Abstract

Background Zoonotic viruses, such as Orthohantavirus andesense (ANDV; the causative agent of hantavirus cardiopulmonary syndrome, HCPS), pose significant public health risks at the human-wildlife interface. Understanding their eco-epidemiological dynamics is critical for elucidating the interplay between reservoir hosts, environmental factors, and spillover to humans. In Chile, the long-tailed pygmy rice rat (Oligoryzomys longi-caudatus) serves as the primary reservoir for ANDV. This study investigates whether protected areas (PA), which typically support higher biodiversity and stable ecosys-tems, exhibit lower ANDV seroprevalence compared to unprotected areas (UPA), where anthropogenic disturbances may alter host-pathogen dynamics. Methodology Between 2001–2008, we conducted small mammal sampling across 22 sites (11 PA and 11 UPA) in natural landscapes of Chile. Seroprevalence of ANDV was assessed via strip immunoassay, while small mammal diversity was evaluated using standardized trapping protocols and diversity indices. We used similarity percentage analysis to identify species contributing to community dissimilarities and applied Renyi diversity profiles to compare small mammal diversity between area types. Main Findings We captured 627 small mammals (PA: 331, 14 species; UPA: 296, 10 species) across 12,898 trap-nights. Seroprevalence in O. longicaudatus was identical in PA and UPA (9.5%). No significant differences were found in the relative abundance or seropositivity of O. longicaudatus between area types. Ecological indices (Shannon-Wiener, Simpson, richness, evenness) and community composition (ANOSIM) also showed no significant differences. Rényi profiles indicated marginally higher diversity in PA, driven by greater richness and evenness. Conclusions These findings suggest that ecological factors, such as habitat type, climatic conditions, and/or human behavior, may play a more critical role in shaping viral prevalence than protection status alone. The study underscores the necessity for con-sistent public health interventions to mitigate the risk of hantavirus cardiopulmonary syndrome across all environments, particularly in regions where human activities intersect with natural habitats. © 2025 Torres-Pérez et al.