Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Study proposal was not accepted for funding and therefore not further explored at this stage.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Victor Babes Hospital, Bucharest, Romania | UNKNOWN |
| Universiteit Antwerpen | OTHER |
Not provided
Not provided
Not provided
Not provided
The investigator hypothesizes that oxidative stress responses to West Nile virus infection in the central nervous system determine the severity of infection and the long-term neurological, neuropsychological and functional sequelae of West Nile Neuroinvasive Disease.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| WNND | 40 subject with West-Nile Neuroinvasive Disease will be recruited | ||
| WNF | 40 subject with West-Nile Fever will be recruited | ||
| controls | 20 control will be recruited. These controls will be aged matched to the cases. |
Not provided
| Measure | Description | Time Frame |
|---|---|---|
| Measure the redox status | A multiparameter indexes of oxidative stress will be calculated to measure and summarize the redox status in cases and age matched controls. Association between the redox status and clinical, neuropsychological and radiological outcomes will be investigated. We will also examine the relative sensitivity of separate biomarkers of oxidative stress and autophagy as clinical predictors of WNV infection severity. | at recruitment, 10 days post-symptom onset and 20 days post symtom onset. |
| Assessment of Neurologic deficits | As part of the descriptive analysis of biomarkers of disease severity and to study to neurologic sequelae of WNV infection. Will be assessed: specifically assessments of cranial nerves II- XII, motor strength in upper and lower extremities, sensory testing for pinprick and vibration, deep tendon reflexes, gait, coordination, and movement abnormalities | At recruitment, month 3 and month 12 |
| Neuropsychologic performance | Study the neuropsychologic sequelae of WNV infection during a 12-month followup period in following key domains: Attention, Memory, Executive Function, Emotion & Social Cognition, Psychomotor Speed | 20 days post-symtom onset, month 3 and month 12 |
| Longitudinal assessment of functional status Study the neurologic and neuropsychologic sequelae of WNV infection during a 12-month followup period. | ECOG/WHO PS during a 12-month followup. | at recruitment, month 3 and month 12 |
| MRI abnormalities | Part of descriptive analysis of clinical markers of disease severity | at recruitment, month 3 and month 12 |
| Brain iron content |
| Measure | Description | Time Frame |
|---|---|---|
| Analysis of laboratory performance characteristics (e.g. sensitivity) of WNV-specific RT-PCR and viral isolation in clinical samples, compared to composite diagnosis of WNV infection | Confirmed WNV infection is defined as one or more of following criteria:
|
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
The study population will be recruited from VBH emergency and outpatient departments in Bucharest, Romania, from the onset of the WNV transmission season in 2020 until November 2023. The incidence of WNV and WNND in South-Eastern Romania was 0.5 per 100,000 inhabitants in 2016, and has been increasing steadily 35. Romania reported 277 WNND cases with 43 deaths in 2018, and 66 WNND cases with 8 deaths in 2019 3. VBH is a tertiary care facility that serves a population of 3 million people (15% of Romania's population). Its catchment area covers more than 80% of the territories in Romania that reported WNV transmission and has in recent years been the largest single medical center to care for WNV infected patients.
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Koen Vercauteren | Institute of Tropical Medicine Antwerp | Principal Investigator |
| Nina Hermans | Universiteit Antwerpen | Principal Investigator |
| Corneliu Popescu | Victor Babes Hospital, Bucharest | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Victor Babes Hospital | Bucharest | Romania |
Not provided
Not provided
Not provided
Not provided
Blood samples
Part of the descriptive analysis of clinical markers of disease severity: Qualitative analysis per neuroanatomical region by iron-sensitive MRI sequence (SWI) |
| at recruitment, month 3 and month 12 |
| Ophthalmological abnormalities | As part of the descriptive analysis of clinical markers of disease severity ophthalmologic abnormalities will be assessed by slit lamp examination | at recruitment, with a follow-up of clinically indicated. |
| serum S100b concentration | As part of the descriptive analysis of clinical markers of disease severity S100b concentration will be measured to asses the Blood-Brain barrier integrity | at recruitment, 10 days post symptom onset and 20 days post symptom onset |
| serum NSE concentration | As part of the descriptive analysis of clinical markers of disease severity NSE concentration will be measured to asses the Blood-Brain barrier integrity | at recruitment, 10 days post symptom onset and 20 days post symptom onset |
| 20 days |
| Description of molecular epidemiology of infecting WNV strain(s) and viral outgrowth diagnostic performance. | The time frame for WNV detection after symptom onset by real-time reverse transcriptase polymerase chain reaction (RT-PCR) or virus isolation by outgrowth from blood or CSF is limited by the fast decline of circulating virus. Because the WNV RNA detection window in urine can be longer (up to 14 days), RT-PCR will be performed on all clinical samples at recruitment. The target sequences are a conserved region in the 5'UTR region and part of the capsid gene of WNV and detects both lineage 1 and 2 WNV. WNV has been successfully isolated from urine, in approx. 40% of samples obtained within 8 days of symptom onset. WNV isolation will be attempted in low-passage Vero E6 cells and BHK21 cells from urine samples with a high WNV RNA load (Cycle threshold (Ct)- values <30). | 20 days |
| Identification of potential genetic signatures that correlate with virulence (neuro-invasion and morbidity) in our cohort. | Whole genome sequencing (WGS) will be performed on a subset of RT-PCR positive serum, urine and CSF samples. This will allow us to investigate the temporal and spatial compartmentalization of the West Nile lineages in Romania as well as expand our understanding of genetic compartmentalization within hosts (urine, serum, CSF). In addition, the obtained isolates will be sequenced (from the viral outgrowth assay) to assess potential adaptations the virus undergoes during isolation. Finally, in a genome wide association study, the obtained viral sequences will be compared with the prospectively collected clinical data, to identify potential genetic signatures that correlate with virulence, neuroinvasion and morbidity. Our data will be compared to existing data on genetic determinants of virulence such as the presence of a glycosylation site in the E protein, substitutions in non-structural proteins 3, 4B or 5, or variation in the 3' noncoding region. | 20 days |
| ID | Term |
|---|---|
| D014901 | West Nile Fever |
| ID | Term |
|---|---|
| D004671 | Encephalitis, Arbovirus |
| D018792 | Encephalitis, Viral |
| D020805 | Central Nervous System Viral Diseases |
| D002494 | Central Nervous System Infections |
| D007239 | Infections |
| D000069544 | Infectious Encephalitis |
| D001102 | Arbovirus Infections |
| D000079426 | Vector Borne Diseases |
| D000096724 | Mosquito-Borne Diseases |
| D014777 | Virus Diseases |
| D012327 | RNA Virus Infections |
| D018177 | Flavivirus Infections |
| D018178 | Flaviviridae Infections |
| D004660 | Encephalitis |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D000090862 | Neuroinflammatory Diseases |
Not provided
Not provided