Rapid spread of a new West Nile virus lineage 1 associated with increased risk of neuroinvasive disease during a large outbreak in northern Italy, 2022: One Health analysis

Abstract

Background: A new strain of WNV lineage 1 (WNV - 1) emerged in the Veneto Region, northern Italy, in 2021, eight years after the last outbreak of WNV - 1 in Italy. The virus, which co-circulates with WNV-2, has become endemic in the Region, where, in 2022, most human cases of neuroinvasive disease (WNND) reported in Europe have occurred.

Methods: Comparative analysis of the epidemiology and clinical presentation of WNV-1 and WNV-2 infection in humans, as well as the temporal and geographic distribution of WNV-1 and WNV-2 among wild birds and Culex pipiens mosquitoes in Veneto, from May 16th to August 21st, 2022, to determine if the high number of WNND cases was associated with WNV-1.

Results: As of August 21st, 2022, 222 human cases of WNV infection were confirmed by molecular testing, including 103 with fever (WNF) and 119 with WNND. WNV lineage was determined in 201 (90.5%) cases, comprising 138 WNV-1 and 63 WNV-2 infections. During the same period, 35 blood donors tested positive, including 30 in whom WNV lineage was determined (13 WNV-1 and 17 WNV-2). Comparative analysis of the distribution of WNV-1 and WNV-2 infections among WNND cases, WNF cases and WNV-positive blood donors showed that patients with WNND were more likely to have WNV-1 infection than blood donors (odds ratio 3.44; 95% CI 95% 1.54 to 8.24; p = 0.0043). As observed in humans, in wild birds WNV-1 had higher infectious rate (IR) and showed a more rapid expansion than WNV-2. At variance, the distribution of the two lineages was more even in mosquitoes, but with a trend of rapid increase of WNV-1 IR over WNV-2.

Conclusions: Comparative analysis of WNV-1 vs WNV-2 infection in humans, wild birds, and mosquitos showed a rapid expansion of WNV-1 and suggested that WNV-1 infected patients might have an increased risk to develop severe disease.

Keywords: West Nile virus; bird; fever; lineage; mosquito; neuroinvasive disease.

Figure 1

Geographical distribution of WNV-1 (right panel) and WNV-2 (left panel) infections in humans, birds and mosquitoes in the Veneto Region as of 12 August 2022.

Figure 2

Temporal distribution of human cases of WNV infection according to WNV lineage, week (aggregated on a biweekly basis) of symptom onset and (A) provinces of the Veneto Region and (B) diagnosis (WNND, WNF, blood donors); (C) distribution of human cases of WNV infection according to WNV lineage and diagnosis; P = 0.0043, Chi-square test for trend).

Figure 3

(A) Number of tested and WNV-positive wild birds per province on a biweekly basis; the dashed line indicates the total number of tested animals (right axis); (B) biweekly MLE for WNV-1 and WNV-2 bird infection rate per province; vertical lines represent the 95% CIs.

Figure 4

(A) Number of tested and WNV-positive Cx. pipiens pools per province on a biweekly basis; the dashed line indicates the total number of tested mosquitoes (right axis); (B) biweekly MLE for WNV-1, and WNV-2 mosquito infection rate per province; vertical lines represent the 95% CIs.