Outbreak of Human Neuroinvasive West Nile Virus Infection in Campania,Italy,August–September 2024

Introduction

West Nile virus (WNV) infection is endemic in Italy, both in humans and animals, especially in the Northeast area of the country (Riccardo et al., 2018).

Campania region, a large and densely populated region of Southern Italy, has never recorded any human case of WNV infection besides a single asymptomatic human case in the province of Salerno in 2023 in a healthy blood donor, with no cases of WNV fever or WNV neuroinvasive disease (WNND) ever recorded so far (de Martinis et al., 2023).

Discussion

This is the first reported outbreak of WNV infection in the Campania region and the first case series in which the use of remdesivir has ever been reported to systematically treat WNND, so far.

Circulation of WNV in Italy among animals dates back to 1998. (Autorino et al., 2002) No relevant circulation of WNV was detected until 2008, when the virus was identified in mosquitoes, birds, horses, and humans in the area surrounding the Po River delta (Rizzo et al., 2012). The circulation of WNV lineage 1 (L1) was sustained in Northern Italy until 2011–2013, when lineage 2 (L2), introduced from Eastern Europe, started to prevail over L1 (Rizzo et al., 2012). In 2022, an early start of WNV activity in Europe was demonstrated at the beginning of June in the Veneto region, northeastern Italy (Barzon et al., 2022). In the same year, a peak of 301 confirmed human infections, including 160 cases of WNND, was reported to the Italian surveillance system (Riccardo et al., 2022).

The Campania region has been considered a low-risk area since the circulation of the virus had never been revealed by either passive or active surveillance until 2020, when two raptor birds were found WNV-L1 positive. No other cases were recorded until the diagnosis of WNV-L1 encephalitis in a horse in Campania in 2023 (de Martinis et al., 2023). Nonetheless, no human cases had ever been recorded in Campania until the finding of a WNV RNA-positive blood donor in the province of Salerno in 2023 (Istituto Superiore di Sanità—ISS, 2023).

This is the largest human outbreak in Southern Italy reported, so far. In our cohort, the proportion of neuroinvasive disease was unexpectedly high, with many patients aged over 80 years old and none with a history of travel in endemic areas. Despite older age and comorbidities, the outcome of these patients was favorable, with two deaths that were attributable to concurrent bacterial infections.

We think that the high proportion of WNND in our outbreak is related to an increased physician alert following the first detected case, rather than a more virulent viral strain. The fact that it is well known that WNND only occurs in <1% of WNV infection leads us to believe that the real circulation of WNV in the summer season of 2024 in the Benevento province was much wider, with our cases representing the tip of the iceberg of the actual prevalence.

Notably, no patients had visible skin rash at the presentation, and all had normal C-reactive protein and a nonspecific EEG, despite a dramatic clinical picture of lethargy and coma.

It is noteworthy that this is one of the first reported systematic use of remdesivir in humans for the treatment of WNV. The rationale behind this therapeutic choice lies in the finding that remdesivir efficiently inhibits RNA-dependent RNA-polymerases of various flaviviruses, including WNV, in in-vitro models (Konkolova et al., 2020). We tried a 10-day course of remdesivir in the transplanted patient, who had the most serious clinical picture at the presentation, and, subsequently, we used a 5-day course in the other three patients. Similarly, Shamsher and colleagues had successfully used a 5-day course of remdesivir in a patient with WNND and multiple sclerosis in the same season of our outbreak, and they published the results during the writing of the present article (Shamsher et al., 2024). In our case series, patients receiving remdesivir had a lower median hospitalization (12 days, IQR: 8–12 vs. 16 days, IQR: 8–34), lower prevalence of in-hospital mortality (0% vs. 25%), and a reduced need for rehabilitation (12% vs. 66%), although these differences did not reach statistical significance.

Conclusions

The surveillance of WNV must be enforced in the Campania region. Clinicians should consider WNV in the differential diagnosis of CNS infection, regardless of the patient’s travel history to endemic areas. Remdesivir might be used in WNND, but its effectiveness must be further studied.

Consent for Publication

Written patient consent was obtained prior to enrollment in the study, and the data were recorded by the investigators anonymously such that subjects could not be identified directly or through identifiers linked to the subject.