In a study conducted in Africa, children aged 6 to 59 months who had severe pneumonia had reduced mortality when receiving zinc in addition to standard antibiotics, a new study has found. In addition, the reduction in mortality was greater among HIV-infected than non-HIV-infected children.
Maheswari G. Srinivasan, from the Department of Pediatrics and Child Health at the School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda, and colleagues reported the findings in an article published online February 8 in BMC Medicine.
"Given these results, zinc could be considered for use as adjunct therapy for severe pneumonia, especially among Highly Active Antiretroviral Therapy naïve HIV infected children in our environment," the authors conclude.
According to the researchers, acute respiratory tract infections is the most common cause of morbidity and mortality in children younger than 5 years of age, and the "burden of acute lower respiratory tract infections is 2 to 10 times more common in developing than in developed countries."
The results with zinc supplementation in this setting have been mixed. "One randomized controlled study from Bangladesh showed that zinc adjunct therapy accelerated recovery of children with severe pneumonia," the authors note, "but other studies have shown no effect," and "no studies have assessed the impact of zinc adjunct therapy on case fatality of children with pneumonia."
To evaluate this issue, the researchers randomly assigned children aged 6 to 59 months who had severe pneumonia to receive either zinc once daily for 7 days (n = 176; 20 mg for children aged 12 months or older and 10 mg for younger children) or a placebo once daily for 7 days (n = 176).
Children also received standard antibiotics for severe pneumonia and were assessed every 6 hours for oxygen saturation, respiratory rate, and temperature.
Among the children receiving zinc, 7 (4.0%) died compared with 21 patients (11.9%) in the placebo group. This represented nearly a 70% reduction in mortality risk in favor of zinc supplementation (relative risk [RR] reduction, 0.67; 95% confidence interval [CI], 0.24 - 0.85).
The greatest risk reduction was seen in HIV-infected children. Among HIV-infected children, case fatality was 7 of 27 children in the placebo group vs 0 of 28 children in the zinc group (RR, 0.1; 95% CI, 0.0 - 1.0).
In contrast, in HIV-uninfected children, no difference in case fatality was observed with zinc vs placebo: case fatality was 7/127 (5.5%) with placebo vs 5/129 (3.9%) among HIV-uninfected children receiving zinc (RR, 0.7; 95% CI, 0.2 - 2.2).
According to the researchers, the excess risk with placebo was substantially greater among HIV-positive children than in HIV-negative children (absolute risk reduction, 26/100 children vs 2/100 children, respectively; P = .006).
They estimated that 13 patients needed to be treated to avert 1 death, and that children who received the placebo were 3 times more likely to die compared with those who received zinc.
"There are two key findings in this study: overall, zinc supplementation in these children significantly decreased case fatality, but did not reduce the time to normalization of the parameters for disease severity," the authors conclude.
According to the researchers, zinc supplementation might increase the immune response by boosting phagocytosis and averting apoptosis of T lymphocytes in HIV-infected patients.
They add that zinc deficiency (present in from 20% to 69% of children in this setting) "compromises immunity through a number of mechanisms, such as T cell dysfunction and dysregulation of intracellular killing."
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