New findings concerning the spread of natural foci of infection in the transpolar region of eastern Siberia]

New materials are presented on the presence of the foci of anthropozoonozes in the Extreme North. For the first time there was established the existence in the subarctic tundra of the Taimyr peninsula of the arbovirus foci of the tick-borne encephalitis complex. A virus of the tick-borne encephalitis complex was isolated in 1973 from the gamasida ticks Haemogamasus ambulans Thorel. and Hirstionyssus isabellinus Oudms. and the nests of the Siberian lemming Lemmus lemmus L. This pointed to the existence in the Transpolar region of the foci or arboviruses in the nest-hole biocenoses of the lemmings outside the bird colonies. Cultures of tularemia bacilli (which proved the etiology of the epizootic among the lemmings observed in 1973 and also the presence of the lemming natural foci of tularemia and their combination with the arbovirus foci) were isolated from the lemmings at the same territory. The results of serological examination of the local population and of the animals pointed to the circulation in the Transpolar region of the causative agents of leptospirosis, toxoplasmosis, Q-fever and of the Asian tick-borne rickettsiosis.     

Combined focus of tick-borne encephalitis, tick-borne rickettsiosis and tularemia in the habitat of Haemaphysalis concinna in south central Siberia

For the first time in the Krasnoyarsk region the population Haemaphysalis concinna ticks were found to be infected with the causative agents of three natural focal tick-borne infections--tick-borne encephalitis, tick-borne rickettsiosis and tularemia. The existence of the combined natural focus of these three infections has been confirmed by epidemiological data. Ticks Dermacentor nuttalli also play a similar role in combined foci of tick-borne encephalitis and tick-borne rickettsiosis in these focal territories.     

Ectoparasites and phoresants of the root vole (Microtus oeconomus Pall.) in the Polesye

Drainage melioration in the Polesye resulted in a sharp increase in the number of tundra vole (Microtus oeconomus Pall.) which quickly included into the parasitocenosis of the drained land. There were found 26 parasitic and nonparasitic species of Gamasoidea, 3 species of Ixodidae and 2 species of Trombiculidae, 10 species of Aphaniptera, 3 species of Anoplura but there was found no species specific only for the tundra vole. All found parasites occur on many hosts. This explains wide parasitic links of the tundra vole with other homothermic animals which especially extensive with the bank vole and it may have important consequences for epizootiology of tularemia and tick-borne encephalitis.     

Epidemiological characterization of Ixodes tick-borne borreliosis in the Krasnoyarsk territory

The analysis of morbidity in tick-borne infections for many years indicates that in the 1960s-1990s in the total structure of the clinical forms of tick-borne encephalitis the erythematic form amounted to 1.4-20.9, which 1.9- to 3.1-fold exceeded the morbidity characteristics for the whole of Russia. The epidemiological analysis of morbidity at the territory for the period of 1992-2001 is indicative of the presence of the combined foci of tick-borne encephalitis and Ixodes tick-born borrelioses (TBB) in 42 regions of the territory. The cyclic character of morbidity and the irregularity of its spread in different regions of the territory can be observed. Among the TBB patients, town dwellers constitute, on the average, 75.8%. These tick-born infections exhibit regional differences connected with landscape variations and the patients age. However official statistics does not reflect the real epidemic situation at the territory: hypodiagnostics is primarily due to the absence of reliable laboratory confirmation in remote regions of the Krasnoyarsk territory.     

Epidemiology of hemorrhagic fever with renal syndrome in the north Volga-Viatka region

The results of the ecological and epidemiological study of hemorrhagic fever with the renal syndrome (HFRS) in the Kirov region for the period of 1987-2000 are presented. HFRS morbidity rate varied from 1.3 to 13.7 per 100,000 population, which corresponded to the figures registered in the Volga Vyatka region. Cases of HRFS were mainly (90%) registered in three southern districts of the region. The moderate degree of correlation between morbidity rate and the number of wild mammals (r = 0.55) was established. Periodic morbidity rise occurred every 3 years. In 1998-2000 the contamination of wild mammals with HFRS virus increased and reached 7.6-9.5%. Infection factors connected with everyday human activities somewhat prevailed, industrial and agricultural types of infection constituting 43.8%. Males aged 20-49 years prevailed among the patients. Morbidity rate among urban dwellers exceeded that among town residents.     

Tick-borne encephalitis in the Estonian SSR

The foci of tick-borne encephalitis (TBE) of 2 types, differing in their morbidity rates, the character of their immunological structures, the species composition of carrier mites and their capacity for TBE virus carriership, have been shown to exist in Estonia. TBE morbidity is characterized by 4- to 5-year cycles, the overwhelming majority of TBE cases being registered in the area of the joint habitat of both species of mites. During the epidemic season 2 peaks of morbidity rise are registered, which corresponds to peaks in the number of mites in nature. Different epidemic importance of 2 species of carrier mites in TBE morbidity in Estonia has been shown.     

Natural focal infections in the north of the Far East. I. The detection of natural foci of infections in Chukot]

Results of a 3-year complex (zoo-parasitological, viral, bacteriological, and serological) studies of mammals and birds in Chukotka demonstrated the presence of natural foci of pseudo-tuberculosis, intestinal yersinosis, salmonellosis (heidelberg), and of tick-borne encephalitis. The existence of natural foci of tularemia and endemic rickettsioses is supposed on the basis of serological data.     

Infectious diseases in natural reservoirs: epidemic situation and morbidity in the Russian Federation and prophylactic measures

The analysis of morbidity in infections with natural foci in Russia for the period of 1999-2000 indicates that a rise in the number of cases of hemorrhagic fever with the renal syndrome, tick-borne encephalitis, Crimean hemorrhagic fever and West Nile fever with a high proportion of urban population among the patients is registered annually. An increase in the epizootic activity of the natural foci of plague is noted in the absence of morbidity among humans. The appearance of the outbreaks of tularemia is linked nor only with the increased activity of the natural foci, but also with the reduced coverage of the population with prophylactic immunization in endemic regions. This analysis infers that morbidity prognosis in infections with natural foci for 2001 remains unfavorable. The growth of morbidity in these infections is mainly due to the reduction of measures for controlling their vectors both is open nature and in settlements, as well as to low coverage with prophylactic immunization. Urgent complex measures which may ensure effective antiepidemic and prophylactic work for controlling infections with natural foci are presented.     

The cyclicity and prognosis of shigellosis morbidity in Russia

The epidemic process (EP) of shigellosis morbidity proceeds in cycles. As shown in this study, cyclic curves are the sum of polyharmonic fluctuations, being the axis of EP. The duration of one cycle is 18 years, and its configuration is stably retained for a long time. In Nizhny Novgorod shigellosis morbidity is strongly correlated with air temperature is summer at the peak of cyclic rises and moderately correlated in the years of low morbidity. In some cities of the Russian Federation fluctuations of air temperature have been found of occur synchronously with disturbances of the magnetic field of the earth. The character and stability of EP cycles provide grounds for the prognostication of shigellosis morbidity. The current cycle will end in the year 2000, and then natural preconditions for a new cyclic rise will appear.     

蜱传脑炎病毒非结构蛋白NS2B-NS3与NS5的研究进展

蜱传脑炎病毒是引起严重的中枢神经系统疾病蜱传脑炎的病原体,每年在欧洲、俄罗斯远东地区、日本和中国北部报道的蜱传脑炎病例数约为10000-12000例,且在我国和多个欧洲国家的发病率逐渐增高,正成为人类健康的潜在危害。主动免疫是预防蜱传脑炎的有效措施,包括我国在内的多个国家已研制出安全性较高的疫苗,但在我国流行省份的疫苗接种较为有限,特异性抗病毒药物的研发或许是治疗蜱传脑炎病毒感染的研究方向之一。蜱传脑炎病毒非结构蛋白NS2B-NS3与NS5因为在病毒基因组复制、加帽和宿主免疫调节中的重要作用,成为关键的抗病毒药物研发靶点。本文综述了蜱传脑炎病毒非结构蛋白NS2B-NS3与NS5的三维结构和抑制剂研发工作,为深入探究该病毒感染的分子机制和抗病毒药物研发提供参考。     

Self-maintenance of foci of bovine leptospirosis]

The relationship between the rate of cattle infection with leptospirosis and the total number of livestock at cattle-breeding farms has been established. The annual dynamics of this infection has been found to give two morbidity rises among the animals, occurring not due to their contacts with the natural foci of leptospirosis, but as a consequence of the animal vertical and horizontal "circulation". The mechanisms of self-maintenance of the foci of leptospirosis among cattle are discussed.     

Effectiveness of the seroprophylaxis of tick-borne encephalitis depending on the titer of homologous gamma-globulin antihemagglutinins

To give a rationale for using homologous gamma globulin with antihemagglutinin titers of 1 : 20 to 1 : 80 for the prophylaxis of tick-borne encephalitis, 5-year observations covering all persons attacked by ticks in one of the intensive natural foci of the disease in the Western Urals have been made. The threefold statistically significant difference in the morbidity rate of tick-borne encephalitis between groups of persons immunized and not immunized with gamma globulin has been shown.     

Epidemic process of pertussis in Moscow

Materials reflecting the dynamics of pertussis morbidity during the period of 1958 - 2003 under the conditions of prolonged mass immunization of the child population with adsorbed DPT vaccine are presented. The planned vaccination of children led to the decrease of pertussis morbidity during the first 10 years, but groundless abstentions from vaccination during the 1980s - 1990s contributed to a sharp rise in morbidity among children of younger age groups. During the recent four years a rise in pertussis morbidity was registered in 2000 (71.79 per 100,000 of the population), followed by the most significant for the last 20 years drop in morbidity in 2002--down to 9.89. But in 2003 the growth of morbidity was again registered (38.67). Recently periodic rises and drops in morbidity occurred simultaneously with the increased coverage of children of younger age groups with vaccination. In recent years changes in the age structure of patients were observed: the specific proportion of school children increased (in 2003 morbidity rates in children aged 6 - 10 years were 288.6 - 270.7), simultaneously high morbidity among children aged up to one year (274.9) was registered. The specific proportion of pertussis-affected children aged above 7 years reached 65%. From the late 1990s until present in 87.1% of cases strains of serotype 1.0.3 prevailed in the population of B. pertussis strains. But in recent years the circulation of strains 1.2.3, spread in the prevaccination period and having toxicity similar to that of strains of serotype 1.0.3, while exceeding them in virulence, in sufficiently high proportion (7.0% in 2002) was noted. This was indicative of the possibility of the unfavorable development of the epidemic process of pertussis infection.     

Geographical variants in the immunological structure of the population in combined foci of tick-borne encephalitis and endemic rickettsiosis in the European part of the USSR

The zonal study of the immunological structure of the population revealed an increase in the number of infective agents with which the population comes into contact in the southern regions. In the medial boreal forest zone contacts of low intensity only with tick-borne encephalitis virus were detected (the immune stratum was found to be 5.5%, 2,178 persons were examined); in the southern boreal forest zone the foci of tick-borne encephalitis actively manifested (the immune stratum reached 38.9%, 2,854 persons were examined), and Q fever was constantly detected (1.6%). In the forest-steppe zone the population was found to have contacts with the causative agent of tick-borne encephalitis (the immune stratum was found to be 13.3%, 2,056 persons were examined), Q fever (1.2%) and tick-borne rickettsiosis (1.1%).     

Polymorphism of <Emphasis Type="Italic">CD209</Emphasis> and <Emphasis Type="Italic">TLR3</Emphasis> genes in populations of North Eurasia

The DC-SIGN (dendritic cell-specific intercellular adhesion molecule (ICAM)-3-grabbing non-integrin) and TLR3 (toll-like receptor 3) proteins are key effectors of the innate immunity and particularly play an important role in the organism’s antiviral defense as pattern-recognition receptors. Previously, we demonstrated that certain genotypes and alleles of single nucleotide polymorphisms (SNPs) rs2287886 (G/A) in the promoter region of the CD209 gene (encoding DC-SIGN) and rs3775291 (G/A, Leu412Phe) in the exon 4 of the TLR3 gene are associated with human predisposition to tick-borne encephalitis in the Russian population. In the present work, the distribution of genotype and allele frequencies for these SNPs was studied in seven populations of North Eurasia, including Caucasians (Russians and Germans (from Altai region)), Central Asian Mongoloids (Altaians, Khakass, Tuvinians, and Shorians), and Arctic Mongoloids (Chukchi). It was found that the CD209 gene rs2287886 SNP A/A genotype and A allele, as well as the TLR3 gene rs3775291 SNP G/G genotype and G allele (the frequencies of which in our previous studies were increased in tick-borne encephalitis patients as compared with the population control (Russian citizens of Novosibirsk)), are preserved with a high frequency in Central Asian Mongoloids (who for a long time regularly came in contact with tick-borne encephalitis virus in places of their habitation). We suggested that predisposition to tick-borne encephalitis in Central Asian Mongoloid populations can be predetermined by a different set of genes and their polymorphisms than in the Russian population.     

Tick-borne encephalitis in the Maritime Territory

On the basis of epidemiological analysis carried out at the period of 1940-1987, a decrease in tick-borne encephalitis (TBE) morbidity was registered; at the same time time the disease invariably took, as before, a clinically severe course. The most dangerous foci of TBE were found to be located in the southern Okhotsk region grown with dark coniferous forests. The subsiding and activation of the natural foci of TBE in different regions of the territory were established and some heretofore unknown foci in southern regions of the Maritime Territory were found. Ixodes mites inhabiting the Maritime Territory were shown to have a low level of virus carriership, thus causing the low level of population immunity to TBE virus. Combined foci of TBE and Powassan encephalitis were found.     

Saliva,Salivary Gland,and Hemolymph Collection from Ixodes scapularis Ticks

Ticks are found worldwide and afflict humans with many tick-borne illnesses. Ticks are vectors for pathogens that cause Lyme disease and tick-borne relapsing fever (Borrelia spp.), Rocky Mountain Spotted fever (Rickettsia rickettsii), ehrlichiosis (Ehrlichia chaffeensis and E. equi), anaplasmosis (Anaplasma phagocytophilum), encephalitis (tick-borne encephalitis virus), babesiosis (Babesia spp.), Colorado tick fever (Coltivirus), and tularemia (Francisella tularensis) ^1-8. To be properly transmitted into the host these infectious agents differentially regulate gene expression, interact with tick proteins, and migrate through the tick ^3,9-13. For example, the Lyme disease agent, Borrelia burgdorferi, adapts through differential gene expression to the feast and famine stages of the tick''s enzootic cycle ^14,15. Furthermore, as an Ixodes tick consumes a bloodmeal Borrelia replicate and migrate from the midgut into the hemocoel, where they travel to the salivary glands and are transmitted into the host with the expelled saliva ^9,16-19.As a tick feeds the host typically responds with a strong hemostatic and innate immune response ^11,13,20-22. Despite these host responses, I. scapularis can feed for several days because tick saliva contains proteins that are immunomodulatory, lytic agents, anticoagulants, and fibrinolysins to aid the tick feeding ^{3,11,20,21,23}. The immunomodulatory activities possessed by tick saliva or salivary gland extract (SGE) facilitate transmission, proliferation, and dissemination of numerous tick-borne pathogens ^3,20,24-27. To further understand how tick-borne infectious agents cause disease it is essential to dissect actively feeding ticks and collect tick saliva. This video protocol demonstrates dissection techniques for the collection of hemolymph and the removal of salivary glands from actively feeding I. scapularis nymphs after 48 and 72 hours post mouse placement. We also demonstrate saliva collection from an adult female I. scapularis tick.     

SiRNA Inhibits Replication of Langat Virus, a Member of the Tick-Borne Encephalitis Virus Complex in Organotypic Rat Brain Slices

Tick-borne encephalitis virus is the causative agent of tick-borne encephalitis, a potentially fatal neurological infection. Tick-borne encephalitis virus belongs to the family of flaviviruses and is transmitted by infected ticks. Despite the availability of vaccines, approximately 2000–3000 cases of tick-borne encephalitis occur annually in Europe for which no curative therapy is available. The antiviral effects of RNA mediated interference by small interfering RNA (siRNA) was evaluated in cell culture and organotypic hippocampal cultures. Langat virus, a flavivirus highly related to Tick-borne encephalitis virus exhibits low pathogenicity for humans but retains neurovirulence for rodents. Langat virus was used for the establishment of an in vitro model of tick-borne encephalitis. We analyzed the efficacy of 19 siRNA sequences targeting different regions of the Langat genome to inhibit virus replication in the two in vitro systems. The most efficient suppression of virus replication was achieved by siRNA sequences targeting structural genes and the 3′ untranslated region. When siRNA was administered to HeLa cells before the infection with Langat virus, a 96.5% reduction of viral RNA and more than 98% reduction of infectious virus particles was observed on day 6 post infection, while treatment after infection decreased the viral replication by more than 98%. In organotypic hippocampal cultures the replication of Langat virus was reduced by 99.7% by siRNA sequence D3. Organotypic hippocampal cultures represent a suitable in vitro model to investigate neuronal infection mechanisms and treatment strategies in a preserved three-dimensional tissue architecture. Our results demonstrate that siRNA is an efficient approach to limit Langat virus replication in vitro.     

Multiyear and seasonal hepatitis A morbidity in different population age groups in certain areas

At the areas with high activity of hepatitis A (HA) epidemic process the duration of epidemic cycles was shown to differ, the intervals between the peaks of morbidity increasing in older age groups. The beginning of seasonal rises exceeding the average annual HA morbidity level in different age groups was found to depend on the activity of the epidemic process. At the areas with the highest activity of the epidemic process children aged 1-2 years were the first to be affected by the seasonal rise of HA. Stable direct correlation between HA morbidity levels at the beginning of seasonal rises and some markers indicative of unfavorable sanitary conditions (the size of the fly population, the purity of water samples deviating from the requirement of the Government Standard) during the preceding year was demonstrated.     

Manifestations of the cyclic nature of the epidemic process in dysentery

Different forms of dysentery, especially those caused by Sh. sonnei and Sh. flexneri, have been found to differ considerably in their cyclic recurrence. The development cycles of the epidemic processes of dysentery have an objective character, occur in the presence of any tendencies in the morbidity rate, and depend on the natural factors. Thus, the cycles of increase and decrease in morbidity are 3, 6, 9, 12 years for dysentery caused by Sh. sonnei and 6, 7, 8 years for dysentery caused by Sh. flexneri.