Lethal cases of lyssavirus encephalitis in humans after contact with bats in the Russian Far East in 2019–2021

Cover Page

Cite item

Full Text

Abstract

Introduction. On the territory of Russia four species of lyssaviruses (genus Lyssavirus) were identified, three of them caused human deaths.

The aim of work: to characterize fatal cases in humans after contacts with bats in the Far East in 2018–2021 and to perform typing of isolated pathogens.

Materials and methods. Lyssavirus infection was confirmed in samples of sectional material from people who died in the Amur Region in 2019, in the Primorsky Krai in 2019 and 2021. Diagnostics was performed by fluorescent antibody test (FAT) and RT-PCR using diagnostic kits of domestic production. Viruses were isolated in a bioassay. The nucleoprotein sequences were analyzed after 1st passage. The analysis of phylogenetic relationships and the construction of a dendrogram were performed using the MEGA7 software.

Results. The viruses that caused the fatal cases in humans in the Amur Region and Primorsky Krai share more than 90% identity to Lyssavirus irkut detected in Russia and China. Together they form a separate monophyletic cluster with 100% bootstrap support.

Conclusion. On the territory of Russia, monitoring of bat populations for infection with lyssaviruses is relevant. The material of people who died from encephalomyelitis of unknown etiology within 10–15 days from the onset of the disease must be examined for lyssavirus infection. It is necessary to develop PCR assays that employ genus-specific primers. The use of molecular biological methods is promising for improving the diagnosis of rabies and epidemiological surveillance, as well as increasing the efficiency of the system of biological safety of the population of the Russian Federation.

About the authors

E. M. Poleshchuk

Omsk Research Institute of Natural Focal Infections

Author for correspondence.
Email: e-poleschuk@yandex.ru
ORCID iD: 0000-0002-8217-5159

Ph.D. (Biol.), Head of Laboratory, Leading Researcher Laboratory of Ecology and Epidemiology of the Rabies

Russian Federation, 644080, Omsk

D. N. Tagakova

Omsk Research Institute of Natural Focal Infections; Omsk State Medical University

Email: e-poleschuk@yandex.ru
ORCID iD: 0000-0001-9890-1031

Junior Researcher Laboratory of Ecology and Epidemiology of the Rabies; PhD student, Department of Epidemiology

Russian Federation, 644080, Omsk; 644099, Omsk

G. N. Sidorov

Omsk Research Institute of Natural Focal Infections; Omsk State Pedagogical University

Email: e-poleschuk@yandex.ru
ORCID iD: 0000-0002-8344-7726

Chief Researcher Laboratory of Ecology and Epidemiology of the Rabies; Professor of the Department of Biology and Biological Education

Russian Federation, 644080, Omsk; 644099, Omsk

T. S. Orlova

Blagoveshchensk City Clinical Hospital

Email: e-poleschuk@yandex.ru
ORCID iD: 0000-0003-3074-0168

Deputy Head Doctor, Pulmonologist, Top Category Doctor

Russian Federation, 675000, Blagoveshchensk

N. S. Gordeiko

Primorye Antiplaque Station

Email: e-poleschuk@yandex.ru
ORCID iD: 0000-0003-2209-2762

Director, Ph.D. (Biol.)

Russian Federation, 692512, Ussuriysk

A. Zh. Kaisarov

Medical and sanitary unit No. 100

Email: e-poleschuk@yandex.ru
ORCID iD: 0000-0002-8411-3971

Epidemiologist

Russian Federation, 692880, Fokino

References

  1. Gribencha S.V., L’vov D.K. Rabies. In: L’vov D.K., ed. Virology Manual [Rukovodstvo po virusologii]. Moscow: MIA; 2013: 811–6. (in Russian)
  2. Botvinkin A.D. Rabies. In: Briko N.I., Onishchenko G.G., Pokrovskiy V.I., eds. Guide to the Epidemiology of Infectious Diseases. Volume 2 [Rukovodstvo po epidemiologii infektsionnykh bolezney. Tom 2]. Moscow: MIA; 2019: 199–223. (in Russian)
  3. Virus Taxonomy. The ICTV Report on Virus Classification and Taxon Nomenclature. Subfamily: Alpharhabdovirinae. Genus: Lyssavirus. Available at: https://talk.ictvonline.org/ictv-reports/ictv_online_report/negative-sense-rna-viruses/w/rhabdoviridae/795/genus-lyssavirus
  4. Nokireki T., Tammiranta N., Kokkonen U.M., Kantala T., Gadd T. Tentative novel lyssavirus in a bat in Finland. Transbound. Emerg. Dis. 2018; 65(3): 593–6. https://doi.org/10.1111/tbed.12833596
  5. Marston D.A., Horton D.L., Ngeleja C., Hampson K., McElhinney L.M., Banyard A.C., et al. Ikoma lyssavirus, highly divergent novel lyssavirus in an African civet. Emerg. Infect. Dis. 2012; 18(4): 664–7. https://doi.org/10.3201/eid1804.111553
  6. Coertse J., Markotter W., le Roux K., Stewart D., Sabeta C.T., Nel L.H. New isolations of the rabies-related Mokola virus from South Africa. BMC Vet. Res. 2017; 13(1): 37. https://doi.org/10.1186/s12917-017-0948-0
  7. WHO expert consultation on rabies: third report. Geneva; 2018. Available at: https://apps.who.int/iris/handle/10665/272364
  8. Banyard A.C., Hayman D., Johnson N., McElhinney L., Fooks A.R. Bats and lyssaviruses. Adv. Virus. Res. 2011; 79: 239–89. https://doi.org/10.1016/B978-0-12-387040-7.00012-3
  9. Banyard A.C., Evans J.S., Luo T.R., Fooks A.R. Lyssaviruses and bats: emergence and zoonotic threat. Viruses. 2014; 6(8): 2974–90. https://doi.org/10.3390/v6082974
  10. Rupprecht C., Kuzmin I., Meslin F. Lyssaviruses and rabies: current conundrums, concerns, contradictions and controversies. F1000Res. 2017; 6: 184. https://doi.org/10.12688/f1000research.10416.1
  11. Markotter W., Coertse J. Bat lyssaviruses. Rev. Sci. Tech. 2018; 37(2): 385–400. https://doi.org/10.20506/rst.37.2.2809
  12. Shipley R., Wright E., Selden D., Wu G., Aegerter J., Fooks A.R., et al. Bats and viruses: emergence of novel lyssaviruses and association of bats with viral zoonoses in the EU. Trop. Med. Infect. Dis. 2019; 4(1): 31. https://doi.org/10.3390/tropicalmed4010031
  13. Regnault B., Evrard B., Plu I., Dacheux L., Troadec E., Cozette P., et al. First Case of Lethal Encephalitis in Western Europe Due to European Bat Lyssavirus Type 1. Clin. Infect. Dis. 2022; 74(3): 461–6. https://doi.org/10.1093/cid/ciab443
  14. Fooks A.R., Cliquet F., Finke S., Freuling C., Hemachudha T., Mani R.S., et al. Rabies. Nat. Rev. Dis. Primers. 2017; 3: 17091. https://doi.org/10.1038/nrdp.2017.91
  15. Kuzmin I.V., Botvinkin A.D., McElhinney L.M., Smith S.S., Orciari L.A., Hughes G.J., et al. Molecular epidemiology of terrestrial rabies in the former Soviet Union. J. Wildlife Dis. 2004; 40(4): 617–31. https://doi.org/10.7589/0090-3558-40.4.617
  16. Deviatkin A.A., Lukashev A.N., Poleshchuk E.M., Dedkov V.G., Tkachev S.E., Sidorov G.N., et al. The phylodynamics of the rabies virus in the Russian Federation. PLoS One. 2017; 12(2): e0171855. https://doi.org/10.1371/journal.pone.0171855
  17. Sidorov G.N. Aspects of the historical development of natural foci of rabies in Europe and North Asia. Veterinarnaya patologiya. 2002; (1): 21–5. (in Russian)
  18. Sidorov G.N., Sidorova D.G., Poleshchuk E.M. Rabies of wild mammals in Russia in the late 20th – early 21st centuries. Zoologicheskiy zhurnal. 2010; 89(1): 26–36. (in Russian)
  19. Poleshchuk E.M., Sidorov G.N., Gribencha S.V. A summary of the data about antigenic and genetic diversity of rabies virus circulating in the terrestrial mammals in Russia. Voprosy virusologii. 2013; 58(3): 9–16. (in Russian)
  20. Poleshchuk E.M., Sidorov G.N., Nashatyreva D.N., Gradoboeva E.A, Pakskina N.D., Popova I.V. Rabies in the Russian Federation: INFORMATIONAL and Analytical Bulletin [Beshenstvo v Rossiyskoy Federatsii: Informatsionno-analiticheskiy byulleten’]. Omsk; 2019. (in Russian)
  21. Poleshchuk E.M., Sidorov G.N. Comparative analysis of features of epizootiological and epidemic situation and risk of rabies infection in the Russian Federation in early XXI century. Problemy osobo opasnykh infektsiy. 2020; (4): 16–25. https://doi.org/10.21055/0370-1069-2020-4-16-25 (in Russian)
  22. Poleshchuk E.M., Kuz’min I.V., Gazaryan S.V., Botvinkin A.D. West Caucasian lyssavirus of bats: lack of vaccine protection. Plecotus et al. 2003; (6): 67–71. (in Russian)
  23. Botvinkin A.D., Poleschuk E.M., Kuzmin I.V., Borisova T.I., Gazaryan S.V., Yager P., et al. Novel lyssaviruses isolated from bats in Russia. Emerg. Infect. Dis. 2003; 9(12): 1623–5. https://doi.org/10.3201/eid0912.030374
  24. Sidorov G.N., Poleshchuk E.M., Sidorova D.G. Changes in the role of mammals in human hydrophobia infection in Russia for a historically graspable period of the 16th to 21st centuries. Zoologicheskiy zhurnal. 2019; 98(4): 437–52. https://doi.org/10.1134/S0044513419040159 (in Russian)
  25. Botvinkin A.D., Kuzmin I.V., McElhinney L.M., Johnson N., Fooks A.R. The diversity of rabies virus in Russia demonstrated by anti-nucleocapsid monoclonal antibody application and limited gene sequencing. Dev. Biol. (Basel). 2006; 125: 79–90.
  26. Gradoboeva E.A., Poleshchuk E.M., Sidorov G.N., Shtrek S.V. To the problem of the application of molecular genetic methods in the diagnosis and epidemiological investigation of human rabies cases. Dal’nevostochnyy zhurnal infektsionnoy patologii. 2019; (37): 37–8. (in Russian)
  27. Selimov M.A., Tatarov A.G., Botvinkin A.D., Klueva E.V., Kulikova L.G., Khismatullina N.A. Rabies-related Yuli virus; identification with a panel of monoclonal antibodies. Acta Virol. 1989; 33(6): 542–6.
  28. Leonova G.N., Somova L.M., Belikov S.I., Kondratov I.G., Plekhova N.G., Krylova N.V., et al. The fatal case of lyssavirus encephalitis in the Russian Far East. In: Tkachev S.E., ed. Encephalitis. Croatia: In Tech; 2012: 231–50. https://doi.org/10.5772/52869
  29. Shcherbak Yu.N. Virology researches on the rabies problem in the Ukrainian SSR. In: Viruses and Viral Diseases [Virusy i virusnye zabolevaniya]. Kiev: Zdorov’e; 1984: 11–6. (in Russian)
  30. Botvinkin A.D., Selnikova O.P., Antonova L.A., Moiseeva A.B., Nesterenko E.Yu. Human rabies case caused from a bat bite in Ukraine. Rabies Bulletin Europe. 2005; 29(3): 5–7.
  31. Coertse J., Grobler C.S., Sabeta C.T., Seamark E., Kearney T., Paweska J.T., et al. Lyssaviruses in insectivorous bats, South Africa, 2003–2018. Emerg. Infect. Dis. 2020; 26(12): 3056–60. https://doi.org/10.3201/eid2612.203592
  32. Grobler C.S., Coertse J., Markotter W. Complete genome sequence of Matlo bat lyssavirus. Microbiol. Resour. Announc. 2021; 10(20): e0024121. https://doi.org/10.1128/MRA.00241-21
  33. Dean D.J., Abelseth M.K., Atanasiu P. The fluorescent antibody test. In: Meslin F.X., Kaplan M.M., Koprowski H., eds. Laboratory Techniques in Rabies. Geneva: WHO; 1996: 88–93.
  34. Koprowski H. The mouse inoculation test. Laboratory techniques in rabies. In: Meslin F.X., Kaplan M.M., Koprowski H., eds. Laboratory Techniques in Rabies. Geneva: WHO; 1996: 80–6.
  35. Meslin F.X., Kaplan M.M., Koprowski H., eds. Laboratory Techniques in Rabies. Geneva: WHO; 1996. Available at: https://apps.who.int/iris/handle/10665/38286
  36. Tordo N., Sacramento D., Bourhy H. The polymerase chain reaction (PCR) technique for diagnosis, typing and epidemiological studies of rabies. In: Meslin F.X., Kaplan M.M., Koprowski H., eds. Laboratory Techniques in Rabies. Geneva: WHO; 1996: 157–74.
  37. Heaton P.R., Johnstone P., McElhinney L.M., Cowley R., O’Sullivan E., Whitby J.E. Heminested PCR assay for detection of six genotypes of rabies and rabies-related viruses. J. Clin. Microbiol. 1997; 35(11): 2762–6. https://doi.org/10.1128/jcm.35.11.2762-2766.1997
  38. Liu Y., Zhang S., Zhao J., Zhang F., Hu R. Isolation of Irkut virus from a Murina leucogaster bat in China. PLoS Negl. Trop. Dis. 2013; 7(3): e2097. https://doi.org/10.1371/journal.pntd.0002097
  39. Kumar S., Stecher G., Tamura K. MEGA7: molecular evolutionary genetics analysis version 7.0 for bigger datasets. Mol. Biol. Evol. 2016; 33(7): 1870–4. https://doi.org/10.1093/molbev/msw054
  40. Botvinkin A.D., Sidorov G.N. Natural foci of rabies in the RSFSR and adjacent territories. In: Materials of the 5th Joint Congress of Hygienists, Epidemiologists, Microbiologists, Parasitologists and Infectious Disease Specialists of Kazakhstan [Materialy 5 ob”edinennogo s”ezda gigienistov, epidemiologov, mikrobiologov, parazitologov i infektsionistov Kazakhstana]. Alma-Ata; 1991: 95–8. (in Russian)
  41. Chen T., Miao F.M., Liu Y., Zhang S.F., Zhang F., Li N., et al. Possible transmission of Irkut virus from dogs to humans. Biomed. Environ. Sci. 2018; 31(2): 146–8. https://doi.org/10.3967/bes2018.017
  42. Kuzmin I.V., Hughes G.J., Botvinkin A.D., Orciari L.A., Rupprecht C.E. Phylogenetic relationships of Irkut and West Caucasian bat viruses within the Lyssavirus genus and suggested quantitative criteria based on the N gene sequence for lyssavirus genotype definition. Virus Res. 2005; 111(1): 28–43. https://doi.org/10.1016/j.virusres.2005.03.008
  43. Smith P.C., Lawhaswasdi K., Vick W.E., Stanton J.S. Isolation of rabies virus from fruit bats in Thailand. Nature. 1967; 216(5113): 384. https://doi.org/10.1038/216384a0
  44. Pal S.R., Arora B., Chhuttani P.N., Broor S., Choudhury S., Joshi R.M., et al. Rabies virus infection of a flying fox bat, Pteropus poliocephalus in Chandigarh, Northern India. Trop. Geogr. Med. 1980; 32(3): 2657.
  45. Hanlon C.A., Kuzmin I.V., Blanton J.D., Weldon W.C., Manangan J.S., Rupprecht C.E. Efficacy of rabies biologics against new lyssaviruses from Eurasia. Virus Res. 2005; 111(1): 44–54. https://doi.org/10.1016/j.virusres.2005.03.009
  46. Liu Y., Li N., Zhang S., Zhang F., Lian H., Wang Y., et al. Analysis of the complete genome of the first Irkut virus isolate from China: comparison across the Lyssavirus genus. Mol. Phylogenet. Evol. 2013; 69(3): 687–93. https://doi.org/10.1016/j.ympev.2013.07.008
  47. Liu Y., Chen Q., Zhang F., Zhang S., Li N., Lian H., et al. Evaluation of rabies biologics against Irkut virus isolated in China. J. Clin. Microbiol. 2013; 51(11): 3499–504. https://doi.org/10.1128/JCM.01565-13

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. Results of testing of samples from people who died after being bitten by bats and material of wild carnivores in the Real-time PCR reaction with a set of reagents for the detection of rabies virus RNA from Syntol LLC using specific detection channels: Yellow: a – human, Amurskaya region, 2019; b – human, Primorsky Krai, 2019; c – human, Primorsky Krai, 2021 and Orange: d – samples of wild carnivores, Amur Region, 2019. In illustrations a, b, c, d curves are to positive reactions for biomaterial samples. С+ – positive reaction control. The X-axis indicates normal fluorescence. The Y-axis indicates the number of cycles.

Download (251KB)
Indexing metadata
3. Fig. 2. Specific immunofluorescence of rabies lyssavirus antigen in brain imprints obtained during MFA using polyclonal Ig (FGBI “Federal Centre for Animal Health”). The prints were made from primary material (brain): a – human, Amur Region, 2019; b – human, Primorsky Territory, 2019; c – human, Primorsky Territory, 2021; d – healthy white mice. Olympus CX41 microscope, ×10 eyepiece, ×100 objective, DP 72 documentation system, oil immersion.

Download (552KB)
Indexing metadata
4. Fig. 3. Phylogenetic dendrogram obtained by the Neighbor-Joining method for 51 isolates of lyssaviruses of known species based on the alignment of the nucleoprotein gene sequences (N, 1258 bp). The nodes indicate the percentage of duplicate trees (bootstrap support, %) in which associated taxa are grouped together in the bootstrap test (1000 repetitions). The values of the bootstrap support indicators reflect the stability of the topology of the dendrogram and are significant at values > 70%. The analysis was performed in MEGA7 software.

Download (526KB)
Indexing metadata
5. Fig. 4. Cases of detection of Irkut lyssavirus (IRKV) in chronological order: 2002 – Russia, Irkutsk, Bat; 2007 – Russia, Primorsky Krai, Yakovlevsky district, Ozernoye village, human; 2012 – China, Jilin province, Bat; 2017 – China, Fuxin County, domestic dog; 2019 – Russia, Amur Region, Blagoveshchensk, human; 2019 – Russia, Primorsky Territory, Fokino, human; 2021 – Russia, Primorsky Krai, Chuguevsky district, Zavetnoe village, human.

Download (369KB)
Indexing metadata

Copyright (c) 2023 Poleshchuk E.M., Tagakova D.N., Sidorov G.N., Orlova T.S., Gordeiko N.S., Kaisarov A.Z.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Согласие на обработку персональных данных с помощью сервиса «Яндекс.Метрика»

1. Я (далее – «Пользователь» или «Субъект персональных данных»), осуществляя использование сайта https://journals.rcsi.science/ (далее – «Сайт»), подтверждая свою полную дееспособность даю согласие на обработку персональных данных с использованием средств автоматизации Оператору - федеральному государственному бюджетному учреждению «Российский центр научной информации» (РЦНИ), далее – «Оператор», расположенному по адресу: 119991, г. Москва, Ленинский просп., д.32А, со следующими условиями.

2. Категории обрабатываемых данных: файлы «cookies» (куки-файлы). Файлы «cookie» – это небольшой текстовый файл, который веб-сервер может хранить в браузере Пользователя. Данные файлы веб-сервер загружает на устройство Пользователя при посещении им Сайта. При каждом следующем посещении Пользователем Сайта «cookie» файлы отправляются на Сайт Оператора. Данные файлы позволяют Сайту распознавать устройство Пользователя. Содержимое такого файла может как относиться, так и не относиться к персональным данным, в зависимости от того, содержит ли такой файл персональные данные или содержит обезличенные технические данные.

3. Цель обработки персональных данных: анализ пользовательской активности с помощью сервиса «Яндекс.Метрика».

4. Категории субъектов персональных данных: все Пользователи Сайта, которые дали согласие на обработку файлов «cookie».

5. Способы обработки: сбор, запись, систематизация, накопление, хранение, уточнение (обновление, изменение), извлечение, использование, передача (доступ, предоставление), блокирование, удаление, уничтожение персональных данных.

6. Срок обработки и хранения: до получения от Субъекта персональных данных требования о прекращении обработки/отзыва согласия.

7. Способ отзыва: заявление об отзыве в письменном виде путём его направления на адрес электронной почты Оператора: info@rcsi.science или путем письменного обращения по юридическому адресу: 119991, г. Москва, Ленинский просп., д.32А

8. Субъект персональных данных вправе запретить своему оборудованию прием этих данных или ограничить прием этих данных. При отказе от получения таких данных или при ограничении приема данных некоторые функции Сайта могут работать некорректно. Субъект персональных данных обязуется сам настроить свое оборудование таким способом, чтобы оно обеспечивало адекватный его желаниям режим работы и уровень защиты данных файлов «cookie», Оператор не предоставляет технологических и правовых консультаций на темы подобного характера.

9. Порядок уничтожения персональных данных при достижении цели их обработки или при наступлении иных законных оснований определяется Оператором в соответствии с законодательством Российской Федерации.

10. Я согласен/согласна квалифицировать в качестве своей простой электронной подписи под настоящим Согласием и под Политикой обработки персональных данных выполнение мною следующего действия на сайте: https://journals.rcsi.science/ нажатие мною на интерфейсе с текстом: «Сайт использует сервис «Яндекс.Метрика» (который использует файлы «cookie») на элемент с текстом «Принять и продолжить».