The current epizootic and epidemiological situation of coxiellosis in the territories of the Southern, North Caucasian Federal Districts, Donetsk, Lugansk People's Republics, Zaporizhia and Kherson regions

Introduction

Q fever (coxiellosis) is a zoonotic infectious disease with natural foci [1-3], characterized by various mechanisms and modes of transmission of the causative agent Coxiella burnetii. Taking into account the high resistance of C. burnetii in the environment, the pathogen transmission aspiration pathway is of particular importance. Due to the fact that the primary natural foci of infection are currently absent in the territory of the Russian Federation [4], the epidemic process at the present stage largely depends on epizootic activity in the anthropurgical foci of a particular territory. Sources of infection for humans in anthropurgical foci are a wide range of agricultural and domestic animals, with goats, sheep, and cattle (large cattle) playing a leading role. In addition, animal critical objects (litter, forage, etc.) contaminated with C. burnetii can be of significant importance in human infection [5][6].

The incidence of Q fever in the Russian Federation is uneven. According to Shpynov et al. [4], in the long-term dynamics of coxiellosis incidence in the Russian Federation, three periods can be traced: from 1957 to 1968, when there was a sharp (up to 12 times) decrease in the incidence; 1969–1999 – stabilization of the epidemic process with an average number reaching 186 cases per year; and 2000–2019 – a moderate decrease in the incidence relative to the previous period. Currently, the highest incidence rate in the country is recorded in the South and North Caucasus Federal Districts, which, among other reasons, is largely due to the availability of laboratory diagnostics and the availability of practical experience among medical personnel [4][7]. In other regions of the Russian Federation, the incidence of Q fever is recorded periodically and, according to a number of authors, does not reflect its actual level [4][7].

In addition, after the Donetsk and Lugansk People's Republics (DPR, LPR), Zaporozhye and Kherson Regions became part of the Russian Federation in 2022, due to the lack of systematic monitoring of Q fever in these territories over the past three decades, the epizootological and epidemiological situation needs to be clarified in order to identify the risks of human disease. According to fragmentary retrospective data, the incidence of Q fever in the Donetsk Region was recorded annually in the period from 2007 to 2010 [8], in the DPR – in 2017 and 2018 – one case of the disease was detected [9], in 2019 – 16 cases¹. In addition, in 2011–2013 and in 2017, a total of 354 febrile patients and 169 persons with occupational risks of infection, as well as those with symptoms of the disease not excluding coxiellosis, were examined for antibodies to C. burnetii using the serological method [9]. It should be noted that, according to the data provided by the Department of Rospotrebnadzor for the DPR, six administrative subject territories, where 12 settlements are located, are endemic for Q fever. In the Kherson and Zaporozhye Regions, against the background of the lack of information on the morbidity of humans and animals in 2019, 60 samples of bovine blood sera were examined: in the Kherson Region, 5.0% of positive samples were detected; in the Zaporozhye Region – 0 [10]. According to the available information, in the LPR from 2015 to 2022, no cases of human disease and positive samples in biological material from animals were registered.

Taking into account the fact that the epidemic process is currently determined by the activity of anthropurgic foci, mainly related to animal husbandry, the main risk group for infection is persons engaged in agricultural work, including in private farm households. According to the 2021 agricultural census, the total sown area of agricultural crops in the Russian Federation was 52,442.8 thousand hectares, of which 7,811.3 thousand hectares (14.9%) were in the Southern Federal District and 2,893.2 thousand hectares (5.5%) – to the North Caucasian Federal District. In the Southern Federal District, the largest sown area is in the Rostov Region (RO) (2,885.2 thousand hectares), the Krasnodar Territory (2,429.7 thousand hectares), and the Volgograd Region (1,834.1 thousand hectares); in the North Caucasus Federal District – the Stavropol Territory (2,322.0 thousand hectares). The number of cattle, goats, and poultry in the Southern Federal District and the North Caucasus Federal District is relatively small and amounts to 10%, 24.5%, and 11.9%, respectively, of the total in the Russian Federation. However, the largest number of sheep in the Russian Federation was noted in the North Caucasus Federal District (1,892.3 thousand heads; 54.8%) and the Southern Federal District (639.1 thousand heads; 18.5%). In the Southern Federal District, the largest number of sheep is in the Republic of Kalmykia (52.4%) and the Volgograd Region (22.0%), in the North Caucasus Federal District – in the Republic of Dagestan (64.7%)². According to the Federal State Statistics Service, for the period from 2014 to 2022, the share of rural residents in the Russian Federation is 25.6%, in the Southern Federal District this figure is 37.4%, and in the North Caucasus Federal District – 50.2%. However, according to the subjects of these federal districts, the share of the rural population varies from 6.8% (Sevastopol) to 54.4% (Republic of Kalmykia) in the Southern Federal District and from 35.8% (Republic of North Ossetia-Alania) to 63.9% (Chechen Republic) in the North Caucasus Federal District³. According to the 2016 All-Russian Agricultural Census, the average annual number of all employees of agricultural companies in the Russian Federation in 2015 was 1,323,958 people, of which 206,288 people were in the Southern Federal District and 76,854 in the North Caucasus Federal District; among persons engaged in agricultural work, the basic amount was men aged 30–59 years (508,250 people; 47.9%), in the Southern Federal District and the North Caucasian Federal District – 50.7% and 50.2%, respectively⁴. The data provided indicate the high risks of human disease with Q fever in the territories of certain subjects of the Southern and North Caucasian Federal Districts. In addition, in the DPR, LPR, Zaporozhye and Kherson Regions, given the ongoing emergency situation and taking into account modern social and economic features, there is a high degree of contact of the population in natural biotopes with carriers and vectors of pathogens, natural focal and zoonotic diseases, including Q fever.

The purpose of the study is to characterize the dynamics and intensity of the incidence of Q fever for the period from 2015 to 2022, to determine the areas of risk of human infection in the Southern and North Caucasian Federal Districts, in the Donetsk, Lugansk People's Republics, Zaporozhye and Kherson Regions.

Materials and methods

For epidemiological analysis, the following data were used: materials of the state reports “On the sanitary and epidemiological situation of the population” in the Republic of Kalmykia, Stavropol Territory, Volgograd and Rostov Regions for the period of 2015–2022, data from analytical reviews “Epidemiological situation of natural focal infectious diseases in the Southern and North Caucasian Federal Districts” for 2015–2022, reporting data of the Departments of Rospotrebnadzor for the Donetsk People's Republic and the Luhansk People's Republic, materials on 37 cases of Q fever for 2022–2023, provided by the Federal State Budgetary Institution “Center of Hygiene and Epidemiology in the Rostov Region”, and the Office of Rospotrebnadzor in the Rostov Region.

In 2023, 251 samples (190 small mammal samples, 47 Ixodidae samples, 14 environmental samples) from six districts of the DPR and 296 samples (285 small mammal samples, 5 Ixodidae samples, 1 flea sample, 5 environmental samples) from seven districts and two cities of the LPR were formed for laboratory research by polymerase chain reaction (PCR) to detect C. burnetii DNA in field samples.

On the territory of the Rostov Region in the period 2022–2023, epizootological monitoring was carried out not only in natural biotopes, but also in private farm households of patients. In 2022, 21 samples of various substrates (forage, litter, poultry droppings, hay, straw, milk, goat corpse), 32 cattle and small cattle serums, and 28 Ixodidae samples taken from big cattle, and one house mouse were taken in private farm households in two districts, field material was also studied (89 Ixodidae samples, 422 small mammal samples, three water samples, 7 birds of prey pellet samples) collected in 21 municipalities. In 2023, 47 samples of various substrates (litter, forage, milk, etc.), presumably contaminated with C. burnetii, were examined in private farm households in three districts, 25 cattle and small cattle serums, three Ixodidae samples from cattle, as well as field material (65 vector samples, 103 – carriers, five – environmental samples) collected in 16 administrative territories. All samples were examined by the PCR method.

Results

In the 21st century, in the territory of the Russian Federation, periods of increase in the incidence of coxiellosis were replaced by periods of decrease to sporadic cases, with a general tendency to increase. From 2000 to 2022, there were three waves of incidence: 2000–2008 (first cycle); 2009–2014 (second cycle); the third cycle began to form in 2015 and is still taking place (Fig. 1). In the first cycle, 832 disease cases were noted, in the second – 909. In the third cycle, despite a sharp decrease in the incidence – large-scale restrictive measures – during the pandemic of a new coronavirus infection, 900 patients with Q fever were registered.

It should be noted separately that in the first two cycles, the incidence in the Russian Federation was formed due to the high level of incidence in the Astrakhan Region (Southern Federal District). In the Russian Federation, 1741 cases of Q fever were registered during this period, the Astrakhan Region accounted for 77.1% (1,342 cases). The share of this region in the total structure of the country varied from 29.4% (2008) to 93.6% (2013); moreover, the Astrakhan Region during this period accounted for 50.0% (2008) to 99.4% (2013) of the total incidence in the Southern Federal District. Taking into account the regularity of the development of the epizootic process in anthropurgic foci and relying solely on statistical data on detected human disease cases, it is reasonable to assume that the epizootic process in the Astrakhan Region is maintained by the transmission of C. burnetii into private farm households free of this infection by sick farm animals or their waste products. In turn, the dominant species of small mammals were included in the epizootic process for the second time. In the third cycle, the Astrakhan Region accounted for 57.6% of cases (627), while the Stavropol Territory accounted for 34.6% (376 cases), and since 2021, the number of cases in the Stavropol Territory (199 cases) has been higher than in the Astrakhan Region (136), which in turn indicates the activity of epidemic and epizootic processes in the territory of this region and, probably, an increase in private farm households affected by Q fever, insufficient veterinary control over farm animals and their movement to other private farm households.

Over an eight-year period (the third cycle, 2015–2022), 973 cases of Q fever were registered in 14 regions of the Russian Federation⁵. The Southern Federal District accounted for 75% of cases (675). As in previous years, the basic number of cases was recorded in the Astrakhan Region (61.7% of all cases registered in 2015–2022, 555 cases), much less in the Rostov (3.0%, 27)⁶ and Volgograd (0.8%, 7)⁷ Regions and the Republic of Kalmykia (0.4%, 4)⁸. In the North Caucasian Federal District, the incidence was recorded only in the Stavropol Territory (30.2%, 263) [11]. Moreover, cases of Q fever were periodically recorded in the Central Federal District – Voronezh Region (1.7%, 15 cases), Moscow (0.3%, 3), and Tver Region (0.1%, 1); Siberian Federal District – Novosibirsk Region (9%, 8); Volga Federal District – Samara (0.7%, 6) and Ulyanovsk (0.1%, 1) Regions; Northwestern Federal District – Leningrad Region (0.1%, 1).

As of October 1, 2023, 188 cases of Q fever were recorded in the Russian Federation in five regions (Stavropol Territory (104 cases), Astrakhan (72), Rostov (10), and Pskov (1) Regions and the Karachay-Cherkess Republic (1)), which is higher (152) compared to the same period in 2022⁹. From January to September 2023, the Southern Federal District accounted for 82 cases (43.6%), and the North Caucasus Federal District – 105 (55.9%).

In the Astrakhan Region, human diseases were reported almost every year, with the exception of 2020, which may be due to the beginning of the pandemic of a new coronavirus infection and the introduction of large-scale restrictive measures. The basic number of diseases occurred in residents of Astrakhan and six municipal districts (Privolzhsky, Krasnoyarsky, Narimanovsky, Ikryaninsky, Kamyzyaksky, and Volodarsky Districts)¹⁰. In these territories, 492 cases were recorded, which amounted to 96.4% for the analyzed period (Table 1). It should be noted that the distribution of morbidity among the districts of the region indicates that territorially these municipalities form a single cluster in the Astrakhan Region with the most unfavorable epidemiological situation (Fig. 2), which in turn implies the need for a comprehensive epizootological survey in order to establish the factors and conditions that contribute to the circulation of C. burnetii in these biocenoses. In these areas, meat and dairy farming and cattle breeding play a leading role, which indirectly determines the possibility of accumulation of the pathogen in farm households and may be a factor in subsequent infection of people¹¹.

In the eight-year period analyzed (the third cycle is 2015–2022), a similar epidemiological situation also developed in the Stavropol Territory, on the territory of which a cluster of municipal districts with an unfavorable epidemiological situation for coxiellosis was also formed (Fig. 2). This cluster included Budennovsky, Blagodarnensky, Kursky, Sovetsky, Arzgirsky, Stepnovsky, and Levokumsky districts, which accounted for 214 human disease cases, which amounted to 81.4% of all registered in the constituent region (Table 1)¹². Statistics show that in these areas, the population is mainly engaged in livestock and poultry farming, including sheep and goats¹³.

Discussion

Analysis of the data available on the results of epizootological monitoring of the circulation of C. burnetii in the territories of the Southern and North Caucasian Federal Districts indicates the lack of a systematic approach. There is no information on the infection of farm, domestic, and wild animals, which does not make it possible to reliably establish the areas of risk of human infection, as well as the number of sick animals, especially in private farm households with uncontrolled movement of animals and their slaughter. The data on the circulation of C. burnetii among small mammals are also fragmentary and do not allow a full assessment of the epizootic process activity in natural stations. Alternatively, it is not always possible to conduct a full-fledged epidemiological investigation of Q fever in humans, identifying the source of infection (to be discussed).

In 2015–2022, epizootological monitoring of C. burnetii circulation in natural biotopes was carried out in seven regions of the Southern Federal District and five regions in the North Caucasian Federal District. However, not all regions were surveyed annually (Table 2) [21–28].

The results of epizootological monitoring in the period from 2015 to 2022 showed Ixodidae involvement in the epizootic process. In the Astrakhan Region, positive findings in Ixodidae samples (Dermacentor niveus, Hyalomma marginatum, Rhipicephalus pumilio, Hyalomma scupense, Dermacentor marginatus) were found in the Privolzhsky, Krasnoyarsky, Narimanovsky, Ikryaninsky, Kamyzyaksky, Akhtubinsky, and Yenotaevsky Districts. In addition, positive findings in Ixodidae samples were detected in the Krasnodar Territory (Uspensky District – H. marginatum, H. scupense, D. marginatus, 2017–2018, Tuapse – Ixodes ricinus, 2021), the Republic of Kalmykia (Tselinny, Ketchenersky, Sarpinsky, Chernozemelsky and Justinsky Districts, 2019).), in the Stavropol Territory (Kislovodsk, Stavropol, Pyatigorsk, Nevinnomysk, Essentuki, Mineralnye Vody and in 23 districts, annually) – 14 Ixodidae species. In the Republic of Dagestan, positive findings in Ixodidae samples were detected annually, with the exception of 2022. During a single epizootological monitoring (2015) to search for C. burnetii DNA in the Republic of Ingushetia (Dzheyrakh, Nazran, Sunzhensky Districts), markers of the pathogen were found in samples of D. marginatus, H. marginatum ticks. Markers of C. burnetii in the Volgograd Region were detected during the study of Ixodidae samples (Rhipicephalus rossicus, D. marginatus, H. marginatum, Dermacentor reticulatus) and small mammals (common field mouse, house mouse, yellow-necked mouse and field mouse, field-vole and Altai birch mouse, white-toothed shrew, typical rat, gray hamster). For the period of 2015–2022, positive findings were detected annually in three cities (Volgograd, Volzhsky, and Uryupinsk) and in all 33 districts (Fig. 2).

In 2023, epizootological monitoring was carried out to establish the circulation of C. burnetii among small mammals in the territory of the DPR and LPR, Zaporozhye and Kherson Regions. For laboratory study of field material from the DPR, 251 samples were formed (190 small mammal samples, 47 Ixodidae samples, 14 environmental samples) in six districts, the LPR – 296 samples (285 small mammal samples, 5 Ixodidae samples, 1 flea sample, 5 environmental samples) in seven districts and two cities. The proportion of positive samples in the DPR was 0.8 %, in the LPR – 0.3%. C. burnetii DNA was detected in small mammal samples (yellow-necked field mouse and pygmy wood mouse), which indicates the circulation of the pathogen in the natural biotopes of the Russian Federation subjects and does not exclude its circulation among farm animals in private farm households, which requires further study. Positive results were not found in the Zaporozhye and Kherson Regions (Fig. 2).

In 2022 and 2023, after a period of prolonged epidemiological well-being, 27 (0.64 ⁰/₀₀₀₀) and ten (0.24 ⁰/₀₀₀₀) cases of Q fever were detected in the Rostov Region, respectively (Table 3).

The basic number of cases of rural residents in the Rostov Region in both 2022 and 2023 was in two districts: Remontnensky (eight and seven, respectively) and Salsky (eight and two), which amounted to 67.6% of all cases in the analyzed period. It is worth noting that in 2023, one new case of Q fever in the Remontnensky District (the village of Remontnoye) was registered in the same private farm households as in 2022. It should be noted that these districts of the Rostov Region, as well as the Dubovsky District, on the territory of which one case of disease was detected in 2023, belong to the territories with developed beef cattle breeding, in particular, a significant number of sheep are kept in private farm households[14]. Among the urban population, 10 disease cases were noted in the city of Salsk (2022), but according to the results of the epidemiological investigation, it was found that the most likely factor in the infection of the urban population was the care of animals in private farm households. The absence of disease cases among the urban population of Salsk in 2023, in our opinion, is due to the effect of anti-epidemic (preventive) measures carried out by the territorial bodies and organizations of Rospotrebnadzor and the veterinary service in 2022. The maximum number of sick people was noted in June, which coincides with the period of cattle grazing, sheep shearing, and other economic activities. Mainly men (81.1%) of working age (70.3%), persons of no definite occupation (32.4%), workers (27.0%), students of higher, secondary (10.8%) and general (16.2%) institutions were affected, which is due to their greater involvement in agricultural labor processes. This fact is confirmed by the presence of private farm households in which farm animals are kept (Table 3).

Meanwhile, an analysis of the conditions causing the infection indicates that individuals had contact with Ixodidae while fishing in the Salsky District: three people in 2022 and two in 2023, which does not exclude their infection in natural biotopes.

As part of the epidemiological investigation of human cases, an epizootological survey of private farm households at the place of residence of the patients was organized and conducted. When sampling in anthropurgic foci, the variety of routes and factors of transmission of the pathogen was taken into account; the figures of the material studied are shown in Table 4. During the laboratory study, the pathogen DNA was detected in six environmental samples in 2022 (28.6%) and in nine Ixodidae samples (Hyalomma marginatum) taken from cattle in 2023 – in 16 environmental samples (29.6%) and in one Ixodidae sample.

In the course of epizootological monitoring in 2023, C. burnetii DNA was detected in 2.9% of cases: gray hamster (Krasnosulinsky District), pygmy wood mouse (Kamensky District), and Ixodidae (Remontnensky District). Positive findings were also detected in Ixodidae and small mammal samples in 2015–2017 and 2022. The data obtained indicate C. burnetii circulation in Ixodidae and small mammals, both in the Rostov Region and in other subjects of the Southern and North Caucasian Federal Districts.

Conclusion

Therefore, the results of the study confirm the leading part of anthropurgic foci of coxiellosis in infecting people from risk groups. However, there are no modern data indicating the leading part of farm animals as the primary link in the epizootic process formation in anthropurgic foci, in particular in previously prosperous farm households, due to the fact that the influence of small mammals, carriers of C. burnetii, has not been fully studied in natural foci on its development and activity.

The territorial distribution of Q fever cases in the Astrakhan Region, the Stavropol Territory, and the Rostov Region indicates that the epidemic process is mainly local, limited in the context of certain territories of Russian Federation subjects, which is typical of natural focal infections. This, in turn, indicates the need for a systematic study of the activity of the epizootic process among both wild animals and small mammals in various natural biotopes and in anthropurgic foci.

It should be noted separately: at present, it is not possible to draw conclusions that the sporadic morbidity registered in other municipal districts of the subjects, as well as in other regions of the Russian Federation, reflects its actual level.