Comparison of standard versus double dose of amoxicillin in the treatment of non-severe pneumonia in children aged 2-59 months: a multi-centre, double blind, randomised controlled trial in Pakistan.

INTRODUCTION: WHO pneumonia case management guidelines recommend oral amoxicillin as first line treatment for non-severe pneumonia. Increasing treatment failure rates have been reported over a period of time, which could possibly be due to increasing minimum inhibitory concentrations of Streptococcus pneumoniae and Haemophilus influenzae for amoxicillin. Microbiological data show that this resistance can be overcome by increasing amoxicillin dosage. Based on this data, we examined whether we can improve the clinical outcome in non-severe pneumonia by doubling the dose of amoxicillin. METHODS: A double blind randomised controlled trial was conducted in the outpatient departments of four large hospitals in Pakistan. Children aged 2-59 months with non-severe pneumonia were randomised to receive either standard (45 mg/kg/day) or double dose (90 mg/kg/day) oral amoxicillin for 3 days and then followed up for 14 days. Final outcome was treatment failure by day 5. RESULTS: From September 2003 to June 2004, 876 children completed the study. 437 were randomised to standard and 439 to double dose oral amoxicillin. 20 (4.5%) children in the standard and 25 (5.7%) in the double dose group had therapy failure by day 5. Including the relapses, by day 14 there were 26 (5.9%) cumulative therapy failures with standard and 35 (7.9%) with double dose amoxicillin. These differences were not statistically significant (p = 0.55 and p = 0.29, respectively). CONCLUSION: Clinical outcome in children aged 2-59 months with non-severe pneumonia is the same with standard and double dose oral amoxicillin. Non-severe pneumonia can be treated effectively and safely with a 3 day course of a standard dose.

Immunogenicity of a recombinant, yeast-derived, anti-hepatitis-B vaccine after alternative dosage and schedule vaccination in Pakistani children.

A controlled, randomized trial was conducted in urban areas of Karachi and Lahore with the aim to look for ways to improve the cost-effectiveness of hepatitis B vaccination. Children under 15 years old (including neonates) were selected and screened for immunization by three regimens according to the frequency and doses of the recombinant vaccine used (Heberbiovac HB, Heber Biotec, Havana). Group A received 10 microg at 0, 1 months; group B (control) received 10 microg at 0, 1 and 2 months (standard regime), and group C received 5 microg at 0, 1 and 2 months. Antibody levels were titrated 2 months after the last dose. Cut-off for seroprotection and hyperresponse were taken as 10 and 100 IU/L, respectively. Nine hundred and ninety children were included and evaluated after discarding those positive for serological hepatitis virus infection markers. Seroprotection rates were 100, 99.7 and 99.7%, and hyperresponse was achieved by 92.7, 99.4, and 97% of the vaccinees in groups A, B, and C, respectively. The same good result was obtained in extreme ages subgroups (< or =1 year and > or =10 years old). The 1-year follow up of the children from Karachi showed good persistence of seroprotection (98, 100, and 99.4%) and hyperresponse (79.7, 96.7, and 87.4%). It is concluded that it is feasible to improve the cost-benefit ratio and compliance of hepatitis B vaccination by means of a two-shots or reduced dose schedule of the vaccine employed in the trial.