BMC Med：儿童补锌能减少呼吸道感染引发的死亡

Zinc adjunct therapy reduces case fatality in severe childhood pneumonia: a randomized double blind placebo-controlled trial

Maheswari G Srinivasan, Grace Ndeezi, Cordelia Katureebe Mboijana, Sarah Kiguli, Gabriel S Bimenya, Victoria Nankabirwa and James K Tumwine

Background

Pneumonia is a leading cause of child deaths in developing countries and hinders achievement of the fourth Millennium Development Goal. This goal aims to reduce the under-five mortality rate, by two thirds, between 1990 and 2015. Few studies have examined the impact of zinc adjunct therapy on the outcome of childhood pneumonia. We determined the effect of zinc as adjunct therapy on time to normalization of respiratory rate, temperature and oxygen saturation. We also studied the effect of zinc adjunct therapy on case fatality of severe childhood pneumonia (as a secondary outcome) in Mulago hospital, Uganda.

Methods

In this double blind randomised placebo-controlled clinical trial, 352 children aged 6-59 months, with severe pneumonia were randomized to zinc (20mg for children [greater than or equal to] 12 months, and 10mg for those below 12 months) or placebo once daily for seven days, in addition to standard antibiotics for severe pneumonia. Children were assessed every 6 hours. Oxygen saturation was normal if it was above 92% (breathing room air) for more than 15 minutes. The respiratory rate was normal if it was consistently (more than 24 hours) below 50 breaths per minute in infants and 40 breaths per minute in children above 12 months of age. Temperature was normal if consistently below 37.5oC. The difference in case fatality was expressed by the risk ratio between the two groups.

Results

Time to normalization of the respiratory rate, temperature and oxygen saturation was not significantly different between the two arms. Case fatality was 7/176 (4.0%) in the zinc group and 21/176 (11.9%) in the placebo group: Relative Risk 0.33 (95% CI 0.15-0.76). Relative Risk Reduction was 0.67 (95% CI 0.24-0.85) while the number needed to treat was 13. Among HIV infected children, case fatality was higher in the placebo (7/27) than the zinc (0/28) group; RR 0.1 (95% CI 0.0, 1.0). Among 127 HIV uninfected children receiving placebo, case fatality was 7/127 (5.5%); versus 5/129 (3.9%) among HIV uninfected group receiving zinc: RR 0.7 (95% CI 0.2, 2.2). The excess risk of death attributable to the placebo arm (Absolute Risk Reduction or ARR) was 8/100 (95% CI: 2/100, 14/100) children. This excess risk was substantially greater among HIV positive children than in HIV negative children [ARR: 26 (95% CI: 9, 42) per 100 versus 2 (95% CI: -4, 7) per 100]; p-value for homogeneity of risk differences = 0.006.

Conclusion

Zinc adjunct therapy for severe pneumonia had no significant effect on time to normalization of the respiratory rate, temperature and oxygen saturation. However zinc supplementation in these children significantly decreased case fatality. The difference in case fatality attributable to the protective effect of zinc therapy was greater among HIV infected than HIV uninfected children. Given these results, zinc could be considered for use as adjunct therapy for severe pneumonia, especially among HAART naive HIV infected children in our environment. Clinical trials registration number: clinicaltrials.gov NCT00373100