Daily Zinc Supplementation for Infection Prevention in Children With Sickle Cell Anemia
Ruth Namazzi, Kagan A. Mellencamp, Irene Bagala, Andrea L. Conroy, Charles Kato, Isaac Birungi, Priscilla Kasembo, Gloria Kyarisiima, Emmanuel Tenywa, Jie Ren, Michael J. Goings, Sarah E. Cusick, Chandy C. JohnImportance
Despite existing prevention strategies, infections remain a major cause of morbidity and mortality in children in Africa with sickle cell anemia.
Objective
To determine the safety and effectiveness of daily zinc supplementation to prevent all-cause infection in children with sickle cell anemia in Uganda.
Design, Setting, and Participants
A randomized, double-blind, placebo-controlled trial of children aged 1.00 to 4.99 years with sickle cell anemia at Jinja Regional Referral Hospital in Jinja, Uganda, from February 10, 2025, to April 30, 2025, with 6 months of follow-up through November 7, 2025.
Interventions
Participants received zinc sulfate at 20 mg daily or placebo daily for 6 months.
Main Outcomes and Measures
The primary outcome was all-cause infections per 100 person-years, using standardized clinical criteria to define infections.
Results
Among 118 children screened for eligibility, 100 were randomly assigned to receive zinc supplementation (n = 50) or placebo (n = 50) (mean [SD] age, 36.0 [13.2] months; 45 female [45%]). At enrollment, 45 participants (45%) were receiving hydroxyurea therapy. All participants initiated or continued receiving hydroxyurea after enrollment. During the 6-month follow-up, there was complete ascertainment for all participants and no loss to follow-up. There were 80 all-cause infections in the zinc group and 124 in the placebo group, corresponding to a significantly lower infection rate in the zinc group than the placebo group (305.7 [95% CI, 242.4-380.4] infections per 100 person-years vs 480.7 [95% CI, 399.8-573.1] infections per 100 person-years; rate difference, −176.0 [95% CI, −300.8 to −51.3]; incidence rate ratio after adjustment for baseline age, sex, and hydroxyurea use, 0.62 [95% CI, 0.45-0.86]). No adverse events requiring discontinuation of the study intervention were observed in either group.
Conclusions and Relevance
Zinc supplementation at 20 mg per day reduced all-cause infection in children with sickle cell anemia younger than 5 years in Uganda. Multisite clinical trials are needed to validate these findings and to assess effectiveness in older children.
Trial Registration
ClinicalTrials.gov Identifier: