Effective Targeted Chemoprophylaxis of Recurrent Liver Echinococcosis with Haplotype CYP1A2F1*A/A: a Clinical Case

Background. One of the main long­term quality criteria for treatment and prevention of echinococcosis is postoperative relapse, which rate varies widely within 3–54% between medical facilities. The genetic traits of recurrent liver echinococcosis comprise an important subject of research into its etiopathogenetic factors for  an effective prognosis of cyst relapse and treatment personalisation.Materials and methods. Bashkir State Medical University (Ufa, Russia) provided facilities to study targeted  chemoprophylaxis efficacy in a case of relapsed liver echinococcosis with haplotype CYP1A2F1*A/A (AA) and the  UM phenotype of ultrarapid albendazole sulfoxide­to­albendazole sulfone metaboliser.Results and discussion. The clinical case presented illustrates the rationale behind personalised  chemoprevention of recurrent echinococcosis with albendazole based on genotyping data. Genotyping allows  detection of an ultrafast metaboliser haplotype in blood implicating a rapid degradation of administered albendazole, reduced antiparasitic impact of drug therapy and more feasible relapse, in contrast with a normal metaboliser phenotype.Conclusion. A successful secondary prevention of relapsed echinococcosis suggests the efficacy of personalising  albendazole­based chemoprophylaxis of recurrent echinococcosis with genotyping data

2018–2019 antiviral drug sensitivity of the influenza virus strains isolated from various regions of Kazakhstan

Influenza is a serious public health problem. The ability of influenza virus to change upon replication is the most serious issue for practical medicine and virology, which can fundamentally alter virus biological properties, such as infectivity and virulence. The high mutational variability of influenza viruses can contribute to rapidly emerging drug resistance. Therefore, the study of antiviral drug sensitivity among influenza viruses is necessary to justify proper drug use for treatment and prevention of influenza infection. The aim of the study was to examine antiviral drug susceptibility of influenza A/H1N1 and B virus strains isolated from various regions of Kazakhstan in the years 2018–2019. Materials and methods. The susceptibility analysis of 20 strains of influenza A/H1N1 and B viruses was carried out by using chemotherapeutic agents including Remantadine, Tamiflu, Arbidol, and Ingavirin. Viruses were cultured in the allantoic cavity of developing 10-day-old chicken embryos for 48 hours at 36оC. The hemagglutinating activity was determined according to the standard method on 96-well plates using 0.75% chicken red blood cell suspension; the infectivity was calculated by the Reed–Muench method. The susceptibility of virus strains to different concentrations of antiviral drugs was evaluated by the level of virus reproductive suppression of 100 lg EID50/0.2 ml in chicken embryos. Statistical analysis was performed using Microsoft Office Excel 2010 software. Results. A study of susceptibility to chemotherapeutic agents demonstrated heterogeneity of influenza A and B virus population isolated in Kazakhstan during the 2018–2019 period. The susceptibility to tamiflu was found in all Kazakhstan strains of influenza A/H1N1 virus and three type B strains (inhibitory concentration was 0.44–25.38 μg/mL). The reproduction of most viruses was effectively inhibited by Tamiflu at a concentration of 0.68–3.23 μg/mL. The inhibitory concentration for three strains of A/H1N1 virus was 7.23–25.38 μg/mL. Remantadine inhibited reproduction of viruses at higher doses (12.60–25.55 μg /mL). All investigated viruses were resistant to Arbidol and Ingavirin. A single type B influenza virus strain was found to be weakly susceptible to Ingavirin. Conclusion. The heterogeneity of influenza virus population in susceptibility to antiviral drugs suggest a need for constant epidemiological surveillance in order to identify drug-resistant variants

Клинический случай эффективной таргетной химиопрофилактики рецидивного эхинококкоза печени у пациента с генотипом CYP1A2F1*A/A

Background. One of the main long­term quality criteria for treatment and prevention of echinococcosis is postoperative relapse, which rate varies widely within 3–54% between medical facilities. The genetic traits of recurrent liver echinococcosis comprise an important subject of research into its etiopathogenetic factors for  an effective prognosis of cyst relapse and treatment personalisation.Materials and methods. Bashkir State Medical University (Ufa, Russia) provided facilities to study targeted  chemoprophylaxis efficacy in a case of relapsed liver echinococcosis with haplotype CYP1A2F1*A/A (AA) and the  UM phenotype of ultrarapid albendazole sulfoxide­to­albendazole sulfone metaboliser.Results and discussion. The clinical case presented illustrates the rationale behind personalised  chemoprevention of recurrent echinococcosis with albendazole based on genotyping data. Genotyping allows  detection of an ultrafast metaboliser haplotype in blood implicating a rapid degradation of administered albendazole, reduced antiparasitic impact of drug therapy and more feasible relapse, in contrast with a normal metaboliser phenotype.Conclusion. A successful secondary prevention of relapsed echinococcosis suggests the efficacy of personalising  albendazole­based chemoprophylaxis of recurrent echinococcosis with genotyping data.Введение. Одним из основных показателей качества лечения и профилактики эхинококкоза в отдаленном послеоперационном периоде является его рецидив, диапазон частоты которого широкий и в разных лечебных учреждениях составляет от 3 до 54 %. Одним из перспективных направлений в поиске этиопатогенетических факторов развития рецидивного эхинококкоза печени является  исследование генетических особенностей заболевания, знание которых позволит  прогнозировать возможное повторное развитие эхинококковых кист, а также подбирать  индивидуальное лечение пациентов.Материалы и методы. На базе Башкирского государственного медицинского  университета (Россия, г. Уфа) проведен анализ клинического случая по оценке  эффективности таргетной химиопрофилактики рецидивного эхинококкоза печени у  пациента с генотипом CYP1A2F1*A/A (АА) с фенотипом — UM «быстрого» метаболайзера альбендазола сульфоксида в альбендазола сульфон.Результаты и обсуждение. Наш клинический случай подтверждает целесообразность  персонализированного подхода к химиопрофилактике рецидивного эхинококкоза  альбендазолом в зависимости от результатов генетического анализа. Генетический  анализ позволяет предположить, что обнаружение в крови пациента генотипа «быстрого» метаболайзера приведет к ускоренному разрушению альбендазола, принимаемого пациентом, и тем самым к снижению антипаразитарной эффективности лекарства по сравнению с фенотипом нормального метаболайзера, что  будет способствовать рецидиву заболевания. Заключение. Результаты успешной вторичной профилактики рецидива эхинококкоза  подтверждают эффективность персонализированного подхода к химиопрофилактике  рецидивного эхинококкоза альбендазолом в зависимости от результатов генетического  анализа.

Detection of influenza virus and pathogens of acute respiratory viral infections in population of Kazakhstan during 2018-2019 epidemic season

Influenza and other acute respiratory viral infections are the most common infectious diseases of our time, causing a significant harm to human health as well as great economic damage. At least five groups of viruses, including more than 300 subtypes, are currently related to ARVI pathogens. Such infectious agents are characterized by a high degree of variability resulting in replaced virus antigenic characteristics augmenting their contagiousness, immunoevasion, and resistance to chemotherapeutic drugs. Of relevance, influenza and other ARVIs also pose a threat due to subsequent rapid formation of bacterially-associated respiratory diseases as well as their continuous variability and emergence of new pathogenic species. In recent years, subtype A (H1N1) and A (H3N2) with predominance of pandemic strain, as well as type B influenza viruses have been simultaneously found in circulation. Most common among the causative agents of noninfluenza ARVIs, are respiratory syncytial virus, rhino- and adenoviruses, as well as I/III parainfluenza viruses. Here we present the results of virological and serological studies of clinical samples collected during the 2018—2019 epidemic season in the territory of the Republic of Kazakhstan after analyzing 2794 clinical samples (2530 nasopharyngeal swabs and 264 blood serum samples) of patients diagnosed with ARVI, ARI, bronchitis, and pneumonia. Examining nasopharyngeal swabs by using RT-PCR showed that the mixed etiology influenza viruses with predominant A/H1N1pdm virus circulated in Kazakhstan. In particular, influenza virus genetic material was found in 511 swabs (20.20% of total examined samples), so that influenza A virus RNA was detected in 508 biological samples such as A/H1N1 — in 289, A/H3N2 — 209, unverified virus subtype — 10 samples. Type B influenza virus was detected in 3 samples. Analyzing 264 blood serum samples by the HAI assay and ELISA showed the presence of antibodies specific to influenza A/H1N1, A/H3N2, and B viruses in the population of various regions of Kazakhstan, thereby indirectly confirming their co-circulation. 42 influenza virus strains were isolated in chicken embryos, of which 28 were assigned to A/H1N1pdm virus, 13 — A/H3N2 virus, and one isolate was identified as influenza B virus. The laboratory diagnostics of clinical samples for ARVIs revealed that respiratory syncytial virus prevailed among identified non-influenza agents, whereas rhino- and adenoviruses were less common. Metapneumoviruses, bocaviruses, coronaviruses, and type I parainfluenza viruses were detected in few cases. Comparison of our study data with the data on 2017—2018 circulation of influenza pathogens showed that in Kazakhstan influenza A and B viruses continued to circulate, with the dominance of A/H1N1pdm virus as it was in the previous epidemic season. Identification of non-influenza viruses, the causative agents of 2018—2019 respiratory infections, showed the predominance of respiratory syncytial virus that correlated with the aforementioned results