Репозиторий Университета

© 2018 Interregional public organization Association of infectious disease specialists of Saint-Petersburg and Leningrad region (IPO AIDSSPbR). All rights reservbed. The creation in the middle of the 20th century vaccines against poliomyelitis (PM) - inactivated vaccine (IPV) and live oral vaccine from Sabin strains (OPV) with various properties, advantages and disadvantages, but highly effective, made it possible to implement the idea of elimination of PM. Since 1988, the WHO Global Program of PM eradication has achieved remarkable success: the incidence of PM caused by wild poliovirus (PV) has been reduced by 10 thousand times, the number of endemic countries has been reduced to 3, the circulation of wild PV has been discontinued in 4 regions of the world the wild type 2 of PV has been eradicated, and wild type 3 of PV has not been detected for almost 5 years. Under conditions of a decrease in the incidence of PM caused by wild PV, the known negative properties of trivalent OPV made its further use problematic. These negative properties are: 1) the ability to cause post-vaccination complications and 2) the genetic instability of Sabin strains, especially PV of type 2, and their ability under certain conditions (primarily in conditions of low collective immunity to PV) to quickly restore neurovirulence, transforming into circulating vaccine-derived PV (VDPV), capable of causing incidents and outbreaks of PM. In order to reduce the risk associated primarily with type 2 PV, WHO proposed a global switch to the use of bivalent OPV from types 1 and 3, completed in 2016. In 2019, WHO plans to complete eradication of type 1 and 3 PVs, and in 2022 completely abandon the OPV. The precondition for the safety of such tactics is the maintenance of high collective immunity to PM. There are several threats to the security of this strategy. PVs can "silently" circulate in the human population for a long time without clinical manifestations of PM, which, with inadequate epidemiological surveillance can lead to the return of PM. The reintroduction of both wild PV and Sabin strains can occur from institutions that preserve / work with PV. The source of VDPV can be people with primary immunodeficiencies, which continuously excrete PV. It is necessary to maintain surveillance over the PM, expand additional types of surveillance for the PV, strict containment of all PVs. The only way to maintain collective immunity is immunization with trivalent IPV. The current global shortage of IPV poses a significant threat to the world's epidemiological well-being. The solution to the problem is the development of a new generation of safe and effective vaccines, improving the ways of introducing IPV, developing antiviral drugs.

© 2018, Dynasty Publishing House. All rights reserved.  Objective: to evaluate the possibility of creating a human model of acute Helicobacter pylori infection in healthy volunteers after infecting them with a mutant rifampicin-resistant strain of H. pylori KM-11 (Rif R ), to obtain evidence of H. pylori survival and invasion into the gastric mucosa, describe the symptoms, and assess the efficacy of H. pylori eradication therapy with Stimbifid plus. Materials and methods. In our experiments, we used conventional white mice of both genders weighing 18–20 g. The concentration of bifidobacteria, lactobacilli, and Escherichia (CFU) in animal faeces was determined by inoculating tenfold dilutions of biomaterial onto solid media and further counting of bacterial colonies grown after the incubation period. Microorganisms were cultivated in an anaerobic incubator and then identified by morphological evaluation and using biochemical identification kits. We created a murine model of H. pylori infection by oral administration of H. pylori KM-11 (Rif R ) suspensions to immunocompromised mice that had earlier undergone intramuscular administration of dexamethasone. For a human model of H. pylori infection, we selected healthy male volunteers. They took suspensions of H. pylori KM-11 (Rif R ) isolates in isotonic sodium chloride solution. Fecal specimens were collected from volunteers on daily basis during the entire follow-up period and then 2 weeks and 1 month after treatment completion. Fecal suspensions in isotonic sodium chloride solution were inoculated onto the selective hemin-containing solid media with rifampicin at a concentration of 160 µg·mL –1 . The results of this experiment (H. pylori colony count) were used to evaluate the efficacy of H. pylori eradication therapy with Stimbifid plus. Results. Both in vitro experiments and murine models demonstrated high anti-H. pylori activity of Stimbifid plus and its ingredients, restoration of the gastric microbiota, restoration of gastric colonization resistance, and eradication of H. pylori KM-11 (Rif R ). Self-infection with H. pylori KM-11 (RifR) caused acute infection in volunteers. The disease manifested with mild ailment, epigastric discomfort, belching, increased stool frequency, and changes in the color of stool. The detection of H. pylori KM-11 (Rif R ) in the faeces of volunteers and isolation of pure cultures prior to treatment initiation indicated bacterial adhesion to gastric mucosa and survival of microorganisms. Treatment with Stimbifid plus caused gradual decrease in the number of bacteria isolated from feces and their complete elimination by day 11 of therapy. All fecal specimens collected 2 weeks and 1 month after therapy completion from volunteers were negative for H. pylori KM-11 (Rif R ). None of the study participants required in-patient treatment. Conclusion. The results of our experiments obtained in both murine and human models of H. pylori infection will be used for more detailed assessment of this pathological process, clinical manifestations, impact of H. pylori virulence factors on the host, choosing new methods for the prevention and treatment of chronic gastritis caused by H. pylori, and monitoring the efficacy of eradication therapy.

Современная терапия, направленная на эрадикацию H.pylori, включает комплекс антисекреторных и антибактериальных препаратов, иногда препаратов висмута. Особенностью современных эрадикационных схем является четырнадцатидневное применение антибактериальных средств, назначаемых в высоких суточных дозах и избираемых преимущественно с учётом резистентности микроорганизма к кларитромицину и метронидазолу в соответствующем регионе. Однако каждый компонент эрадикационной схемы может иметь достаточно серьёзные неблагоприятные побочные реакции, а также влиять на биодоступность, биотрансформацию, выведение и потенцирование эффектов лекарственных препаратов, которые больной может принимать одновременно с антихеликобактерной терапией. В статье перечислены наиболее серьёзные и распространённые варианты лекарственных взаимодействий компонентов эрадикационных схем, дано описание механизма их развития, если таковой выяснен. До появления практических рекомендаций относительно профилактики лекарственных взаимодействий препаратов, включаемых в эрадикационные схемы, следует использовать общедоступные базы данных, содержащие сведения о таких взаимодействиях.

Современная терапия, направленная на эрадикацию H.pylori, включает комплекс антисекреторных и антибактериальных препаратов, иногда препаратов висмута. Особенностью современных эрадикационных схем является четырнадцатидневное применение антибактериальных средств, назначаемых в высоких суточных дозах и избираемых преимущественно с учётом резистентности микроорганизма к кларитромицину и метронидазолу в соответствующем регионе. Однако каждый компонент эрадикационной схемы может иметь достаточно серьёзные неблагоприятные побочные реакции, а также влиять на биодоступность, биотрансформацию, выведение и потенцирование эффектов лекарственных препаратов, которые больной может принимать одновременно с антихеликобактерной терапией. В статье перечислены наиболее серьёзные и распространённые варианты лекарственных взаимодействий компонентов эрадикационных схем, дано описание механизма их развития, если таковой выяснен. До появления практических рекомендаций относительно профилактики лекарственных взаимодействий препаратов, включаемых в эрадикационные схемы, следует использовать общедоступные базы данных, содержащие сведения о таких взаимодействиях.