West Nile virus infection in individuals with pre-existing Usutu virus immunity, northern Italy, 2018

Abstract

In 2018, there was a large West Nile virus (WNV) outbreak in northern Italy. We observed five atypical cases of WNV infection that were characterised by the presence of WNV RNA and WNV IgG at the time of diagnosis, but no IgM response during follow-up. Neutralisation assays demonstrated pre-existing Usutu virus immunity in all patients. Besides challenging diagnosis, the immunological crosstalk between the two viruses warrants further investigation on possible cross-protection or infection enhancement effects.

Human West Nile Virus Lineage 2 Infection: Epidemiological, Clinical, and Virological Findings

“…Laboratory diagnosis of WNV infection relies on the detection of viral RNA in blood, urine, or CSF and the demonstration of a specific antibody response in serum or CSF. Based on the results of this study and on our previous experience with the diagnosis of WNV infection [6,14,21,23], we recommend an integrated approach, combining serology and molecular testing, to increase diagnostic sensitivity and specificity. In fact, within the first week after symptom onset, WNV-specific antibodies were absent in 20-40% of cases, while WNV RNA was detectable in the blood or urine of 80% of patients.…”

“…Molecular testing provides a rapid etiological diagnosis of WNV infection, at variance with antibody detection, which needs confirmation by neutralization assays. In areas where multiple flaviviruses are endemic and co-circulate, like WNV and USUV in the Veneto region, neutralization assays against these viruses should be run in parallel [12,23]. However, in patients with previous flavivirus immunity, such as the blood donor described in this study, neutralization assays may be inconclusive.…”

“…In addition, it should be kept in mind that some patients with WNND remain seronegative because of their underlying immunosuppressed condition, such as five of our patients with severe encephalitis. Moreover, subjects with previous flavivirus immunity may have a blunted or absent WNV IgM response, especially in the cases of subsequent infections with antigenically related viruses like WNV and USUV [23]. The complementarity of serology and molecular testing was observed in particular when analyzing CSF samples from patients with WNND, in which WNV RNA was generally detectable when WNV IgM antibodies were absent.…”

“…Notably, seven cases (five blood donors, one cord blood donor, one WNF case) did not develop WNV IgM antibodies during follow-up or had a blunted WNV IgM response but developed WNV IgG Viruses 2020, 12, 458 9 of 14 antibodies. Five of these cases, who had previous USUV immunity, have already been described [23]. The other two cases were blood donors, including a man in his 60s who developed myalgia and who had been vaccinated against yellow fever 10 years before and a man in his 40s who developed rash, asthenia, and lymphadenopathy and already had high levels (>320) of neutralizing antibodies against WNV and USUV at 12 days after the index donation.…”

Comprehensive response to Usutu virus following first isolation in blood donors in the Friuli Venezia Giulia region of Italy: Development of recombinant NS1-based serology and sensitivity to antiviral drugs

“…USUV co-circulates with WNV in many European countries and share host and vector species [13]. The year 2018 showed a dramatic increase of USUV and WNV infections in Europe with increased transmission to humans [18,29], including the neighboring Veneto Region [30]. Furthermore, circulation of USUV in mosquitoes has been described in the region [31].…”