Evidence of rat hepatitis E virus across human and swine populations in Nigeria

Abstract Background. Rocahepevirus ratti (rat hepatitis E virus, ratHEV) is an emerging zoonotic hepevirus maintained in rodents and increasingly recognized as a cause of acute and chronic hepatitis in humans. In Africa, available evidence is confined to rodent reservoirs and environmental matrices; neither human serological exposure nor infection of a domestic animal host has been documented. Methods. We conducted a cross-sectional study in southwestern Nigeria. Serum from 527 participants recruited into three cohorts with differing expected exposure (livestock-contact workers, rural villagers, students) was tested for ratHEV-specific IgG using a dot blot assay. Human sera were additionally screened for ratHEV RNA by multiplex real-time RT-PCR targeting two ORF1 regions. In parallel, 544 swine fecal samples from the same setting were screened by the same assay, with confirmatory nested PCR and sequencing. Cohort seroprevalences were compared and potential associations were estimated by Firth penalized logistic regression with profile penalized-likelihood intervals. Results. RatHEV-specific IgG was detected in 15/527 participants (2.8%; 95% CI 1.7–4.6). Seropositivity was highest in the livestock-contact cohort (12/281; 4.3%; 95% CI 2.2–7.3), intermediate in students (2/79; 2.5%; 95% CI 0.3–8.9) and lowest in villagers (1/167; 0.6%; 95% CI 0.02–3.3). In the penalized model, livestock contact was associated with higher odds of seropositivity than village residence (OR 5.15; 95% CI 1.23–47.56; p = 0.022), whereas the student–villager contrast was not (OR 3.58; 95% CI 0.47–39.61; p = 0.212). No human serum pool was positive for ratHEV RNA. RatHEV RNA was detected in 4/544 swine fecal samples (0.7%; 95% CI 0.2–1.9). The four swine-derived sequences shared 98.3–99.7% nucleotide identity with each other and were assigned to genotype C1, subtype Ia, clustering with strains reported from a human case in France and from rodents in Sierra Leone. Conclusions. These findings extend African evidence on rat-associated hepeviruses from reservoir and environmental compartments to human serological exposure and molecular detection in domestic swine. The co-occurrence of human exposure and detection of ratHEV RNA in swine feces in a single setting supports integrated follow-up combining rodent, swine, environmental and clinically targeted human sampling in West Africa.