Dengue fever (neurological) Infections and Infestations Dengue fever [classical dengue]
Conditions
Interventions
Blood tests:
At day of inclusion and at day 6 (or at discharge if patients are discharged before day 6), 4 ml of ethylenediaminetetraacetic acid (EDTA) blood will be drawn. The following blood tests w
Sponsors
University of Oxford (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Cases: 1. Aged between 6 months and 16 years, either sex 2. Consent given by parents or legal guardians 3. History of fever with altered or reduced conscious level (Glasgow coma scale less than or equal to 14) lasting longer than 1 hour 4. History of illness of less than 7 days 5. One or more of the following on admission: 5.1. Hepatomegaly 5.2. Skin or any organ bleeding 5.3. Platelet count less than 150,000/mm^3 5.4. Haematocrit greater than 42% 5.5. Serum glutamic oxaloacetic transaminase (SGOT)/prothrombin time (PT) greater than 100 5.6. Albumin less than 3.2 g/dL 5.7. Positive rapid test for Dengue NS1 (plasma or cerebrospinal fluid [CSF]), or any of the following at Hospital for Tropical Diseases (HTD)/Oxford University Clinical Research Unit (OUCRU): 5.7.1. Positive Dengue immunoglobulin M (IgM)/NS1 enzyme-linked immunosorbent assay (ELISA) (plasma or CSF) 5.7.2. Positive dengue reverse transcription polymerase chain reaction (RT-PCR) (plasma or CSF) Control group 1: 1. First consecutive, age-matched hospitalised dengue patient 2. Confirmed by rapid NS1-detection 3. Parents/legal guardians give informed consent to participate in the study Control group 2: 1. First two consecutive, age-matched patients admitted with suspected viral encephalitis 2. Parents/legal guardians give informed consent to participate in the study based on: 2.1. History of fever with altered or reduced conscious level lasting longer than 1 hour 2.2. History less than 7 days 2.3. Two or more of the following signs or symptoms: 2.3.1. Seizures* 2.3.2. Agitation/delirium/behavioural changes 2.3.3. Abnormal movements 2.3.4. Facial/limb paresis/paralysis 2.3.5. Dysconjugate gaze 2.3.6. Extrapyramidal signs/symptoms (e.g. ataxia, tremor, rigidity, masked facies) 2.3.7. Neck stiffness 2.3.8. Tense fontanel 2.3.9. CSF pleiocytosis 2.3.10. Electroencephalogram (EEG)/neuroimaging findings consistent with encephalitis, or 2.4. Laboratory evidence of viral aetiology of encephalitis *Children between six months and five years with a single convulsion lasting less than 15 minutes who recovered consciousness within 60 minutes are considered to have had a simple febrile convulsion
Exclusion criteria
Exclusion criteria: 1. Bacterial, mycobacterial or parasitological causes as evidenced by microscopy or culture of CSF 2. Pre-existing neurological conditions, e.g. cerebral palsy, epilepsy, cerebral infarction/haemorrhage 3. Pre-existing chronic liver or renal disease
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. To compare the clinical, radiological and laboratory findings in paediatric dengue patients with and without neurological manifestations and in children with Japanese encephalitis or other viral encephalitides and relate this to outcome | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. To evaluate antigen detection-based assays for the diagnosis of DENV and JEV infection in children with neurological manifestations. We will use currently available, or if necessary, re-configured NS1 Ag detection assays as a diagnostic tool, and compare sensitivity and specificity with serology. 2. To measure virological parameters in paediatric dengue patients with and without neurological manifestations, and in patients with JE (or other viral encephalitides) and study the genome of these viruses. We will compare plasma viral loads and NS1 concentrations at baseline in dengue cases with and without CNS involvement. We will sequence the complete genomes of viruses isolated from the CSF and plasma of all dengue and JE cases. 3. To define and characterise the CSF pleiocytosis resulting from DENV or JEV infection by flow cytometry and relate this to outcome. Potential qualitative and quantitative differences in the CSF cellular response between patients with true encephalitis (e.g. JE) and patients with dengue-associated neurological symptoms may provide insight into the pathogenesis of dengue-associated neurological disease. 4. To define the inflammatory response, including cytokines, chemokines and their receptors in plasma and CSF, as well as soluble markers of neuronal damage and macrophage activation in CSF, and relate these to outcome 5. To determine whether there are host genetic factors associated with the development of neurological manifestations resulting from DENV or JEV infection | — |
Countries
Viet Nam
Outcome results
None listed