Rat hepatitis E virus RNA detection in isolated cases of acute undifferentiated febrile illness without acute hepatitis.

Authors

Lucia Rios-Muñoz, Claudia Ferreira-Tata, Marina Gallo-Marin, Ana Belen Perez, Maria Casares-Jimenez, Diana Corona-Mata, Javier Caballero-Gomez, Serafin Gutierrez, Mario Frias, Pedro Lopez-Lopez, Pedro Gámez-Beltrán, João R Mesquita, Antonio Rivero-Juarez, Antonio Rivero

Published in

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases. Pages 109227. Nov 08, 2026. Epub Nov 08, 2026.

Abstract

Rat hepatitis E virus (ratHEV; Rocahepevirus ratti) is an emerging zoonotic pathogen whose clinical spectrum is predominantly hepatic. Whether ratHEV causes acute undifferentiated febrile illness (AUFI) without acute hepatitis has not been systematically evaluated.
This retrospective observational study at a southern Spain tertiary hospital (April 2021-October 2023) evaluated patients tested for Rickettsia spp. and/or Coxiella burnetii. AUFI was defined as community-acquired fever ≥38°C lasting <21 days without localizing features or initial etiology; patients with acute hepatitis were excluded. AUFI cases were compared with contemporaneous febrile patients presenting with a localizing focus. The primary outcome was sequence-confirmed infection. Detections without sequence recovery were classified as probable infections.
Of 1,684 patients assessed, 312 were eligible: 81 with AUFI (median age 53 years [IQR, 37-64]; 54 [66.7%] men) and 231 comparators. Sequence-confirmed ratHEV infection occurred in 1/81 AUFI patients (1.2%; 95% CI, 0.2-6.7) and 0/231 comparators (0%; 95% CI, 0-1.6; P = 0.260). Two additional AUFI patients had detectable ratHEV RNA without sequence recovery. Combining confirmed and probable infections, ratHEV RNA was detected in 3/81 AUFI patients (3.7%; 95% CI, 1.3-10.3; P = 0.017). The confirmed infection presented as a self-limiting febrile illness without liver dysfunction, ratHEV RNA cleared upon fever resolution. The recovered genotype C1 sequence clustered with ratHEV rodent sequences from the same region.
RatHEV RNA was detected exclusively among AUFI patients. These findings support prospectively evaluating ratHEV as a potential cause of AUFI where the virus circulates in animal reservoirs.

PMID:
43000095
Bibliographic data and abstract were imported from PubMed on 09 Nov 2026.

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