First cases of human Usutu virus neuroinvasive infection in Croatia, August–September 2013: clinical and laboratory features

Abstract

Few reports of human Usutu virus (USUV) infection have been reported to date. We describe the first three patients with USUV neuroinvasive infection in Zagreb and its surroundings from 30 August to 7 September 2013 during a West Nile virus (WNV) outbreak. Patients were aged 29, 56, and 61 years. The two older patients had several comorbidities (arterial hypertension, hyperlipidemia, and diabetes mellitus). All patients presented with meningitis and meningoencephalitis closely resembling WNV neuroinvasive disease. The main clinical features in all patients were headache, fever, nuchal rigidity, hand tremor, and hyperreflexia. Neuroimaging studies were normal and electroencephalography (EEG) revealed diffusely slow activity. The 29 years old, a previously healthy female patient, was deeply somnolent and disoriented for 4 days. Her recovery was slow and even 10 weeks after disease onset, she had memory and speech-fluency difficulties. The other two patients recovered promptly. USUV IgG antibodies were detected in all patients by ELISA with seroconversion documented in two of them. Titers of USUV-neutralizing antibodies were 10, 80, and 10, respectively. Because USUV and WNV share many clinical characteristics, USUV infection could be misdiagnosed as WNV. Testing for USUV should be considered in all suspected cases of meningoencephalitis, especially in areas where both viruses cocirculate.

Spatio-temporal trends and risk factors affecting West Nile virus and related flavivirus exposure in Spanish wild ruminants

“…Even though human infections are believed to be clinically mild or asymptomatic, neuroinvasive illness associated with USUV infection has been reported in Italy and Croatia [51, 52]. In our study, USUV infection was confirmed in red deer from bioregions 1, 3 and 5 in 2007 and 2008.…”

Extinction of Zika Virus and Usutu Virus by Lethal Mutagenesis Reveals Different Patterns of Sensitivity to Three Mutagenic Drugs

“…Although severe disease in humans is rare, there is growing evidence that cases of neurologic disorders associated with USUV have been historically misdiagnosed as WNV (22, 97). The diagnosis of disease caused by USUV is further complicated by the resemblance of pathology to WNV cases and the serological cross-reactivity in diagnostic tests (11, 13, 18, 22–24, 97, 98). A mouse model for USUV infection has been recently established, and it represents a valuable tool to test the in vivo antiviral effect of 5-fluorouracil or novel antivirals (98, 99).…”

“…USUV has caused recent epidemics in birds across Europe, with elevated mortality in some species, such as blackbirds, owls, and other wild and captive animals (15, 19). Recent sporadic cases of human disease geographically connected to these outbreaks are raising concerns of USUV becoming a potential threat to global health (11, 13, 15, 18, 20–24). …”

Usutu virus: current knowledge and future perspectives

“…91 Later on, the only USUV neuroinvasive infection in humans outside Italy was described in Croatia in 2013 during a WNV outbreak. 92 The main clinical features in all patients were headache, fever, nuchal rigidity, hand tremor, and hyperreflexia. USUV neutralizing antibodies were detected in all patients, and seroconversion was documented by enzymelinked immunosorbent assay (ELISA) in two of them.…”