Introduction: Orthohantaviruses are zoonotic diseases transmitted mainly by rodents, particularly mice and rats, associated with multiple outbreaks in different continents. Despite its epidemiological relevance, there is a lack of systematic reviews and meta-analyses. Objective: To determine the combined global prevalence of Orthohantavirus infection in rodents. Methods: A systematic literature review was carried out in six databases (Web of Sciences, Scopus, PubMed, SciELO, Lilacs, Google Scholar) to evaluate the proportion of rodents infected with Orthohantavirus, defined by molecular and immunological techniques. The meta-analysis used a random effects model for the pooled prevalence and 95% confidence intervals (95%CI). Heterogeneity measures, Cochrane's Q, the I2 index and the tau-squared test were estimated. Results: A total of 35,706 rodents (229 studies) were evaluated for ELISA, in which 3360 were found positive, for seroprevalence of 4.9% (95%CI 4.3–5.4%) (τ2 = 0.001; Q = 4027.708; I2 = 94.339%, p < 0.001). For PCR (N = 8812, 91 studies) it was 3.2% (95%CI 2.5–3.9%) (τ2 = 0.001; Q = 397.483; I2 = 77.358%; p < 0.001). For IFA (N = 555, 7 studies) it was 18.8% (95%CI 9.4–28.2%) (τ2 = 0.011; Q = 51.239; I2 = 88.29%, p < 0.001). At the genus level, the studies evaluated Oligoryzomys (8.98%), Reithrodontomys (8.98%), Peromyscus (8.20%), Rattus (8.20%), and Akodon (6.64%). Conclusions: The global prevalence of Orthohantavirus is worrisome, with an increase in its report in certain regions, including Latin America. In this context, rodents have a role as reservoirs. The data of the present meta-analysis showed considerable seroprevalences with great variations by years, countries and Orthohantavirus species.
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