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Published Date: 2012-09-06 16:51:51
Subject: PRO/AH/EDR> West Nile virus - Eurasia (07): Italy
Archive Number: 20120906.1283932

WEST NILE VIRUS - EURASIA (07): ITALY
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Date: Thu 6 Sep 2012
Source: Eurosurveillance, Volume 17, Issue 36 [edited]
http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20260

Reference
Barzon L, Pacenti M, Franchin E, Martello T, Lavezzo E, Squarzon L, Toppo S, Fiorin F, Marchiori G, Scotton GP, Russo F, Cattai M, Cusinato R, Pale G. Clinical and virological findings in the ongoing outbreak of West Nile virus Livenza strain in northern Italy, July to September 2012 . Euro Surveill. 2012;17(36):pii=20260

Abstract
In July-September 2012, one month earlier than in previous years, 13 confirmed human cases of West Nile virus infection were diagnosed in northern Italy, including 5 with neuroinvasive disease, 3 with West Nile fever, and 5 West Nile virus (WNV)-positive blood donors. In 9 cases, the presence of the WNV lineage 1a Livenza strain, characterised in 2011, was ascertained. Symptomatic patients had prolonged viruria with high viral load.

Introduction [summarized]
In 2012, West Nile virus (WNV) infection has become a concern for many public health experts. Earlier occurrence in this year [2012] of an increased number of human cases has been reported by European countries to the European Centre for Disease Prevention and Control (ECDC).

We recently reported the case of a WNV ribonucleic acid (RNA)-positive blood donation identified in northern Italy in July 2012, which suggested circulation of WNV one month earlier than in previous years [3]. Partial sequencing of the WNV RNA (GenBank accession numbers: JX417422 and JX470578) demonstrated identity with the genome of a lineage 1a WNV strain, called Livenza strain, which had been identified in the same area in 2011 (WNV-Livenza/2011 strain) and which was divergent from the strain responsible for the 2008-09 outbreak in northern Italy.

Discussion
This report describes 13 confirmed human cases of WNV infection diagnosed in northeastern Italy between July and September 2012. Cases occurred one month earlier than previously reported, and this could be attributable to the ongoing very hot summer season, probably responsible for the very high mosquito density, that has been observed in the affected areas. In 9 cases for whom viral RNA sequencing was successful, infection with the recently identified WNV Livenza strain was demonstrated. The new WNV strain did not appear particularly virulent and lethal, since cases had no severe symptoms and positive outcomes. However, due to their small number, the virulence and lethality of the new WNV lineage 1a Livenza strain remains to be defined. To this aim, studies on animal models will be conducted with the viral isolate. The Livenza strain is classified within the Mediterranean cluster but has several novel amino acid substitutions in non-structural proteins that are not present in other European and non-European strains, which could be relevant for virus transmissibility and neuroinvasive potential [8].

Clinical evaluation demonstrated variability of symptoms among patients, including retinitis, meningitis, gastrointestinal symptoms, respiratory failure and lower limb neuritis, besides fever, headache, asthenia, arthralgia, and myalgia. Asthenia was a common symptom in blood donors, and one donor only recalled it in retrospect. Thus, asking blood donors about this symptom before donation, in areas where WNV is endemic, could help to recognise potentially infected individuals. To this end, interviews are useful, and one of our patients with WN fever was identified by interview at the visit for blood donation. Detection of WNV RNA in urine was very useful for early laboratory diagnosis of WNV infection, since in some patients viral RNA was detectable only in urine and not in blood. Remarkably, patients with WNND or West Nile fever had WNV shedding at high loads in urine for several days after symptom onset and seroconversion, and even after the appearance of IgG antibodies, when viral RNA was no longer detectable in blood or CSF. In addition, the high viral load in urine allowed sequencing of WNV RNA in most cases.

In conclusion, this study reports an increased WNV activity in northern Italy and describes the clinical presentation of infection with the new endemic WNV Livenza strain, which appears to be responsible for the outbreak.

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[This is a follow-up report to one issued by the same group in Eurosurveillance on 2 Aug 2012 (see ProMED-mail archive no. 20120805.1228964), and reiterates the earlier than usual seasonal appearance of WNV in Italy, as has been the case in several areas in the USA. The detection of WNV RNA in urine is noteworthy and will be of diagnostic value. The high virus load in urine raises the question of renal damage in these cases and whether chronic kidney disease (CKD) might occur in convalescent individuals. Researchers in the USA studied 139 patients who had been infected with West Nile virus. About 83 per cent of the patients were 4-9 years post-infection. Of the study participants, 40 per cent had evidence of CKD, with 10 per cent having Stage III or greater and 30 per cent with Stage I or II. The researchers further found that 26 per cent of patients had proteinuria, and 23 percent had hematuria (see ProMED-mail archive no. 20120714.1202043). It would be of interest to see whether the group of WNV infection convalescent people might also develop CKD in the future.

A HealthMap/ProMED-mail interactive map of Italy can be accessed at http://healthmap.org/r/00uE. - Mod.TY]

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