Most cited article - PubMed ID 19526924
Alimentary transmission of tick-borne encephalitis in the Czech Republic (1997-2008)
Matrix metalloproteinases (MMPs) play an important role in central nervous system infections. We analysed the levels of 8 different MMPs in the cerebrospinal fluid (CSF) of 89 adult patients infected with tick-borne encephalitis (TBE) virus and compared them with the levels in a control group. MMP-9 was the only MMP that showed significantly increased CSF levels in TBE patients. Serum MMP-9 levels were subsequently measured in 101 adult TBE patients at various time points during the neurological phase of TBE and at follow-up. In addition, serum MMP-9 was analysed in 37 paediatric TBE patients. Compared with control levels, both paediatric and adult TBE patients had significantly elevated serum MMP-9 levels. In most adult patients, serum MMP-9 levels peaked at hospital admission, with higher serum MMP-9 levels observed in patients with encephalitis than in patients with meningitis. Elevated serum MMP-9 levels were observed throughout hospitalisation but decreased to normal levels at follow-up. Serum MMP-9 levels correlated with clinical course, especially in patients heterozygous for the single-nucleotide polymorphism rs17576 (A/G; Gln279Arg) in the MMP9 gene. The results highlight the importance of MMP-9 in the pathogenesis of TBE and suggest that serum MMP-9 may serve as a promising bioindicator of TBE in both paediatric and adult TBE patients.
- Keywords
- Cerebrospinal fluid, Matrix matalloproteinase, Neuroinfection, Tick-borne encephalitis,
- MeSH
- Biomarkers MeSH
- Child MeSH
- Adult MeSH
- Polymorphism, Single Nucleotide MeSH
- Encephalitis, Tick-Borne * diagnosis cerebrospinal fluid MeSH
- Humans MeSH
- Matrix Metalloproteinase 9 genetics MeSH
- Encephalitis Viruses, Tick-Borne * genetics MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Biomarkers MeSH
- Matrix Metalloproteinase 9 MeSH
- MMP9 protein, human MeSH Browser
The aim of this review is to follow the history of studies on endemiv arboviruses and the diseases they cause which were detected in the Czech lands (Bohemia, Moravia and Silesia (i.e., the Czech Republic)). The viruses involve tick-borne encephalitis, West Nile and Usutu flaviviruses; the Sindbis alphavirus; Ťahyňa, Batai, Lednice and Sedlec bunyaviruses; the Uukuniemi phlebovirus; and the Tribeč orbivirus. Arboviruses temporarily imported from abroad to the Czech Republic have been omitted. This brief historical review includes a bibliography of all relevant papers.
- Keywords
- arthropods, birds, mammals, mosquitoes, ticks,
- MeSH
- Arbovirus Infections history MeSH
- Arboviruses physiology MeSH
- History, 20th Century MeSH
- History, 21st Century MeSH
- Humans MeSH
- Animals MeSH
- Check Tag
- History, 20th Century MeSH
- History, 21st Century MeSH
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Historical Article MeSH
- Review MeSH
- Geographicals
- Czech Republic epidemiology MeSH
Vaccination against tick-borne encephalitis (TBE) is based on the use of formalin-inactivated, culture-derived whole-virus vaccines. Immune response following vaccination is primarily directed to the viral envelope (E) protein, the major viral surface antigen. In Europe, two TBE vaccines are available in adult and pediatric formulations, namely FSME-IMMUN® (Pfizer) and Encepur® (GlaxoSmithKline). Herein, we analyzed the content of these vaccines using mass spectrometry (MS). The MS analysis revealed that the Encepur vaccine contains not only proteins of the whole virus particle, but also viral non-structural protein 1 (NS1). MS analysis of the FSME-IMMUN vaccine failed due to the high content of human serum albumin used as a stabilizer in the vaccine. However, the presence of NS1 in FSME-IMMUN was confirmed by immunization of mice with six doses of this vaccine, which led to a robust anti-NS1 antibody response. NS1-specific Western blot analysis also detected anti-NS1 antibodies in sera of humans who received multiple doses of either of these two vaccines; however, most vaccinees who received ≤3 doses were negative for NS1-specific antibodies. The contribution of NS1-specific antibodies to protection against TBE was demonstrated by immunization of mice with purified NS1 antigen, which led to a significant (p < 0.01) prolongation of the mean survival time after lethal virus challenge. This indicates that stimulation of anti-NS1 immunity by the TBE vaccines may increase their protective effect.
- Keywords
- NS1, flavivirus, tick-borne encephalitis, vaccination, vaccine,
- Publication type
- Journal Article MeSH
Tick-borne encephalitis (TBE) is a serious acute neuroinfection of humans caused by a tick-borne flavivirus. The disease is typically seasonal, linked to the host-seeking activity of Ixodes ricinus (predominantly nymphs), the principal European tick vector species. To address the need for accurate risk predictions of contracting TBE, data on 4,044 TBE cases reported in the Czech Republic during 2001-2006 were compared with questing activity of I. ricinus nymphs monitored weekly at a defined location for the same 6-year period. A time shift of 21 days between infected tick bite and recorded disease onset provided the optimal model for comparing the number of cases of TBE with numbers of questing nymphs. Mean annual distribution of TBE cases and tick counts showed a similar bimodal distribution. Significantly, the ratio of TBE cases to questing nymphs was highest in the summer-autumn period even though the number of questing nymphs peaked in the spring-summer period. However, this pattern changed during a period of extreme meteorological events of flooding and abnormally high temperatures, indicating that changes in climate affect the incidence of TBE. Previous studies failed to link human behavior with changes in incidence of TBE but showed extrinsic temperature impacts arbovirus replication. Hence, we hypothesize the apparent discrepancy between peak nymphal tick activity and greatest risk of contracting TBE is due to the effect of temperature on virus replication in the tick vector. Relative proportions of questing nymphs and the numbers of weeks in which they were found were greater in summer-autumn compared with spring-summer at near-ground temperatures >5°C and at standard day and weekly average temperatures of >15°C. Thus, during the summer-autumn period, the virus dose in infected tick bites is likely greater owing to increased virus replication at higher microclimatic temperatures, consequently increasing the relative risk of contracting TBE per summer-autumn tick bite. The data support the use of weather-based forecasts of tick attack risk (based on daytime ambient temperature) supplemented with weekly average temperature (as a proxy for virus replication) to provide much-needed real-time forecasts of TBE risk.
- Keywords
- Ixodes ricinus, TBEV, arbovirus, climate change, seasonality, tick-borne encephalitis,
- MeSH
- Arachnid Vectors physiology virology MeSH
- Incidence MeSH
- Ixodes physiology virology MeSH
- Encephalitis, Tick-Borne epidemiology transmission virology MeSH
- Humans MeSH
- Weather MeSH
- Seasons MeSH
- Temperature MeSH
- Encephalitis Viruses, Tick-Borne genetics isolation & purification physiology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic epidemiology MeSH
UNLABELLED: This study of 170 children in the Czech Republic examines the clinical course and sequelae for tick-borne encephalitis. Evaluated were demographic and epidemiological data, signs and symptoms at admission, clinical course during hospital stay and laboratory findings. Cerebrospinal fluid was analysed for white blood cells, protein, impairment of blood-cerebrospinal fluid (CSF) barrier and tick-borne encephalitis virus (TBEV)-specific antibodies. Subjective complaints and objective neurological deficits were investigated. Tick bites were reported in 74 % of the children. The illness had a biphasic clinical course in 58 % of cases. The second phase was characterized by headache in 98 %, high fever in 86 % (more than 38.5 °C), vomiting in 64 % and meningeal signs in 92 % of children. Meningitis (77 %) dominated over meningoencephalitis (13 %). Inflammatory changes in CSF were found in 90 % of children. Immunoglobulin M (IgM) antibodies against TBEV in serum were found early in the infection in 99 %. IgM positivity lasted up to 1,126 days. Neurocognitive abnormalities were found in 19 (11 %) of children. Acquired aphasia, lasting tremor of the upper extremities, speech impairment, inversion of sleep and wakefulness, abnormal hyperkinetic movements and vertigo were found to be permanent but not progressing. Severe sequelae persisted in two children (1 %) while in three (2 %) were classified as mild or moderate. CONCLUSION: Tick-borne encephalitis in children has a benign course with minimal sequelae. Meningitis with biphasic course is the prevalent involvement and the duration of IgM antibodies in serum and index of positivity are not decisive for postencephalitic disorders.
- MeSH
- Child MeSH
- Enzyme-Linked Immunosorbent Assay MeSH
- Immunoglobulin G blood MeSH
- Immunoglobulin M blood MeSH
- Encephalitis, Tick-Borne cerebrospinal fluid diagnosis MeSH
- Infant MeSH
- Comorbidity MeSH
- Humans MeSH
- Adolescent MeSH
- Child, Preschool MeSH
- Antibodies, Viral blood MeSH
- Encephalitis Viruses, Tick-Borne immunology MeSH
- Check Tag
- Child MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
- Names of Substances
- Immunoglobulin G MeSH
- Immunoglobulin M MeSH
- Antibodies, Viral MeSH
In the Czech Republic, the incidence of human tick-borne encephalitis (TBE) has been increasing over the last two decades. At the same time, populations of game have also shown an upward trend. In this country, the ungulate game is the main host group of hosts for Ixodes ricinus female ticks. This study examined the potential contribution of two most widespread game species (roe deer [Capreolus capreolus] and wild boar [Sus scrofa]) to the high incidence of TBE in the Czech Republic, using the annual numbers of culls as a proxy for the game population. This was an ecological study, with annual figures for geographical areas-municipalities with extended competence (MEC)-used as units of analysis. Between 2003 and 2011, a total of 6213 TBE cases were reported, and 1062,308 roe deer and 989,222 wild boars were culled; the culls of roe deer did not demonstrate a clear temporal trend, but wild boar culls almost doubled (from 77,269 to 143,378 per year). Statistical analyses revealed a positive association between TBE incidence rate and the relative number of culled wild boars. In multivariate analyses, a change in the numbers of culled wild boars between the 25th and 75th percentile was associated with TBE incidence rate ratio of 1.23 (95% confidence interval 1.07-1.41, p=0.003). By contrast, the association of TBE with culled roe deer was not statistically significant (p=0.481). The results suggest that the size of the wild boar population may have contributed to the current high levels and the rising trend in incidence of TBE, whereas the regulated population of roe deer does not seem to be implicated in recent geographical or temporal variations in TBE in the Czech Republic.
- Keywords
- Game, Incidence, Roe deer, Tick-borne encephalitis, Wild boar,
- MeSH
- Arachnid Vectors virology MeSH
- Animals, Wild MeSH
- Incidence MeSH
- Tick Infestations epidemiology veterinary virology MeSH
- Ixodes virology MeSH
- Encephalitis, Tick-Borne epidemiology virology MeSH
- Humans MeSH
- Swine Diseases epidemiology virology MeSH
- Statistics, Nonparametric MeSH
- Swine MeSH
- Sus scrofa virology MeSH
- Encephalitis Viruses, Tick-Borne isolation & purification MeSH
- Deer virology MeSH
- Geography MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic epidemiology MeSH