Резюме. Два нових коронавіруси були виділені від людини у двадцять першому столітті: коронавірус SARS-CoV тяжкого гострого респіраторного синдрому (ТГРС) та коронавірус MERSCoV Близькосхідного респіраторного синдрому (БСРС). Обидва з них спричиняють гострий респіраторний дистрес-синдром (ГРДС) і пов'язані з високими показниками летальності. В огляді описані ключові біологічні та молекулярно-генетичні особливості коронавірусів, у тому числі тропізм до різних культур клітин, будова вірусної частки та організація вірусного геному. Приділено значну увагу вірусологічній діагностиці, епідеміологічним особливостям збудників, клінічним проявам та принципам лікування захворювань, спричинених цими вірусами. Ключові слова: коронавіруси, тяжкий гострий респіраторний синдром, Близькосхідний респіраторний синдром, вірусологічна діагностика, лікування. Резюме. Два новых коронавируса были выделены от человека в двадцать первом веке: коронавирус SARS-CoV тяжелого острого респираторного синдрома (ТОРС) и коронавирус MERS-CoV Ближневосточного респираторного синдрома (БСРС). Оба из них вызывают острый респираторный дистресс-синдром (ОРДС) и связанны с высокими показателями летальности. В обзоре описаны ключевые биологические и молекулярно-генетические особенности коронавирусов, в том числе тропизм к разным культурам клеток, строение вирусной части и организация вирусного генома. Уделено значительное внимание вирусологической диагностике, эпидемиологическим особенностям возбудителей, клиническим проявлениям и принципам лечения заболеваний, вызванных этими вирусами. Ключевые слова: коронавирусы, тяжелый острый респираторный синдром, Ближневосточный респираторный синдром, вирусологическая диагностика, лечение. Summery. Two new coronavirus were isolated from humans in the twenty-first century: the coronavirus SARS-CoV of severe acute respiratory syndrome (SARS) and coronavirus MERS-CoV of Middle East respiratory syndrome (MERS). Both of them cause acute respiratory distress syndrome (ARDS), and are associated with high rates of mortality. This review describes the key biological and molecular-genetic features of coronaviruses, including tropism for different cell cultures, viral structure and organization of the viral genome. Considerable attention is paid to virological diagnosis, epidemiology of pathogens, clinical manifestations and principles of treatment of diseases caused by these viruses.
In Ukraine, cervical cancer (CC) is the second most frequent cancer among women of reproductive age and causes more than two thousand deaths per year. The results of clinical and laboratory studies indicate the high prevalence of human papillomaviruses (HPV) of high carcinogenic risk in Ukraine, being the cause of the development of CC. The concept of pharmaceutical prevention is becoming more and more relevant today as it includes a set of measures aimed at preserving and promoting health, improving the quality of life, preventing the occurrence of pathological conditions and diseases; and if they occur - the progression and worsening of a patient's condition, relapse and transition to chronic form, as well as prevention of possible negative or undesirable consequences. The aim of the work – рharmacoeconomic research using mathematical modeling of prevention technologies of HPV-associated cervical pathologies based on vaccination and diagnostic screening among women of different ages. Pharmacoeconomic analysis of prevention technologies for women aged 18 years and more proposed a developed mathematical model, the overall idea of which reflected the current scientific understanding of the causes and development of CC. The detection of severe dysplasia is the primary purpose of diagnostic screening, and the establishment of diagnostic status in the presence of HPV infection is additional information that allows refining the diagnostic screening scheme. Minimization of total costs implies the simultaneous achievement of the maximum possible socio-economic effect from the introduction of complex technology for the prevention of HPV-associated pathologies of the cervix. It may be seen in the reduction of the total number of undiagnosed persons with severe dysplasia, which will be affected by both HPV vaccination and diagnostic screening. This justification is the basis for formalizing the pharmacoeconomic evaluation of complex technology for the prevention of HPV-associated cervical pathologies in the form of a cost-effectiveness factor. The proposed method of pharmacoeconomic assessment was put into practice using retrospective data of 145 women with a prevalence of young ones aged 22 to 36 years. On the basis of the received frequency, clinical and epidemiological data, it was possible to determine the coefficient of influence of the persistence of HPV on the development of severe forms of dysplasia, as an additional criterion for pharmacoeconomic evaluation. Analytical studies have shown that at constant costs for the diagnosis or vaccination of one person, the cost-effectiveness ratio of complex prevention technology is significantly dependent on the impact of HPV persistence. A case study was examined, in which the cost of diagnostic screening was 10 times lower than the cost of vaccination per person, the HPV vaccination efficiency was 90%, the vaccination coverage rate was 10%, and the non-vaccinated diagnostic screening rate was 80%. In this example, it was shown that the use of HPV persistence as additional weight in the calculation of diagnostic screening coverage allows for more pharmacologically sound prevention regimens due to the lower cost-effectiveness ratio, all else being equal. A method of pharmacoeconomic evaluation based on determining the utility of the costs of diagnostic screening and vaccination for HPV infection as a complex technology for the prevention of HPV-associated cervical pathologies is proposed. An additional criterion for pharmacoeconomic evaluation is the coefficient of the impact of HPV persistence on the development of severe dysplasia, which is equal to the ratio of the proportion of women with severe dysplasia to the proportion of women with HPV at the previous time. Analytical studies have shown that the use of HPV persistence as additional weight in the calculation of diagnostic screening coverage allows for more pharmacologically sound prevention regimens due to the lower cost-effectiveness ratio, all things being equal.
Introduction: Several studies has shown that rotaviruses play a leading role in the structure of acute intestinal infections (AII) of viral etiology in children. In the National vaccination calendar of Ukraine, vaccination against rotavirus infection (RVI) is classified as recommended, with the expected goal of reducing the number of severe RVI cases among under five-year-old children. Nevertheless, despite the positive epidemiological and clinical effects of vaccination against RVI, it remains unclear how appropriate the introduction of rotavirus vaccines is in terms of potential costs and benefits, as well as determining the optimal level of subsidy required to cover part of the costs of voluntary vaccination of the population. The aim: Study of optimal subsidy level of rotavirus vaccine in Ukraine using epidemiological and pharmacoeconomic modeling. Materials and methods: The retrospective epidemiological data of the monthly RVI incidence in Ukraine as well as the population number from 2010 to 2016 formed the information basis for determining the transmission parameter of the viral agent. The scenario of RVI epidemic process as an acute intestinal infection from the point of view of mathematical epidemiology is best described by developed mathematical model. Cost-benefit of rotavirus vaccination was studied with the use of developed pharmacoeconomic criteria. Results and conclusions: Prediction of possible implications of RVI vaccination and finding optimal level of vaccine supply involves a comprehensive study of the epidemic process peculiarities of this infection with development of an adequate epidemiological model. We have proposed a model of RVI epidemiological process in Ukraine, determining its main parameters with the use of available retrospective data of anual number of RVI cases for the period from 2010 to 2016. The developed model was used as an analytical tool for analyzing influence of different levels of vaccine supply on vaccination cost-benefit. The results of research showed that the use of epidemiological modeling in pharmacoeconomic analysis of rotavirus vaccination made it possible to determine analytically optimal level of vaccination subsidy level.
I. V. Dziublyk, O. P. Trokhimenko, S. O. Soloviov, G. L. Gumeniuk, O. Ya. Dziublyk, N. I. Gumeniuk, O. K. Yakovenko Abstract The aim of the study is a preclinical evaluation of the antiviral activity of aminocaproic acid (ACA) against the prototype strain IBV (Infectious bronchitis virus) of Coronavirus family in vitro. Material and methods. During the research, modern methods were used to determine the cytotoxic effect of the evaluation on a monolayer of BHK-21 cell culture in vitro; cultivation, accumulation and determination of the infectious titer of IBV by cytopathic action on a monolayer of cell cultures; assessment of the antiviral effect of the drug — the establishment of the inhibitory concentration and the chemotherapeutic index (CTI) of ACA in various modes of drug administration: 2 hours before infection, simultaneously with infection and 2 hours after infection. Results. With the introduction of ACA 2 hours before infection, a decrease in the infectious titer of the IBV virus was not established. The antiviral activity of ACA was detected when the drug was added in 2 modes: simultaneously and 2 hours after infection. The introduction of ACА into the medium for cell cultivation at non-toxic concentrations of 7.91–15.82 mg / ml led to a decrease in the infectious titer of the virus by 1.4–2.0 lg TCD50 / 0.1 ml. The CTI of the ACA was 6 in the indicated concentrations and modes, which is an indicator of its promising potential for further studies of antiviral activity in vivo, including clinical studies. Conclusions. The direct antiviral effect of ACA against the prototype H-120 virus strain from the Coronaviridae family in vitro was revealed. The suppression of viral reproduction with an established low toxicity of the drug, a decrease in the infectious titer of IBV by 1.4–2.0 lg TCD50 / 0.1 ml and with a CTD equal to 6.0, indicate the prospects for further study of the antiviral properties of ACA in clinical trials. Key words: aminocaproic acid, coronavirus, antiviral activity.
A couple of studies have shown that viruses cause from 25 to 60% of acute intestinal infections (AII) cases, among which rotaviruses play a leading role in the structure of children's AII of viral etiology. According to the WHO recommendations, vaccination against rotavirus infection should be included into national immunization programs. Due to a wide diversity of circulating rotavirus genotypes, the issue of RVI vaccine efficiency, taking into account the dynamics of the molecular-genetic spectrum of RVI pathogens over time, remains relevant. The aim of the work – мodeling the dynamics of the molecular genetic spectrum of RVI pathogens and bioinformation analysis of f rotavirus vaccine efficiency. The object of the analysis was the results of molecular and epidemiological studies of RVI in Kyiv, conducted from 2007 to 2015. The dynamics of the genotypic spectrum was modeled using a Markov model, which involved replacing shares of the molecular genetic spectrum of rotaviruses with others ones according to homology with the vaccine strain: homology in both G and P genotypes, homology in G genotype or P genotype, no homology in both G and P genotypes. The method of rotavirus vaccine efficiency evaluation is based on data from clinical observations of vaccine efficiency, where different degrees of its efficiency against severe gastroenteritis caused by rotaviruses with different genotypes were shown. The shares of each genotype group in the general circulation of genotypes were taken as weights of the degree of homology relative to the vaccine strain, and the effectiveness of the vaccine against the strains of a specific homology group was obtained from clinical observations. The results of the analysis based on the constructed distribution curves of the molecular genetic spectrum of rotaviruses due to rotavirus vaccine strain homology in Kiev showed that, despite the observed dynamics of the molecular genetic spectrum of RVI pathogens, the expected genotype-specific efficiency of rotavirus vaccine would be constant with a value of 0.835 or 83.5% against rotavirus gastroenteritis with a Vesikari severity of > 11 points. It was proposed mathematical model for prediction of molecular genetic spectrum of rotaviruses dynamics, taking into account the homology of the genotypes of RVI pathogens with respect to the vaccine strain. According to the literature data of molecular and epidemiological studies of rotaviruses in Kyiv, the parameters of the proposed mathematical model and the dynamics of the molecular genetic spectrum of RVI pathogens were determined. Using mathematical modeling, the expected genotype-specific efficiency of the rotavirus vaccine was determined based on Kyiv regional retrospective molecular and epidemiological data.
In the early 21st century, pneumonia remains an important medical and social problem. In Ukraine, within the structure of acute and chronic bronchopulmonary pathologies, community-acquired pneumonia (CAP) is at the forefront. According to contemporary views, the main and most common cause of CAP is bacterial pathogens. Meanwhile, the outcomes of numerous microbiological studies carried out in recent years strongly suggest that viruses definitely rank second in the etiology of CAP. Today, as the complex therapy of respiratory tract diseases proved to be successful, antiviral therapy is used, allowing to reduce the severity of the disease and to minimize the risk of complications. Goal – pharmacoeconomic analysis of additional antiviral pharmacotherapy of CAP with the use of vitaglutam based on mathematical modeling. The efficacy analysis of pharmacotherapy with the inclusion of vitaglutam was based on the retrospective data of 114 patients with viral-bacterial moderate-flow CAP. Patients were randomly assigned to two subgroups depending on the technology of empirical antimicrobial chemotherapy. In the 1st main subgroup (48 patients), antibiotic therapy was combined with the vitaglutam antiviral drug, whereas in the 2nd control group (66 patients) only antibacterial therapy was used. For each homogeneous group of patients, the application of a pharmacoeconomic model based on a «cost of disease» analysis was proposed, which is a basic method of pharmacoeconomic assessment and takes into account the efficiency of the conducted pharmacotherapy, expressed in the achievement of recovery using various technologies of pharmacotherapy in the presence and absence of a viral infection. Analysis of the results of clinical, and laboratory, and radiological studies showed that pharmacotherapy contributed to the positive results for both options. Meanwhile, time to achieve positive results in both groups of patients was significantly different. Pharmacoeconomic modeling, conducted for a group of 1000 simulated patients with CAP, revealed that in 27% of cases the strategy of non-inclusion of vitaglutam in pharmacotherapy scheme for patients with CAP will be dominant. However, for 73% of the simulated results, a maximum cost ratio of 16.97 was established, with an average value being 3.55. Thus, on average, the use of vitaglutam as additional antiviral pharmacotherapy is reasonable if the cost of additional antiviral pharmacotherapy is less than 3.5 times the cost per day of baseline therapy. Studies conducted in recent years have convincingly demonstrated the rationality of antiviral drugs inclusion in the pharmacotherapy scheme for patients with CAP.
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