BackgroundJapanese encephalitis (JE) virus (JEV) is a mosquito-borne flavivirus found across Asia that is closely related to West Nile virus. There is no known antiviral treatment for any flavivirus. Results from in vitro studies and animal models suggest intravenous immunoglobulin (IVIG) containing virus-specific neutralizing antibody may be effective in improving outcome in viral encephalitis. IVIG’s anti-inflammatory properties may also be beneficial.Methodology/Principal FindingsWe performed a pilot feasibility randomized double-blind placebo-controlled trial of IVIG containing anti-JEV neutralizing antibody (ImmunoRel, 400mg/kg/day for 5 days) in children with suspected JE at two sites in Nepal; we also examined the effect on serum neutralizing antibody titre and cytokine profiles. 22 children were recruited, 13 of whom had confirmed JE; 11 received IVIG and 11 placebo, with no protocol violations. One child (IVIG group) died during treatment and two (placebo) subsequently following hospital discharge. Overall, there was no difference in outcome between treatment groups at discharge or follow up. Passive transfer of anti-JEV antibody was seen in JEV negative children. JEV positive children treated with IVIG had JEV-specific neutralizing antibody titres approximately 16 times higher than those treated with placebo (p=0.2), which was more than could be explained by passive transfer alone. IL-4 and IL-6 were higher in the IVIG group.Conclusions/SignificanceA trial of IVIG for JE in Nepal is feasible. IVIG may augment the development of neutralizing antibodies in JEV positive patients. IVIG appears an appealing option for JE treatment that warrants further study.Trial RegistrationClinicalTrials.gov NCT01856205

BackgroundAcute encephalitis syndrome (AES) is commonly seen among hospitalized Nepali children. Japanese Encephalitis (JE) accounts for approximately one-quarter of cases. Although poor prognostic features for JE have been identified, and guide management, relatively little is reported on the remaining three-quarters of AES cases.MethodsChildren with AES (n = 225) were identified through admission records from two hospitals in Kathmandu between 2006 and 2008. Patients without available lumbar puncture results (n = 40) or with bacterial or plasmodium infection (n = 40) were analysed separately. The remaining AES patients with suspected viral aetiology were classified, based on positive IgM antibody in serum or cerebral spinal fluid, as JE (n = 42) or AES of unknown viral aetiology (n = 103); this latter group was sub-classified into Non-JE (n = 44) or JE status unknown (n = 59). Bad outcome was defined as death or neurological sequelae at discharge.ResultsAES patients of suspected viral aetiology more frequently had a bad outcome than those with bacterial or plasmodium infection (31% versus 13%; P = 0.039). JE patients more frequently had a bad outcome than those with AES of unknown viral aetiology (48% versus 24%; P = 0.01). Bad outcome was independently associated in both JE and suspected viral aetiology groups with a longer duration of fever pre-admission (P = 0.007; P = 0.002 respectively) and greater impairment of consciousness (P = 0.02; P < 0.001). A higher proportion of JE patients presented with a focal neurological deficit compared to patients of unknown viral aetiology (13/40 versus 11/103; P = 0.005). JE patients weighed less (P = 0.03) and exhibited a higher respiratory rate (P = 0.003) compared to Non-JE patients.ConclusionsNepali children with AES of suspected viral aetiology or with JE frequently suffered a bad outcome. Despite no specific treatment, patients who experienced a shorter duration of fever before hospital admission more frequently recovered completely. Prompt referral may allow AES patients to receive potentially life-saving supportive management. Previous studies have indicated supportive management, such as fluid provision, is associated with better outcome in JE. The lower weight and higher respiratory rate among JE patients may reflect multiple clinical complications, including dehydration. The findings suggest a more systematic investigation of the influence of supportive management on outcome in AES is warranted.

Fever with seizure, a common presentation with which a child may present to the emergency is mainly due to febrile seizure, but it may also be due to meningitis. This study was done to find out the incidence of meningitis and to find out whether lumbar puncture is necessary in different age groups of children presenting with first episode of fever with seizure. A prospective study was conducted in the emergency department of Kanti Children's Hospital. Children who presented with first episode of fever and seizure in the age group of 6 months to 5 years were included. Meningitis was diagnosed on the basis of either cytological and biochemical criteria or if a bacterial pathogen was isolated. Of the 175 children included, 17% were diagnosed to have meningitis. Cerebrospinal fluid was positive for a bacterial pathogen in 4.5% of the cases. In the age group of 6 months to 12 months, 30% of the children had meningitis as compared to 20 % and 5% in other age groups of 12- 18 months and above 18 months respectively. All children with culture proven bacterial meningitis were in the age group of 6-12 months and had no evidence of meningeal irritation. Signs of meningeal irritation had high specificity in diagnosing meningitis. Organisms grown were Haemophilus influenza in three cases, Streptococcus pneumoniae in two cases and Staphylococcus aureus in three cases. In conclusion, incidence of meningitis was found to be high in children presenting with first episode of fever and seizure. Lumbar puncture to rule out meningitis should especially be considered in children in the younger age group even without evidence of meningeal irritation.JNMA J Nepal Med Assoc. 2008 Jul-Sep;47(171):109-112.