Shtrek, Sergey V

Shtrek S.V., Rudakov N.V., Shpynov S.N., Blokh A.I., Trankvilevsky D.V., Pen’evskaya N.A., Kumpan L.V., Sannikov A.V.

The aim of the review is to forecast the incidence of rickettsial infections and Q fever in the Russian Federation for 2024 based on an analysis of the epidemiological situation in 2010–2023. The epidemic potential associated with these infections in Russia and other countries where there is an increased activity of foci with an expansion of the area of pathogen circulation has been assessed. An analysis of the incidence of epidemic typhus, Brill’s disease, Siberian tick-borne typhus (STT), Astrakhan spotted fever (ASF), Q fever, human granulocytic anaplasmosis, human monocytic ehrlichiosis in the Russian Federation in 2023 in comparison with long-term average values in 2010–2019 (COVID-19 pre-pandemic period) has been carried out. In 2023, the rates of registered incidence of rickettsial infections and Q fever in Russia as a whole decreased relative to the long-term average level of 2010–2019, and there is a significant downward trend in most regions. The exception is the Far Eastern Federal District, where the incidence rate of STT in 2023 increased by 1.5 times as compared to the period of 2010–2019, and the city of Sevastopol, where an increase in the incidence of Marseilles fever was detected. When assessing the intra-annual distribution of incidence in 2023, registration of STT in Russia was carried out from March to November inclusive, ASF – from May to October, and Q fever – from May to August.

Blokh A.I., Pen'evskaya N.A., Rudakov N.V., Shtrek S.V., Shpynov S.N., Egorova O.F., Manokhina K.A., Saveliev D.A., Krasotkina S.Y.

Relevance. Altai Krai (AK) is one of the least prosperous subjects of the Russian Federation in terms of the incidence of acute respiratory infections (ARI). Results of studying long-term and intra-annual dynamics of the incidence of ARI and community-acquired pneumonia (CAP) in various population groups of the AK in 2011–2021 led to a conclusion about possible connection between the characteristics of the epidemic process of ARI and environmental factors, primarily air pollution, as well as the widespread distribution of natural and atropurgic foci of tick-borne transmissible and zoonotic infections in the territory of the AK, along with the problems of diagnostics. Aim. Assessment of the possible influence of environmental factors on the formation of a high level of registered incidence of ARI in the Altai Territory, as well as diagnostics of some natural focal and zoonotic infections with fever and respiratory symptoms. Materials and methods. A retrospective epidemiological study was conducted based on annual and monthly official statistical reporting during 2011–2021 about the morbidity of the population, demographic and environmental features of the territory of the AK for each of the municipalities (MU), the average long-term incidence rates of ARI, VBP, tuberculosis, Siberian tick typhus (STT), ixodid tick-borne borreliosis, tick-borne viral encephalitis were calculated; appeals of the population regarding tick bites; population density and annual average sulfur dioxide (SO2) emissions. Pearson correlation coefficient was used to assess the strength of the relationship between the analyzed indicators; and seasonality coefficients and the method of trend-seasonal decomposition were used to assess the intra-annual dynamics of the incidence of ARI and CAP (for the period 2011-2019). To study seroprevalence of antibodies to C. burnetii, R. sibirica and SARS-CoV-2 in febrile patients with symptoms of ARI blood samples were collected in October 2022 from ten rural districts of the AK. Results and discussion. It was established that there was a significant direct correlation between the incidence of ARI and the amount of SO2 emissions into the atmosphere (r = 0.61, p < 0.001), as well as between the incidence of ARI and population density (r = 0.53, p < 0.001). The largest share (69%) of the total number of ARI cases in the Altai Territory in 2011–2021 was attributed to the cities of Barnaul, Biysk, Rubtsovsk, Zarinsk and Novoaltaisk, which are characterized by maximum SO2 emissions and population density. An additional contribution (8% total) to the incidence of ARI in the Altai Territory was attributed to 7 rural areas with the highest levels of SO2 emissions. Regardless of the ranking for the incidence of ARI and CAP, in 9 out of 10 areas selected for the study, patients had both anamnestic and diagnostic titers of antibodies to C. burnetii and/or R. sibirica. At the same time, coxiellosis cases in these areas were not registered for 12 years, and the number of cases of STT was much less than the probable number based on the proportion of patients which were seropositive to R. sibirica and had symptoms of ARI. IgM to SARS-CoV-2 were detected in 5 out of 203 examined samples, IgG – in 188 out of 203 examined samples, moreover 13.8% of samples had 118 to 499 BAU/ml, 40.9% of samples had 500 to 5000 BAU/ml, and the rest of samples had more than 5000 BAU/ml. Conclusion. Among all the variables analyzed in the study, the greatest role in the formation of the high level of registered incidence of ARI in the AK for many years belong to the high level of air pollution with SO2 emissions, high population density and, especially, their combination. Underdiagnosis of tick-borne rickettsioses and coxiellosis is of particular importance due to the unavailability of test kits for laboratory verification. Starting from 2020, a new coronavirus infection made some contribution to the registered incidence of ARI.

Pen’evskaya N.A., Rudakov N.V., Shpynov S.N., Blokh A.I., Trankvilevsky D.V., Savel’ev D.A., Shtrek S.V., Sannikov A.V.

The aim of the review was to characterize the epidemiological situation on tick-borne rickettsioses (TR) in the Russian Federation in 2022 in comparison with the pandemic years of 2020–2021 and the pre-pandemic period of 2013–2019, to give the forecast for 2023. During 2013–2022, a pattern was observed in the incidence of rickettsiosis of the tick-borne spotted fever group (with the exception of Astrakhan spotted fever – ASF), that is also characteristic of most other natural focal infections (NFIs): a sharp decrease in registered incidence rates in 2020–2021 with the subsequent increase in 2022 almost up to pre-pandemic levels or even exceedance in some regions. The absence of a defining influence of the frequency of contacts of the population with vectors on the decrease in the incidence in the period of 2020–2021 and the rise in the value in 2022 confirms the registration-related nature of the changes. Given due attention to the problem of effective detection and reporting of NFIs, we expect the incidence of tick-borne rickettsioses to remain within the confidence intervals of long-term average values in most endemic regions in 2023. Relaxed vigilance to the problem of NFIs may lead to a decline in the reported incidence of Siberian tick-borne typhus in the Krasnoyarsk and Zabaikalsky Territories, Republics of Tuva and Khakassia, Novosibirsk and Amur Regions; reduction in the incidence of ASF in Astrakhan Region. The main issue in detecting and registration of the tick-borne rickettsiosis incidence, objective assessment and forecasting of the epidemic situation as regards this group of infections is conditioned by the lack of domestic certified diagnostic test kits for laboratory verification of rickettsioses. Close cooperation between epidemiologists and clinicians is required to establish and register cases of TR based on clinical and epidemiological data.

Kirichenko A., Kireev D., Lapovok I., Shlykova A., Lopatukhin A., Pokrovskaya A., Bobkova M., Antonova A., Kuznetsova A., Ozhmegova E., Shtrek S., Sannikov A., Zaytseva N., Peksheva O., Piterskiy M., et. al.

In Russia, antiretroviral therapy (ART) coverage has significantly increased, which, in the absence of routine genotyping testing, could lead to an increase in HIV drug resistance (DR). The aim of this study was to investigate the patterns and temporal trends in HIV DR as well as the prevalence of genetic variants in treatment-naïve patients from 2006 to 2022, using data from the Russian database (4481 protease and reverse transcriptase and 844 integrase gene sequences). HIV genetic variants, and DR and DR mutations (DRMs) were determined using the Stanford Database. The analysis showed high viral diversity, with the predominance of A6 (78.4%), which was the most common in all transmission risk groups. The overall prevalence of surveillance DRMs (SDRMs) was 5.4%, and it reached 10.0% in 2022. Most patients harbored NNRTI SDRMs (3.3%). The prevalence of SDRMs was highest in the Ural (7.9%). Male gender and the CRF63_02A6 variant were association factors with SDRMs. The overall prevalence of DR was 12.7% and increased over time, primarily due to NNRTIs. Because baseline HIV genotyping is unavailable in Russia, it is necessary to conduct surveillance of HIV DR due to the increased ART coverage and DR prevalence. Centralized collection and unified analysis of all received genotypes in the national database can help in understanding the patterns and trends in DR to improve treatment protocols and increase the effectiveness of ART. Moreover, using the national database can help identify regions or transmission risk groups with a high prevalence of HIV DR for epidemiological measures to prevent the spread of HIV DR in the country.

Rudakova S.A., Teslova O.E., Mutalinova N.E., Kuzmenko Y.F., Strek S.V., Penyevskaya N.A., Rudakov N.V.

Aim. To improve emergency diagnostic measures and preventive antimicrobial therapy in patients with ixodid tick bites using molecular genetic techniques for identification of Вorrelia spp.Materials and Methods. Borrelia strains were isolated by inoculation of tick suspension on the BSK-H medium. Molecular genetic screening of Вorrelia spp. was performed by real-time polymerase chain reaction (PCR) and sequencing. In total, we examined 4,276 patients including 272 bitten by Ixodes persulcatus and 3,108 bitten by Dermacentor reticulatus. In addition, we investigated blood of 896 patients for molecular signatures of Borrelia spp.Results. Borrelia spp. was detected by PCR in 30.1% of Ixodes persulcatus and 3.2% of Dermacentor reticulatus suspensions. However, detection of Borrelia spp. in blood was rare, reaching only 1.1% in those bitten by Ixodes persulcatus and two cases of Dermacentor reticulatus bites. Genotyping of Borrelia spp. in 8 tick suspensions showed the presence of Borrelia garinii in 1 sample, Borrelia afzelii in 5 samples, Borrelia bavariensis in 1 sample, and Borrelia miyamotoi in 1 sample.Conclusion. Molecular genetic screening showed the significant proportion of Ixodid ticks bearing Borrelia spp., indicating the need in specific antimicrobial therapy.

Shtrek S.V., Rudakov N.V., Shpynov S.N., Sannikov A.V., Samoylenko I.E., Shchuchinova L.D., Trotsenko O.E., Dragomeretskaya A.G., Matushchenko E.V.

The aim of the study was to verificate of the causative agent of Siberian tick-borne typhus (STT) upon ixodic tick mixed infection on the territory of the Altai Republic and Khabarovsk Krai using an integrated molecular biological approach. Materials and methods. The material for the study was presented as 304 imago of ixodic mites of six species. The ticks were collected on the territory of the Altai Republic and the Khabarovsk Krai in the years 20142022. Rickettsia DNA was identified by two-round PCR using genus- and species-specific primers for gltA and ompA genes, followed by sequencing and using PCR reagent kits RealBest DNA R. sibirica/R. heilongjiangensis (Vector-Best, Novosibirsk). Results. The detection of rickettsia in ticks in the Altai Republic was 82.6% (CI: 69.196.1), in the Khabarovsk Krai 53.1% (CI: 44.961.3). The species composition of rickettsias in various species of ixodic mites in these territories, endemic to Siberian tick typhus, is characterized by the presence of mixed forms. Rickettsia sibirica and R. raoultii were found in ticks Dermacentor nuttalli, Haemaphysalis concinna, D. silvarum. Only Candidatus R. tarasevichiae were detected in Ixodes persulcatus, I. pavlovsky mites and I. pavlovsky/persulcatus hybrids. The DNA of R. heilongjiangensis was found in H. mites. concinna in the Khabarovsk Krai. The DNA of Candidatus R. tarasevichiae is also present in the ticks of D. nuttalli and H. concinna from the Altai Republic. The DNA of the classic pathogenic species, R. sibirica, was detected in ticks D. nuttalli and H. concinna in the Altai Republic, ticks D. silvarum, H. concinna and H. japonica douglasi in the Khabarovsk Krai. In addition, in the Khabarovsk Krai, the DNA of R. heilongjiangensis was detected in H. concinna ticks, and a DNA fragment common to R. sibirica subsp. mongolitimonae and R. conorii was detected in H. japonica douglasi ticks, which requires further study. Candidatus R. tarasevichiae is common in Ixodes mites (I. persulcatus, I. pavlovsky and their hybrids), in the Altai Republic in D. nuttalli and H. concinna. R mites. raoultii was detected in ticks of the genus Dermacentor D. nuttalli in the Altai Republic and D. silvarum in the Khabarovsk Krai. Conclusions. During molecular biological monitoring of rickettsias in endemic territories, the detection of R. raoultii masks the presence of the etiological agent of STT R. sibirica. This phenomenon makes it possible to explain the high incidence of STT in the studied territories, with the rare detectability of R. sibirica DNA during molecular biological screening in ixodic mites.

Shtrek S.V., Blokh A.I., Samoylenko I.E., Sannikov A.V., Bobrova O.A., Shpynov S.N., Rudakov N.V.

Using the example of the clinical strain of R. sibirica «Bayevo 105/87», the possibility of quantitative determination of rickettsias in clinical samples from patients with Siberian tick-borne typhus by real-time polymerase chain reaction (PCR-RT) was evaluated. Cultivation was carried out in the yolk sacs of developing chicken embryos, from which a piece of the yolk sac or chorion was taken. A total of 125 samples were examined. A set of reagents “RealBest DNA Rickettsia species (kit1)” was used for PCR-RT. The obtained values of the threshold amplification cycle (Ct) were compared with the results of microscopy of smear preparations stained by the Zdrodovsky method, the values of which were divided into ranks: the I rank - single rickettsias in individual fields of vision, the II rank - single rickettsias in each field of vision, the III rank - from 10 to 25 rickettsias in each field of vision, the IV rank - from 25 to 50 rickettsias in each field of view. The median Ct value for rank I was 17.6 (16.37; 18.58), for the II - 16.0 (15.0; 16.41), for the III - 15.0 (14.0; 15.1) and for the IV - 15.0 (13.7; 14.64). A significant average correlation was established between the number of rickettsias in the preparation under microscopy and the value of the threshold cycle in PCR RT (r=-0, 4849542; p=9.968e-09). When determining the correlation between the pathomorphological characteristic and the value of the threshold cycle, its absence was established. The detection of rickettsias in the blood vessels of the chorion of developing chicken embryos was of interest. In 10 samples, the yolk sac and chorion were taken for the study, and in parallel they were examined by PCR-RT. The use of modern, more sensitive molecular biological methods allows for quantitative analysis of DNA in the chorion, while preserving the volumes of the most valuable material - the yolk sac.

Shtrek S., Levakhina L., Blokh A., Pasechnik O., Pen’evskaya N.

The Siberian Federal District is among the most affected regions with a high prevalence of HIV-infection and is characterized by high HIV-infection incidence rate and high mortality among the HIV-infected population. HIV drug resistance poses a major threat to public health and is associated with increased mortality, HIV incidence, and cost of epidemic control programs. A total of 1281 samples from HIV-infected patients were sequenced and analyzed with the DEONA and HIVdb Program to assess the prevalence of drug resistance mutations in patients in the Siberian Federal District in 2016–2018. The federal surveillance data obtained from 0.5% of HIV-infected patients during the long-term follow-up care in 2021 were also used. The incidence rate of HIV infection in the Siberian Federal District has declined since 2016: from 135.8 per 100 thousand population to 81.1 per 100 thousand population in 2021. Mutations associated with resistance to NRTI and NNRTI were found in 10.3% of the samples in 2016–2018 and in 28.4% of the samples in 2020. The rising prevalence of drug resistance in HIV-infected patients indicates that it is increasingly important to continuously monitor and improve the approaches to the use of effective treatment regimens.

Akimkin V.G., Popova A.Y., Khafizov K.F., Dubodelov D.V., Ugleva S.V., Semenenko T.A., Ploskireva A.A., Gorelov A.V., Pshenichnaya N.Y., Yezhlova E.B., Letyushev A.N., Demina Y.V., Kutyrev V.V., Maksyutov R.A., Govorun V.M., et. al.

Background. The ongoing pandemic of the novel coronavirus infection (COVID-19) draws attention to the significance of molecular and genetic monitoring of the SARS-CoV-2 spread among the population of the Russian Federation. The aim of the study was to analyze the dynamics of circulation of SARS-CoV-2 genetic variants in Russia.Materials and methods. The analysis of the circulation dynamics for SARS-CoV-2 genetic variants in Russia was carried out, covering the period from 28/12/2020 to 26/6/2022. The analysis included the data from Rospotrebnadzor Report No. 970 "Information about Infectious Diseases in Individuals with Suspected Novel Coronavirus Infection" and the Virus Genome Aggregator of Russia (VGARus). The presence of SARS-CoV-2 RNA was confirmed by the real-time reverse transcription polymerase chain reaction. The primer panels developed at the Central Research Institute of Epidemiology were used for amplification of genomic fragments and the subsequent sequencing.Results and discussion. Using the Russian VGARus platform developed by the Central Research Institute of Epidemiology, we received the data on mutational variability of SARS-CoV-2. By monitoring the circulation of SARS-CoV-2 genetic variants in Russia from 28/12/2020 to 26/6/2022, we found that Delta and Omicron genetic variants prevailed at different stages of the epidemic.Conclusion. The data of molecular and genetic studies are an essential component of epidemiological surveillance, being critically important for making executive decisions aimed at prevention of further spread of SARS-CoV-2 and laying the groundwork for creating new vaccines.

Rudakov N.V., Pen’evskaya N.A., Kumpan L.V., Blokh A.I., Shpynov S.N., Trankvilevsky D.V., Shtrek S.V.

The aim of the review was to characterize the epidemiological situation on rickettsiosis of the tick-borne spotted fever (TSF) group in the constituent entities of the Russian Federation in 2012–2021 and provide a long-term forecast for 2022–2026. In 2020–2021, indicators of registered incidence of tick-borne rickettsiosis in Russia on the whole decreased relative to the average long-term pre-pandemic level in 2012–2019 by 2 fold for all forms of the TSF group on average (Siberian tick-borne typhus – STT, Astrakhan spotted fever and Mediterranean fever). A comparative analysis of the territories revealed a correlation between the incidence of STT and the number of medical facility visits due to “tick bites” (r=0.67, p=0.015), which, against the background of an increase in the frequency of contacts of the population with vectors in 2020–2021 in most regions and a decrease in the incidence in the same regions indicates the credible nature of the changes. The ranking of territories according to average long-term incidence rates made it possible to classify the Republic of Altai and the Altai Territory as regions of extremely high epidemic hazard as regards STT; high hazard – the Republic of Tuva; above average – the Republic of Khakassia, Khabarovsk Territory and the Jewish Autonomous Region. The established downward trend in the incidence of tick-borne rickettsiosis among the population will be sustained in most entities of the Russian Federation within the next 5 years, excluding the Republic of Altai, the Altai Territory, the Republic of Crimea and the city of Sevastopol, where current incidence or an increase should be expected. The results of the analysis indicate the need to put more emphasis on natural-focal infections at the time of COVID-19 pandemic.

Rudakova S.A., Rudakov N.V., Shtrek S.V., Teslova O.E., Kaneshova N.E.

Aim. To study the gene-specific composition of Borrelia spp. in ixodid ticks inhabiting the foci of ixodid tick-borne borreliosis (ITBB) in the south of Western Siberia.Materials and Methods. The gene-specific composition of Borrelia spp. in ixodid ticks was determined by inoculation on a BSK-H nutrient medium, real-time polymerase chain reaction, and sequencing (1148 specimens of ixodid ticks collected from vegetation and 2183 specimens withdrawn from humans).Results. Infection of ticks with borrelia ranged from 22.4% in the Altai Republic to 56.9% in the Novosibirsk Region. There were no significant differences in the levels of Borrelia infection between two major ixodides, I. persulcatus and I. pavlovskiy (average infection levels 40.0% and 38.8%, respectively). At least five gene species of pathogenic Borrelia (B. garinii, B. afzelii, B. bavariensis, B. miyamotoi, and B. spielmanii) have been identified. The GenBank database contains 45 nucleotide sequences of the intergenic spacer rrf (5S)-rrl (23S). Prevalence of gene species B. garinii and B. afzelii in different ticks (I. persulcatus and I. pavlovskiy) did not differ significantly, yet B. garinii was found to be more frequent than B. afzelii. The frequency of infection of I. persulcatus ticks with B. miyamotoi was significantly (3.5-fold) as compared to those of B. garinii and B. afzelii. In D. reticulatus ticks, the DNA of B. spielmanii and B. miyamotoi was detected.Conclusion. It is necessary to continue studies to assess the role of the meadow ticks D. reticulatus in the circulation of different Borrelia spp. in various natural foci within the Russian Federation.

Rudakov N.V., Samoylenko I.E., Shtrek S.V., Rudakova S.A., Kumpan L.V., Igolkina Y.P., Rar V.A., Zhirakovskaya E.V., Tkachev S.E., Tikunova N.V., Kostrykina T.V., Blokhina I.A., Lents P.A.

The Siberian tick-borne typhus (STT) is the most common tick-borne rickettsiosis (TBR) in Russia, registered in 17 administrative territories of the Southern Siberia and the Far East. The aim of this study was to describe clinical picture, pathological data and results of laboratory diagnostics during fatal mixed infection caused by two Rickettsia species most common in Russia — pathogenic Rickettsia sibirica and poorly examined Candidatus R. tarasevichiae, including identification of its etiological agents. A four-year-old girl in Krasnoyarsk Krai in a hyperendemic focus of the Siberian tick-borne typhus after tick sucking revealed typical TBR symptoms (scab at the site of tick suction, fever, spotted rash, myalgia) and meningeal syndrome, which is not typical for the Siberian tick-borne typhus. The child died on the seventh day of illness. Autopsy data (hepatosplenomegaly; cerebral edema, which was the immediate cause of death) and the results of histological examination (productive vasculitis of the brain, spinal cord and skin, polymorphic cell perivascular infiltrates in the liver and lungs, serous meningitis, myeloid hyperplasia of the spleen and lymph nodes, interstitial lymphoid infiltration in the myocardium) confirmed the clinical diagnosis of tick-borne rickettsiosis. The patient’s blood and brain samples were tested for a wide range of tick-borne pathogens and enteric viruses that cause brain damage using PCR followed by sequencing of the positive samples. The DNA of Rickettsia sibirica and Candidatus Rickettsia tarasevichiae was found in both blood and brain samples. R. sibirica was identified by the nucleotide sequences of gene fragments gltA, ompA and ompB, and Candidatus R. tarasevichiae — by the gltA and ompB genes using nested PCR and sequencing. All amplified fragments were sequenced in both directions; the obtained sequences were deposited in the GenBank database under the inventory numbers MK048467–MK048475. We have not identified other tick-borne pathogens or intestinal viruses in the patient samples able to result in meningeal syndrome. The area where the child was sucked by the tick belongs to the regions with a high incidence of STT. Several species of mites coexist in this area; of these, Haemaphisalis concinna, the carrier of R. sibirica, dominates the populations of Ixodes mites, while Ixodes persulcatus, the main reservoir of Candidatus R. tarasevichiae, is less common. As a result of the conducted studies, for the first time in the Russian Federation, a verified case of a lethal infection associated with two species of Rickettsia — Rickettsia sibirica and Candidatus R. tarasevichiae — was identified and described.

Rudakov N.V., Shpynov S.N., Pen’evskaya N.A., Blokh A.I., Reshetnikova T.A., Samoylenko I.E., Kumpan L.V., Shtrek S.V., Savel’ev D.A., Abramova N.V., Trankvilevsky D.V.

Objective is to analyze the incidence of Siberian tick typhus (STT) in the Russian Federation over the period of 2010–2020, Astrakhan spotted fever (ASF) and Mediterranean fever (MF) since the official registration, and to forecast the development of the epidemic process for endemic rickettsioses for 2021. The analysis of the incidence of STT, ASF and MF in Russia for the period of 2010–2020, 2013–2020 and 2014–2020, respectively, has been carried out. The forecast of endemic rickettsioses morbidity in the European and Asian parts of Russia for 2021 has been made. The average long-term incidence of STT for 2010–2020 in the Russian Federation as a whole was 1.04 (CI95 1.02÷1.05) 0/0000, with no tendency to change. The maximum relative incidence of STT is typical for the Siberian Federal District (SFD), where the average long-term incidence rate for 2010–2020 was 6.20 (CI95 6.08÷6.31) per 100 thousand of the population. The Far Eastern Federal District (FEFD) – 4.70 (CI95 4.53÷4.87) 0/0000 came in second place, the third place was taken by the Ural Federal District (UFD) – 0.08 (CI95 0.07÷0.10) 0/0000. When assessing the 11-year dynamics of the relative incidence of STT by the Federal Districts, we have detected a tendency to its stabilization in the SFD and the FEFD. In the UFD, a significant downward trend was revealed. The upward trend in the incidence of STT remained in the Altai Republic. Major decline in STT incidence was observed in the Kurgan Region, Trans-Baikal Territory, Krasnoyarsk Territory, and the Republic of Khakassia. There was a declining trend in the incidence of Astrakhan spotted fever in the Astrakhan Region and the Republic of Kalmykia. In the Republic of Crimea and the city of Sevastopol there is no trend to increase the incidence of Mediterranean fever.

Rudakova S.A., Teslova O.E., Kaneshova N.E., Shtrek S.V., Yakimenko V.V., Penyevskaya N.A.

Rudakov N.V., Penyevskaya N.A., Saveliev D.A., Rudakova S.A., C.V. Shtrek, Andaev E.I., Balakhonov S.V.

Research objective. Differentiation of natural focal areas of Western Siberia by integral incidence rates of tick-borne infectious diseases for determination of the strategy and tactics of their comprehensive prevention. Materials and methods. A retrospective analysis of official statistics for the period 2002-2018 for eight sub-federal units in the context of administrative territories was carried out. The criteria of differentiation were determined by means of three evaluation scales, including long-term mean rates of tick-borne encephalitis, tick-borne borreliosis, and Siberian tick-borne typhus. As a scale gradation tool, we used the number of sample elements between the confidence boundaries of the median. The integral assessment was carried out by the sum of points corresponding to the incidence rates for each of the analyzed infections. Results. The areas of low, medium, above average, high and very high risk of tick-borne infectious diseases were determined. Recommendations on the choice of prevention strategy and tactics were given. In areas of very high and high incidence rates, a combination of population-based and individual prevention strategies is preferable while in other areas a combination of high-risk and individual strategies is recommended. Discussion. Epidemiologic zoning should be the basis of a risk-based approach to determining optimal volumes and directions of preventive measures against natural focal infections. It is necessary to improve the means and methods of determining the individual risk of getting infected and developing tick-borne infectious diseases in case of bites, in view of mixed infection of vectors, as well as methods of post-exposure disease prevention (preventive therapy).

Dixit R., Manikandan S., Gopalan N., Mohanty B.S., Behera S.K.

Tokarevich N.K., Isaeva G.S., Karmokov I.A., Baimova R.R., Grechishkina D.I., Lyzenko I.S., Riabiko E.G., Freylikhman O.A., Khalilov E.S., Gilyazutdinova G.F., Isaeva R.A., Savitskaya T.A., Trifonov V.A., Patyashina M.A.

The official statistic data on Q fever cases in Russia do not reflect the real spread of this infection. One of the reasons for Q fever significant underdiagnosis is the difficulty of its clinical diagnosis due to the pronounced polymorphism of the disease manifestations and the absence of pathognomonic symptoms.The study objective was to determine the level of seroprevalence of the population to the Coxiella burnetii in the Republic of Tatarstan.Materials and methods. ELISA was used to detect IgG antibodies to Q fever pathogen in blood sera sampled from volunteers (480 samples). The volunteers whose serum samples proved to be IgG–positive were offered a questionnaire intended to reveal the risk factors for contamination with the Q fever causative agent, and their blood was re-sampled after 5-6 months in order to determine the duration of IgG antibodies persistence.Results. IgG antibodies to C. burnetii were revealed in 7.7% of the surveyed volunteers. The re-examination of seropositive persons revealed the corresponding antibodies in 82% of them. Based on the results of the questionnaire survey it was concluded that the majority of the respondents were involved in pet care or farm animals keeping, and 80% of the respondents had suffered febrile illness during past two years. The highest seroprevalence was detected in humans over 40, while more often in women than in men.Conclusion. The results obtained indicate the existence of active foci of Q fever on the territory of the Tatarstan Republic, where residents come into contact with C. burnetii. It is likely that ELISA is a useful assay for detecting IgG antibodies over rather long period of time after contamination with the causative agent of Q fever. The revealed irregularity of the territorial distribution of infected residents argues for the advisability of further research in order to identify the infection sources, first of all, in areas with high seroprevalence. The detected rather high C. burnetii seroprevalence in the population of the Republic of Tatarstan in the absence of reported Q fever incidence bear witness to significant underdiagnosis of the infection, and hence justifies the needs of effective preventive measures development taking into account the local conditions.

Alvarez‑Londoño J., Martínez-Sánchez E.T., Ramírez-Chaves H.E., Castaño-Villa G.J., Rivera‑Páez F.A.

Infectious diseases, especially zoonotic, represent a significant global threat to both human and animal health. Ticks are among the primary vectors of pathogens affecting wild and domestic animals, some of which can also cause severe human diseases. To effectively face zoonotic diseases, the "One Health" approach is being promoted to integrate the health of human, animals, and ecosystems. Here, we identify the associations between ticks, rickettsiae, wild and domestic mammals, and humans in the Andean region of Colombia. A total of 366 ticks of 17 species belonging to the genera Amblyomma, Dermacentor, Ixodes, Ornithodoros, and Rhipicephalus were collected as free-living organisms, or parasitizing humans, wild (22 species) and domestic (3 species) mammals. Infection with Rickettsia parkeri strain NOD, Rickettsia cf. monacensis and 'Candidatus Rickettsia tarasevichiae' was detected in 3.4 % of the ticks analyzed (n = 3). This study highlights the diversity of ticks in humans and wild and domestic mammals in Colombia. It also underscores the risk these ectoparasites represent to human and animal health due to the potential transmission of zoonotic pathogens such as Rickettsia spp.

Kuznetsova A.I., Kim K.V., Antonova A.A., Lebedev A.V., Ozhmegova E.N., Tumanov A.S., Munchak Y.M., Orlova-Morozova E.A., Pronin A.Y., Prilipov A.G., Kazennova E.V.

The aim of the study. The comparison of genetic diversity of Rev protein in HIV-1 sub-subtype A6 in people living with HIV (PLHIV) with different stages of the disease.Materials and methods. 227 whole blood clinical samples received from PLHIV who have not had previously treatment and observed in Moscow Regional Center for the Prevention and Control of AIDS and Infectious Diseases were analyzed. The extraction of proviral DNA, the amplification of the first and the second rev exons with the followed sequencing was carried out. Subtyping was conducted by analyzing the rev second exon. Then the conservatism and amino acid substitutions in Rev sequences were compared in patients from different groups.Results and discussion. 220/227 (96.9%) samples contained HIV-1 sub-subtype A6. In patients with IV stage of the disease the conservation in Rev was significantly lower. There were found two substitutions (L13I, S113P) with a statistically significant difference in occurrence in PLHIV with different stages of HIV infection.Conclusion. The results obtained confirm the hypothesis of correlation between Rev structure and course of HIV infection and indicate the necessity for further research on this field.

Kirichenko A.A., Kireev D.E., Sidorina Y.N., Abashina N.D., Brusentseva E.E., Akimkin V.G.

Introduction. As a result of routine testing of HIV-1 drug resistance (DR), a significant amount of viral nucleotide sequences and epidemiological data of HIV-infected individuals have been collected. Combined with the increasing use of bioinformatics methods in practice, it has become possible to study the features of HIV-1 resistant variants spread using molecular clustering analysis. The aim of the study was to validate the molecular clustering analysis in a pilot region of Russia using a significant number of nucleotide sequences to study the features of the spread of HIV-1 resistant variants. Materials and methods. HIV-1 nucleotide sequences were obtained from 899 HIV-infected patients who were registered at the Oryol AIDS Center in 2016–2021. HIV-1 genetic variants were determined using the Stanford University database, REGA and HIV BLAST. Resistance mutations and prognostic HIV-1 DR were determined using the Stanford University database. Phylogenetic analysis was carried out using the MEGA program. HIV-1 molecular clusters were identified using Cluster Picker software. Results. In the pilot region, sub-subtype A6 dominated (85.7%); an increase in the share of CRF63_02A6 was noted. HIV-1 resistance was found in 13.6% of patients without antiretroviral therapy (ART) experience and in 52.0% with ART experience. Molecular clusters were more often formed by HIV-1 nucleotide sequences from ART-naïve patients. HIV-1 DR variants were less likely to fall into molecular clusters. The sources of transmitted mutations were more often patients with ART experience. The most actively and efficiently transmitted mutations were K103N, V179E/T, Y181C and G190S, associated with virus resistance to efavirenz and nevirapine.

Antonova A.A., Lebedev A.V., Ozhmegova E.N., Shlykova A.V., Lapavok I.A., Kuznetsova A.I.

Introduction. HIV-1 non-structural proteins are promising targets for vaccine development and for creating approaches to personalized medicine. HIV-1 sub-subtype A6 has become the dominating strain in Russia. However, the geographic, economic and demographic characteristics of the country can contribute to the formation of differences between A6 variants circulating in different regions. The aim of the study is a comparative analysis of the consensus sequences of non-structural proteins in A6 variants circulating in the Amur Region, in Arkhangelsk, Irkutsk and Murmansk. Materials and methods. 48 whole blood samples obtained from HIV-infected patients without experience of therapy observed at the AIDS Centers in Arkhangelsk, Irkutsk, Murmansk and Amur Region were analyzed. HIV-1 whole-genome nucleotide sequences were obtained and were subtyped. Consensus sequences of sub-subtype A6 variants non-structural proteins for each analyzed region were formed. Furthermore, reference sequences of sub-subtype A6 non-structural proteins were formed based on whole-genome sequences retrieved from the international Los Alamos database. Comparison of consensus sequences and references was performed using the MEGA v.10.2.2 and the PSIPRED programs. Results. Vif, Vpr and Nef reference sequences have been obtained for HIV-1 sub-subtype A6. There was not difference in consensus sequences of Vpr in different regions. Characteristic features were found for consensus sequences of Tat, Rev, Vpu, Vif and Nef proteins in different regions. Conclusion. A limitation of the study is a small sample size. Overall, the results demonstrate the existing diversity of non-structural proteins in sub-subtype A6 variants in different regions and indicate the relevance of studying the polymorphism of non-structural proteins of virus variants in different regions.

Riabiko E.G., Grechishkina D.I., Baimova R.R., Karmokov I.A., Buts L.V., Khalilov E.S., Lyzenko I.S., Tokarevich N.K.

The aim of the study was to determine the prevalence of leptospiroses and hemorrhagic fever with renal syndrome (HFRS) among residents of some administrative districts of the Leningrad Region. Materials and methods. 958 blood serum samples of conventionally healthy individuals living in the following territories of the Leningrad Region: Boksitogorsky, Volosovsky, Vyborgsky, Kingiseppsky, Lodeynopolsky, Luzhsky, Podporozhsky, Priozersky, Slantsevsky and Tikhvinsky districts – were analyzed by enzyme immunoassay. The retrospective epidemiological analysis of the incidence of leptospirosis and HFRS in the population of the Leningrad Region in 2011–2020 was carried out based on the data from the Rospotrebnadzor Administration and Forms No. 2 “Information on infectious and parasitic diseases”. Results and discussion. All in all, 54 cases of leptospirosis and 104 cases of HFRS were registered in the Leningrad Region in 2011–2020. The long-term average annual incidence rate (LTAAIR) for leptospirosis was 0.32. In Boksitogorsky, Vyborgsky, Lodeynopolsky, Podporozhsky and Slantsevsky districts, cases of leptospirosis were not recorded, but IgG-antibodies to Leptospira interrogans were detected in residents of those areas. The LTAAIR for HFRS was 0.63. There are no registered cases of HFRS in the Kingiseppsky, Podporozhsky, and Slantsevsky districts. IgG-antibodies to Orthohantavirus were detected in volunteers in all surveyed areas. The detection of specific antibodies in the blood sera of conventionally healthy people living in the Leningrad Region indicates contact of the population with pathogens of leptospirosis and HFRS. The lack of registered morbidity in some areas is probably due to their hypo-diagnosis, as evidenced by the detection of antibodies to the pathogens of these infections in people living in the corresponding territories.

Shtrek S.V., Rudakov N.V., Shpynov S.N., Blokh A.I., Trankvilevsky D.V., Pen’evskaya N.A., Kumpan L.V., Sannikov A.V.

The aim of the review is to forecast the incidence of rickettsial infections and Q fever in the Russian Federation for 2024 based on an analysis of the epidemiological situation in 2010–2023. The epidemic potential associated with these infections in Russia and other countries where there is an increased activity of foci with an expansion of the area of pathogen circulation has been assessed. An analysis of the incidence of epidemic typhus, Brill’s disease, Siberian tick-borne typhus (STT), Astrakhan spotted fever (ASF), Q fever, human granulocytic anaplasmosis, human monocytic ehrlichiosis in the Russian Federation in 2023 in comparison with long-term average values in 2010–2019 (COVID-19 pre-pandemic period) has been carried out. In 2023, the rates of registered incidence of rickettsial infections and Q fever in Russia as a whole decreased relative to the long-term average level of 2010–2019, and there is a significant downward trend in most regions. The exception is the Far Eastern Federal District, where the incidence rate of STT in 2023 increased by 1.5 times as compared to the period of 2010–2019, and the city of Sevastopol, where an increase in the incidence of Marseilles fever was detected. When assessing the intra-annual distribution of incidence in 2023, registration of STT in Russia was carried out from March to November inclusive, ASF – from May to October, and Q fever – from May to August.

Ravishankar V., Narayanan S., Shandil R.K.

Rickettsial infections present a substantial public health burden in India. Recent years have witnessed an increase in the incidence of Rickettsial infection-associated morbidity and mortality. These infections are primarily transmitted by vectors such as ticks, fleas, mites, and lice. This review aims to capture epidemiology, diagnosis and emerging disease trends of rickettsial infections, particularly Orientia tsutsugamushi (O. tsutsugamushi) in the Indian context. Diagnosis and treatment of Orientia infections remain challenging due to the lack of sensitive and specific diagnostic tools vis-a-vis clinical treatment in the absence of specific drugs targeting Rickettsial pathogens. Consequently, clinicians often rely on symptoms and epidemiological factors for diagnosis, highlighting the urgent need for improved diagnostics and therapeutic tools. A comprehensive understanding of the epidemiology of rickettsial diseases is essential for formulating effective preventive and control strategies. Identification of high-risk regions and populations by serological and genetic techniques may help the development of targeted interventions. Therefore, enhancing awareness among healthcare professionals and the public regarding epidemiology, clinical features, diagnosis and treatment interventions of rickettsiosis is crucial. This review summarizes the significance of comprehensive epidemiological investigations and diagnostic systems for understanding rickettsial infections in India.

Sun Y., Xing J., Xu S., Li Y., Zhong J., Gao H., Cheng S., Dong J., Zhang T., Lu G., Baele G., Zhang G.

ABSTRACT Cats ( Felidae ) have become an integral part of many households. However, our understanding of the full spectrum of pathogens affecting cats (referred to as the infectome) is limited, mainly due to the inadequacy of commonly used diagnostic tools in capturing the complete diversity of potential pathogens and the prevalence of pathogen co-infections. In this study, we employed a meta-transcriptomic approach to simultaneously characterize the infectome contributing to different disease syndromes and to investigate spatial, demographic, and ecological factors influencing pathogen diversity and community composition in a cohort of 27 hospitalized cats and seven stray cats. We identified 15 species of pathogens, with Candidatus Rickettsia tarasevichiae and Tritrichomonas foetus representing potential spillover risks. Importantly, although most cases of ascites hyperplasia were explained by coinfection with multiple pathogens, we identified the potential novel clinical outcomes of M. aubagnense infection among cats. We demonstrated that the increase in infectome diversity can be explained by a variety of predictors including age growth, temperature increase, and a higher proportion of females, with age growth presenting the strongest effect. Fine-scale analysis indicated that a higher diversity of infectomes were harbored in young cats rather than adult ones. Our results demonstrated that most feline diseases are better explained by the presence of virus–bacteria or virus–virus coinfection. This study serves as a timely endorsement for clinical diagnosis by vets to consider the cause of a disease based on a panel of cryptical co-infecting pathogens rather than on individual infectious agents. IMPORTANCE Frequent studies reported the risks of cats as an intermediate host of zoonotic pathogens (e.g., SARS-CoV-2). Cats have a physically close interaction with their owners through activities like petting, kissing, and being licked on the cheek and hands. However, there are still limited studies that systematically investigate the infectome structure of cats. In this study, we employed a meta-transcriptomics approach to characterize 15 species of pathogens in cats, with Candidatus Rickettsia tarasevichiae first characterizing infection in diseased cats. Most feline diseases were better explained by the presence of virus–bacteria or virus–virus coinfection. The increase in infectome diversity could be influenced by a variety of predictors including age growth, temperature increase, and a higher proportion of females. A higher diversity of pathogens was harbored in young cats rather than adults. Importantly, we showed the value of linking the modern influx of meta-transcriptomics with comparative ecology and demography and of utilizing it to affirm that ecological and demographic variations impact the total infectome.

Kotov I.

Introduction. In response to the COVID-19 pandemic in the Russian Federation, comprehensive response measures were taken. One of these measures was the development of a viral genome aggregation platform (VGARus) to monitor virus variability. The aim of this paper is to describe the role of the VGARus platform in tracking genetic variation in SARS-CoV-2. Materials and methods. VGARus utilizes sequencing data and bioinformatics tools to monitor genetic variations in SARS-CoV-2. The viral genomes were aligned using NextClade, which also translated them into amino acids and identified mutations. The viral variability over time was analyzed by counting the number of amino acid changes compared to the reference sequence. Results. The analysis of data within VGARus enabled the identification of new virus variants, contributing to improved diagnostic tests and vaccine development. The platform allowed for the prediction of epidemiologic trends, facilitating a rapid response to changes in the epidemiologic situation. For example, using VGARus, an increase in COVID-19 incidence was accurately predicted in the summer of 2022 and early 2023, which were associated with the emergence of Omicron subvariants BA.5 and XBB. Data from the platform helps validate the effectiveness of primers and DNA probes to ensure high diagnostic accuracy and reduce the risk of false negatives. Conclusion. VGARus demonstrates the growing role of genomic surveillance in combating COVID-19 and improving preparedness for future infectious disease outbreaks. The platform is a powerful tool for generating evidence-based solutions to combat a pandemic and mitigate its health, economic and societal impacts. It provides the ability to promptly obtain information on the epidemiologic situation in a particular region of the Russian Federation, use genomic data for phylogenetic analysis, compare the mutational spectrum of SARS-CoV-2 sequences with foreign samples. VGARus data allow for both retrospective analysis and predictive hypotheses. For example, we can clearly see the dynamics of the change of different virus variants: sequences belonging to the Alpha, Beta, Delta, Omicron lineages and many less common ones, clearly form the upsurges of morbidity, the interaction of which is reflected in the epidemiological picture. It is also currently being expanded to monitor other pathogens, increasing its public health relevance.

Monakhov N.E., Ermakov A.I., Obizhaeva E.S., Vinogradova T.N., Lioznov D.A.

The aim of the study: to assess the genetic diversity of HIV-1 variants circulating in St. Petersburg.Materials and methods. The study included 289 patients with virological ART failure in 2022 in the St. Petersburg AIDS Center. Fragments of the pol gene encoding integrase, reverse transcriptase and protease were analyzed by polymerase chain reaction and Sanger sequencing. Phylogenetic tree created by the Neighbor-joining method with 1000 repeats of nucleotide sequences, bootstrap values >70. To assess the circulation of HIV genovariants in dynamics in St. Petersburg, sequences and clinical and laboratory parameters obtained from 544 patients since 2018. The total sample included 833 samples (289 were collected in 2022), compared with the results of a study from 1104 HIV-infected patients in 2006–2011.Results and discussion. Monovariants of HIV dominated in the examined patients (95.1%, 275 people), subtype A6 — 88.2% (255 people); subtype B — 5.9% (17 people); C — 0.3% (1 person); G — 0.7% (2 people), the proportion of recombinant forms — 4.9% (14 people). In the sample collection, the proportion of new HIV cases of non-A subtype was 13.3% in 2006–2011, and 11.1% in 2018–2022. A significant increase in the incidence of recombinant forms of HIV-1 was revealed from 1.6% to 3.5% (c2=6.111; p=0.014). In the group (2018–2022), the recombinant form of CRF63_02A6 was more common (15/29 people).Conclusion. Phylogenetic analyses makes it possible to determine HIV subtypes, but also to establish the potential geographical origin of the virus, to identify transmission clusters taking into account the socio-demographic indicators of HIV-infected patients. Molecular epidemiological monitoring can be used to develop and implement programs to counter the spread of HIV among the population. The dominant genetic variant of HIV circulating in St. Petersburg is sub-subtype A6, as it was 10 years ago. The proportion of new cases of infection with non-A subtype of HIV remains stable, with a downward trend. The increase in the frequency of detection of recombinant forms of HIV-1 is probably related to the migration processes of the population.

Smelyansky V.P., Zhukov K.V., Nikitin D.N., Kargashin S.A., Klimina I.A., Taratutina M.N., Romasova E.I., Kondratenko E.V.

The article is devoted to the analysis of the epidemiological situation of natural focal infections (NFI) in the Volgograd region in 2022. Materials and methods: The work used the official statistics of the institutions of Rospotrebnadzor on NFI for 2022. The main research method is epidemiological analysis. Results and discussion: It has been established that the numbers of small mammals, potential carriers of NFI, as well as ixodid ticks in the territory of the Volgograd region in the season of 2022 were higher than the same indicators of the previous year (SIPY). The number of mosquitoes, carriers of arbovirus infections, did not exceed the average long-term indicators in any species. When examining environmental objects for the presence of markers of NFI pathogens, a slight increase in the proportion of positive samples compared to SIPY in all nosological forms was noted. Sporadic cases of West Nile fever (WNF), Crimean hemorrhagic fever (CHF), hemorrhagic fever with renal syndrome (HFRS), ixodes ricinus-borne diseases (TBDs), Q fever have been registered; no cases of tularemia, rabies, leptospirosis were detected. The morbidity rates of the population of the Volgograd region for all NFI were at the level or lower than those for the Russian Federation and the Southern Federal District.

Komarovsky Y.Y., Gorbenko A.S., Vasilyeva D.I., Kuznetsova I.P., Oskorbin I.P., Filipenko M.L., Stolyar M.A., Olkhovsky I.A.

Chekanova T.A., Rakov A.V., Petremgvdlishvili K., Timonin A.V., Lukyanenko N.V., Safyanova T.V., Shirokostup S.V., Lukyanenko N.Y., Kalinina U.V., Pashchenko I.G.

Relevance. The Altai Кray with its administrative center, Barnaul, is an endemic region for tick–borne rickettsioses. The contribution of other tick-borne infections (TBI) to the structure of overall morbidity in the subject is significantly lower. To assess the risks of complication of the epidemiological situation for bacterial TBI (tick-borne rickettsioses, borrelioses, human granolucytic anaplasmoses, human monocytic ehrlichiosis, coxiellosis) and understand the level of their diagnosis in the region, it is important to study the occurrence of their pathogens in ticks, comparing them with the officially registered incidence. The aim is the study of the epidemiological and epizootological situation in Barnaul for bacterial tick-borne infections as well as an analysis of the factors influencing the registration of the incidence of these infections. Materials and methods. The materials were official statistical reporting data, information, analytical materials, accounting and reporting documentation of the Department of Rospotrebnadzor and the Ministry of Health of the Altai Region. The infection of ticks collected in the biotopes of Barnaul with different landscapes by pathogens of tick-borne encephalitis, human granulocytic anaplasmosis (HGA), human monocytic ehrlichiosis (HME), borrelioses, rickettsioses, and Q fever were studied using molecular biological methods. The species of Rickettsia were determined by Sanger sequencing followed by phylogenetic analysis. Results. Rickettsia conorii subsp. raoultii detected in the Dermacentor ticks with a high occurrence (61.9%), DNA of R. helvetica detected in the Ixodes ticks (5.1%). R. sibirica was not been detected. The infection rate of ticks by Borrelia burgdoferi s.l. was 27.8%; 5.1% of imagos contained B. miyamotoi DNA. Pathogens of HGA, HME were founded in 6.2%, 1.0% of individuals of Ixodes ticks, respectively. In two copies out of 300, the causative agent of Q fever identified. The dynamics of the number of people affected by tick bite over the period 2014-2023 did not tend to decrease, and against this background, there is a continuing high incidence of Siberian tick typhus, in contrast to the incidence of borreliosis. Other bacterial TBI have not been noted in Barnaul officially. Conclusions. In Barnaul, high risks of complications of the epidemiological situation of ixodic tick-borne borreliosis (including non-erythemic forms) have identified, and underdiagnosis of the disease is likely. The question of the etiological structure of tick-borne rickettsiosis, the occurrence of infected individuals with an atypical picture remains unknown. The difficulty of diagnostic of tick-borne rickettsiosis without rash is aggravated by the shortage of reagent kits, primarily for the detection of specific antibodies. The landscape confinement of Dermacentor and Ixodes ticks should take into account when organizing long-term stationary observation sites for monitoring and forecasting the epidemiological and epizootological situation. The risks of Barnaul population infection by HGA, MECH and Q fever pathogens were also noted. Special attention should be paid to the introduction into clinical practice of reagent kits for complex laboratory verification of tick-borne infections. 

Teng Z., Yang L., Zhao N., Li X., Dai L., Zhang X., Shao T., Han L., Zheng R., Wen B., Kan B., Xu J., Lu X., Qin T.

Four laboratory-confirmed Astrakhan rickettsial fever (ARF) cases were identified in the Xinjiang Uygur Autonomous Region (XUAR) of China

Han L., Zhang Y., Jin X., Ren H., Teng Z., Sun Z., Xu J., Qin T.

ObjectivesWe conducted a systematic analysis of the notifiable rickettsial diseases in humans in China during 1950–2022.MethodsWe utilized descriptive statistics to analyze the epidemiological characteristics, clinical manifestations, and diagnostic characteristics of typhus group rickettsiosis (TGR) and scrub typhus (ST) cases.ResultsSince the 1950s, there have been variations in the incidence rate of TGR and ST in China, with a downtrend for TGR and an uptrend for ST. The South became a high-incidence area of TGR, whereas the North was previously the high-incidence area. ST cases were concentrated in the South and the geographic area of ST spread northward and westward. The seasonality of TGR and ST were similar in the South but distinct in the North. Most TGR and ST cases were reported by county-level medical institutions, whereas primary institutions reported the least. Delayed diagnosis was associated with fatal outcomes of TGR and ST. Cases in low-incidence provinces, confirmed by laboratory tests and reported from county/municipal-level institutions had higher odds of delayed diagnoses.ConclusionsOur study revealed significant changes in the epidemiological characteristics of TGR and ST in China, which can provide useful information to enhance the control and prevention strategies of rickettsial diseases in China.

Blokh A.I., Pen`evskaya N.A., Rudakov N.V., Egorova O.F., Manokhina K.A., Abdrashitova L.V., Saveliev D.A.

Relevance. The Altai Krai (AK) is among the least prosperous subjects of the Russian Federation in terms of the incidence of acute respiratory infections (ARI).Aim: to analyze the causes and conditions for the formation of a high incidence of ARI among the population of the Altai Krai based on an assessment of the long-term and intra-annual dynamics of the epidemic process in 2011–2021.Materials and methods. In the course of a retrospective epidemiological study according to the annual forms No. 2 of the state statistical observation (SOS) for 2011-2021 a comparative analysis of the incidence of ARI and community-acquired pneumonia (CAP) in various groups of the population of the AK, the Siberian federal district (SFD) and the population of the Russian Federation as a whole was carried out. Data for 2020–2021 («covid» period) was analyzed separately in comparison with the precovid period of 2011–2019. The intra-annual dynamics of the incidence of ARI and CAP in the AK were studied using the method of trend-seasonal decomposition according to the monthly forms No. 2 of the SOS.Results and discussion. It is established that in 2011–2021. the epidemic process of ARI in the AK was characterized by a higher level and rate of increase in the incidence of all population groups (adults and children, urban and rural) compared to the all-Russian and average for the Siberian Federal District; a higher proportion of children in the overall structure of ARI cases, despite the fact that the proportion of the child population did not exceed (or was even less) than in other regions; no decrease in the incidence of ARI in children in the period 2020–2021; the presence of a trend towards an increase in the incidence of ARI in both urban and rural residents in the pre-covid period; higher incidence in the rural population in 2011–2019 compared to the whole of the Russian Federation or the Siberian Federal District. A less pronounced role of the seasonal component in the registration of CAP was revealed, in comparison with ARI. In some years, an increase in the registration of CAP was observed in the spring-summer period. For 2020-2021 there was a close coincidence of the curves of the intra-annual dynamics of the registered incidence of ARI and COVID-19 among the general population, CAP and COVID-19.Conclusion. The obtained results indicate the need to study the possible impact of environmental factors, as well as the shortcomings of the etiological interpretation and differential diagnosis of some natural focal and zoonotic infections that occur with fever and respiratory symptoms on the formation of a high incidence of ARI in the Altai Territory.

Xu N., Liu H., Qu C., Wen S., Zou W., Chang C., Wang G.

China is not considered as an endemic area of Rickettsia conorii, so there is no routine clinical way to diagnose this infection. This study aims to determine whether 2 febrile patients who had a tick bite in East China were indeed infected with R. conorii. The citrate synthase gene (gltA) was amplified with universal rickettsial primers by real-time fluorescent PCR from the patients’ blood samples. Nested PCR was used to amplify the outer membrane protein A gene (ompA) for positive specimens. PCR products were further identified and analyzed through nucleic acid sequencing. Positive amplification of the gltA and ompA genes was found in both patients. The nucleotide sequences (303 bp) of the ompA gene of the 2 patients had high homology (99%) with the R. conorii Indian tick typhus strain in GenBank. A more than 4-fold increase in IgG against R. conorii provided supportive evidence of SFG Rickettsia infection. And the rapid recovery after doxycycline treatment also supported a rickettsial cause for the disease. Physicians in East China should be aware of human infections with R. conorii. PCR-based diagnostic methods offer a rapid and precise way to diagnose rickettsiosis, improving patient identification and management.

Pen’evskaya N.A., Rudakov N.V., Shpynov S.N., Blokh A.I., Trankvilevsky D.V., Savel’ev D.A., Shtrek S.V., Sannikov A.V.

The aim of the review was to characterize the epidemiological situation on tick-borne rickettsioses (TR) in the Russian Federation in 2022 in comparison with the pandemic years of 2020–2021 and the pre-pandemic period of 2013–2019, to give the forecast for 2023. During 2013–2022, a pattern was observed in the incidence of rickettsiosis of the tick-borne spotted fever group (with the exception of Astrakhan spotted fever – ASF), that is also characteristic of most other natural focal infections (NFIs): a sharp decrease in registered incidence rates in 2020–2021 with the subsequent increase in 2022 almost up to pre-pandemic levels or even exceedance in some regions. The absence of a defining influence of the frequency of contacts of the population with vectors on the decrease in the incidence in the period of 2020–2021 and the rise in the value in 2022 confirms the registration-related nature of the changes. Given due attention to the problem of effective detection and reporting of NFIs, we expect the incidence of tick-borne rickettsioses to remain within the confidence intervals of long-term average values in most endemic regions in 2023. Relaxed vigilance to the problem of NFIs may lead to a decline in the reported incidence of Siberian tick-borne typhus in the Krasnoyarsk and Zabaikalsky Territories, Republics of Tuva and Khakassia, Novosibirsk and Amur Regions; reduction in the incidence of ASF in Astrakhan Region. The main issue in detecting and registration of the tick-borne rickettsiosis incidence, objective assessment and forecasting of the epidemic situation as regards this group of infections is conditioned by the lack of domestic certified diagnostic test kits for laboratory verification of rickettsioses. Close cooperation between epidemiologists and clinicians is required to establish and register cases of TR based on clinical and epidemiological data.

Yankovskaya Y.D., Chekanova T.A., Kutateladze M.V., Petremgvdlishvili K., Chernobrovkina T.Y.

Aim of the work: to demonstrate the difficulty of verifying the diagnosis of Q fever with negative results of PCR (DNA of Coxiella burnetii) in the blood and to assess the occurrence of serological markers among patients selected for this study based on a combination of clinical and epidemiological data. Materials and methods: plasma/serum samples of 111 patients according to clinical and epidemiological data studied due ELISA and PCR for specific antibodies to Coxiella burnetii and DNA of pathogen. Additionally, in the presence IgG to C. burnetii phase II, IgG / IgA to phase I and the avidity of specific IgG were studied. Results: the specific antibodies to C. burnetii antigens at negative results of PCR detected in 10 cases. The article provides the description of three clinical cases for demonstration of difficulties of coxiellosis diagnosis with analysis of serological profiles, titers and avidity of antibodies. Conclusion: the results of the study indicate that negative results of PCR testing do not exclude C. burnetii infection. For patients who, according to clinical and epidemiological data, Q fever is not excluded, it is advisable to prescribe a complex of laboratory tests to verify the diagnosis, which includes not only studies of the pathogen’s DNA, but also specific antibodies. To clarify the stage of the disease and reduce the risk of developing complications of coxiellosis, it is necessary to monitor the dynamics of antibody titers to C. burnetii in phase I and II phase states differentially.

Сhekanova T.A., Petremgvdlishvili K.

Relevance. Q fever in the absence of pathognomic signs is difficult to verify, so the incidence rate of coxiellosis depends on the level of its laboratory diagnosis.Aim. To analyze the incidence of Q fever in the Russian Federation for the time of its official registration (1957–2021) with an assessment of the level of laboratory diagnosis of diseases in different years. The high interest to Q fever in the middle of the last century gave impetus to the commercial production of inactivated Coxiella antigens and kits. The subsequent shortage of economically available diagnostic kits reflected in the official incidence of Q fever. Hypodiagnosis is caused not only by the clinical incidence of infection, but also often by the lack of the possibility of conducting a comprehensive clinical study of the material (detection of antibodies and DNA pathogen). The article presents historical facts for understanding of the rise and incidence of Q fever during the time of its official registration.Conclusions. An analysis of the epidemiological situation should carried taking into account the assessment of the level of diagnosis of Q fever in the regions and the country asa whole. It is necessary to record all newly diagnosed cases of the disease at any stage.

van de Klundert M.A., Antonova A., Di Teodoro G., Ceña Diez R., Chkhartishvili N., Heger E., Kuznetsova A., Lebedev A., Narayanan A., Ozhmegova E., Pronin A., Shemshura A., Tumanov A., Pfeifer N., Kaiser R., et. al.

The HIV epidemic in Eastern Europe and Russia is large and not well-controlled. To describe the more recent molecular epidemiology of HIV-1, transmitted drug resistance, and the relationship between the epidemics in this region, we sequenced the protease and reverse transcriptase genes of HIV-1 from 812 people living with HIV from Ukraine (n = 191), Georgia (n = 201), and Russia (n = 420) before the initiation of antiretroviral therapy. In 190 Ukrainian patients, the integrase gene sequence was also determined. The most reported route of transmission was heterosexual contact, followed by intravenous drug use, and men having sex with men (MSM). Several pre-existing drug resistance mutations were found against non-nucleoside reverse transcriptase inhibitors (RTIs) (n = 103), protease inhibitors (n = 11), and nucleoside analogue RTIs (n = 12), mostly polymorphic mutations or revertants. In the integrase gene, four strains with accessory integrase strand transfer inhibitor mutations were identified. Sub-subtype A6 caused most of the infections (713/812; 87.8%) in all three countries, including in MSM. In contrast to earlier studies, no clear clusters related to the route of transmission were identified, indicating that, within the region, the exchange of viruses among the different risk groups may occur more often than earlier reported.

Semenenko T.A., Akimkin V.G., Burtseva E.I., Nozdracheva A.V., Simonova E.G., Tutelyan A.V., Ugleva S.V., Kuzin S.N.

Annualy, SARS occupy a leading position in terms of morbidity and the magnitude of the economic damage caused both in the world and in the Russian Federation. Currently, the most widespread pandemics are caused by the influenza A (H1N1) pdm09 virus and the new SARS-CoV-2 coronavirus, which occupy a common ecological niche and require studying the manifestations of the epidemic process of ARVI for further development of measures to improve epidemiological surveillance of this group of infections. Aim of the study was to investigate the current manifestations of the epidemic process of ARVI and influenza, including in the context of a new coronavirus infection (COVID–19) pandemic, on the territory of Russia and in Moscow. Materials and methods. The assessment of the long-term dynamics of the incidence of ARVI and influenza (from 1999 to 2021), as well as its age structure in the territory of the Russian Federation and in Moscow, was carried out. The main sources of information were: WHO: «The situation with COVID-19 in the European region», the domestic information portal Stopkoronavirus.rf, as well as data from Federal State Statistical Observation forms No. 2 and No. 6. Results. During the period 2013–2019, a strong positive correlation was revealed between the incidence rates of ARVI in the Russian Federation and Moscow (p = 0.8, with p < 0.05), which became negative with the spread of SARS-CoV-2: in the country, the incidence rate of ARVI increased by 11.5% in 2020 and 15.6% in 2021., in Moscow there was a decrease of 45.1% than the average in Russia, which could be due to the quality of differential diagnosis of ARVI and COVID-19. In 2021 the incidence rate of influenza decreased by more than 2 times in all Federal Districts of the country, with the exception of the capital region, where it became the maximum - 65.9 per 100 thousand population in 2021 (against 14.1 in 2019). In the age structure of influenza incidence, as well as ARVI, for the period from 2019 to 2021. the child population prevailed with the highest rates in the age groups of 1–2 years and 3–6 years. As the circulation of SARS-Cov-2 decreased to 15–19%, the activity of influenza viruses and other pathogens of the ARVI group increased (from 0.7–3.0% during the developed pandemic to 5.6–6.6% at the stage of its decline), which indicates a pronounced interference of pathogens detected at the global level in the system of Global Hospital Surveillance for flu. Conclusion. The forecast for the upcoming epidemic season 2022–2023 largely depends on the spread of the new coronavirus SARS-CoV-2, as well as its variability and the emergence of new variants. Nevertheless, there may be a significant increase in the incidence caused by the influenza A(H1N1)pdm09 virus, whose high activity was recorded in the current epidemic season in a number of countries in the Southern hemisphere.

Shpynov S.N., Rudakov N.V., Zelikman S.Y., Trankvilevskiy D.V.

Rudakov N.V., Pen’evskaya N.A., Kumpan L.V., Blokh A.I., Shpynov S.N., Trankvilevsky D.V., Shtrek S.V.

The aim of the review was to characterize the epidemiological situation on rickettsiosis of the tick-borne spotted fever (TSF) group in the constituent entities of the Russian Federation in 2012–2021 and provide a long-term forecast for 2022–2026. In 2020–2021, indicators of registered incidence of tick-borne rickettsiosis in Russia on the whole decreased relative to the average long-term pre-pandemic level in 2012–2019 by 2 fold for all forms of the TSF group on average (Siberian tick-borne typhus – STT, Astrakhan spotted fever and Mediterranean fever). A comparative analysis of the territories revealed a correlation between the incidence of STT and the number of medical facility visits due to “tick bites” (r=0.67, p=0.015), which, against the background of an increase in the frequency of contacts of the population with vectors in 2020–2021 in most regions and a decrease in the incidence in the same regions indicates the credible nature of the changes. The ranking of territories according to average long-term incidence rates made it possible to classify the Republic of Altai and the Altai Territory as regions of extremely high epidemic hazard as regards STT; high hazard – the Republic of Tuva; above average – the Republic of Khakassia, Khabarovsk Territory and the Jewish Autonomous Region. The established downward trend in the incidence of tick-borne rickettsiosis among the population will be sustained in most entities of the Russian Federation within the next 5 years, excluding the Republic of Altai, the Altai Territory, the Republic of Crimea and the city of Sevastopol, where current incidence or an increase should be expected. The results of the analysis indicate the need to put more emphasis on natural-focal infections at the time of COVID-19 pandemic.

Miranda M.N., Pingarilho M., Pimentel V., Martins M.D., Kaiser R., Seguin-Devaux C., Paredes R., Zazzi M., Incardona F., Abecasis A.B.

BackgroundThe increased use of antiretroviral therapy (ART) has decreased mortality and morbidity of HIV-1 infected people but increasing levels of HIV drug resistance threatens the success of ART regimens. Conversely, late presentation can impact treatment outcomes, health costs, and potential transmission of HIV.ObjectiveTo describe the patterns of transmitted drug resistance (TDR) and acquired drug resistance (ADR) in HIV-1 infected patients followed in Europe, to compare its patterns in late presenters (LP) vs non-late presenters (NLP), and to analyze the most prevalent drug resistance mutations among HIV-1 subtypes.MethodsOur study included clinical, socio-demographic, and genotypic information from 26,973 HIV-1 infected patients from the EuResist Integrated Database (EIDB) between 1981 and 2019.ResultsAmong the 26,973 HIV-1 infected patients in the analysis, 11,581 (42.9%) were ART-naïve patients and 15,392 (57.1%) were ART-experienced. The median age was 37 (IQR: 27.0–45.0) years old and 72.6% were males. The main transmission route was through heterosexual contact (34.9%) and 81.7% of patients originated from Western Europe. 71.9% of patients were infected by subtype B and 54.8% of patients were classified as LP. The overall prevalence of TDR was 12.8% and presented an overall decreasing trend (p for trend &lt; 0.001), the ADR prevalence was 68.5% also with a decreasing trend (p for trend &lt; 0.001). For LP and NLP, the TDR prevalence was 12.3 and 12.6%, respectively, while for ADR, 69.9 and 68.2%, respectively. The most prevalent TDR drug resistance mutations, in both LP and NLP, were K103N/S, T215rev, T215FY, M184I/V, M41I/L, M46I/L, and L90M.ConclusionOur study showed that the overall TDR (12.8%) and ADR (68.5%) presented decreasing trends during the study time period. For LP, the overall TDR was slightly lower than for NLP (12.3 vs 12.6%, respectively); while this pattern was opposite for ADR (LP slightly higher than NLP). We suggest that these differences, in the case of TDR, can be related to the dynamics of fixation of drug resistance mutations; and in the case of ADR with the more frequent therapeutic failure in LPs.

Gafarova M.T., Bondarenko E.I., Maliy K.D., Alieva E.E., Evstafiev I.L., Tovpinec N.N., Malaya N.K., Kubyshkin A.V.

The paper presents the results of a study of the prevalence of Ixodid ticks - potential carriers of tick-borne rickettsiosis pathogens. Ectoparasites were collected in various natural and climatic zones of the Crimean Peninsula within the year 2016-2018. As a result of screening with the help of real-time PCR analysis (PCR-RT), a genetic marker (a section of the gltA gene) of the rickettsia group of tick-borne spotted fever was detected in ticks. The most common DNA marker of rickettsia was found in ticks in the eastern regions of the steppe zone - 50,6 %, in the north-western part of the steppe zone this value was 12,0 %. The least amount of rickettsia target DNA was detected in ticks collected in the mountain forest and south bank zones - 4,5 %. As a result of sequencing of positive DNA samples from fragments of the gltA, ompA, ompB, and sca4 genes, the species composition of rickettsias was established. The DNA of 8 species of rickettsia was identified: Circulation of three R. conorii, R. massiliae, R. sibirica subsp. mongolotimonae, R. slovaca, R. aeschlimannii, R. monacensis, R. helvetica, R. raoultii. R. massiliae, R. slovaca, and R. helvetica were established in the Crimean Peninsula for the first time. The peculiarities of the geographical distribution of the identified rickettsia species were determined, which was due to the spread of mites-carriers of pathogens. The revealed diversity of rickettsia species and their vectors, due to the isolation of the areas of the main feeding animals and the established routes of migratory birds, suggests the circulation of other rickettsia species on the territory of the Crimean Peninsula. The obtained results suggest that the diseases of tick-borne rickettsiosis in the Crimean Peninsula can be caused not only by R. conorii, as previously thought, but also by other types of rickettsii.

Piterskiy M.V., Gusev A.G., Khodakov O.A., Zakharova Y.A., Semenov A.V.

Introduction. Ural Federal District (UFD) has been one of the most HIV-affected areas in the Russian Federation during past 20 years. The total number of people living with HIV/AIDS (PLWH) and receiving antiretroviral therapy (ART) exceeds 100,000 (61.7% of all PLWH in the UFD), which creates opportunities for the wide spread of resistant HIV strains.Research aim was to determine the distribution of HIV-1 subtypes, evaluate the genetic heterogeneity of HIV-1 strains, and analyze the prevalence of HIV-1 drug resistance mutations (DRM) and the incidence of acquired resistance to antiretroviral drugs (ARVDs) in PLWH receiving ART in the UFD.Materials and methods. 223 patients receiving ART at stage III–IV of HIV infection living in the UFD were examined. To determine the subtypes and the DRM in the HIV-1 pol gene, molecular genetic studies were performed using the AmpliSense® HIV-Resist-Seq kit by Sanger sequencing on the Applied Biosystems 3500 Genetic Analyzer. The genetic heterogeneity was evaluated by calculating the identity of the genome region of the isolated strains in comparison with the genomes of foreign HIV strains, as well as using phylogenetic analysis.Results. In the studied group of patients, 5 subtypes of HIV-1 were identified: subtype A6 prevalence was 91.03%, that of subtype B was 2.69%, 3 recombinant subtypes (CRF03_A6B, CRF02_AG, CRF63_02A6) accounted for 6.28%. Among analyzed HIV-1 strains, 43.9% had a significant genetic similarity (identity of at least 97%) with the strains isolated from patients from neighboring countries (Belarus, Kazakhstan, Kyrgyzstan, Uzbekistan, Lithuania), 35.9% were similar to the strains isolated from patients from far-abroad countries (USA, China, South Korea, Australia, Sweden, Germany). A high heterogeneity of the circulating genetic variants of HIV-1 strains in the territory of the UFD region was established, which is an unfavorable factor for the diagnosis and treatment of HIV. The most common DRMs to both nucleoside reverse transcriptase inhibitors (NRTI) and non-nucleoside reverse transcriptase inhibitors (NNRTI) were detected in 81 specimens (36.3%). NRTI resistance-forming M184V DRM was more common than any other DRM with statistical significance (p = 0,0008) and was detected in 88 specimens (39.5%).Conclusion. In the subtype structure of HIV-1, the dominant subtype was subtype A6, the most common in the countries that were formerly part of the USSR. The heterogeneity of the HIV-1 strains circulating in the UFD suggests that HIV-1 infection continues to be introduced into the UFD from populations outside the Russian Federation. The findings confirm the high prevalence of DRMs (62.8%) and secondary drug resistance of HIV-1 (60.1%) among PLWH in the territory of the UFD. At the same time, high-level resistance was detected in 56.5% of patients, which requires increasing the coverage of HIV resistance testing, including the introduction of monitoring for primary resistance, in order to optimize first-line ART regimens. 

Kuznetsova A., Lebedev A., Gromov K., Kazennova E., Zazzi M., Incardona F., Sönnerborg A., Bobkova M.

General consensus suggests that even singleton E138A mutations in HIV reverse transcriptase at baseline are associated with resistance to rilpivirine (RPV). We detected 11 pre-existing E138A carriers treated with RPV in the pan European EuResist database. However, all 11 patients presented with full virological efficacy for first-line RPV-based ART regimens.