Likhanov I.D., Borshchevsky V.S., Tsepelev V.L., Maslo E.Yu., Tsybikov N.N. Effect of imunofan on the level of proinflammatory cytokines and indices of systemic inflammatory reaction in patients with acute purulent peritonitis. Annals of surgery. 2012. № 3. P. 30—33.
  12. Ostrovskaya P.Yu., Flax G.A., Korsunskaya I.M., Syuch N.I. Glutoxim in the complex therapy of urogenital infections in patients of reproductive age. Bulletin of St. Petersburg University. Series: medicine. 2011. № 2. P. 139—146.
  13. Khaitov R.M., Pinegin B.V., Andronova Т.М. Domestic immunotropic drugs of the latest generation and the strategy of their use. Pharmacology. 2002.
  14. Nemirovskaya T.I., Kovtun V.P., Abramtseva M.V., Aleksandrova N.V., Tarasov A.P., Salakhova R.D., Volkov V.A., Merkulov V.A. Immunomodulators of bacterial nature registered in the Russian Federation. Biopreparations. 2014. № 3. P. 19—26.
  15. Ilyukhin V.I., Viktorov D.V., Piven N.N., Abramenko A.V., Timoshin V.B. Cross-reacting antigens of pathogenic burkholderia and some dangerous pathogens of infectious diseases. Journal of Microbiology, Epidemiologists and Immunobiology. 2005. № 2. P. 14—19.
  16. Manzenyuk I.N., Tanina E.A., Dorokhin V.V., Kalachev I.Ya., Borzenkov V.N. Svetoch E.A. Burkcholderia mallei and Burkcholderia pseudomallei. The study of immunopathogenesis of glanders and melioidosis. Heterologous vaccines. Antibiotics and chemotherapy. 1999. № 6. P. 21—26.
  17. Plekhanova N.G., Alekseev V.V., Ilyukhin V.I., Senina T.V., Tikhonov S.N., Perepelitsyna S.V. Prospects for the use of Burkcholderia thailandensis and Francisella tularensis 15 NIIEG for immunization with burkchlderiosis. Problems of especially dangerous infections. 2004. № 2. P. 56—57.
  18. Ilyukhin V.I., Kislichkin N.N., Plekhanova N.G., Senina T.V., Stanova O.V. Experimental substantiation of the possibility of using tularemia live vaccine to increase resistance to heterologous infectious diseases. Journal of Microbiology, Epidemiologists and Immunobiology. 2005. № 2. P. 38—42.
  19. Ashmarin I.P., Vorobiev A.A. Statistical methods in microbiological studies. L., 1962. P. 180.
  20. Lebedeva I.A., Toporkov A.V., Zhukova S.I., Rotov K.A., Snatenkov E.A. Synthetic peptides and recombinant cytokines in the scheme of emergency prophylaxis of experimental melioidosis. Cytokines and inflammation. 2016. Vol. 15. № 2. P. 181—185.
  21. Kombarova T.I., Pavlov V.M., Kravchenko T.B., Titareva G.M., Bakhteeva I.V., Borzilov A.I., Korobova O.V., Vakhrameeva G.M., Mironova R.I., Mokrievich A.N. Comparative evaluation of reactivity of tularemia vaccine on various biomodels. Epidemiology and vaccine prevention. 2013. Vol. 71. № 4. P. 54—62.
  22. Haque A., Easton A., Smith D., O'Garra A., Van Rooijen N., Lertmemongkolchai G., Titball R.W., Bancroft G.J. Role of T-cells in innate and adaptive immunity against murine Burkholderia pseudomallei infection. J. Infect. Dis. 2006. Vol. 193. No. 3. P. 370—379.
  23. Santanirand P., Harley V.S., Dance D.A., Drasar B.S., Bancroft G.J. Obligatory role of gamma interferon for host survival in a murine model of infection with Burkholderia pseudomallei. Infect. Immun. 1999. Vol. 67. No. 7. P. 3593—3600.
  24. Karaulov A.V. Clinical and immunological efficacy of imunofan in opportunistic infections. The attending physician. 2000. № 4. P. 52—55.
  25. Petrov A.V., Pigareva N.V., Simbirtsev A.S. The study of the action of the immunomodulator is topical when administered orally to an antigen-specific immune response. Mater. Int. Congress “Immunity and Disease: from theory to practice” 3—7 Oct 2005. 2005, RAGS. P. 84—85.

Copyright (c) 2018 Khabarova I.A., Zhukova S.I., Rotov K.A., Snatenkov E.A., Toporkov A.V., Viktorov D.V.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies