Optimization of scientifico-practical aspects of West Nile fever causative agent’s monitoring (by the example of the Volgograd region)

Introduction

The wide territorial distribution of West Nile fever (WNF) in the Russian Federation and the ongoing expansion of the pathogen, the emergence of large epidemic outbreaks with the registration of severe (neuroinvasive) forms of the disease determined the importance of this disease for national epidemiologic surveillance [1][2]. The main components of epidemiologic surveillance of WNF, based on the known structure of the epizootic and epidemic process, include monitoring of morbidity, studying the immune layer among sample groups of the healthy population, and zooentomological monitoring¹.

Generalization of the results of long-term monitoring of the WNF pathogen opens up prospects for further improvement of the strategy and tactics of its implementation and increasing the effectiveness of sanitary and anti-epidemic (preventive) measures. It is reasonable to conduct these studies by the example of a subject of the Russian Federation with the established long-term circulation of the WNF pathogen, which is the Volgograd Region [3][4]. Since the registration of the first epidemic outbreak in 1999 up to the present time, 1324 cases of WNF have been registered in this area, which amounted to about 43% of all cases in the Russian Federation.

The aim of the study was to assess the quality and effectiveness of monitoring of WNF pathogen in the Volgograd Region and to develop a set of measures for its optimization.

Materials and Methods

The materials of the study included the information on cases of detection of WNF patients, provided by the Department of Rospotrebnadzor in the Volgograd Region to the Reference Center for monitoring of WNF pathogen on the basis of the Volgograd Research Anti-Plague Institute of Rospotrebnadzor (hereinafter – Reference Center) in 1999–2021, data from the Center of Hygiene and Epidemiology in the Volgograd Region on the results of research for the presence of West Nile virus (WNV) markers of clinical (from feverish patients and sample groups among the healthy population) and zooentomological material on the territory of the Volgograd Region in 2009–2021, and the results of the Reference Center's own research.

A comprehensive methodological approach including statistical and epidemiologic methods was used in this work. Data processing was carried out using Microsoft Excel 2016 (Microsoft Corporation, USA).

Results

Monitoring of Morbidity. In accordance with the normative principle of organization of epidemiological surveillance of WNF, detection of cases is carried out actively through examination during the epidemic season of patients with fever, clinical manifestations of central nervous system damage (meningitis, meningoencephalitis, encephalitis), as well as other symptoms similar to the disease. Thus, one of the main criteria for the quality of detection of WNF patients is the scope of examination of persons who underwent inpatient or outpatient treatment with symptoms that do not exclude the disease.

The analysis for the period of 2009–2021 showed that since 2013, there has been a steady trend toward a decrease in the number of febrile patients examined for WNF in the Volgograd Region (Y = -16.176x + 348.07). Since the same period, there has been a significant decrease in the number of diagnosed cases of WNF in the area; and in some years (2015, 2017, and 2020), the incidence was not officially registered. It should be emphasized that in 2015 and 2017, the number of examined febrile patients decreased by 2.5 and 4.7 times compared to the average annual value, and in 2020, there was no active detection of WNF cases (Fig. 1). In the epidemic season of 2021, a record low number of patients (44 persons) was examined for the presence of pathogen markers during the entire observation period.

The relationship between the number of examined patients and the number of cases was confirmed by the correlation analysis of these indicators, which demonstrated a high strength of the statistical relationship (the correlation coefficient for the period of 2009–2021 was 0.93; p<0.001). Thus, the observed decrease in morbidity in the Volgograd Region in recent years does not reflect the real epidemiologic situation in the subject. It could be explained by a significant decrease in the vigilance of medical personnel with regard to this infection, including against the background of the dominance of COVID-19 issues in health care in recent years.

This suggestion can be supported by the high rate of discrepancies between preliminary and final WNF diagnoses, as well as the untimeliness of the etiologic interpretation of cases.

In the period of 2009–2021, over 30 different provisional diagnoses were made for WNF patients, the most common being “acute viral infection of unspecified etiology” (33.4%), “acute respiratory viral infection” (22.2%), and “fever of unclear etiology” (18.7%). Only 6.6% of patients received a provisional diagnosis of WNF. It is necessary to pay attention to the fact that, according to epidemiologic investigations, 75.1% of patients informed a medical worker about mosquito bites (the main vectors of WNF). All cases of WNF were registered in the season of possible transmission (June-October), except for 1 patient (registered in November). Thus, medical workers underreported the epidemiologic history of patients.

As for the etiologic verification of cases, on average, outpatients were diagnosed 6.5 days after seeking medical care, with the maximum on day 34. Among hospitalized patients, laboratory confirmation of WNF was performed on average within 5 days. The tendency to increase the time of etiologic verification of WNF diseases against the background of a decrease in the number of registered cases in the subject is noteworthy (Fig. 2). Thus, in the years of epidemic upsurges of morbidity (2010 and 2012), outpatients were diagnosed in an average of 5 days, while inpatients were diagnosed in 4 days. In subsequent years, along with sporadic morbidity, this indicator gradually increased (except for 2019), reaching the highest value in 2021 (7.6 and 7.8 days in outpatient and inpatient settings, respectively).

An objective criterion of the quality of clinical diagnostics is also the detection of mild forms of the disease, since medical workers are first of all suspicious of WNF patients with moderate and severe courses of the disease. The proportion of mild forms of the disease in the Volgograd Region for the period of 2009–2021 amounted to 21.7% (95% CI: 18.85–24.55%; p<0.001) of the total number of cases, which is higher than in Russia as a whole (17.3%; 95% CI: 15.67–18.97%; p<0.001). At the same time, in the Voronezh Region, where only 183 cases of WNF have been registered since 2010 (7.2 times lower compared to the Volgograd Region), the detection rate of mild forms was significantly higher and amounted to 31.7% (95% CI: 24.95-38.44%; p<0.001).

Attention should also be paid to the low volume of diagnostic tests to detect WNF patients in the region districts. Thus, over the last five years, active monitoring of morbidity was conducted only in 19 out of 39 administrative territories, with the region districts accounting for 10.7% of all investigations, while in Volgograd city – 77.5% and Volzhsky city – 11.8%. This circumstance determined the low specific weight in the structure of morbidity of rural residents (14.5%), despite their living in close proximity to natural habitats and intensive contact with transmitting agents.

Study of the immune interlayer among selected healthy population groups. Assessing the organization and conduct of serological monitoring in the Volgograd Region, the authors noted the compliance of the number of conducted studies with the indicator regulated in the current regulatory and methodological documents (at least 100 subjects) in relation to two sample groups (donors and residents of certain settlements). The exception is 2020, when studies on the immune layer to WNV were not performed. Less indicative is the third indicator group (livestock breeders), which was screened irregularly and has not been screened since 2015. In general, the structure of seroepidemiological studies for the analyzed period is as follows: donors – 33.5%, livestock breeders – 4.2%, and residents of certain settlements – 62.3%.

It should be noted that not all territories are covered by serologic screening with adequate periodicity. Immunologic screening is carried out almost annually in two large cities (Volgograd and Volzhsky). With a frequency of 2–5 times for the period of 2009–2021, it is carried out in 30 districts (76.9% of all territories) without a clear periodicity. However, in six districts of the Volgograd Region (Kotovsky, Kumylzhensky, Novonikolayevsky, Olkhovsky, Serafimovichsky, and Chernyshkovsky), serologic examination for the entire period of registration of epidemic manifestations of WNF was carried out only 2 times. In 1 district (the city of regional significance Frolovo), it was not performed, which does not allow obtaining objective data on the intensity of contact of the population with the pathogen in these areas.

The results of the studies indicate the presence of an immune layer to WNV in residents of 38 out of 39 administrative territories of the region, while cases of the disease were registered only in 32. In some districts, which reported sporadic cases of the disease, a high level of seroprevalence was observed, which confirms the ineffective monitoring of the incidence and missed cases of WNF. For example, in the Alekseevsky and Bykovsky districts of the region, one case of WNF was laboratory confirmed during 1999–2021, and the immune layer among the population in these areas amounted to 11.5% and 18.2%, respectively.

When assessing the quality of serologic monitoring, the low percentage of positive findings in 2021 (3.5%) is noteworthy, which seems unlikely in areas with high epidemiologic risk, which includes the Volgograd Region. In 2021, according to the results of the study of the immune layer to WNF, conducted by specialists of the Reference Center, specific antibodies were detected in 23% of healthy residents of the region. In the authors’ opinion, a possible reason for the obtained results may be non-compliance with the regulated terms of collection and delivery of clinical material for the study.

Zooentomological monitoring. Among the problematic issues of zooentomological monitoring, the key issues are those related to the volume and quality of monitoring of the main transmitters of WNV (mosquitoes). Based on the results of the assessment of the structure of monitoring studies of environmental objects for the presence of WNV markers in the long-term aspect, a high proportion of the main transmitters was established, averaging 58.1% (Fig. 3). However, since 2015, a downward trend in the absolute number of conducted studies of mosquito transmitters of WNV was observed. This observation requires further study due to the full staffing of FBUZ “Center for Hygiene and Epidemiology in the Volgograd Region” with entomologists and technical equipment with automatic tools for catching transmitters, making it possible to extract significantly higher volumes of entomological material compared to the method “on their own”. The share of positive samples in mosquito research in 2009–2021 amounted to 0.6% (the last samples identified in 2019). A number of districts of the region (Alekseevsky, Nekhaevsky, Elansky, Kikvidzensky, and Surovikinsky) are not covered by entomological monitoring, which is due to the lack of staffing with entomologists and requires the inclusion of these areas in the plans of field visits of specialists of the Federal Budgetary Institution “Center of Hygiene and Epidemiology in the Volgograd Region”.

The share of studies of secondary transmitters (ticks), on the contrary, is characterized by an increasing trend. At the same time, positive findings were obtained only in 2012 and 2013; the total detectability of WNV markers amounted to 0.2%.

Monitoring of morbidity and infection of large mammals with WNV as “indicators” of possible complications of the epidemiological situation in the region is not carried out on a regular basis, which is due to the lack of a regulative procedure for interaction with the veterinary service. Selective screening studies performed by the Reference Center specialists in 2018–2021 demonstrated the presence of virus-specific antibodies in 28–59% of tested blood sera of farm animals [5][6], which indicates an intensive circulation of WNV and confirms the need for research of marker animal species.

There was a significant decrease in the volume of studies of the main carriers (birds); on average, 34 samples of ornithological material were examined annually in 2009–2021. The total detectability of WNF markers was 0.9%; positive findings for the analyzed period were obtained in 2009, 2010, and 2019. In 2015–2021, the Reference Center examined 2.7 times more material (661 samples compared to 248); the proportion of positive samples was 5.6%. No pathogen markers have been detected in small mammals since 2014, and the annual number of studies is characterized by a significant reduction in 2020–2021.

In general, the overall low proportion of positive samples should be noted. WNV markers are not detected every year. In 2020–2021, the circulation of the pathogen in the epizootic cycle, according to the results of monitoring studies, was not established. As possible reasons for the low detection rate of pathogen markers, it should be noted that the volume of field material under study is insufficient, and, apparently, the violation of the “cold chain” during transportation of the material.

Main directions to optimize the monitoring of the WNF pathogen. Taking into account the justified decrease in the efficiency of some components of WNF pathogen monitoring in the Volgograd Region, practical recommendations for its optimization have been developed.

In order to improve the quality of morbidity monitoring before the beginning of the epidemic season, healthcare bodies and institutions were recommended to provide theoretical and practical training of medical organizations’ staff on the epidemiology, clinical picture, and diagnostics of WNF in the conditions of the priority of anti-epidemic and preventive measures against COVID-19. Special attention should be paid to the training of medical specialists at institutions located in the districts of the region. Rospotrebnadzor bodies and institutions should assess the readiness of medical organizations to promptly identify and diagnose WNF patients, and during the epidemic season – ensure control over the timeliness and completeness of WNF screening of patients under outpatient and inpatient treatment with symptoms that do not exclude the disease.

In order to optimize serological monitoring, it is advisable to conduct an annual survey of the population of large cities, while in the districts of the region, the study of the immune layer should be carried out once every 5 years. Taking into account the insufficient coverage of the six above-mentioned districts of the region and one city of regional significance with the serologic examination, these territories should be considered as the first-priority ones when planning studies on the immune layer to WNV. As one of the indicator groups (livestock breeders) stopped to be screened, it is necessary to consider the possibility of selecting another indicator group, which could include residents of rural areas or cities whose professional activity is associated with visiting natural habitats or staying outdoors at night (during the period of the maximum activity of the most effective vector of WNV – Culex pipiens).

Revision of the strategy and tactics of zooentomological monitoring includes an increase in the volume of the main vectors studied through the active use of automatic trapping devices and formation of a network of control points for monitoring vector infectivity (in natural and anthropourgic foci, in 1–2 landscape zones within 3–11 administrative districts characterized by the highest epidemiological risk). Based on the experience of the Reference Center, the minimum volumes of annual studies of field material were determined, which make it possible to assess the intensity of circulation in the epizootic cycle: mosquitoes – 500 samples, ticks – 100 samples, large mammals – 50 specimens, small mammals – 100 specimens, and birds – 100 specimens.

Obtaining additional objective data on the circulation of the pathogen in the epizootic cycle can be ensured by approving at the level of the subject the procedure for the operational exchange of information with veterinary institutions on the detection of diseases and the results of monitoring of the WNF pathogen among “marker” animal species.

All the above proposals were reflected in the draft Methodological Guidelines “Organization of prophylactic (anti-epidemic) measures for West Nile fever” of the federal level of implementation, as well as recommendations of the Reference Center for inclusion in the Comprehensive Plan of Measures for the Sanitary Protection of the Territory of the Volgograd Region (section “Prevention of West Nile fever”).

Discussion

The results of the analysis show a decrease in the effectiveness of WNF pathogen monitoring in the Volgograd Region, a territory characterized by the most intensive course of the epidemic process in Russia. One of the priority problems of monitoring is the insufficient and untimely detection of cases among the population by medical workers. The reason that complicates the clinical diagnosis of WNF may be the absence of a specific symptom complex of the disease, which in the vast majority of cases has flu-like manifestations. At the same time, medical specialists often do not take into account the epidemiologic history of patients, such as residence in an endemic area, contact with transmitters, the coincidence of the season of transmission of WNV, and the time of disease onset. With regard to serologic monitoring, there is a clear need to determine the frequency of testing, to select a different indicator group of the population subject to serologic testing, and to comply with the regulated terms of collection and delivery of clinical material. Analysis of the parameters of monitoring of environmental objects indicates the insufficient volume of tests for the presence of WNV markers (primarily the main carriers), which determines the low proportion of positive findings and, therefore, does not allow assessing the intensity of the epizootic process in the natural focal area. There is also insufficiently effective planning of field work of the zooentomological team of FBUZ “Center of Hygiene and Epidemiology in Volgograd region”, as a result, remote areas of the region are not covered by monitoring.

Conclusion

Based on the analysis of the key aspects of monitoring for the WNF pathogen in the Volgograd Region, the main directions for its optimization are proposed: increasing the anti-epidemic preparedness of sanitary-epidemiological and medical institutions, establishing the frequency of serological monitoring, and increasing the volume of monitoring studies of environmental objects for the presence of pathogen markers. The proposed recommendations to optimize monitoring will improve the efficiency of epidemiological surveillance of WNF and develop a science-based forecast of the epidemiological situation.