Zinc administration in children with acute diarrhea reduces the duration and risk of persistence and may be more effective in children with severe inflammation

Abstract

Presenter: Dr. Tor Strand; Centre for International Health; University of Bergen, Norway

Authors: Tor A Strand†, Ram K Chandyo*, Pushpa R Sharma*, Manjeswori Ulak*, Ramesh K Adhikari*, Rajiv Bahl††, Nita Bhandari**†, Rune J Ulvik††, Maharaj K Bhan**, Halvor Sommerfelt†

†Centre for International Heath, University of Bergen, Norway; *Department of Child Health, Tribhuvan University, Kathmandu, Nepal; **Department Paediatrics, All India Institute of Medical Sciences, New Delhi, India; ††Institute of Clinical Biochemistry, University of Bergen, Norway. ††World Health Organization, Geneva, Switzerland.

Persistent diarrhea (episode duration ≥ 14 days) is the leading cause of diarrheal deaths in children of developing countries. The therapeutic effect of zinc on acute diarrhea has been well documented particularly in reducing diarrhoeal duration. It has been suggested that children with low plasma zinc concentration and with malnutrition benefit more from zinc administration than other children but the additional effects in these subgroups have been inconsistent and relatively low. We wanted to examine the effect of zinc administration during acute diarrhea on the risk for persistent diarrhea and whether the effect of zinc was different among various sub-groups. A double blind randomized placebo-controlled trial in 1792 children 6 to 35 months of age was undertaken. The main outcomes were time to recovery from diarrhea and proportion with persistent diarrhoea. Cox proportional hazards models with interaction terms were used to assess the effect of zinc in different sub-groups and to estimate the precision of any interactions. The unadjusted relative hazard (RH) for termination of diarrhea was 1.26  (95% CI: 1.09, 1.46) higher in the zinc than in the placebo group. The effect of zinc was higher in the children who had low plasma zinc levels at enrolment, high fever, or other markers of severe infection.

Zinc administration significantly reduced the risk of persistent diarrhea from 5.4 to 2.9 %, a risk difference of 2.5. % (95% CI: 0.3, 5%). Thus, the numbers needed to treat to prevent one case of persistent diarrhea are 40. One 20 mg zinc tablet cost EURO 0.015 (Nutriset, Malaunay, France), if we assume a mean treatment time of seven days, the price of a course during acute diarrhea will be EURO 0.105. The drug cost to prevent one episode of persistent diarrhea is accordingly EURO 4.2. Locally prepared zinc tablets or syrup are likely to be cheaper so this cost may be reduced further.

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