Clinical and virological findings in patients with Usutu virus infection, northern Italy, 2018

Pacenti, Monia; Sinigaglia, Alessandro; Martello, Thomas; Rui, Maria Elena De; Franchin, Elisa; Pagni, Silvana; Peta, Elektra; Riccetti, Silvia; Milani, Adelaide; Montarsi, Fabrizio; Capelli, Gioia; Doroldi, Carlo Giovanni; Bigolin, Francesco; Santelli, Luca; Nardetto, Lucia; Zoccarato, Marco; Barzon, Luisa

doi:10.2807/1560-7917.es.2019.24.47.1900180

Cited by 52 publications

(63 citation statements)

References 32 publications

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“…The immune response to primary flavivirus infections is usually characterized by a rapid rise of specific IgM antibodies, which appear to play an important protective role in the early phase of infection [35]. In sequential infections, however, the extent of IgM antibody formation may be reduced and/or delayed [36]. Furthermore, in patients with Zika virus infection and previous DENV immunity, a similar pattern was described [37].…”

Section: Discussionmentioning

confidence: 89%

West Nile or Usutu Virus? A Three-Year Follow-Up of Humoral and Cellular Response in a Group of Asymptomatic Blood Donors

Percivalle

Cassaniti

Sarasini

et al. 2020

Viruses

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West Nile virus (WNV) and Usutu virus (USUV) are two related arboviruses (genus Flavivirus, family Flaviviridae), with birds as a reservoir and mosquitoes as transmitting vectors. In recent years, WNV epidemiology changed in many European countries with increased frequency of outbreaks posing the issue of virus transmission risks by blood transfusion. USUV emerged for the first time in birds of the Tuscany region (Italy) in 1996 and in 2001 in Austria. While WNV is responsible for both mild and neuroinvasive diseases, USUV infection is usually asymptomatic and neuroinvasive symptoms are rare. Since WNV and USUV co-circulate, the surveillance of WNV allows also the detection of USUV. Due to the great similarity in amino-acid sequence of major surface proteins of the two viruses, a high cross-reactivity can lead to misinterpretation of serological results. Here, we report the results obtained from 54 asymptomatic blood donors during a three-year follow-up showing an unexpected high positivity (46.3%) for USUV. The major obstacle encountered in the differential diagnosis between these two viruses was the high cross-reactivity found in neutralizing antibodies (NT Abs) and, in some cases, a long follow-up was mandatory for a correct diagnosis. Moreover, two new ELISpot assays were developed for a more rapid and specific differential diagnosis, especially in those cases in which NT Abs were not determinant. Using a combination of Enzyme-linked immunospot (ELISpot), molecular, and serological tests, we could identify 25 true positive WNV and 25 true positive USUV blood donors. Our data highlight the importance of raising awareness for increasing USUV infections in endemic countries involved in blood transfusion and organ donation.

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Section: Discussionmentioning

confidence: 89%

West Nile or Usutu Virus? A Three-Year Follow-Up of Humoral and Cellular Response in a Group of Asymptomatic Blood Donors

Percivalle

Cassaniti

Sarasini

et al. 2020

Viruses

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“…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.…”

Section: Discussionmentioning

confidence: 99%

“…The presence of WNV IgM and IgG antibodies in serum and CSF was determined by a commercial ELISA (WNV IgM capture DxSelect e IgG DxSelect, Focus Diagnostics, CA, USA). Serum samples with positive results were further tested for confirmation by the plaque reduction neutralization test (PRNT) against WNV and the microneutralization titer assay against USUV [12].…”

Section: Laboratory Methodsmentioning

confidence: 99%

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

Pacenti

Sinigaglia

Franchin

et al. 2020

Viruses

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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.

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“…In humans, USUV infection was first described in Africa (Central African Republic and Burkina Faso in 1981 and 2004, respectively), with mild clinical signs such as fever and skin rash reported [12]. In Europe, the recent epizootics were also accompanied by several descriptions of human neurological disorders, including facial paralysis, encephalitis, meningitis and meningoencephalitis, in immunocompromised and immunocompetent patients, representing to date around 30 cases [7,[18][19][20][21][22][23][24][25]. Moreover, molecular and serologic evidence of USUV infection in Italian, German, Austrian and Dutch blood donors indicates that the virus is also circulating silently among asymptomatic humans in Europe and could potentially be a concern PLOS NEGLECTED TROPICAL DISEASES for blood transfusions [26][27][28][29].…”

Section: Introductionmentioning

confidence: 99%

Study of Usutu virus neuropathogenicity in mice and human cellular models

et al. 2020

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Usutu virus (USUV), an African mosquito-borne flavivirus closely related to West Nile virus, was first isolated in South Africa in 1959. USUV emerged in Europe two decades ago, causing notably massive mortality in Eurasian blackbirds. USUV is attracting increasing attention due to its potential for emergence and its rapid spread in Europe in recent years. Although mainly asymptomatic or responsible for mild clinical signs, USUV was recently described as being associated with neurological disorders in humans such as encephalitis and meningoencephalitis, highlighting the potential health threat posed by the virus. Despite this, USUV pathogenesis remains largely unexplored. The aim of this study was to evaluate USUV neuropathogenicity using in vivo and in vitro approaches. Our results indicate that USUV efficiently replicates in the murine central nervous system. Replication in the spinal cord and brain is associated with recruitment of inflammatory cells and the release of inflammatory molecules as well as induction of antiviral-responses without major modulation of bloodbrain barrier integrity. Endothelial cells integrity is also maintained in a human model of the blood-brain barrier despite USUV replication and release of pro-inflammatory cytokines. Furthermore, USUV-inoculated mice developed major ocular defects associated with inflammation. Moreover, USUV efficiently replicates in human retinal pigment epithelium. Our results will help to better characterize the physiopathology related to USUV infection in order to anticipate the potential threat of USUV emergence.

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Clinical and virological findings in patients with Usutu virus infection, northern Italy, 2018

Cited by 52 publications

References 32 publications

West Nile or Usutu Virus? A Three-Year Follow-Up of Humoral and Cellular Response in a Group of Asymptomatic Blood Donors

West Nile or Usutu Virus? A Three-Year Follow-Up of Humoral and Cellular Response in a Group of Asymptomatic Blood Donors

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

Study of Usutu virus neuropathogenicity in mice and human cellular models

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