Assessing natural herd immunity to tick-borne encephalitis in Republic Sakha (Yakutia)

Tick-borne encephalitis (TBE) is a natural focal viral neuroinfection vastly spread in the mid-latitude climate zone of theEurasia. Lethal cases and disability related to TBE determine its high epidemiological significance as well as underlie undiminished attention to prevent it in endemic territories. At the same time, TBE epidemiologic features significantly differ in various geographic areas. Importantly, Republic Sakha (Yakutia) is not among TBE endemic areas in theRussian Federation. However, in the last decade an increased incidence of ixodic tick bites was registered in the Republic Sakha. A pattern of pathogen-specific population immunity is one of the most valuable criteria for assessing magnitude of epidemic process in TBE foci. Hence, our study was aimed at assessing natural herd immunity TBEV in Republic Sakha associated with elevated incidence of tick bite visits. Here, we analyzed the data regarding the rate of tick attacks in the period of 2001–2007 in Republic Sakha. Residents and individuals unvaccinated against TBEV in the city ofYakutskas well as various administrative regions were examined to record the peak incidence of tick attacks. It was found that a range of the administrative regions recording with registered of ixodic tick attacks and elevated incidence of tick bites was expanded. Moreover, the top incidence of tick bites was annually recorded in the south regions of the republic Aldanian, Neryungri, Olyekminsk, Leninsk, Khangalassky districts, city ofYakutskand its suburbs. Furthermore, TBEV-specific immunoglobulins were detected in 5.7±0.68% of the residents examined suggesting about contacts with the pathogen. In addition, the peak count of seropositive people (8.9±1.85%) was identified in Namsky district located in the central part of the republic. Overall, detection rate of TBEV-specific antibodies among general adult population (6.9±0.95%) was significantly higher compared to those observed in children (3.9±0.89%, р < 0.05). no significant differences in urban (5.8±1.12%) vs. rural population (5.63±0.84%) was found

Разработка стандартного образца черноземной почвы, аттестованного на показатели плодородия

The authors provide information on the need to develop a reference material (RM) of the southern middle loamy black soil certifiedfor fertility indicators. The information about the stages of RM development is described: selection and preparation of soil material in the field; procedure of averaging soil material.In the determination of the RM metrological characteristics, the heterogeneity and stability characteristics of the RM are evaluated.The authors demonstrated the results of the RM certification for agrochemical indicators. The correctness of these results is confirmed by the results obtained in twenty-three accredited laboratories.The developed RM is registered in the State Register of the Approved Types of Certified Reference Materials under the number GSO 11369-2019-the RMfor composition (of agrochemical indicators) of the southern middle loamy black soil (SACHyuzhP-02).The RM is intended for metrological support of agroecological monitoring of agroindustrial complex laboratories.В статье авторами представлена информация о необходимости разработки стандартного образца почвы чернозема южного среднесуглинистого, аттестованного на показатели плодородия. Описаны сведения об этапах разработки стандартного образца: отбор и подготовка почвенного материала в полевых условиях; процедура усреднения почвенного материала.При определении метрологических характеристик стандартного образца оценены характеристики неоднородности и стабильности материала стандартного образца.Авторами работы получены результаты аттестации стандартного образца по агрохимическим показателям, корректность установления которых подтверждена результатами в двадцати трех аккредитованных лабораториях.Разработанный стандартный образец зарегистрирован в Государственном реестре утвержденных типов стандартных образцов под номером ГСО 11369-2019-стандартный образец состава (агрохимических показателей) почвы чернозем южный среднесуглинистый (САЧюжП-02). Стандартный образец предназначен для метрологического обеспечения агроэкологического мониторинга лабораторий агропромышленного комплекса

Susceptibility to tuberculosis is associated with variants in the ASAP1 gene encoding a regulator of dendritic cell migration

Human genetic factors predispose to tuberculosis (TB). We studied 7.6 million genetic variants in 5,530 people with pulmonary TB and in 5,607 healthy controls. In the combined analysis of these subjects and the follow-up cohort (15,087 TB patients and controls altogether), we found an association between TB and variants located in introns of the ASAP1 gene on chromosome 8q24 (P = 2.6 × 10−11 for rs4733781; P = 1.0 × 10−10 for rs10956514). Dendritic cells (DCs) showed high ASAP1 expression that was reduced after Mycobacterium tuberculosis infection, and rs10956514 was associated with the level of reduction of ASAP1 expression. The ASAP1 protein is involved in actin and membrane remodeling and has been associated with podosomes. The ASAP1-depleted DCs showed impaired matrix degradation and migration. Therefore, genetically determined excessive reduction of ASAP1 expression in M. tuberculosis–infected DCs may lead to their impaired migration, suggesting a potential mechanism of predisposition to TB

Стандартные образцы кормов в системе метрологического обеспечения лабораторий агропромышленного комплекса

The authors provided information about the developed matrix feed reference materials, certified for quality, nutritional value and toxicological contamination indicators for metrological support of analytical work in the article to confirm the compliance of products with requirements of national standards. Information on the stages of development of feed reference materials (selection and preparation of reference material, studies of heterogeneity and stability of feed reference material) is presented. There are demonstrated the results of reference materials certification according to certified indicators, their correctness confirmed by the results of thirty accredited laboratories.The developed reference material of sunflower meal is registered in the State Register of approved types of reference materials under the number GSO 11612-2020. Reference materials of the composition of toasted soybean feed meal and complete feed for poultry (broilers) are approved as Industry-Specific by the Ministry of Agriculture of the Russian Federation (Department of Plant Production, Mechanization, Chemicalization and Plant Protection).Feed reference materials are intended for metrological support of agro-industrial complex laboratories.В статье представлены сведения о разработанных матричных стандартных образцах кормов, аттестованных на показатели качества, питательной ценности и токсикологического загрязнения для метрологического сопровождения аналитических работ в целях подтверждения соответствия продукции требованиям национальных стандартов. Представлены сведения об этапах разработки стандартных образцов кормов (отбор и подготовка материала стандартного образца, исследования неоднородности и стабильности материала стандартного образца). Продемонстрированы результаты аттестации стандартных образцов по аттестуемым показателям, корректность установления которых подтверждена результатами в тридцати аккредитованных лабораториях.Разработанный стандартный образец шрота подсолнечного зарегистрирован в Государственном реестре утвержденных типов стандартных образцов поД номером ГСО 11612-2020. Стандартные образцы состава шрота соевого кормового тостированного и комбикорма полнорационного для сельскохозяйственной птицы (бройлеров) утверждены в качестве отраслевых в Министерстве сельского хозяйства Российской Федерации (Департамент растениеводства, механизации, химизации и защиты растений).Стандартные образцы кормов предназначены для метрологического обеспечения лабораторий агропромышленного комплекса

Pharmacogenetic Warfarin Dosing Algorithm in the Russian Population

Background. To date, there are many pharmacogenetic algorithms for selecting the dose of warfarin. However, there is very little information about the predictive accuracy of the algorithms. We decided to evaluate the predictive accuracy of the Gage algorithm, using a calculator, located on the web site (http://www.warfarindosing.org) in two ethnic groups (Caucasians and Asians), living in Russia.Aim. To compare the actual warfarin dose (AWD) to the calculated warfarin dose (CWD), using the algorithm in two ethnic groups taking warfarin.Materials and methods. We included 114 patients (66 Caucasians and 48 Asians): the mean age was60.91 ± 12.34 years; 61 (53.51 %) men, and 53 (46.49 %) women. The comparative characteristics of the algorithm were tested using the mean absolute error (MAE) between AWD and CWD, and percentage of patients, whose CWD fell within 20 % of AWD (percentage within 20 %). Genotyping for CYP2C9*2, CYP2C9*3, CYP4F*2 and VKORC1 was performed by real-time polymerase chain reaction (RT-PCR) method using Pharmacogenetics Warfarin reagent kits (DNA technology, Russia).Results. The Gage algorithm produced the predictive accuracy with MAE = 1.02 ± 0.16 mg/day and percentage within 20 % for Asian patients was 39.6 %. We obtained MAE = 1.33 ± 0.16 mg/day and percentage within 20 % for Caucasian patients was 40.9 %. In two ethnic groups (Caucasians and Asians) of the Russian population, overall performance of warfarin pharmacogenetic dosing by the Gage algorithm was similar.Conclusions. Despite the performance limitation of the current warfarin pharmacogenetic dosing Gage algorithm, constant international normalized ratio monitoring is important

Опыт диагностики и лечения болезни Кавасаки в клинике Санкт-Петербургского государственного педиатрического медицинского университета и Д етской городской больнице №1 Санкт-Петербурга

Kawasaki disease (KD) is acute systemic vasculitis of unknown etiology. Approximately 20–25% of untreated patients develop coronary artery changes with a range of severity from asymptomatic coronary artery dilatation to giant coronary artery aneurysms with thrombosis, myocardial infarction, and sudden death. To date there is no official data on the incidence of KD in Russia. In Russia, the disease is not enough known now to a wide circle of physicians and often masks other more common diseases. Since 2010, the detection rate of KD has dramatically increased in Saint-Petersburg.Objective: to analyze the experience in diagnosing and treating KD in two largest hospitals of Saint Petersburg.Patients and methods. The retrospective study included data on 30 children (18 boys, 12 girls) who were hospitalized with a diagnosis of KD in the Saint-Petersburg State Pediatric Medical University Clinic and Children’s Hospital One (Saint Petersburg) between January 2011 and September 2016. Data are represented by median and extreme values. The age of the children was 2.8 (0.2; 4.6) years; of them 5 (16.7%) patients were under the age of 1 year. The children were hospitalized on 5 (1; 14) days of disease onset; KD was diagnosed on 9 (3; 52) day of the disease.Results. Immediately after diagnosis, 27 (90%) children received aspirin. In early stages (before 10 days of the disease), intravenous immunoglobulin (IVIG) therapy was performed in 15 (50%) children, one of them received IVIG before disease day 5 (on day 3), but without effect. On disease days 11-20 (immediately after diagnosis), 10 (33.3%) children were prescribed with IVIG; thereafter fever was abolished in all the patients. Their body temperature became normal on day 11 (6; 23). Ultrasonography revealed coronary artery lesions in 13 (43.3%) patients. Out of the 30 children followed up, one baby who fell ill at the age of 3 months and received IVIG died on day 30 of the disease.Conclusion. Currently, there continues to be a delayed diagnosis of KD. IVIG therapy was effective, especially in cases of timely diagnosis. It is necessary to increase awareness of KD among clinicians and ultrasound diagnosticians.Болезнь Кавасаки (БК) – остро протекающий системный васкулит неизвестной этиологии. Примерно у 20–25% не получивших лечения больных развиваются изменения коронарных артерий различной степени тяжести – от бессимптомной дилатации до гигантских аневризм, тромбоза, инфаркта миокарда и внезапной смерти. До настоящего времени официальных данных о заболеваемости БК в России нет. В нашей стране БК недостаточно известна широкому кругу врачей и часто проходит под маской других более распространенных заболеваний. В Санкт-Петербурге после 2010 г. резко возросла выявляемость БК.Цель исследования – проанализировать опыт диагностики и лечения БК в двух крупных стационарах Санкт-Петербурга.Пациенты и методы. В ретроспективное исследование были включены данные о 30 детях (18 мальчиков, 12 девочек), находившихся на стационарном лечении с диагнозом БК в клинике Санкт-Петербургского государственного педиатрического медицинского университета и Детской городской больнице №1 Санкт-Петербурга с января 2011 г. по сентябрь 2016 г. Данные представлены медианой и крайними значениями. Возраст детей составил 2,8 [0,2; 4,6] года, из них 5 (16,7%) пациентов были в возрасте до 1 года. Дети были госпитализированы на 5-е [1; 14] сутки болезни, диагноз БК установлен на 9-й [3; 52] день болезни.Результаты. Сразу после установления диагноза получили аспирин 27 детей (90%). В ранние сроки (до 10-го дня болезни) терапия внутривенным иммуноглобулином (ВВИГ) проводилась у 15 (50%) пациентов, из них 1 получил ВВИГ ранее 5-го дня болезни (на 3-й день), однако без эффекта. На 11–20-й день болезни (сразу после установления диагноза) ВВИГ назначен 10 (33,3%) детям, после чего лихорадка была купирована у всех пациентов. Температура тела нормализовалась на 11-й [6; 23] день. Поражение коронарных артерий при УЗИ выявлено у 13 (43,3%) пациентов. Из 30 находившихся под наблюдением детей у 1 ребенка, заболевшего в возрасте 3 мес и получившего ВВИГ на 30-й день болезни, зафиксирован летальный исход.Выводы. В настоящее время БК продолжает диагностироваться с опозданием. Терапия ВВИГ была эффективной, особенно в случаях своевременного установления диагноза. Необходимо повышение осведомленности клиницистов и врачей ультразвуковой диагностики о БК

Tuberculosis cases caused by heterogeneous infection in Eastern Europe and their influence on outcomes

INTRODUCTION: Mycobacterium tuberculosis superinfection is known to occur in areas with high rates of tuberculosis (TB) and has a significant impact on overall clinical TB management. AIM: We aimed to estimate the superinfection rate in cohorts of drug sensitive and multi-drug resistant tuberculosis (MDR TB) patients from Eastern Europe and the potential role of a second MDR TB strain infecting a patient with active non-MDR TB in treatment outcome. METHODS: The study population included 512 serial M. tuberculosis isolates obtained from 84 MDR- and 136 non-MDR TB patients recruited sequentially at sites in Lithuania, Latvia and Russia in 2011-2013. Strains were genotyped using standardized 24-loci Mycobacterial Interspersed Repetitive Unit-Variable Number Tandem Repeat (MIRU-VNTR) typing. RESULTS: Changes in two or more MIRU-VNTR loci suggesting superinfection were detected in 13 patients (5.9%). We found 4 initially non-MDR TB patients superinfected with an MDR TB strain during treatment and 3 of them had an unsuccessful outcome. CONCLUSIONS: An unsuccessful treatment outcome in patients initially diagnosed with drug sensitive TB might be explained by superinfection with an MDR TB strain. Bacteriological reversion could be indicative of superinfection with another strain. Archiving of all serial isolates and their genotyping in case of culture reversion could support therapeutic strategies in high MDR TB burden settings if resources are available

Invasive aspergillosis in children and adolescents with solid tumors: clinical cases and registry analysis

We presented two cases of invasive aspergillosis (IA) in children with solid tumors, data of IA patients register, and a literature review. In the register of patients with IA (1997–2018), we found 57 patients with IA from 0 to 18 years. It was established that the number of patients with solid tumors was 15.7 %. Background diseases were: central nervous system tumors – 33.5 %, neuroblastoma – 33.5 %, osteosarcoma – 11.0 %, Wilms tumor – 11.0 %, hemangioblastoma – 11.0 %. Chemotherapy-induced neutropenia was reported in 100 % of IA cases in children and adolescents with solid tumors. The additional risk factors were treatment in intensive care unit – 22.2 %, high-dose chemotherapy with autologous hematopoietic stem cell transplantation – 22.2 %, concomitant bacterial infection – 33.0 %. Surgical intervention for the underlying disease was performed in 77.7 % of patients. The most common clinical site of IA was the lungs – 88.9 %. The predominant clinical sign was fever – 66.7 %, cough and respiratory failure were seen less frequently – 33.4 % and 33.4 %, respectively. The etiological agents of IA were Aspergillus fumigatus – 33.3 %, Aspergillus nidulans – 33.3 % and Aspergillus ustus – 33.3 %. 88.9 % of patients received antimycotic therapy, voriconazole predominantly – 66.7 %. Combination therapy was used in 33.3 % of patients. The overall 12-week survival in children and adolescents with IA in case of solid tumors was 77.8 %

COMBINATION OF INVASIVE ASPERGILLOSIS AND MUCORMYCOSIS IN ONCOHEMATOLOGICAL PATIENTS

Objective. Data analysis of the register of patients with invasive aspergillosis (IA), which was founded in Saint Petersburg (1998–2017), and clinical case description of successful treatment of IA and mucormycosis with lungs involvement in a patient with Hodgkin’s lymphoma.Materials and methods. In the study were included 29 oncohematological patients with IA and mucormycosis. In control group were included 483 oncohematological patients with IA. We used criteria EORTS/MSG, 2008 for IA and mucormycosis diagnosis.Results. We identified that the combination of IA and mucormycosis significantly often develops in patients with acute lymphoblastic leukemia (32 %, р = 0.001), and allogeneic hematopoietic stem cells transplants (allo-HSCT) recipients (52 %, р = 0.001). In mixed-infection Aspergillus nidulans was frequent IA etiological agent (11 %, р = 0.001). The main mucormycosis etiological agents were Rhizopus spp. (45 %), Lichtheimia corуmbifera (20 %). The main sites of the localization were lungs (76 %), disseminated process and paranasal sinuses involvement were identified more frequently (45 % and 17 % (р = 0.0001; р = 0.002), respectively). Typical clinical feature of IA and mucormycosis combinations was hemoptysis (24 %, р = 0.008), radiological signs – lesions with cavities destruction (38 %), hydrothorax (29 %) and a “reverse halo” symptom (17 %). Antifungal therapy received 76 % of patients, surgery – 34 %.Conclusion. Mucormycosis was revealed in 5.7 % of patients with IA. The main risk factors for co-infection are allo-HSCT, long-term agranulocytosis, lymphocytopenia and glucocorticosteroid therapy. Overall 12 weeks survival in patients with mixed-infection was 38 %, significantly lower than in patients with IA (р = 0.005). An unfavorable prognosis factor was dissemination of mycotic infection (р = 0.009)