Tick-borne encephalitis: A 43-year summary of epidemiological and clinical data from Latvia (1973 to 2016).

BACKGROUND: The incidence of tick-borne encephalitis (TBE) varies significantly over time. To better understand the annual incidence of all TBE cases in Latvia we investigated the disease burden in the country from 1973-2016 using several available sources and case definitions. METHODS: We identified cases of TBE from an electronic database (maintained by the Centre for Disease Prevention and Control of Latvia [CDPC]) by the use of ICD-10 diagnosis codes for TBE (A84; A84.0; A84.1; A84.8; A84.9). In addition, previously unreported TBE cases were found by review of TBE diagnoses according to ICD-10 codes in four hospital databases. RESULTS: From 1973 to 2016 a total of 15,193 TBE cases were reported to the CDPC, 2,819 of which were reported from January 2007 through December 2016, additionally for this time period, 104 cases were identified via hospital survey. From all 2,923 reported cases (2007-2016), 1,973 met TBE case definition criteria and were included in the TBE study analysis. The highest average 10 year incidence was observed from 1990-1999 (27.9 cases per 100,000; range 4.6-53.0), however, the average 10-year incidence from 2007-2016 using officially adopted TBE case definition was 9.6 cases per 100,000 (range 5.8-14.6). For this 10-year time period most cases were adults (95.1%) and male (52.2%). The most common clinical form of TBE was meningitis (90.6%). A tick bite prior to TBE onset was reported in 60.6% of TBE cases and 98.2% of cases were not vaccinated against TBE. CONCLUSION: The data demonstrate that the incidence of TBE varies by about one third based on the case definition used. TBE occurs almost entirely in the unvaccinated population. Regular TBE awareness campaigns could encourage the population in Latvia to use protective measures to further control TBE in the country, either via vaccination or tick avoidance.

More than 20 years after re-emerging in the 1990s, diphtheria remains a public health problem in Latvia.

In 1994, the World Health Organization (WHO) declared the goal of eliminating diphtheria within the WHO European Region by the year 2000. However, in 1990 an epidemic emerged within the Russian Federation and spread to other countries, including Latvia, by 1994. We describe national surveillance and immunisation coverage data in Latvia from 1994 to 2014 and present historical data from 1946. We defined a laboratory-confirmed case as a clinical case in which toxin-producing Corynebacterium diphtheriae, C. ulcerans or C. pseudotuberculosis was isolated. From 1994 to 2014, 1,515 cases were reported, giving an average annual incidence of 3.2 cases per 100,000 inhabitants (range 0.1-14.8), with the highest incidence in age groups 5-19 and 40-49 years (4.4 and 4.3/100,000, respectively); 111 deaths were reported, 83.8% cases were laboratory-confirmed. Most cases occurred in unvaccinated adults. To improve disease control a supplementary immunisation campaign for adults was initiated in 1995, and by the end of 1998 national coverage among adults reached 70%, and reached 77% in 2003, but declined to 59% by 2014. Diphtheria remains a problem in Latvia with continued circulation of toxin-producing strains of C. diphtheriae. We recommend to strengthen immunisation to cover adults, as well as the education of health professionals and a serological survey.

Immunogenetic Markers Definition in Latvian Patients with Lyme Borreliosis and Lyme Neuroborreliosis.

The aim of this study was to determine the human leukocyte antigen (HLA)-DRB1 alleles in two groups of patients in Latvia: patients with Lyme borreliosis and patients with Lyme neuroborreliosis. The study included 216 patients with Lyme borreliosis, 29 patients with Lyme neuroborreliosis and 282 control persons. All surveyed persons were residents of Latvia. The HLA-DR genotyping was performed by polymerase chain reaction- sequence specific primer (PCR-SSP). The predisposition to the Lyme borreliosis is associated with the HLA-DRB1*07, -DRB1*17(03), -DRB1*04, -DRB1*15(02) alleles. The allele -DRB1*11(05), -DRB1*14(06) and -DRB1*13(06) were significantly more frequent in controls. In-group with Lyme neuroborreliosis differences were found for the -DRB1*07 and -DRB1*04 alleles, but only HLA-DRB1*07 allele was statistically significant after Bonferroni correction and associated with Lyme neuroborreliosis in Latvian patients.

Legionella pneumophila Seropositivity-Associated Factors in Latvian Blood Donors.

Continuous environmental exposure of humans to Legionella may induce immune responses and generation of antibodies. The aim of this study was to investigate the seroprevalence of Legionella pneumophila serogroups (SG) 1-6 in the general healthy population and identify the associated host-related and environmental risk factors. L. pneumophila SG 1-6 seroprevalence among a total of 2007 blood samples collected from healthy donors was 4.8%. Seroprevalence was higher in women (5.9%) than men (3.3%) and in areas with a larger number of inhabitants, ranging from 3.5% in rural regions to 6.8% in the capital, Riga. Blood samples from inhabitants of apartment buildings tested positive for L. pneumophila in more cases (5.8%) compared to those from inhabitants of single-family homes (2.7%). Residents of buildings with a municipal hot water supply system were more likely to be seropositive for L. pneumophila (OR = 3.16, 95% CI 1.26-7.91). Previous episodes of fever were additionally identified as a risk factor (OR = 2.42, 95% CI 1.43-4.1). In conclusion, centralized hot water supply, female gender and previous episodes of fever were determined as the main factors associated with L. pneumophila seropositivity in our study population.

Associations of HLA DR and DQ molecules with Lyme borreliosis in Latvian patients.

BACKGROUND: Many autoimmune diseases are associated with variants of HLA genes such as those encoding the MHC complex. This correlation is not absolute, but may help in understanding of the molecular mechanism of disease. The purpose of this study was to determine HLA-DR,-DQ alleles in Latvian patients with Lyme borreliosis and control (healthy) persons. Case patients and control subjects were similar in age, gender and ethnic heritage and differed only as regards the presence of Borrelia burgdorferi infection. The study included 25 patients with clinical stage - erythema migrans and 30 control (healthy) persons. HLA genotyping was performed by PCR with sequence-specific primers. RESULTS: The results show difference in HLA-DRB1 alleles distribution between patients and control subjects. The frequencies of HLA-DRB1 *04 (OR 11.24; p < 0.007) and HLA-DRB1 *17 (03) (OR 8.05; p < 0.033) were increased in the Lyme disease patients. And the frequency of allele DRB1*13 (OR 0.12; p < 0.017) was lower in Borreliosis patients and higher in control group. But, significant differences in frequencies of HLA-DQ alleles we did not detect. CONCLUSIONS: HLA predisposition to Lyme borreliosis appears not to be limited to HLA molecules, but some HLA-DR alleles also have a significant influence, and, may have implications in our understanding of pathogenesis of this disease. In particular, HLA-DRB1*04 and DRB1 *17 (03) may contribute to the Lyme borreliosis development in Latvian population.

Diphtheria in the postepidemic period, Europe, 2000-2009.

Diphtheria incidence has decreased in Europe since its resurgence in the 1990s, but circulation continues in some countries in eastern Europe, and sporadic cases have been reported elsewhere. Surveillance data from Diphtheria Surveillance Network countries and the World Health Organization European Region for 2000-2009 were analyzed. Latvia reported the highest annual incidence in Europe each year, but the Russian Federation and Ukraine accounted for 83% of all cases. Over the past 10 years, diphtheria incidence has decreased by >95% across the region. Although most deaths occurred in disease-endemic countries, case-fatality rates were highest in countries to which diphtheria is not endemic, where unfamiliarity can lead to delays in diagnosis and treatment. In western Europe, toxigenic Corynebacterium ulcerans has increasingly been identified as the etiologic agent. Reduction in diphtheria incidence over the past 10 years is encouraging, but maintaining high vaccination coverage is essential to prevent indigenous C. ulcerans and reemergence of C. diphtheriae.

Behavioural responses to perceived risk of tick-borne encephalitis: vaccination and avoidance in the Baltics and Slovenia.

Tick-borne encephalitis (TBE) incidence increased markedly in the Baltics and Slovenia in the early 1990s, but then declined again in some places. Our analyses of temporal and spatial data on TBE incidence and vaccination revealed that over 1970-2005 up-take of vaccination varied in both time and space according to incidence, i.e. was apparently responsive to perceived risk. Since 1999, however, decreases in incidence in many counties within each country have far exceeded vaccination rates or immunity through natural exposure, and in Latvia and Lithuania these changes are correlated with previous incidence. Survey data on human activities in Latvia revealed that people in socio-economic groups whose behaviour put them at highest risk of exposure to ticks in forests, including people with lower education and lowest incomes, are least likely to be vaccinated. We conclude that risk avoidance through changing human behaviour has driven incidence-dependent decreases in TBE infection, but targeted vaccination campaigns could provide more secure protection.

Tick-borne encephalitis in the Baltic States: identifying risk factors in space and time.

This paper presents preliminary results in our investigations of the biological (abiotic and biotic) and non-biological causes of the spatial heterogeneity and temporal change of tick-borne encephalitis (TBE), both within and between Estonia, Latvia, and Lithuania. Spatial analysis revealed that the land cover and precise seasonal patterns of climatic indices (temperature and normalized difference vegetation index) can explain 55% of the observed spatial variation in TBE incidence over the period 1993-98 across all the Baltic States. Temporal analysis of climatic variables indicates a very specific change in spring temperature conditions from 1993 onwards that could enhance the transmission of TBE virus. Further time series analysis of climate, together with analysis of biotic factors, socio-economic conditions, and human behaviour is being undertaken to explain the epidemiological patterns more fully.

Tick-borne encephalitis in childhood--consensus 2004.

Tick-borne encephalitis (TBE) is a communicable disease caused by a flavi-virus, ticks being the main vectors. The nervous system is affected, four clinical features of different severity are observed: meningitis, meningoencephalitis, meningoencephalomyelitis, meningoradiculoneuritis. TBE is a preventable disease, which is rapidly becoming a growing public health problem in Europe. So far no causal treatment is possible but an efficient, safe vaccination is available. During the 6th meeting of the International Scientific Working Group on TBE with the main conference issue "Tick-borne encephalitis in childhood" an international consensus was achieved. In countries where TBE is endemic--and not prevented by immunization--both children and adults are affected. The disease in children is generally milder, although severe illness may occur and even lead to permanent impairment of the quality of life due to neuropsychological sequelae. Therefore immunization should be offered to all children living in or traveling to endemic areas.

Vectors of tick-borne diseases and epidemiological situation in Latvia in 1993-2002.

During the period of 1993-2002 an increase and the remarkable changes in the incidence of tick-borne encephalitis (TBE) and Lyme borreliosis (LB) as well as annual activities of vector species were noticed. The highest increase of TBE morbidity in Latvia has been observed in 1994 and 1995, and less expressed also in 1998 which was followed by a significant decrease during subsequent years. Whereas the highest peak of LB morbidity has been noticed in 1998 with only a minor decrease during subsequent years. Two epidemiologically significant Ixodes tick species are common in Latvia. Ixodes ricinus L. spread in the western and central part of Latvia; but rarely and in small numbers also in the eastern part. Ixodes persulcatus P. Sch. seems to dominate only in the eastern part of the country. The changes of seasonal and annual activities of I. ricinus were observed in two types of monitoring sites--sylvatic and peridomestic, located in the central part of Latvia. Observations of I. persulcatus were made in the eastern districts. Comparing geographically the Tick-borne diseases (TBD) incidence data for three tick distribution regions (I. ricinus dominated, I. persulcatus dominated and mixed regions), it was observed that the trend of annual changes in LB incidence during the last decade is almost of the same kind for all regions. Whereas TBE incidence extremes in 1994 and 1995 were observed almost only in I. ricinus dominated region. The annual field-collected adult tick infection rate with TBE virus (TBEV) from 1993 to 2002 for I. ricinus adults varied between 1.7% and 26.6% and for I. persulcatus--between 0% and 37.3%. The infection level in ticks removed from humans was much higher and from 1998 to 2002 surpassed 30%. TBEV investigations of removed adults and nymphs in 2002 discovered a high TBEV prevalence also in I. ricinus nymphs (43%). Typing of TBE virus isolated from ticks and patient serum samples in collaboration with German and Swedish virologists revealed that all three TBEV subtypes were co-circulating in Latvia. The mean annual tick infection rate with Borrelia burgdorferi s.l. analysed by means of a nested polymerase chain reaction of OspA gene fragment during the period of 1999-2001 was 18%-38% for I. ricinus adults and 25%-51% for I. persulcatus adults. Typing of Borrelia-positive DNA samples indicated that B. afzelii was dominant in Borrelia-positive I. ricinus (64.9%) and I. persulcatus (81.2%) followed by B. garinii (I. ricinus: 24.3%; in I. persulcatus: 14.5%). Investigations of Ehrlichia phagocytophila genogroup (by nested PCR targeted the 16S rRNA gene) revealed the presence of Ehrlichia sp. in I. ricinus from the central part of Latvia. Obtained data on TBD vectors and the epidemiological situation during the last decade indicates the complex impact of different factors influencing TBE and LB morbidity in Latvia.