MATERIALS AND METHODS 1. The study design: Prospective, Randomized controlled, Opened-labelled trial 2.

The Place of study: Paediatric ward, Department of Paediatrics. AGMC & GBP Hospital, Agartala.Tripura.India. 3. The study period: 2 (Two) years 4. INCLUSION CRITERIA: All the admitted patients in Paediatric ward diagnosed as Malaria (Pf) by Slide method and QBC Assay and satisfying the WHO criteria for Severe Malaria. 5. EXCLUSION CRITERIA: a. ECG with QTc interval > 0.45 sec b.Known case of G6 PD deficiency c. Multi-species infestation d. Patients with contraindication to any of the above two drugs 6. END POINTS OF THE STUDY: a. Parasite Clearance Time (PCT100 ): Time in hours from the initiation of the therapy to the first negative blood sample. b. Parasite Clearance Time (PCT 50) Time in hours from the initiation of the therapy to 50% reduction in parasitemia. c. Fever Clearance Time (FCT): Time in hours from the initiation of the therapy to the time the patients temperature falls permanently below 990F d. Coma Resolution Time (CRT): Time in hours from initiation of the therapy to the time patient is fully conscious with GCS of 15.

7. PLAN OF THE WORK: The study population will be randomized to receive either Quinine or Artesunate infusion as per WHO guidelines. The end points will be Parasites Clearance Time (PCT), Fever Clearance Time (FCT), Coma Resolution Time (CRT) and Mortality. All patients will invariably receive at least 24 hours of intravenous therapy and a complete 7 days course. Oral therapy will be substituted as soon as the patients could tolerate. Patients in the Quinine arm will be given a loading dose of 20mg/kg of quinine salt and infused over four hours followed by 10 mg/Kg infused over 4 hours 8 hourly till the patient is able to take orally. No dose adjustment will be made during first 48 hours of the treatment even with ARF or liver failure. In Artesunate arm a dose of 2.4 mg/kg IV will be given at first followed by 2.4mg/kg repeated at 12 and 24 hours then 2.4mg/kg/day. All patients will be admitted in the General Paediatric ward except those with coma and ARDS who will be shifted to PICU for intensive monitoring purpose. All patients will be kept for at least 7 days. Supportive care will be given to all patients as advocated by WHO. All patients will be weighed and a through clinical and laboratory examination work up will be done on admission and regularly thereafter. The vital signs will be recorded 4 hourly. The systemic and fundus examination will be done on daily basis. The CNS examination will be repeated at the time of regaining consciousness. 8. Registration: Patients of 12 years or below admitted in the Paediatric ward and fulfilling the inclusion criteria will be registered for the study. 9. History taking; A detailed history including residence, travel history, previous treatment, drug history and vaccination will be recorded. 10. Clinical examinations: Through general examination, vitals, organomegaly, detailed neurological examination, GCS scores etc. will be recorded. The axillary temperature will be recorded 6 hourly.

11. INVESTIGATIONS: a. Complete Blood Count b. ESR c. Urine-routine examination d. ECG and RBS before, during and after loading dose of the antimalarial drug. e. Hb%, haematocrit-on admission and on day 14 and day 28 and after blood transfusion if any. f.Platelet counts, blood urea, serum creatinine and LFT-will be done according to the presentation. g. Contrast enhanced CT scan: all patients with delayed response to the antimalarial or with seizures and signs of raised intracranial tension. The mainstay of the Diagnosis and assessment of the treatment response will be blood slide for MP and serial QBC Assay for MP (Pf).Blood sample will be send for QBC Assay and blood for MP at the time of admission and thereafter on 2,3,7,14 and on 28 days of follow up. Parasitemia quantification will be done. All patients will be screened for: a.Hypoglycemia (<45mg/dl) b. ECG abnormalities. 12. Follow up: All the patients will be called for follow up after 14 & 28 days from the date of discharge.

13. PRESENTATION OF DATA: All the data will be presented in appropriate tables, charts, Pie diagram etc.

14. STATISTICAL ANALYSIS: Data collection and compilation will be done at the end of the study period. Presented data will be analyzed to find out the outcome of the study. Recorded data will be analyzed by using T-test and ANOVA. 15. DISCUSSION: The result obtained will be discussed in the light of available literature.