The eligible participants will be enrolled consecutively. A predesigned case record form will be filled. Each eligible child will be subjected to demographic details (age, gender, socioeconomic status). A detailed history will be recorded. Complete neurological examination would be performed. All eligible participants would be admitted in Pediatric Intensive Care Unit. Management of children with acute encephalitis would be as per the standard protocol. Eligible participants would be randomized into interventional group (Azithromycin plus conventional treatment) and control group (conventional treatment).

Intervention group will be given Azithromycin plus conventional treatment and in control group only conventional treatment will be given.

Intravenous Azithromycin would be given in the dose of 10mg/kg over 5 days. Adverse events if any would be managed symptomatically and recorded. Conventional empirical treatment of acute encephalitis syndrome will be as per the consensus guidelines on evaluation and management of suspected acute encephalitis in children in India.

1.      Management of seizures with anti epileptic medication.

2.      Management to decrease raised intracranial pressure:3% Nacl or Mannitol

3.      Antimicrobial protocol:

a.       Intravenous Ceftriaxone (100 mg/kg/day in 2 divided doses)

b.      Intravenous Vancomycin (60 mg/kg/day in 4 divided doses)

c.       Intravenous acyclovir (20 mg/kg/dose every 8 hours) [To be stopped once CSF HSV PCR is negative]

d.      IV artesunate: 2.4-3  mg/kg once a day to be stopped if peripheral smear for malarial parasite is negative

4.      Management of associated systemic complication as per standard PICU protocol.

 Vital signs including heart rate, respiratory rate, mean arterial pressure would be recorded at least every 6 hourly. Level of consciousness in terms of Glasgow coma score and four scores will be evaluated every 6 hourly respiratory pattern, presence of oculo cephalic reflex, pupil size and reaction, brainstem function, fundus evaluation would be recorded at-least every 12 hourly. Need for mechanical ventilation, need for inotropic support, evidence of multi-organ dysfunction would be recorded. Once the patient is hemodynamically stable and feeding has been established, the patient would be shifted to the ward. Any adverse event following drug administration would be recorded. Common adverse events that would be recorded include fever, dyspnea, vomiting, irritable, skin rash, hypotension, Malena.

Neuroimaging including MRI Brain and EEG would be performed as soon as the patient is hemodynamically stable. Blood sample would be obtained for ELISA for scrub typhus, HIV serology and for obtaining thick and thin peripheral smear for malarial parasite. Cerebrospinal fluid (CSF) [5 ml] would be obtained for testing for Japanese encephalitis using ELISA. Glasgow coma score, FOUR scores, Liverpool outcome score, ICF-CY scoring will be performed at the time of discharge.