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

BACKGROUND: Pneumonia is a leading cause of children's 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, randomized, placebo-controlled clinical trial, 352 children aged 6 to 59 months, with severe pneumonia were randomized to zinc (20 mg for children ≥ 12 months, and 10 mg for those < 12 months) or a placebo once daily for seven days, in addition to standard antibiotics for severe pneumonia. Children were assessed every six 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 37.5°C. 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 to 0.76). Relative Risk Reduction was 0.67 (95% CI 0.24 to 0.85), while the number needed to treat was 13. Among HIV infected children, case fatality was higher in the placebo (7/27) than in the zinc (0/28) group; RR 0.1 (95% CI 0.0, 1.0).Among 127 HIV uninfected children receiving the 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 Highly Active Antiretroviral Therapynaïve HIV infected children in our environment. CLINICAL TRIALS REGISTRATION NUMBER: clinicaltrials.gov NCT00373100.

Respiratory cryptosporidiosis in HIV-seronegative children in Uganda: potential for respiratory transmission.

BACKGROUND: Respiratory cryptosporidiosis is recognized as a late-stage complication in persons with human immunodeficiency virus (HIV) infection and AIDS. However, respiratory signs and symptoms are common in otherwise healthy children with intestinal cryptosporidiosis, which suggests that respiratory infection may occur in immunocompetent hosts. METHODS: We recruited children 9-36 months of age who presented with diarrhea to Mulago Hospital in Kampala, Uganda, from November 2007 through January 2009. Children with stool samples positive or negative for Cryptosporidium species were selected for further evaluation, including sputum induction in those with cough or unexplained respiratory signs and collection of saliva and blood specimens. Sputum samples were subjected to comprehensive bacteriologic testing, and both sputum and saliva specimens were tested for Cryptosporidium species by nested polymerase chain reaction. RESULTS: Of 926 fecal samples screened, 116 (12.5%) were positive for Cryptosporidium. Seventeen (35.4%) of 48 sputum samples tested from children with positive stool samples were positive for Cryptosporidium. Sixteen (94.1%) of the 17 children with confirmed respiratory cryptosporidiosis were HIV seronegative, and 10 (58.8%) of 17 children were not malnourished. None of the 12 sputum specimens from children with negative stool samples tested positive for Cryptosporidium (P = .013, compared with children who tested positive for Cryptosporidium in the stool). Parasite DNA was detected in only 2 (1.9%) of 103 saliva samples (P < .001, compared with sputum samples). CONCLUSIONS: Respiratory cryptosporidiosis was documented in one-third of HIV-seronegative children who were tested. These novel findings suggest the potential for respiratory transmission of cryptosporidiosis. Trial registration. ClinicalTrials.gov identifier: NCT00507871.