Elsevier

The Lancet

Volume 363, Issue 9422, 22 May 2004, Pages 1683-1688
The Lancet

Articles
Zinc for severe pneumonia in very young children: double-blind placebo-controlled trial

https://doi.org/10.1016/S0140-6736(04)16252-1Get rights and content

Summary

Background

Pneumonia is a leading cause of morbidity and mortality in young children. Early reversal of severity signs—chest indrawing, hypoxia, and tachypnoea—improves outcome. We postulated that zinc, an acute phase reactant, would shorten duration of severe pneumonia and time in hospital.

Methods

In a double-blind placebo-controlled clinical trial in Matlab Hospital, Bangladesh, 270 children aged 2–23 months were randomised to receive elemental zinc (20 mg per day) or placebo, plus the hospital's standard antimicrobial management, until discharge. The outcomes were time to cessation of severe pneumonia (no chest indrawing, respiratory rate 50 per min or less, oxygen saturation at least 95% on room air) and discharge from hospital. Discharge was allowed when respiratory rate was 40 per minute or less for 24 consecutive hours while patients were maintained only on oral antibiotics.

Findings

The group receiving zinc had reduced duration of severe pneumonia (relative hazard [RH]=0·70, 95% Cl 0·51–0·98), including duration of chest indrawing (0·80, 0·61–1·05), respiratory rate more than 50 per min (0·74, 0·57–0·98), and hypoxia (0·79, 0·61–1·04), and overall hospital duration (0·75, 0·57–0·99). The mean reduction is equivalent to 1 hospital day for both severe pneumonia and time in hospital. All effects were greater when children with wheezing were omitted from the analysis.

Interpretation

Adjuvant treatment with 20 mg zinc per day accelerates recovery from severe pneumonia in children, and could help reduce antimicrobial resistance by decreasing multiple antibiotic exposures, and lessen complications and deaths where second line drugs are unavailable.

Introduction

Pneumonia is a leading cause of morbidity and mortality in children less than 5 years old. About 20% of deaths in such children are attributable to pneumonia (1·9 million deaths per year).1 Two-thirds of these deaths happen during infancy, and more than 90% are in developing countries.

Zinc is reported to prevent pneumonia,2, 3, 4, 5 and to prevent and treat diarrhoea.4, 6, 7, 8 It might act in the acute phase response to infection,9, 10 helping to boost the body's immune response through a defence cascade, beginning with mobilisation and sequestration of zinc to metallothionein-rich tissue, rapid upregulation of immune defence-specific protein synthesis, activation of immune defence activity such as macrophages, lymphocytes, and natural killer cells, and antibody-dependent cytotoxicity.11 Children with good zinc status may have a more robust immune response than those with poor zinc status.12, 13 Thus, our aim was to see whether zinc, along with antibiotics, would improve the outcome of severe pneumonia.

Section snippets

Methods

We undertook a double blind randomised placebo-controlled clinical trial in hospitalised children who were between 2 and 23 months old at the time of admission to the Matlab Hospital, International Centre for Diarrhoeal Disease Research, Bangladesh Centre of Health and Population Research, a rural facility 50 km south of the capital Dhaka. Specifically, we investigated whether 20 mg zinc per day could shorten the duration of severe pneumonia and hospitalisation. We also measured the time to

Results

In total, 270 children were enrolled between Aug 23, 1999, and Aug 19, 2001. Of these, six (three from each group) left hospital against medical advice, and one (from the placebo group) withdrew from the study, but completed treatment in hospital (figure 1). Most (172 [64%]) patients were younger than 12 months, and most (177 [65%]) were male, which results from local health-seeking practices.

The mean duration of illness before hospitalisation was 2·5 days (SD 1·5), with no difference between

Discussion

We have shown clinically and statistically significant reductions in recovery time from severe pneumonia and overall hospital stay in children less than 2 years old given zinc with standard antimicrobial therapy. This improvement seems to result from substantial reductions in the resolution times of each of the severe pneumonia indicators, including chest indrawing, severely raised respiratory rate, and hypoxia, indicating a consistency between these specific signs and the diagnosis of severe

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