Spatiotemporal changes in the incidence of tick-borne encephalitis in the Kirov region over a thirty-year period

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Introduction

Currently, cases of tick-borne encephalitis (TBE) are officially registered in 29 European countries and 6 Asian countries. In Russia, the overwhelming majority of cases of TBE are registered in three federal districts: Siberian, Ural, and Volga [1]. The Kirov Region is an active natural focus of this disease. The modern definition of the term "natural focus" is a geographically specific region where populations of disease pathogens along with all the biotic and abiotic components of ecosystems that support their existence [2]. The Kirov Region is part of the Ural-West Siberian province of the Eurasian taiga (coniferous forest) region, situated in the Kamsk-Pechora-West Siberian subprovince. In accordance with the vegetation zones, the region is divided as follows: the northern part of the region is located within the middle taiga zone, the central part within the southern taiga zone, and the southern part within the mixed coniferous-broadleaf forest zone.

The climate of the Kirov Region is classified as continental temperate. In the region, there are vertebrates typical of the forest zone, which serve as hosts for ixodid ticks, carriers of the TBE virus. Animals form zoocenoses closely associated with the biocenoses of natural and anthropogenic landscapes. The main carriers of tick-borne encephalitis in the Kirov Region are ixodid ticks of two genera: Ixodes persulcatus (taiga tick) and Dermacentor reticulatus (meadow tick). Taiga ticks are the dominant species.

For the first time, TBE was mentioned in the Kirov territory in the mid-20th century (Fig. 1). In most cases (60%), people became infected by consuming unboiled goat's milk. The concentration of goat herds in private farms during that period was noted in the southern part of the region in the zone of coniferous-broadleaf forests, which is why the leaders in terms of TBE incidence were the Malmyzhsky, Kilmezsky, and Urzhumsky districts [3]. In the 1970s and 1980s, the DDT insecticide was actively used in the forested areas of the region, which led to a sharp decrease in the incidence of TBE. In the 1990s, there was a sharp increase in the number of infection cases. This fact is explained by the ban on the use of this insecticide. In the 21st century, the incidence of TBE remained at a high level, fluctuating between 2.6 and 18.5 per 100,000 population. Cases of TBE were registered in all districts of the Kirov Region and in the regional center, the city of Kirov. The main route of TBE infection has become transmissible. However, the change in the temporal and spatial configuration of the natural focus of TBE is due not only to historical fluctuations related to the use of insecticides but also to long-term climate trends, changes in land use structure, and main transmission routes, which have led to the redistribution and formation of new foci of infection activity and changes in the epidemiological profile of the region.

 

Fig. 1. The incidence of TBE (number of cases per 100,000 population) in the Kirov Region in 1965–2023.

 

This is evidenced by the change in the geography of registered cases of TBE, which is particularly pronounced in the regions of the European North of Russia [4, 5] and in certain countries of Northern Europe [6]. The emergence of new foci of TBE or the redistribution of the intensity of the epidemiological process within already existing ones can pose a serious problem for public health. This will require the implementation of new approaches to the diagnosis, treatment, and prevention of a disease that was previously rare or atypical for this area.

The study of the epidemiology of TBE in the Kirov Region has been ongoing for a long time [3, 7], however, against the backdrop of changing ecological and epidemiological conditions (landscape transformation, change in the dominant transmission route, climate warming), the understanding of the boundaries, structure, and intensity of the TBE focus in the region cannot be static. The lack of systematic data on the long-term spatiotemporal dynamics of the natural focus of TBE in the Kirov Region hinders accurate epidemiological forecasting and reduces the effectiveness of planning anti-epidemic measures.

The aim of this study is to identify the spatiotemporal characteristics of TBE incidence in the Kirov Region over a 30-year period (1994–2023).

Materials and methods

The methodological basis of the study consisted of epidemiological analysis and statistical research methods. The primary information on the incidence of TBE was obtained from the official registers of infectious disease accounting of the Territorial Administration of Rospotrebnadzor for the Kirov Region. The calculation of the incidence rates of TBE (number of cases per 100,000 population) by administrative districts of the Kirov region was carried out using demographic data from the Territorial Body of the Federal State Statistics Service for the Kirov Region for each year of the study period according to the formula:

$Average incidence of TBE = \frac{\overline{TBE}}{\overline{S_{pop}}} \times 100,000,$

where $\overline{TBE}$ — average annual number of TBE cases (the ratio of the total number of TBE cases for the period to the number of years in the period); $\overline{S_{pop}}$ — average population over a 10-year period.

In accordance with the administrative-territorial division, the Kirov Region includes 39 municipal districts and the regional center, the city of Kirov. For the analysis of the spatial distribution of TBE incidence, the districts were grouped by vegetation zones: 11 districts were included in the middle taiga zone, 14 districts and the city of Kirov in the southern taiga zone, and 14 districts in the coniferous-broadleaf forest zone (Fig. 2).

 

Fig. 2. Division of the territory of the Kirov Region by vegetation zones.

1 — middle taiga zone; 2 — southern taiga zone; 3 — coniferous-broadleaf forest zone.

 

Considering the presence of districts in the Kirov Region with a population of up to 10,000 population and extremely low absolute rates of TBE incidence, the administrative units have been consolidated. Some neighboring districts belonging to the same vegetation zone were grouped together. As a result, instead of 39 administrative units, 27 groups of districts (hereinafter referred to as consolidated districts) have been formed, with 9 groups in each vegetation zone and a minimum population of at least 20,000 people in each group.

For the analysis of temporal dynamics, the 30-year observation period is divided into three 10-year periods: 1994–2003, 2004–2013, and 2014–2023.

Statistical data processing was carried out using the software packages MS Excel 19 and Statistica 10.0. The statistical hypothesis tests were conducted at a significance level of 0.05.

The step-by-step algorithm for statistical analysis is as follows:

1. Identification of the trend and seasonal component of TBE incidence in the Kirov Region using the analysis of the autocorrelation function of the time series.
2. Testing the hypothesis of normality of the distribution of the intensive incidence rate of TBE (number of cases per 100,000 population) in the Kirov Region for each year from 1993 to 2023 using the Shapiro–Wilk test.
3. Comparison of the intensity of TBE incidence between aggregated districts of different vegetation zones in each of the three 10-year periods using the Kruskal-Wallis test.
4. Identification of statistically significant changes in the intensive level of TBE incidence in each vegetation zone thru pairwise comparisons of 10-year period indicators using the Wilcoxon criterion.
5. Assessment of the relationship between the initial level of TBE incidence in the vegetation zones of the Kirov Region and the direction of its change using Spearman's rank correlation coefficient.

Results

The territory of the Kirov Region is an active natural focus of TBE. Over the past 30 years, between 35 and 310 cases of the disease have been registered annually (Fig. 3).

 

Fig. 3. Dynamics of TBE cases in the Kirov Region as a whole and in the city of Kirov.

 

To assess the nature of the dynamics of TBE incidence, an analysis of the autocorrelation function of the time series was conducted. The analysis of the first-order autocorrelation coefficient did not reveal a statistically significant relationship (p > 0.05), indicating the absence of a pronounced long-term trend. In this regard, the analysis of the epidemiological situation over the entire 30-year period (1994–2023) appears to be uninformative due to the high annual variability of the indicators. To smooth out random fluctuations and identify stable patterns, the method of interval aggregation was applied. When choosing the duration of the intervals, it was taken into account that it is usually determined by the period of the identified cyclical or seasonal fluctuations. However, the examination of the second and higher-order autocorrelation coefficients also did not reveal a statistically significant periodic component (p > 0.05). In the absence of both trend and seasonal components, the 30-year observation period was divided into three decadal intervals (1994–2003, 2004–2013, and 2014–2023).

The Kirov Region is a large region located in the northeast of the Russian Plain, with an area of 120.4 thousand km². In the center of the region, there is an urban agglomeration consisting of the regional center, the city of Kirov, and satellite towns, around which a significant area is occupied by citizens' garden and summer cottage plots, cemeteries, and places for the active recreation of urban residents. About half of the entire population of the Kirov region lives in the Kirov agglomeration — approximately 500,000 people (the population of the region is 1,120,000 people). Information on the number of cases of TBE registered in the city of Kirov is presented in Fig. 4. A significant (at the 5% significance level) direct (positive) correlation (r = 0.855; p <  0.0001) has been established between the number of diseases in Kirov and the overall Kirov Region. Thus, the overall picture in the Kirov Region is largely determined by the situation in the city of Kirov. Further analysis of the dynamics of TBE incidence in the Kirov Region is presented without the number of cases in the city of Kirov.

 

Fig. 4. Distribution of TBE cases in the Kirov Region depending on vegetation zones.

 

Considering the extent of the Kirov region from north to south (570 km), from west to east (440 km), and its location in 3 vegetation zones, an analysis of the dynamics of TBE cases depending on this factor was conducted (Fig. 5).

 

Fig. 5. Dynamics of the TBE incidence rate (number of TBE cases per 100,000 population) in the Kirov Region in different vegetation zones.

 

A statistically significant direct (positive) correlation was found between the number of TBE cases in the Kirov Region and the number of cases in the middle taiga zones (r = 0.728; p <  0.0001) and the southern taiga (r = 0.779; p <  0.0001), whereas in the broadleaf-coniferous forest zone, the direct (positive) correlation was statistically insignificant (r = 0.149; p = 0.1827). This justified the feasibility of analyzing the dynamics of the TBE disease pattern not by the region as a whole, but by vegetation zones.

Table 1 presents absolute and intensive indicators characterizing the epidemiological situation of TBE in the Kirov Region depending on the vegetation zone for the years 1994–2023.

 

Table 1. Absolute and intensive incidence TBE rates in Kirov Region by vegetation zones for the years 1994–2023

Indicator	Period, years	Middle taiga zone	Southern taiga zone	Coniferous-broadleaf forest zone	Kirov city	Kirov region
Average annual number of TBE cases	1994–2003	45.4	16.6	17.5	25.6	98.7
	2004–2013	33.3	29.9	7.4	37.6	102.2
	2014–2023	30.2	40.3	2.9	52.7	118
Average human population	1994–2003	313,040	348,943	329,206	503,043	1,494,232
	2004–2013	256,695	299,465	270,624	498,381	1,325,165
	2014–2023	204,701	230,530	201,719	496,941	1,133,891
The incidence rate of TBE (per 100,000 population)	1994–2003	14.50	4.76	5.32	5.09	6.61
	2004–2013	12.97	9.98	2.73	7.54	7.71
	2014–2023	14.75	17.46	1.44	10.60	10.41

 

The intensive incidence indicators of TBE allow for a comparative assessment of the epidemiological situation in different vegetative zones of the Kirov Region, as well as the identification of common patterns in the dynamics of the epidemic process. The comparison was conducted across 27 consolidated districts in 3 vegetation zones (9 groups in each zone).

To select statistical criteria for comparing the intensity of TBE incidence indicators in different vegetation zones and analyzing its dynamics, an assessment of the data distribution was conducted. The hypothesis test for the normality of the distribution of the intensity indicators of TBE incidence across the consolidated districts of the Kirov Region for each 30-year observation period was conducted using the Shapiro-Wilk test. Over all the years of the study, the distribution of the intensive level of TBE incidence significantly differed from normal (p <  0.0001). In this regard, for further comparative analysis and assessment of the dynamics of incidence, non-parametric methods that do not require the assumption of normality of distribution were used.

To compare the intensity of TBE incidence levels between consolidated districts classified into different vegetation zones, the Kruskal-Wallis non-parametric test was used. It was found that the intensity levels of TBE incidence in different vegetative zones of the Kirov Region significantly differed in each of the three 10-year periods: (p = 0.0419 in 1994–2003, p = 0.0071 in 2004–2013, and p = 0.0008 in 2014–2023). The obtained data confirm that the division of the Kirov territory into vegetation zones is methodologically justified for the spatial analysis of the epidemiological situation of TBE.

To assess statistically significant changes in the intensity of TBE incidence between consecutive 10-year periods, the non-parametric Wilcoxon signed-rank test was applied, which is designed to compare two dependent groups with a distribution different from normal. Different dynamics of the epidemic process were identified in different vegetation zones of the Kirov Region (Table 2).

 

Table 2. Comparison of the TBE incidence rates (number of cases per 100.000 population) in the Kirov Region across different vegetation zones over time (1994–2023). Ме [Q₁; Q₃]

Vegetation zone	1994–2003	2004–2013	2014–2023
Middle taiga zone (n = 9)	20.2 [4.43; 28.53]	12.5 [9.80; 34.41]	24.4 [9.70; 26.63]
South taiga zone (n = 9)	3.5 [0.44; 8.02]	8.6* [5.11; 18.66]	11.5+ [4.90; 31.60]
Coniferous-broadleaf forest zone (n = 9)	3.7 [1.29; 12.77]	2.1 [1.33; 5.83]	0.7 [0.51; 3.26]

Note. *p <  0.05 compared to 1994–2003. ⁺p <  0.05 compared to 2004–2013.

 

In the middle taiga zone, the median indicator showed a wave-like dynamic. However, these fluctuations are not statistically significant. The wide interquartile range indicates high inter-district variability and the maintenance of unstable and high epidemic tension in this area.

In the southern taiga zone, a reliable increase in the intensive incidence rate of TBE is observed. The widening of the interquartile range indicates an increase in the uneven distribution of TBE and the formation of new local disease foci.

In the coniferous-broadleaf forest zone, a statistically significant downward trend has been identified. After a slight decrease in the second decade, the intensive incidence rate of TBE in the third decade significantly decreased. At the same time, the narrowing of the interquartile range indicates a leveling of the situation between districts and the stabilization of the epidemic process in this area.

The epidemiological situation regarding TBE in Kirov Region is characterized by divergent dynamics: from stable growth in the southern taiga zone to a pronounced decline in the coniferous-broadleaf forest zone, while maintaining high variability in the middle taiga zone.

To assess the relationship between the initial level of TBE incidence and the direction of its change, the Spearman rank correlation coefficient r_S was used, applicable for analyzing data with a distribution different from normal.

The consolidated districts of the Kirov Region by the level of TBE incidence were divided into 3 groups:

• low level of TBE incidence — up to 5.0 per 100,000 population;
• medium level of TBE incidence — from 5.0 to 15.0 per 100,000 population;
• high level of TBE incidence — more than 15.0 per 100,000 population.

A significant inverse (negative) correlation has been identified between the initial level of TBE incidence in 1994–2003 and its change in 2004–2013 (r_S = –0.39; p <  0.05). This means that in consolidated areas with initially low incidence rates, a statistically significant decrease was observed from 2004 to 2013. Conversely, in the favorable areas, a significant deterioration of the epidemiological situation is observed. Thus, there is a redistribution of the intensity of the epidemiological process in the northern and central districts of the Kirov Region, which are located in the southern and northern taiga zones (Fig. 6).

 

Fig. 6. The TBE incidence by districts of the Kirov Region in 1994–2003 and the direction of its change in 2004–2013.

Circles — the level of TBE incidence in 1994–2003: green — low; yellow — medium; red — high. Arrows — increase or decrease in the TBE incidence in 2004 - 2013: green — decrease; red — increase.

 

A weak inverse (negative) correlation was identified between the initial level of TBE incidence in 2004–2013 and its change in 2014–2023, which is not statistically significant. This indicates that in the last decade of observation, the "regression to the mean" pattern characteristic of the previous decade has ceased to manifest. In areas with a high incidence rate from 2004–2013, no systematic decrease in indicators was observed, and in favorable areas, no significant deterioration in the epidemiological situation was recorded (Fig. 7). This may indicate the stabilization of the epidemiological process of TBE and the formation of new patterns of territorial distribution of incidence that are not related to its initial level.

 

Fig. 7. The TBE incidence by districts of the region in 2004–2013 and the direction of its change in 2014–2023.

Circles — the level of TBE incidence in 2004–2013: green — low; yellow — medium; red — high. Arrows — increase or decrease in the TBE incidence in 2014–2023: green — decrease; red — increase.

 

Discussion

The epidemic process of TBE in the Kirov Region is characterized by the temporal dynamics of correlation relationships: from a pronounced "regression to the mean" in the 1990s to 2000s and the absence of statistically significant patterns in the 2010s to 2020s.

In the 1990s, the highest incidence rates were recorded in the middle taiga zone (northern districts of the Kirov Region). This can be explained by the fact that these areas have a high forest cover ratio (77.5–91.1%). During that period, there was large-scale deforestation for the purpose of logging, and the incidence of TBE was predominantly tied to this profession. The proportion of those infected from professional risk groups was 21% [8].

From 2004 to 2013, the epidemiological situation regarding TBE in the Kirov Region began to change. A trend has emerged toward the transition of the epidemic process into a new phase, characterized by the stabilization of the territorial distribution of incidence and the formation of stable local foci, not subject to pronounced cyclicity, predominantly in the southern taiga zone.

In the following decade, the incidence of the disease in the middle taiga zone remained at a consistently high level. The concentration of incidence in the northwestern part of the region may be related to professional activities, as these areas have a forest cover ratio of 50.0–84.1% and small logging enterprises are located on their territory. A statistically significant reduction in incidence by 5.3 times, along with a simultaneous decrease in the variability of indicators, has been achieved in the coniferous-broadleaf forest zone. This may be related to changing climatic conditions, as well as the migration of the population from this area of the Kirov Region.

Thus, at the present time, the highest risks of TBE development are characteristic of the central and northern districts of the Kirov Region. In total, 82.2% of the region's population (about 930,000 people) live in these areas.

A similar unfavorable situation regarding tick-borne infections is also recorded in regions bordering the central and northern parts of the Kirov Region and located in the same vegetation zones: to the north — in the Komi Republic and Arkhangelsk Region [4, 9], to the west — in Vologda, Kostroma, and Nizhny Novgorod regions [10, 11], to the northeast and east — in Perm Krai and the Udmurt Republic [12, 13]. To date, a significant expansion of endemic territories for TBE in a northern direction has been described, especially in the European North of Russia [4, 14].

The incidence of TBE is influenced by a number of abiotic and biotic factors. TBE is a climate-dependent disease [13, 14]. All stages of tick development are sensitive to temperature and humidity. Moreover, these indicators are important not only during the activity period of ixodids but also determine the number of imagos in the following year, as they affect the processes of embryogenesis and the survival of overwintering individuals [15]. Due to global warming, ticks are migrating to more northern regions of Russia [4, 14, 16, 17]. In the northern areas of the Kirov Region, the occurring climate changes are favorable for tick activity, which contributes to an increase in the incidence of tick-borne infections [18].

In recent decades, significant changes have occurred in the structure of the vegetation cover of the territories. In the northern regions of the Kirov Region, which are located in the middle taiga zone, the share of agricultural and non-forested areas does not exceed 8-10%, while the main arable lands are located in the central and southern parts of the region. As a result of deforestation, the cessation of haymaking, and the cultivation of arable land, the area of young broadleaf trees and shrubs increases, making them attractive to hares, rodent-like mammals, and small predators — the main hosts of ixodid ticks. Therefore, the transformation of vegetation can have a significant impact on the spread of ixodid ticks and the incidence of TBE. This fact is described in the literature [4, 19], however, it has not been thoroughly studied in relation to the Kirov Region, which could be the focus of future research.

The influence of social factors on the incidence of TBE has been proven. It may be closely related to the level of economic development of the territories, employment and income of the population, the state of healthcare in the region, and the coverage of specific prevention measures [19].

Conclusion

In the last three decades, significant changes in the incidence of TBE in the Kirov Region have been observed. In the temporal aspect, there is a steady increase in this indicator, which indicates the activity of this natural focus. Spatial changes concern the redistribution of the intensity of the epidemic process to areas located in the southern taiga zone, while maintaining it in the northern part of the region. Numerous biotic and abiotic factors may influence this process, the role of which requires further study.

The new knowledge obtained during the study about the spatiotemporal characteristics of TBE incidence in the Kirov Region justifies the necessity for preventive measures taking them into account. In the northern and northwestern regions, where the focus remains consistently active, it is necessary to monitor the rational management of forestry, and it is advisable to prioritize vaccination coverage for professional risk groups with a target rate of at least 80% of the contingent.

In the southern taiga zone, it is necessary to increase the volumes of population vaccination by targeting suburban residents, dacha owners, and participants in "nature" recreation. Optimize acaricide treatments in accordance with SanPiN 3.3686-21 in urbanized landscapes by treating areas with high recreational and social loads: parks, gardening associations, cemeteries, children's and adult recreation areas, followed by entomological monitoring.

To improve the effectiveness of informing the population in disadvantaged areas, it is possible to develop targeted materials for people of different ages: leaflets for dacha owners and tourists, short videos for social networks, and information for parents about the possibility of vaccinating children. Considering the high social and economic significance of the TBE problem, further study of the issue is necessary to optimize existing preventive programs.

About the authors

Olga N. Lyubeznova

Kirov State Medical University

Author for correspondence.
Email: lyubolga@mail.ru
ORCID iD: 0009-0002-9529-4365

Cand. Sci. (Med.), Associate Professor, Associate Professor, Department of infectious diseases

Russian Federation, Kirov

Larisa V. Karaulova

Kirov State Medical University

Email: krabot1@mail.ru
ORCID iD: 0000-0003-4618-8443

Cand. Sci. (Pedagogy), Head, Department of Physics, medical informatics and mathematics

Russian Federation, Kirov

References

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