Zinc for infection prevention in children with sickle cell anemia: a randomized double-blind placebo-controlled trial

Document Type



Paediatrics and Child Health (East Africa)


Data from small clinical trials in the USA and India suggest zinc supplementation reduces infection in adolescents and adults with sickle cell anemia (SCA), but no studies of zinc supplementation for infection prevention have been conducted in young children with SCA living in Africa, who have higher infection rates. We conducted a randomized double-blind placebo-controlled trial to assess the effectiveness of zinc supplementation for prevention of severe or invasive infections in Ugandan children 1.00-4.99 years with SCA. Of the 252 enrolled participants, 124 were assigned zinc (10 mg) and 126 assigned placebo once daily for 12 months. The primary outcome was incidence of protocol-defined severe or invasive infections. Infection incidence did not differ between treatment arms (282 vs. 270 severe or invasive infections per 100 person-years, respectively, incidence rate ratio of 1.04 [95% confidence interval (CI), 0.81, 1.32, p=0.78]), adjusting for duration on hydroxyurea. There was also no difference between treatment arms in incidence of serious adverse events or SCA-related events. Children receiving zinc had increased serum levels after 12-months, but at study exit, 41% remained zinc deficient (<65 μg/dL). In post-hoc analysis, occurrence of stroke or death was lower in the zinc treatment arm (adjusted hazard ratio (95% CI), 0.22 (0.05, 1.00); p=0.05). Daily 10 mg zinc supplementation for 12 months did not prevent severe or invasive infections in Ugandan children with SCA, but many supplemented children remained zinc deficient. Optimal zinc dosing and the role of zinc in preventing stroke or death in SCA warrant further investigation.


This work was published before the author joined Aga Khan University.

Publication (Name of Journal)

Blood Advances