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

Abstract

West Nile virus (WNV) lineage 2 is expanding and causing large outbreaks in Europe. In this study, we analyzed the epidemiological, clinical, and virological features of WNV lineage 2 infection during the large outbreak that occurred in northern Italy in 2018. The study population included 86 patients with neuroinvasive disease (WNND), 307 with fever (WNF), and 34 blood donors. Phylogenetic analysis of WNV full genome sequences from patients’ samples showed that the virus belonged to the widespread central/southern European clade of WNV lineage 2 and was circulating in the area at least since 2014. The incidence of WNND and WNF progressively increased with age and was higher in males than in females. Among WNND patients, the case fatality rate was 22%. About 70% of blood donors reported symptoms during follow-up. Within the first week after symptom onset, WNV RNA was detectable in the blood or urine of 80% of patients, while 20% and 40% of WNND and WNF patients, respectively, were WNV IgM-seronegative. In CSF samples of WNND patients, WNV RNA was typically detectable when WNV IgM antibodies were absent. Blunted or no WNV IgM response and high WNV IgG levels were observed in seven patients with previous flavivirus immunity.

The Value of West Nile Virus RNA Detection by Real-time PCR in Urine Samples From Patients With Neuroinvasive Forms

“…Previous studies such one conducted in northeastern Italy in 2012, one in Greece in 2013 and another in Hungary in 2014, revealed positivity rates in urine samples of 43,8% (14/32), 40% (14/35) and 27,3% (3/11), respectively (Barzon et al, 2013a;Papa et al, 2014;Nagy et al, 2016). We also found that WNV RNA detection was more effective in urine samples than in CSF which con rms previous ndings (Barzon et al, 2015(Barzon et al, , 2013a(Barzon et al, , 2012Pacenti et al, 2020). While 50,5% of urine samples from our patient were positive, only one CSF, sampled on day 3 after symptom onset, was positive.…”

“…Barzon et al Pacenti et al found that viral shedding in urine samples starts within the rst week after symptom onset then lasts up to 30 days(Barzon et al, 2012;Pacenti et al, 2020). In our series, WNV RNA could be detected in urine samples from 1 up to 41 days after symptom onset.…”

Epidemiology of West Nile Virus Infections in Humans, Italy, 2012–2020: A Summary of Available Evidences

“…Last but not least, our data lack a significant information represented by the viral genotyping of the reported cases. According to available data, earlier reports on WNV in Italy were mostly associated with lineage 1 [ 45 ], with a subsequent cocirculation of lineage 1 and 2 between 2013 and 2018 [ 45 , 59 ], while the 2018 incidence peak was largely associated with infections by lineage 2 [ 59 ], which was the predominant pathogen during the European summer season 2018 [ 45 ]. In other words, without an appropriate tracking of incident cases also in terms of phylogenetic analysis, we could lose significant details, being eventually unable to properly track the actual spreading of WNV across Italy, possibly anticipating the emergence of human cases by properly identifying suitable reservoirs, and particularly certain species of migratory birds.…”

Antiviral Natural Products for Arbovirus Infections

“…Serious manifestations of WNND include encephalitis, meningitis, and acute flaccid paralysis [42]. Additionally, some patients suffer fatigue, muscle weakness, and persistent tremors, lasting weeks to years even after recovery [43][44][45]. Unfortunately, only supportive treatment is available for patients who suffer from severe and debilitating effects of WNND.…”