Unnoticed high human infection incidence for West Nile virus and Usutu virus in the Netherlands: evidence from a longitudinal nationwide cohort, 2020-2023
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Background
Ecological surveillance indicates (regional) establishment of West Nile virus (WNV) and Usutu virus (USUV) in the Netherlands. However, the incidence of human infections remains unknown.
Methods
We identified WNV and USUV infections in the Netherlands in 2020-2023, using a longitudinal, nationwide population-based cohort, applying a two-tiered serology approach based on protein micro-array and virus neutralization. IgG data were used to estimate overall seroprevalence and infection incidence, and to study antibody longevity. Study set-up enabled tracking of the period of seroconversion and linking of self-reported travel history. The analyses took account of the survey design and weights were incorporated to match the Dutch population distribution following census data.
Findings
Among 4290 participants, we identified 113 probable WNV and/or USUV cases, including 55 seroconversions. Thirty-six cases were confirmed by antibody neutralization, of which 12 seroconverted. Six confirmed seroconverters were identified as autochthonous infections. The overall weighted seroprevalence was estimated at 0.54% (0.21-0.87%) for WNV and 0.25% (0.09-0.40%) for USUV. The weighted incidence for autochthonous WNV and USUV infection was estimated as respectively 0.06% (95% CI 0-0.12%) and 0.04% (95% CI 0-0.09%).
Interpretation
The estimated infection incidence and seroprevalence of WNV and USUV indicate a substantial underdiagnosis of clinical cases in the Netherlands in 2020-2023. These observations highlight the need for increased awareness among physicians to identify cases and the need for continued paired syndromic-laboratory surveillance for these viruses.
Funding
This study was funded by the ministry of Health, Welfare and Sports, the Netherlands.
Research in context Evidence before this study
Regional outbreaks of West Nile virus (WNV) have occurred with increasing frequency and magnitude in various regions of Europe in the past decade, and the virus is still spreading to new areas. Usutu virus (USUV) has been circulating in Europe for decades. To get an overview of the existing evidence on WNV and USUV infections and circulation in the Netherlands, we searched PubMed for studies published until January 12, 2026 using search terms “west nile virus” OR “usutu virus” AND “the Netherlands”. We also reviewed reports from the Dutch National Institute for Public Health and the Environment (RIVM) and the European Centre for Disease Prevention and Control (ECDC). At the start of our study, only eight autochthonous confirmed human WNV infections were detected in the Netherlands, all in 2020. No human cases were reported since while ecological data from wild birds, horses and mosquitoes pointed at local circulation. USUV is known to circulate in the Netherlands since 2016, but evidence of the occurrence of human infections is limited to a single study among blood donors. There were no data on nationwide human infection incidence and seroprevalence in the Netherlands and no data on USUV IgG longevity in humans in general.
Added value of this study
This study is the first comprehensive and nationwide longitudinal serological study to investigate both human WNV and USUV infection in the Netherlands. It uses an extensively validated multiplex serological tool in combination with specialized virus neutralization techniques in a cohort representative of the general population. The longitudinal approach enabled tracking of seroconversion in time, and the study design supported the identification of autochthonous cases and linkage to symptom data. The unique study set-up enabled the estimation of the overall seroprevalence for WNV and USUV in the general Dutch population in fall/winter 2023 and the weighted local infection incidence for the period 2020-2023 to provide insight into the level of underreporting of human cases. Furthermore, the longitudinal follow-up of individual participants provided more insight into the longevity of WNV-specific IgG responses and provided previously unknown information on the longevity of USUV IgG in humans.
Implications of all the available evidence
This study is the first to demonstrates the occurrence of unrecognized, autochthonous human infections with WNV and USUV in the Netherlands in the period 2020-2023. While these viruses have a low symptomatic rate in humans, the estimated infection incidence and overall seroprevalence in this study are indicative of a significant underdiagnosis of (severe) clinical cases, especially for WNV. Our observations will strengthen the awareness among clinicians to include WNV (and USUV) in their differential diagnosis of patients with neurological complaints of unknow aetiology and underline the increasing need to create awareness among the general public for prevention of mosquito bites, which is highly relevant also given the recent resurgence of clinical cases and fatalities. This study complements sporadic ecological evidence of local circulation of both WNV and USUV in the Netherlands and highlights the growing relevance of continued WNV and USUV surveillance. The data on the longevity of USUV IgG informs an accurate interpretation of serological diagnostic tests in the context of orthoflavivirus cross-reactivity.
