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Abstract

Background

Rat hepatitis E virus (ratHEV) is an emerging virus causing acute and chronic hepatitis in humans. Rats are the main natural reservoir of this pathogen. Large-scale studies assessing ratHEV circulation in rodents in Spain are lacking.

Aim

We aimed to determine the prevalence of ratHEV in rats in Spain and evaluate potential transmission risk to humans.

Methods

We designed a cross-sectional nationwide study where black () and Norway () rats were collected and analysed between 2022 and 2023 for ratHEV infection using real-time (RT)-qPCR testing of liver tissue. Sequencing and analysis of ratHEV shedding in faeces were carried out in positive animals.

Results

RatHEV was detected in 125 of the 481 rats analysed, supposing a prevalence of 26.0% (95 CI%: 22.3–30.1). Positive rats were found in urban (25.6%), and farm (29.8%) settings. Black rats (31.3%) had 1.5 times higher odds of being infected by the virus than Norway rats (22.5%) (p = 0.049). Significantly higher prevalence of ratHEV was detected in rodents sampled from southern (31.9%) than northern (17.8%) Spain (p = 0.003). Viral RNA was detected in faeces from 45.5% of infected rats. Phylogenetic analysis evidenced a wide genetic diversity of ratHEV sequences, some showing high homology with ratHEV strains found in patients from Spain.

Conclusions

Circulation of ratHEV appears to be heterogeneous and the virus appears to be endemic among rat populations in Spain, highlighting the possible risk of zoonotic transmission of this emerging virus in this country.

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This work is licensed under a Creative Commons Attribution 4.0 International License.
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2025-03-27
2025-04-01
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References

  1. Benavent S, Carlos S, Reina G. Rocahepevirus ratti as an emerging cause of acute hepatitis worldwide. Microorganisms. 2023;11(12):2996.  https://doi.org/10.3390/microorganisms11122996  PMID: 38138140 
  2. Sridhar S, Yip CCY, Lo KHY, Wu S, Situ J, Chew NFS, et al. Hepatitis E virus species C infection in humans, Hong Kong. Clin Infect Dis. 2022;75(2):288-96.  https://doi.org/10.1093/cid/ciab919  PMID: 34718428 
  3. Rivero-Juarez A, Frias M, Perez AB, Pineda JA, Reina G, Fuentes-Lopez A, et al. , HEPAVIR and GEHEP-014 Study Groups. Orthohepevirus C infection as an emerging cause of acute hepatitis in Spain: First report in Europe. J Hepatol. 2022;77(2):326-31.  https://doi.org/10.1016/j.jhep.2022.01.028  PMID: 35167911 
  4. Reuter G, Boros Á, Pankovics P. Review of hepatitis E virus in rats: evident risk of species Orthohepevirus C to human zoonotic infection and disease. Viruses. 2020;12(10):1148.  https://doi.org/10.3390/v12101148  PMID: 33050353 
  5. Sridhar S, Yip CCY, Wu S, Cai J, Zhang AJX, Leung KH, et al. Rat hepatitis E virus as cause of persistent hepatitis after liver transplant. Emerg Infect Dis. 2018;24(12):2241-50.  https://doi.org/10.3201/eid2412.180937  PMID: 30457530 
  6. Wu H, Zhou L, Wang F, Chen Z, Lu Y. Molecular epidemiology and phylogeny of the emerging zoonotic virus Rocahepevirus: A global genetic analysis. Infect Genet Evol. 2024;118:105557.  https://doi.org/10.1016/j.meegid.2024.105557  PMID: 38244748 
  7. Casares-Jimenez M, Garcia-Garcia T, Suárez-Cárdenas JM, Perez-Jimenez AB, Martín MA, Caballero-Gómez J, et al. Correlation of hepatitis E and rat hepatitis E viruses urban wastewater monitoring and clinical cases. Sci Total Environ. 2024;908:168203.  https://doi.org/10.1016/j.scitotenv.2023.168203  PMID: 37914110 
  8. Casares-Jimenez M, Rivero-Juarez A, Lopez-Lopez P, Montes ML, Navarro-Soler R, Peraire J, et al. Rat hepatitis E virus (Rocahepevirus ratti) in people living with HIV. Emerg Microbes Infect. 2024;13(1):2295389.  https://doi.org/10.1080/22221751.2023.2295389  PMID: 38095070 
  9. Caballero-Gómez J, Pereira S, Rivero-Calle I, Perez AB, Viciana I, Casares-Jiménez M, et al. Acute hepatitis in children due to rat hepatitis E virus. J Pediatr. 2024;273:114125.  https://doi.org/10.1016/j.jpeds.2024.114125  PMID: 38815747 
  10. Rodriguez C, Marchand S, Sessa A, Cappy P, Pawlotsky JM. Orthohepevirus C hepatitis, an underdiagnosed disease? J Hepatol. 2023;79(1):e39-41.  https://doi.org/10.1016/j.jhep.2023.02.008  PMID: 36806365 
  11. Casares-Jimenez M, Corona-Mata D, Garcia-Garcia T, Manchado-Lopez L, Rios-Muñoz L, de Guia-Castro M, et al. Serological and molecular survey of rat hepatitis E virus (Rocahepevirus ratti) in drug users. Emerg Microbes Infect. 2024;13(1):2396865.  https://doi.org/10.1080/22221751.2024.2396865  PMID: 39193634 
  12. Thrusfield MV. Veterinary Epidemiology. 3rd ed. Oxford: Blackwell Publishing; 2005.
  13. Mulyanto, Suparyatmo JB, Andayani IG, Khalid, Takahashi M, Ohnishi H, et al. Marked genomic heterogeneity of rat hepatitis E virus strains in Indonesia demonstrated on a full-length genome analysis. Virus Res. 2014;179:102-12. 10.1016/j.virusres.2013.10.029 PMID: 24231359 
  14. Rodríguez JL. Guía de campo de los Mamíferos Terrestres de España. [Field guide to terrestrial mammals of Spain]. Barcelona: Edicones Omega; 1993. Spanish.
  15. Kumar S, Stecher G, Li M, Knyaz C, Tamura K. MEGA X: Molecular Evolutionary Genetics Analysis across computing platforms. Mol Biol Evol. 2018;35(6):1547-9.  https://doi.org/10.1093/molbev/msy096  PMID: 29722887 
  16. Semenza JC, Menne B. Climate change and infectious diseases in Europe. Lancet Infect Dis. 2009;9(6):365-75.  https://doi.org/10.1016/S1473-3099(09)70104-5  PMID: 19467476 
  17. Ecke F, Han BA, Hörnfeldt B, Khalil H, Magnusson M, Singh NJ, Ostfeld RS. Population fluctuations and synanthropy explain transmission risk in rodent-borne zoonoses. Nat comm. 2022;13(1):7532.
  18. Johne R, Heckel G, Plenge-Bönig A, Kindler E, Maresch C, Reetz J, et al. Novel hepatitis E virus genotype in Norway rats, Germany. Emerg Infect Dis. 2010;16(9):1452-5.  https://doi.org/10.3201/eid1609.100444  PMID: 20735931 
  19. Ryll R, Bernstein S, Heuser E, Schlegel M, Dremsek P, Zumpe M, et al. Detection of rat hepatitis E virus in wild Norway rats (Rattus norvegicus) and Black rats (Rattus rattus) from 11 European countries. Vet Microbiol. 2017;208:58-68.  https://doi.org/10.1016/j.vetmic.2017.07.001  PMID: 28888650 
  20. Porea D, Raileanu C, Crivei LA, Gotu V, Savuta G, Pavio N. First detection of hepatitis E virus (Rocahepevirus ratti genotype C1) in synanthropic Norway rats (Rattus norvegicus) in Romania. Viruses. 2023;15(6):1337.  https://doi.org/10.3390/v15061337  PMID: 37376636 
  21. De Sabato L, Monini M, Galuppi R, Dini FM, Ianiro G, Vaccari G, et al. Investigating the hepatitis E virus (HEV) diversity in rat reservoirs from Northern Italy. Pathogens. 2024;13(8):633.  https://doi.org/10.3390/pathogens13080633  PMID: 39204234 
  22. Simanavicius M, Juskaite K, Verbickaite A, Jasiulionis M, Tamosiunas PL, Petraityte-Burneikiene R, et al. Detection of rat hepatitis E virus, but not human pathogenic hepatitis E virus genotype 1-4 infections in wild rats from Lithuania. Vet Microbiol. 2018;221:129-33.  https://doi.org/10.1016/j.vetmic.2018.06.014  PMID: 29981698 
  23. Widén F, Ayral F, Artois M, Olofson AS, Lin J. PCR detection and analysis of potentially zoonotic Hepatitis E virus in French rats. Virol J. 2014;11(1):90.  https://doi.org/10.1186/1743-422X-11-90  PMID: 24886183 
  24. Murphy EG, Williams NJ, Jennings D, Chantrey J, Verin R, Grierson S, et al. First detection of Hepatitis E virus (Orthohepevirus C) in wild brown rats (Rattus norvegicus) from Great Britain. Zoonoses Public Health. 2019;66(6):686-94.  https://doi.org/10.1111/zph.12581  PMID: 31033238 
  25. Rios-Muñoz L, Gonzálvez M, Caballero-Gomez J, Castro-Scholten S, Casares-Jimenez M, Agulló-Ros I, et al. Detection of rat hepatitis E virus in pigs, Spain, 2023. Emerg Infect Dis. 2024;30(4):823-6.  https://doi.org/10.3201/eid3004.231629  PMID: 38526410 
  26. Palombieri A, Di Profio F, Sarchese V, Fruci P, Suffredini E, Martella V, et al. Surveillance for rat hepatitis E in wastewater networks, Italy. Microbiol Spectr. 2023;11(6):e0267523.  https://doi.org/10.1128/spectrum.02675-23  PMID: 37850788 
  27. Li TC, Yoshizaki S, Ami Y, Suzaki Y, Yasuda SP, Yoshimatsu K, et al. Susceptibility of laboratory rats against genotypes 1, 3, 4, and rat hepatitis E viruses. Vet Microbiol. 2013;163(1-2):54-61.  https://doi.org/10.1016/j.vetmic.2012.12.014  PMID: 23317806 
  28. Wang H, Neyvaldt J, Enache L, Sikora P, Mattsson A, Johansson A, et al. Variations among viruses in influent water and effluent water at a wastewater plant over one year as assessed by quantitative PCR and metagenomics. Appl Environ Microbiol. 2020;86(24):e02073-20.  https://doi.org/10.1128/AEM.02073-20  PMID: 33036988 
  29. Ayral F, Artois J, Zilber AL, Widén F, Pounder KC, Aubert D, et al. The relationship between socioeconomic indices and potentially zoonotic pathogens carried by wild Norway rats: a survey in Rhône, France (2010-2012). Epidemiol Infect. 2015;143(3):586-99.  https://doi.org/10.1017/S0950268814001137  PMID: 24838220 
  30. Robinson SJ, Borlang J, Himsworth CG, Pearl DL, Weese JS, Dibernardo A, et al. Rat hepatitis E virus in Norway rats, Ontario, Canada, 2018-2021. Emerg Infect Dis. 2023;29(9):1890-4.  https://doi.org/10.3201/eid2909.230517  PMID: 37610234 
  31. de Cock MP, de Vries A, Fonville M, Esser HJ, Mehl C, Ulrich RG, et al. Increased rat-borne zoonotic disease hazard in greener urban areas. Sci Total Environ. 2023;896:165069.  https://doi.org/10.1016/j.scitotenv.2023.165069  PMID: 37392874 
  32. Feng A, Himsworth CG. The secret life of the city rat: a review of the ecology of urban Norway and black rats (Rattus norvegicus and Rattus rattus). Urban Ecosyst. 2014;17(1):149-62.  https://doi.org/10.1007/s11252-013-0305-4 
  33. Li W, Guan D, Su J, Takeda N, Wakita T, Li TC, et al. High prevalence of rat hepatitis E virus in wild rats in China. Vet Microbiol. 2013;165(3-4):275-80.  https://doi.org/10.1016/j.vetmic.2013.03.017  PMID: 23623690 
  34. Caballero-Gómez J, Casares-Jiménez M, Gallo-Marín M, Pereira-Pardo S, Beato-Benítez A, Poyato A, et al. Rat hepatitis E virus as an aetiological agent of acute hepatitis of unknown origin. J Hepatol. 2025;S0168-8278(25)00136-9.  https://doi.org/10.1016/j.jhep.2025.02.027  PMID: 40020930 
National survey of the rat hepatitis E virus in rodents in Spain, 2022 to 2023
<p class="citation"> <span>Citation style for this article:</span> <span class="meta-value authors"> <a href="/search?value1=Javier+Caballero-G%C3%B3mez&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Caballero-Gómez Javier</a>, <a href="/search?value1=Tom%C3%A1s+Fajardo-Alonso&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Fajardo-Alonso Tomás</a>, <a href="/search?value1=Luc%C3%ADa+R%C3%ADos-Mu%C3%B1oz&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Ríos-Muñoz Lucía</a>, <a href="/search?value1=Adri%C3%A1n+Beato-Ben%C3%ADtez&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Beato-Benítez Adrián</a>, <a href="/search?value1=Mar%C3%ADa+Casares-Jim%C3%A9nez&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Casares-Jiménez María</a>, <a href="/search?value1=Ignacio+Garc%C3%ADa-Bocanegra&option1=author&noRedirect=true" class="nonDisambigAuthorLink">García-Bocanegra Ignacio</a>, <a href="/search?value1=Ra%C3%BAl+Cuadrado-Mat%C3%ADas&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Cuadrado-Matías Raúl</a>, <a href="/search?value1=Alba+Mart%C3%AD-Marco&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Martí-Marco Alba</a>, <a href="/search?value1=Javier+Mart%C3%ADnez&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Martínez Javier</a>, <a href="/search?value1=Remigio+Mart%C3%ADnez&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Martínez Remigio</a>, <a href="/search?value1=Eva+Mart%C3%ADnez+Nevado&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Nevado Eva Martínez</a>, <a href="/search?value1=Francisco+Ruiz-Fons&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Ruiz-Fons Francisco</a>, <a href="/search?value1=Jo%C3%A3o+Rodrigo+Mesquita&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Mesquita João Rodrigo</a>, <a href="/search?value1=M%C3%A0rius+Fuentes&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Fuentes Màrius</a>, <a href="/search?value1=Diana+Corona-Mata&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Corona-Mata Diana</a>, <a href="/search?value1=Mois%C3%A9s+Gonz%C3%A1lvez&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Gonzálvez Moisés</a>, <a href="/search?value1=V%C3%ADctor+Lizana&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Lizana Víctor</a>, <a href="/search?value1=Pilar+Soriano&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Soriano Pilar</a>, <a href="/search?value1=Pilar+Foronda&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Foronda Pilar</a>, <a href="/search?value1=Dietmar+Crailsheim&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Crailsheim Dietmar</a>, <a href="/search?value1=Antonio+Rivero-Ju%C3%A1rez&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Rivero-Juárez Antonio</a>, <a href="/search?value1=Antonio+Rivero&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Rivero Antonio</a></span>. National survey of the rat hepatitis E virus in rodents in Spain, 2022 to 2023. <a href="/content/ecdc">Euro Surveill.</a> 2025;30(12):pii=2400473. <a href="https://doi.org/10.2807/1560-7917.ES.2025.30.12.2400473" title="doi link" target="_blank">https://doi.org/10.2807/1560-7917.ES.2025.30.12.2400473</a> <span class="ES_Article_citation"> <span class="generated">Received</span>: 18 Jul 2024;&nbsp;&nbsp; <span class="generated">Accepted</span>: 17 Oct 2024 </span> </p>
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