TOPLINE

A randomized trial in Uganda found that daily zinc supplementation reduced infection rates among young children with sickle cell anemia (SCA) by 38%. Severe bacterial infections were cut by two-thirds.

METHODOLOGY

• Children with SCA, the most severe form of sickle cell disease, are particularly susceptible to infections. Zinc deficiency is common among children and adults with SCA worldwide, and it’s thought to play a role in their increased infection risk. However, a previous clinical trial in Uganda found no benefit from giving children supplemental zinc at 10 mg/d. 
• The new trial, conducted at Jinja Regional Referral Hospital in Uganda, looked at whether higher-dose zinc might be effective. Researchers randomly assigned 100 children aged 12-59 months with confirmed SCA (HbSS genotype) to receive either oral zinc sulfate at 20 mg daily or placebo daily for 6 months. 
• Both groups received standard care including pneumococcal vaccination, twice-daily penicillin V potassium prophylaxis, daily folic acid supplementation, and monthly malaria prophylaxis. All children initiated or continued hydroxyurea therapy after enrollment. 
• The primary outcome was all-cause infections per 100 person-years. Incidence rate ratios and rate differences were adjusted for baseline age, sex, and hydroxyurea use at time of study entry. 

TAKEAWAY

• Over 6 months, there were 80 infections among children in the zinc group vs 124 in the placebo group, corresponding to 305.7 vs 480.7 infections per 100 person-years (adjusted incidence rate ratio [aIRR], 0.62; P = .005). 
• The benefit was driven by reduced rates of upper respiratory tract infections (aIRR, 0.61) and suspected severe bacterial infections (aIRR, 0.32). Children in the zinc group also had lower rates of pneumonia (aIRR, 0.34) and diarrhea (aIRR, 0.25), but those differences did not reach statistical significance. There was no reduction in incidence of vaso-occlusive crises with zinc. 
• Mean serum zinc levels in the zinc group increased by 8.0 μg/dL from baseline to 6 months, and the percentage of children with zinc deficiency declined from 46% to 26%. 
• There were no adverse events requiring discontinuation of the study treatment. Nearly all adverse events were related to infection, vaso-occlusive crises, or anemia, and the overall incidence was lower in the zinc group than in the placebo group (aIRR, 0.64). 

IN PRACTICE

“The study findings suggest that zinc supplementation at 20 mg daily could be a safe and inexpensive way to prevent infections in young children with SCA,” the study authors wrote. They noted that in North America, children with SCA have zinc deficiency rates of 44%-57%, on par with children in Uganda — suggesting that similar trials of zinc supplementation in high-income countries may be warranted.

SOURCE

The study was led by Ruth Namazzi, MMED, of Makerere University College of Health Sciences in Kampala, Uganda, and Chandy C. John, MD, of Indiana University School of Medicine in Indianapolis. It was published online in JAMA.

LIMITATIONS

The trial was limited to a single center and children younger than 5 years. It was powered to detect only very large differences in rates of specific infections, infections requiring hospitalization, or vaso-occlusive crises between the zinc and placebo groups. Although zinc appeared safe and well-tolerated, there could be adverse events not captured in the study, such as a reduction in copper levels.

DISCLOSURES

The trial received grants from Indiana University School of Medicine and Cures Within Reach. The authors had no financial disclosures.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.