Extrapolation and comparison of West Nile virus- and Usutu virus-associated neurological diseases in humans: linking pathology to clinical symptoms.

SUMMARYMosquito-borne orthoflaviviruses pose an ever-increasing risk to public health. A prime example is West Nile virus (WNV), which continues to expand its geographical distribution, leading to new outbreaks of severe disease in humans and animals. In contrast, the closely related Usutu virus (USUV) has rarely been associated with neurological disease despite its wide distribution in Europe where human cases of WNV-associated disease largely outnumber those of USUV. Thus, the risk to human health posed by USUV appears to be lower compared with WNV. However, considering their close relation and similarities in ecology, it is still not known why the clinical impact differs for these viruses. In this review, we explore the potential pathogenesis of USUV in human infection by comparing the clinical presentations reported in the few cases of USUV-associated disease with the extensive clinical and pathological data available for WNV. With such a comparison, we aim to determine the clinical significance of USUV and identify key differences between WNV and USUV, which could explain the disparity in the incidence of neurological disease. We identify that while the clinical reports of USUV infection do indicate involvement of similar brain regions as WNV, clinical presentations are not as severe and not as frequent and do not seem to progress to the same extent as many cases of WNV-related neuroinvasive disease. Additionally, we highlight the urgent need to standardize reporting of (arbo)viral meningoencephalitis cases to allow for a better comparison and understanding of viral pathogenesis and the risks posed by new and emerging arboviruses.