Vol 5, No 1 (2015)

Plague has been the cause of three pandemics and has led to the death of millions of people. Plague is a typical zoonosis caused by Yersinia pestis that circulates in populations of wild rodents inhabiting natural plague foci on all continents except for Australia. Transmission of plague is provided by flea bites. Circulation of Y. pestis in natural plague foci is supported by a numerous of pathogenicity factors. This review explores one of them, plasminogen activator Pla. This protein is one of representatives of omptins, a family of enterobacterial outer membrane proteases that are responsible for colonization of specific organs or even infection generalization as a result of successful overcoming of the host innate immunity. The review reflects the history of its discovery and studying of its genetic control, biosynthesis, isolation and purification, physicochemical properties. Highly purified preparations of plasminogen activator are deficient in enzymatic activities but renaturation in the presence of Y. pestis lipooligosaccharide restores enzymatic properties of Pla. This pathogenicity factor is absent in representatives of the most ancient phylogenetic group of the plague pathogen, bv. caucasica, while the ancestor of other groups of Y. pestis subsp. microtus obtained in result of horizontal transfer Pla isoform with characteristics similar to properties of omptins from the less virulent enterobacteria. After that in the course of microevolution the “classic” isoform of Pla with increased protease activity was selected that is typical of all highly virulent for humans strains of Y. pestis subsp. pestis. The “classic” isoform of Pla Y. pestis is functionally similar to mammalian plasminogen activators transforming plasminogen into plasmin with the help of limited proteolysis. Pla protease activating plasminogen and also degrading the main plasmin inhibitor — α2-antiplasmin and, respectively, determining Y. pestis ability to lyse fibrin clots preventing bacteria dissemination after bites of infected fleas or subcutaneous challenge is believed to be the main Y. pestis factor responsible for generalization of infectious process. Pla-mediated ability of Y. pestis for selective binding with extracellular matrix and basal membranes may promote further hydrolysis of these structures by the host’s plasmin and overcoming tissue barriers by the pathogen. Y. pestis plasminogen activator also hydrolyses C3 complement component, human antimicrobial peptide — cathelicidin LL-37 and such cytokines as tumor necrosis factor α, interferon γ, interleukin 8 and protein 1 of monocyte chemotaxis. The main endogenic TFPI tissue factor pathway inhibitor also highly susceptible to proteolytic action of Pla, and efficiency of TFPI inactivation is much higher than efficacy of plasminogen activation. The review also debates the possibility of using Pla as a molecular target for prophylaxis and treatment of plague. 

The CRM197 is a non-toxic mutant of diphtheria toxin having a single amino acid substitution of a glycine for a glutamic acid in position 52. Being naturally nontoxic, CRM197 is a promising adjuvant and ideal carrier protein for conjugate vaccines. Typically, production of diphtheria toxin and some of the non-toxic proteins are carried out by Corynebacterium diphtheriae. Production of recombinant protein CRM197 in Escherichia coli is advantageous. It is simple, cheap and permits production of the target protein in a short time using a non-pathogenic microorganism. In this study patented high-yield-producing E. coli strain was used. As a part of the study the following steps were taken: protocol adjustment for induction of crm197 gene, production and purification of recombinant CRM197 by ion-exchange, hydrophobic and gel-filtration chromatography. The purity of the final preparation reached 97%.

The modified algorithm for laboratory confirmation and differential diagnosis of measles infection was developed and used in the laboratory studies of the Russian Laboratory Network (RLN) on Measles/Rubella Surveillance within the routine and active measles infection control. The algorithm consists in detecting the IgM, IgG and IgG avidity measles virus antibodies. To approve the modified algorithm sera samples of 637 patients with the measles diagnosis and 423 patients with rush and fever were studied. The IgG avidity measles testing is advisable in the following cases: a) only one serum sample is available, b) the recommended time interval between the 1st and 2nd sera samples taking is not observed, c) no diagnostic increase in titers of the IgG measles virus antibodies is evidenced, d) for determination of the type of immune response (primary or secondary) and e) to exclude the “false positive” results at the stage of detecting the measles virus IgM antibodies. Moreover the data obtained evidenced the involvement of the nonvaccinated (79.7%) as well as of vaccinated with 1 or 2 doses of measles vaccine (20.3%) population into the measles epidemical process. 

There are 4 programs of electronic monitoring over influenza and ARI in the Kyrgyz Republic. The computer monitoring of infectious diseases (CMID) was implemented in the country since 2005. Three more advanced software for the electronic surveillance over ARI and influenza were introduced in 2010–2011. The analysis of monthly data on influenza and ARI cases is possible in 49 cities and districts of the country using CMID. At the beginning of 2010, the data started to be transferred to the World Health Organization on a weekly basis and to be published at the EuroFlu site. The implementation of new program of sentinel surveillance sites allowed to obtain information about the incidence and etiology of influenza and ARI on-line. Since 2012 the electronic system of monitoring, mapping and analysis (MMA) was introduced in all regions of the country for assessment of the epidemiological situation; this system allows to transfer data by mobile phones . The use of different programs improved the prompt access to information, provided an opportunity to analyze the epidemical situation in real-time regime. 

Immunization against hepatitis В is the most effective method of preventing this disease. Study of quantitative characteristics of postvaccinal immunity against viral hepatitis В in 214 health care workers from different institutions of St. Petersburg has shown that HBV vaccine provides a long term immunity in 80% of cases with the absence of manifest forms of the disease. The duration of circulation of high titers of antibodies depended on the age of people when vaccination was provided. The highest level of immunity was observed in people vaccinated before the age of 30 years (84,0–90,6%). Reduction of immunity level in vaccinated health care workers after 5 years from the date of vaccination requires revaccination against viral hepatitis B after pre-vaccination screening.