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Integrated prevention of anthrax

Integrated prevention of anthrax
IPC classes for russian patent Integrated prevention of anthrax (RU 2216349):
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The invention relates to medicine, infectious diseases and can be used for integrated prevention of anthrax. Prevention is done according to the following scheme: in the first 6 hours after infection injected once subcutaneously in one human-dose antibiotic combination anthrax vaccine within 5 days to introduce immunomodulator and a broad-spectrum antibiotic. This invention allows you to create long-lasting preventive protection against infection with high doses of a pathogen (100 LD50with the first day of the combined use of complex means of specific prophylaxis of anthrax. table 4.

The invention relates to medicine, namely to methods for prevention and treatment of infectious diseases, and can be used for emergency integrated prevention of anthrax in epidotization in epitacio.

Famous traditional way of emergency prevention of anthrax in apalachee antibiotic doxycycline (in Russia) and ciprofloxacin (in USA) or doxycycline (Europe and USA). Scheme of application of each of them provides their oral ISPI diagnosis, prevention and treatment of anthrax in humans. M, 1982; Guidance on protection against chemical and biological weapons, Fort Detrick, 3 edition, 1998).

The disadvantage of the existing schemes are relatively low level of protection in the early (1...5 day) time development of anthrax infection and the lack of protection in remote (6 weeks or more) terms.

The first circumstance is due to the fact that preventive treatment only provides a level of protection to 70% of the relatively small infecting doses: 10. . . 30 LD50 and does not provide protection from higher doses of the pathogen (over 50 LD50in cases of massive infection capsular cells (more virulent than spores) when cutting the carcasses or meat of infected animals (Onishchenko gg, Marinin L. I. and other Microbiological diagnosis of anthrax. M , 1999), or airborne contamination disputes workers Kozhevennaya enterprises, or with possible sabotage act of bioterrorists in crowded places (Siegrist D. W. therent of biological attack: why concern now? // Emerg. Inf. Dis.-1999.-Vol 5, N 4 - p. 505-508).

The second circumstance is due to the fact that after the termination of the 5-day course for emergency prophylaxis antibiotic, so-called "dormant" in the lymphatic system non-debate is facilitated numerous cases of human infection 6 weeks after primary infection and preventive antibiotic treatment (T. V. Inglesby, M. D., D. A. Henderson, M. D., J. G. Barlett et al. Anthrax us a Biological Weapon//American Medical Assotiation, Jama, May 12, 1999.- Vol. 281, No. 18, p. 143).

The known method for the specific prevention of anthrax, which consists in the formation of immunity by vaccination of people live, or combination, or chemical anthrax vaccines, allowing respectively after two immunizations within 30 days (live vaccine), or after a single vaccination within 7 days (combined vaccine) or after 3 times of immunization for 2 months (chemical vaccine) to possible contamination to form a tight immunity and allow staff to focus of infection (RF patent 2115433, 1998). However, these schemes known method of forming a protection against anthrax have also two drawbacks. One of them is the "breakdown" of the immune system during the first 14 days (for a living) and 1... 5 day (for combination and chemical) vaccines due to the weak formation of antibacterial and antitoxic immunity. The second drawback is associated with high sensitivity spore component vaccines to antibiotics that if their combined use with antibacterial drugs adversely affect the formation of immunity in bol.

The objective of the invention is to provide a guaranteed (100%) and long-lasting preventive protection against infection with high doses of a pathogen (100 LD50with the first day of the combined use of complex means of specific prophylaxis of anthrax.

The problem is solved due to the fact that emergency prevention antibacterial drug further includes the combined use of immunomodulator - licopid or polyoxidonium and antibiotic combination of anthrax vaccine in the moment of infection, and 6 hours after infection.

Comparing the level of protection in subcutaneous and airborne infection virulent cultures of Bacillus anthracis with the dynamics of cellular and humoral indicators of the specific resistance against the background of antibiotic prophylaxis, it is possible to extrapolate that the medical center: antibiotic + immunomodulator + antibiotic-resistant combination vaccine suppresses the development of anthrax infection in the first 6 days due to improve therapeutic-prophylactic efficacy of antibiotic and accelerate the formation of vaccine specific resist the strenuous protivovirusnogo antibacterial and antitoxic immunity.

Integrated prevention of lesions of anthrax in the following manner. During the first 6 hours after infection were in apalachee contingent injected subcutaneously once 1 person-dose antibiotic-resistant combination vaccine containing (5010)106living spores vaccine strain STI-OL-4 and 355 EID50protective antigen (FS 42-32-98-96). At the same time is receiving doxycycline or pefloksatsina inside 2 times a day for 5 days and the use of licopid or polyoxidonium 1 daily dose daily for 5 days.

Enablement of the claimed invention is shown in the following examples.

Example 1. The influence of emergency prevention on the strength of post-vaccination immunity Antibiotic combination vaccine received on the regulation of the production of dry combination, live and chemical vaccines scientifically defense Ministry 862-99 with the inclusion in its membership as spore component strain STI-PR-4 (RF patent 2173342). To determine the tension of post-vaccination immunity in animals (rabbits) were immunized once subcutaneously com>protective antigen and prototype vaccines: combined (STI-1 in a dose of 10020 million live spores and 355 EID50), live (STI-1) at a dose of 100 million live spores and chemical (dose of 80 EID50). The antibiotic by the pefloxacin mesilate was carried out 2 times a day for 5 days at a dose equivalent to the human dose.

Infected animals was virulent test strain 4-7 subcutaneously every 21 days at a dose of 100 LD50according to the requirements of FS on the combination vaccine (FS 42-3298-96). Tension immunity was determined by the percentage of surviving animals and indicator preventive properties of blood serum (Burgassy P. R. and others//Ukr. microbiol., Epidemiol. and immunol.-1972.- 6, -S. 142-147). The results are shown in table 1. Analysis of the data presented in table 1, shows that despite the application of emergency prevention live vaccine does not create an intense immunity for all 3 months of follow-up: the level of protection was 0...30%. Protective effect of chemical vaccines in long term (3 months) quenched and reduced 7-9 times. High efficiency combination vaccine (75...100% indicator surviving animals) is stored in rangipo compared with the same vaccine, containing sensitive to antibiotics spore component that provides a higher level of protection. Increasing the degree of protection was as follows: 30% on indirect indicator of preventive properties of whey (PSS) and 20% survival of animals.

Example 2. The synergistic effect of combined application of licopid (or polyoxidonium) and the combined vaccine against phagocytic activity of neutrophils in rabbit.

To identify synergies in the early (1...5 day) time combined use of the immunostimulant - licopid or polyoxidonium (SSC - Institute of immunology MZ the Russian Federation, Moscow) (in a dose equivalent to the human dose) and combined vaccines (human-dose) in blood samples taken from rabbits at 1, 2, 3, 5 and 21 days, determine the content of active neutrophils and their absorption (latex) ability (index of phagocytosis) (Immunological methods/edited, Primes. - M., 1987). As follows from the obtained data, the values of phagocytic activity of neutrophils in 1. . .5 days was higher in the variant with combined single use of combination vaccines and licopid. So, on the 3rd day of absolute concentration of active neutrophils increased from 68 to 76%, and the index of fagozyt is Nargiza combined effect of licopid or polyoxidonium and antibiotic against anthrax infection in rabbits.

In experiments on rabbits demonstrated a positive effect of the combined use of licopid or polyoxidonium in a dose equivalent to a daily dose for a person with pefloxacin in a dose equivalent to a daily dose for a person during the course of emergency prevention.

The results are shown in table 2. As shown in the table 2 data, Likopid or polyoxidonium, used alone did not increase protection against anthrax, pefloxacin protected 60% of the animals treated after 3 hours, and 50% treated within 24 hours after infection with a massive dose of anthrax (100 LD50). At the same time, in the prevention and treatment of anthrax infection concomitant use pefloksatsina with Likopid or polyoxidonium received 90% and 80% protective effect. Thus, the effectiveness of the antibiotic due to Likopid increased by 30%. The mechanism of the improvement is associated with increased activity of the cells of the reticulo-endothelial system (RES), which locate the source of the infection in primary complexes, which creates conditions for effective treatment.

Example 4. The effectiveness of the proposed method preventive protection in comparison with the traditional way in ronnieg fashion and traditional in early (1...5 day) time after the start of the emergency prevention, presented in table 3.

As can be seen from the above results, implementing emergency prevention (the traditional way of preventive protection) under given conditions provides 1. . . 5 day level of protection equal to 50...70%. At the same time, the inventive method includes the combined use of antibiotic combination vaccine, antibiotic and licopid (polyoxidonium), allows to obtain at the same time 100% level of protection in case of infection with a high dose of a pathogen (100 LD50).

Example 5. Persistence protective effect of the proposed method preventive protection compared to traditional long-term after completion of the course prevention.

Advantages in the efficiency of the proposed method preventive protection compared to traditional long-term after completion of the course of the emergency prevention demonstrated by the results given in table 4. After 2 weeks and 1.5 months after a course of antibiotic prophylaxis in the traditional way (including antibiotic prolonged action) reinfection of animals (rabbits and monkeys) dose of microbes, 100 LD50resulted in 100% mortality. In this length of time remaining to nice, and research objects exposed to repeated illness. At the same time in a group of infected animals, for preventative treatment which was used by the inventive method, the survival of animals in these terms was 90...100%. Therefore, the objects of this group are protected in a high enough degree from infection by anthrax due to the formation of a busy immunity induced by a specific component of the proposed complex of preventive protection.

Claims

Integrated prevention of anthrax, including subcutaneous administration of antibiotic-resistant combination of anthrax vaccine in combination with antibiotic and immunomodulating agent, and prevention carried out according to the following scheme: in the first 6 hours after infection injected once subcutaneously in one human-dose antibiotic-resistant combination anthrax vaccine within 5 days to introduce immunomodulator and a broad-spectrum antibiotic.

 

 

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