Dermacentor reticulatus: a vector on the rise.

Dermacentor reticulatus is a hard tick species with extraordinary biological features. It has a high reproduction rate, a rapid developmental cycle, and is also able to overcome years of unfavourable conditions. Dermacentor reticulatus can survive under water for several months and is cold-hardy even compared to other tick species. It has a wide host range: over 60 different wild and domesticated hosts are known for the three active developmental stages. Its high adaptiveness gives an edge to this tick species as shown by new data on the emergence and establishment of D. reticulatus populations throughout Europe. The tick has been the research focus of a growing number of scientists, physicians and veterinarians. Within the Web of Science database, more than a fifth of the over 700 items published on this species between 1897 and 2015 appeared in the last three years (2013-2015). Here we attempt to synthesize current knowledge on the systematics, ecology, geographical distribution and recent spread of the species and to highlight the great spectrum of possible veterinary and public health threats it poses. Canine babesiosis caused by Babesia canis is a severe leading canine vector-borne disease in many endemic areas. Although less frequently than Ixodes ricinus, D. reticulatus adults bite humans and transmit several Rickettsia spp., Omsk haemorrhagic fever virus or Tick-borne encephalitis virus. We have not solely collected and reviewed the latest and fundamental scientific papers available in primary databases but also widened our scope to books, theses, conference papers and specialists colleagues' experience where needed. Besides the dominant literature available in English, we also tried to access scientific literature in German, Russian and eastern European languages as well. We hope to inspire future research projects that are necessary to understand the basic life-cycle and ecology of this vector in order to understand and prevent disease threats. We conclude that although great strides have been made in our knowledge of the eco-epidemiology of this species, several gaps still need to be filled with basic research, targeting possible reservoir and vector roles and the key factors resulting in the observed geographical spread of D. reticulatus.

[The Omsk hemorrhagic fever: research results (1946-2013)].

The main aspects of epidemiology and epizootology of the Omsk hemorrhagic fever (OHF) are analyzed. The discovery of the virus OHF in 1947, as well as the first outbreak of new diseases in the districts of the Omsk region, is described. Comprehensive work for decryption of the etiology of the OHF by specialists from the Omsk and Moscow Institutes is carried out. Long-term dynamics of activity of natural foci of OHF contains four periods of variable intensity of epidemic and epizootic processes. The main reservoir of the virus OHF in natural foci and the source of human infection is muskrat. Metaxenosis provides maintaining of the population of the virus, which is of some significance for hosts. Independent position of the virus OHF in the group of the Flaviviruses of mammals transmitted by ticks is established. There are two aenovariants of the virus OHF.

Evaluation of the European tick-borne encephalitis vaccine against Omsk hemorrhagic fever virus.

This study focused on the antigenic cross-reactivity between tick-borne encephalitis virus (TBEV) and Omsk hemorrhagic fever virus (OHFV) to assess the efficacy of the commercial TBE vaccine against OHFV infection. Neutralization tests performed on sera from OHFV- and TBEV-infected mice showed that neutralizing antibodies are cross-protective. The geometric mean titers of antibodies against TBEV and OHFV from TBEV-infected mice were similar. However, the titers of anti-TBEV antibodies in OHFV-infected mice were significantly lower than those of anti-OHFV antibodies in the same animals. In mouse vaccination and challenge tests, the TBE vaccine provided 100% protection against OHFV infection. Eighty-six percent of vaccinees seroconverted against OHFV following complete vaccination, and the geometric mean titers of neutralizing antibodies against OHFV were comparable to those against TBEV. These data suggest that the TBE vaccine can prevent OHFV infection.

Comparative analysis of immune responses to Russian spring-summer encephalitis and Omsk hemorrhagic fever viruses in mouse models.

Omsk hemorrhagic fever virus (OHFV) and Russian spring-summer encephalitis virus (RSSEV) are tick-borne flaviviruses that have close homology but different pathology and disease outcomes. Previously, we reported that C57BL/6 and BALB/c mice were excellent models to study the pathology and clinical signs of human RSSEV and OHFV infection. In the study described here, we found that RSSEV infection induced robust release of proinflammatory cytokines (IL-1α, IL-1ß, IL-6 and TNF-α) and chemokines (MCP-1, MIP-1ß, RANTES and KC) in the brain at 9 and 11dpi, together with moderate to low Th1 and Th2 cytokines. In contrast, OHFV infection stimulated an early and prominent induction of IL-1α, TNF-α, IL-12p70, MCP-1, MIP-1α and MIP-1ß in the spleen of infected mice. Collectively our data suggest that a differential host response to infection may lead to the alternate disease outcomes seen following OHFV or RSSEV infection.

Omsk haemorrhagic fever.

Omsk haemorrhagic fever is an acute viral disease prevalent in some regions of western Siberia in Russia. The symptoms of this disease include fever, headache, nausea, severe muscle pain, cough, and moderately severe haemorrhagic manifestations. A third of patients develop pneumonia, nephrosis, meningitis, or a combination of these complications. The only treatments available are for control of symptoms. No specific vaccine has been developed, although the vaccine against tick-borne encephalitis might provide a degree of protection against Omsk haemorrhagic fever virus. The virus is transmitted mainly by Dermacentor reticulatus ticks, but people are mainly infected after contact with infected muskrats (Ondatra zibethicus). Muskrats are very sensitive to Omsk haemorrhagic fever virus. The introduction of this species to Siberia in the 1930s probably led to viral emergence in this area, which had previously seemed free from the disease. Omsk haemorrhagic fever is, therefore, an example of a human disease that emerged owing to human-mediated disturbance of an ecological niche. We review the biological properties of the virus, and the epidemiological and clinical characteristics of Omsk haemorrhagic fever.

Tick-borne virus diseases of human interest in Europe.

Several human diseases in Europe are caused by viruses transmitted by tick bite. These viruses belong to the genus Flavivirus, and include tick-borne encephalitis virus, Omsk haemorrhagic fever virus, louping ill virus, Powassan virus, Nairovirus (Crimean-Congo haemorrhagic fever virus) and Coltivirus (Eyach virus). All of these viruses cause more or less severe neurological diseases, and some are also responsible for haemorrhagic fever. The epidemiology, clinical picture and methods for diagnosis are detailed in this review. Most of these viral pathogens are classified as Biosafety Level 3 or 4 agents, and therefore some of them have been classified in Categories A-C of potential bioterrorism agents by the Centers for Disease Control and Prevention. Their ability to cause severe disease in man means that these viruses, as well as any clinical samples suspected of containing them, must be handled with specific and stringent precautions.

[Tick-borne human pathogenic microorganisms found in Europe and those considered nonpathogenic. Part I: Ticks and Viruses]. / Durch Zecken übertragene humanpathogene und bisher als apathogen geltende Mikroorganismen in Europa. Teil I: Zecken und Viren.

The importance of tick-borne encephalitis (TBE) and Lyme borreliosis-the main European tick-borne diseases-is steadily growing. This fact is due to many different factors including climate changes. However, across Europe many other human pathogenic viruses, bacteria, and parasites are found in ticks. This article gives an overview of tick-borne human pathogenic viruses present in Europe as well as those considered nonpathogenic. It also deals with the various species of vector-competent ticks. Among these ticks, viruses from 6 families encompassing 8 genera and 35 species are found,whereby the families Flaviviridae, Bunyaviridae, and Reoviridae with the genera flavivirus, nairovirus, and orbivirus are the most prevalent. Because of their special importance Omsk hemorrhagic fever, louping-ill disease, tick-borne encephalitis, and Crimean-Congo hemorrhagic fever are discussed in detail. Although West Nile virus is mainly transmitted to man by mosquitoes, it is discussed in detail, because West Nile fever has become a good example for a new and rapidly spreading vector-borne disease in the USA and for a recurrent one in Europe. Secondly, besides the mosquito-bird cycle an interesting tick--bird cycle is emerging. The overview clearly demonstrates that in Europe (particularly in Germany) tick-borne viruses, with the exception of TBE, constitute an extremely ignored research subject. This lack of attention is in contrast to their importance and results in a lack of necessary scientific data.

[Effectiveness of virazol, realdiron and interferon inductors in experimental Omsk hemorrhagic fever]. / Effektivnost' virazola, real'dirona i induktorov interferona pri éksperimental'noi omskoi gemorragicheskoi likhoradke.

Efficacy of drug therapy of Omsk hemorrhagic fever (OHF) was tested experimentally using cell culture and laboratory animals infected with the OHF virus strain Ondatra. Screening tests showed that high concentrations of Virazol or interferon inducers Larifan and Rifastin caused moderately pronounced suppression of virus reproduction in cell culture. Realdiron was found to be a high-efficacy preparation causing complete inhibition of virus reproduction in cell. Larifan demonstrated the highest antiviral efficacy against OHF virus in experiments with laboratory animals. This drug prevented the death of 65% infected mice and significantly decreased infection process severity in rabbits.

[Omsk hemorrhagic fever--current status of the problem]. / Omskaia gemorragicheskaia likhoradka, sovremennoe sostoianie problemy.

The author sums up the data on the history of discovery and research of Omsk hemorrhagic fever (OHF), comparative characteristics of its natural foci, and clinical features of epizootic and epidemic processes at the end of the 1940s and at present. Presents the modern concept of OHF virus ecology and discusses differences of its biological properties in the strains isolated from different sources. Based on analysis of many-year findings and major publications, the author offers a long-term epizootological and epidemic prognosis for OHF in endemic territories.

[The clinico-epidemiological characteristics of Omsk hemorrhagic fever in 1988-1992]. / Kliniko-épidemiologicheskaia kharakteristika Omskoi gemorragicheskoi likhoradki v period 1988--1992 gg.

Materials on morbidity in Omsk hemorrhagic fever at the period of 1988-1992 in the districts of the Novosibirsk region are presented. Cases of the disease were registered mainly in September-October (83.3% of cases). Transmission of the disease by contact played the leading role in the epidemiology of Omsk hemorrhagic fever. The disease took the course of medium severity with faintly pronounced hemorrhagic syndrome.

Nucleotide and deduced amino acid sequence of the envelope glycoprotein of Omsk haemorrhagic fever virus; comparison with other flaviviruses.

The gene encoding the envelope glycoprotein of Omsk haemorrhagic fever (OHF) virus was cloned and sequenced. A freeze-dried preparation of infected suckling mouse brain suspension was used as the source material for viral RNA. The derived cDNA was amplified using the polymerase chain reaction and the cloned DNA sequenced by dideoxynucleotide sequencing. Alignment of the OHF virus sequence with those of other known tick-borne flaviviruses showed that they shared N-glycosylation sites, cysteine residues, the fusion peptide and a hexapeptide (EHLPTA) that identifies tick-borne flaviviruses. OHF virus was distinguishable from the other viruses but shared closest amino acid identity (93.0%) with the tick-borne encephalitis viruses. A sequence of three amino acids (AQN; amino acids 282 to 234), which was previously shown to be specific for the tick-borne encephalitis viruses, was altered to MVG in OHF virus. This is predicted to have a higher hydrophobicity than the AQN sequence and may therefore have significant implications for the phenotypic characteristics of OHF virus. The results demonstrate close phylogenetic relationships between these viruses but also show their distinct evolutionary development. Sequence changes within the envelope glycoprotein of OHF virus have been identified that may be responsible for the distinct tropism of this flavivirus. These results support and enlarge upon previous data obtained from serological analysis.

Viral haemorrhagic fever in Sweden: experiences from management of a case.

The first recognized case in Scandinavia with potential man to man transmission of viral haemorrhagic fever occurred in Linköping, Sweden, in January 1990. Following a visit to Kenya a 21-year-old male student suffered a very severe illness including extremely prolonged high grade fever, rash, disseminated intravascular coagulation with thrombocytopenia and severe bleedings. This necessitated one month of intensive care support including respirator treatment. The patient was discharged after 2 1/2 months in good condition, with a partial femoral nerve paresis. About 100 medical personnel were exposed to aerosol or blood before a strict containment regimen was established. No secondary cases occurred.

[The typing of tick-borne encephalitis virus strains by the soluble antigen]. / Tipirovanie shtammov virusa kleshchevogo éntsefalita po rastvorimomu antigenu.

Sucrose-acetone-treated antigens (SAA) and soluble antigens (SA) prepared from them by treatment with 8 M urea for eight TBE virus strains isolated in different parts of the virus distribution area were studied in cross CFT with immune ascitic fluids (IAF) for these strains as well as for OHF and Powassan viruses. With SAA, the difference in titres with homologous and heterologous IAFs, as a rule, did not exceed twofold, whereas with SA was 32-fold. It was also noted that in the homologous system the titre of SA decreased not more than 4-fold as compared with that of the initial SAA while in the heterologous system it declined from 4- to 16-fold or more. The level of antigenic relationship of strains was expressed by the formula HAg = SA titre/SA titre X 100%. It was shown that at HAg greater than or equal to 25% the strains used for antigen and antibody generation were closely related and at HAg less than or equal to 6.25% belonged to different subtypes. The analysis of the data suggested the existence of a fourth, "Urals-Siberian" antigenic variant of TBE virus. Using the developed criteria, the 20 strains under study (with one exception) were alloted into one of the four antigenic variants or qualified as intermediate.

[Morphological study of Omsk hemorrhagic fever (OHF) virus with the electron microscope].

Morphological characterization of OHF virus was studied by means of thin section electron microscopy in the brains of mice infected with Omsk hemorrhagic fever virus. The crystals, microvesicles, vacuoles and as beehive structures were observed in the virus-infected cells. The possible relationship between the characteristic structures and virus morphogenesis is discussed. It is indicated that these characteristic structures may be important to morphological characterization of OHF virus.

Flavivirus vaccines.

Diseases caused by flavivirus infection have been a scourge of mankind for over three centuries; with yellow fever, dengue fever and Russian spring-summer encephalitis causing epidemics resulting in thousands of fatalities. Due to the development of a safe and efficacious live-attenuated vaccine against yellow fever, this disease is no longer such a threat in countries where adequate vaccination is practised. A similarly safe and efficacious inactivated vaccine against central-European tick-borne encephalitis has also been developed and this has drastically reduced the incidence of this disease in many countries where it is endemic. In spite of these successes, the development of vaccines against other pathogenic flaviviruses, causing diseases such as dengue fever and Russian spring-summer encephalitis, have not been successful. This review attempts to summarize the development of flavivirus vaccines to date and identify areas for future improvements. Problems associated with designing flavivirus vaccines are discussed and the advantages and disadvantages of future strategies for vaccine development are considered.