A Case of Central Nervous System Infection Due to West Nile Virus Lineage-1 in Ankara Province, Turkey

Abstract

West Nile virus (WNV) is a mosquito-borne Flavivirus (family Flaviviridae), maintained in an enzootic cycle between birds as amplifying hosts and mosquito vectors. While WNV exposure in humans frequently remain subclinical, a febrile illness called West Nile fever occurs in about 20% and neuroinvasive disease in less than 1% of the affected individuals. For the last two decades, WNV has caused outbreaks of severe neuroinvasive disease in humans and horses in Europe, the Mediterranean Basin and emerged in the American continent. Although, previous serosurveillance reports have revealed human WNV exposure in various regions in Turkey; well-characterized clinical cases have only been reported after 2009-2010. In this report, a case of WNV encephalitis caused by a Lineage 1 virus strain and identified in Ankara province, Central Anatolia, Turkey, was presented. An 87 year-old woman with a history of hypertension and a recent febrile episode was admitted to Hacettepe University Hospital in late May 2012, with altered consciousness, myoclonic jerks in facial muscles and left extremity. Hyponatremia and increased alanine and aspartate aminotransferase levels were noted in blood analyses. Initial electroencephalogram (EEG) demonstrated diffuse slow waves. Areas of restricted diffusion in right dorsal thalamus was observed in cranial magnetic resonance imaging (MRI). Despite supportive therapy, the patient's neurological condition worsened. Follow-up EEG displayed paroxysmal lateralizing epileptiform discharges (PLEDs) in the right hemisphere and T2-hyperintense lesions in the right temporoparietal cortex, insula and thalamus with components of cytotoxic and vasogenic edema were observed in MRI. A cerebrospinal fluid (CSF)-serum pair was evaluated to identify potential causes of encephalitis. CSF biochemical and microscopic findings were within normal limits except for decreased glucose levels. Bacterial, mycobacterial and fungal cultures, antigen assays and polymerase chain reaction (PCR) employed for Herpes simplex virus types 1 and 2 were negative. Commercial and in house assays for WNV, tick-borne encephalitis virus, Toscana virus (TOSV) antibodies revealed TOSV IgG in serum. Previously described nested PCRs targeting WNV envelope glycoprotein and phlebovirus consensus sequences demonstrated WNV positive results in serum and CSF, which were further characterized via cycle sequencing of amplicons as WNV Lineage 1 Clade 1a. Four serum samples obtained within 23 days after the diagnosis were negative for viral RNA and specific antibodies via commercial assays and WNV plaque reduction neutralization assay. During follow-up with supportive therapy and anti-epileptics, the patient's general and neurological condition improved mildly and control EEG and MRI demonstrated regression of previous lesions. However, the patient passed away on the 10th week of hospital admission due to nosocomial infections. These findings confirmed the inital data which indicated the circulation of WNV Lineage 1 strains in Central Anatolia, Turkey. WNV seroconversion may be delayed or absent in elderly individuals without overt diseases associated with immunosuppression. Thus investigation of WNV RNA together with the specific serological tests may help the accurate diagnosis of suspected cases.