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Zinc supplementation significantly decreased pediatric pneumonia fatalities
Srinivasan MG.BMC Medicine 2012; doi:10.1186/1741-7015-10-14
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Compared with standard antibiotic therapy alone, adjunct therapy with zinc supplements significantly decreased fatality rates among children with severe pneumonia in Uganda. However, zinc supplementation did not shorten the course of illness, according to results of a recent study.
To assess the effect of zinc adjunct therapy on the outcome of childhood pneumonia (including case fatality), researchers in Uganda enrolled 352 children, aged 6 to 59 months, who were admitted to the Mulago Hospital pediatric emergency ward with severe pneumonia.
In a double blind, randomized, placebo-controlled trial, the children were randomly selected to receive either zinc (20 mg for children aged 12 months and older and 10 mg for children aged younger than 12 months) or a daily placebo, in addition to standard antibiotic treatment. Study participants were assessed every 6 hours for 7 days of treatment, measuring the normalization of oxygen saturation, respiratory rate and temperature.
The investigators reported zinc supplementation did not reduce the recovery time or normalization period of the respiratory rate, temperature and oxygen saturation in patients with severe pneumonia. However, the findings revealed a statistically significant decrease in deaths among patients who received zinc supplements: case fatality was 4% (7/176) in the zinc group and 11.9% (21/176) in the placebo group (RR=0.33; 95% CI, 0.15-0.76).
In a subset of children with severe pneumonia who were HIV-positive, fatality rate was higher in the placebo group (7/27) compared with the zinc group (0/28). Among 127 children without HIV who received placebo, case fatality was 5.5% (7/127) vs. 3.9% (5/129) among children without HIV who received zinc (RR=0.7; 95% CI, 0.2-2.2).
Therefore, the researchers concluded that zinc could be considered for use as adjunct therapy for severe pneumonia, especially among highly active antiretroviral therapy-naive children with HIV in Uganda.
“Zinc is known to bolster the immune system and zinc deficiency is rife all over the developed, and developing, world,” researcher James K. Tumwine, PhD, said in a press release. “In Uganda, where this study was performed, zinc deficiency in some areas can be as high as 70%. We would only need to give 13 of these children with pneumonia zinc on top of their antibiotics to save one life. This equates to about $4 (US dollars) — a small price to pay.”
Disclosure: The researchers report no relevant financial disclosures.
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Three hundred fifty-two children aged 6 to 59 months with severe pneumonia were randomly assigned to zinc or placebo once daily for 7 days in addition to antibiotic therapy. Children were assessed for time to normalization of the respiratory rate, temperature and oxygen saturation, as well as mortality. The important differences observed were those in mortality: Overall case fatality was 7/176 (4%) in the zinc group and 21/176 (11.9%) in the placebo group. The effect of zinc appeared to be most striking in children known to be infected with HIV and was not significant in those known to not be infected. In the HIV-infected children, the mortality was 7/27 (nearly 25%) in the placebo group and 0/28 in the zinc group. Although these results are intriguing and the hypothesis deserves further study, there are many questions about the study population that are unanswered. For example, although we know that the children received either chloramphenicol or ceftriaxone for treatment, the antibiotic treatment and blood culture results of the patients who died are not detailed.
We also know that, in the 25% of children with positive blood cultures, the isolates were Streptococcus pneumoniae, Staphylococcus aureus and Salmonella. Were the bacteremic patients receiving an appropriate antibiotic? A child with staphylococcal disease may not be adequately treated with ceftriaxone or chloramphenicol. A child with S. pneumoniae may not be adequately treated with chloramphenicol. It is imperative to have this information. How many of the children in whom blood cultures were not drawn were bacteremic? Forty-one children were not tested for HIV, and accordingly, their HIV status is unknown. Mean time to death was 2.57 days. How many of these children were in extremis when admitted to hospital? It is a bit surprising that zinc would have an all-or-none effect. That is, zinc prevents mortality but has no effect on the course of the disease as measured by return to normal respiratory rate, temperature and oxygen saturation.
Ellen R. Wald, MD
Infectious Diseases in Children Editorial Board member
Disclosure: Dr. Wald reports no relevant financial disclosures.
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