Certain Iron Deficiencies May Protect Against Malaria in African Children

Iron deficiency may protect African children against malaria infection when defined using ferritin and transferrin saturation, according to a study recently published in Clinical Infectious Diseases.

In pre-school-aged, African children, iron deficiency is the most common nutrient deficiency and remains an important public health problem associated with poor brain development and long-term behavioral and cognitive impairments. Malaria also remains an important public health problem, and is responsible for additional devastating health effects in children. The safety of iron supplementation has been a long-standing concern in malaria-endemic areas and is recommended to be coupled with malaria treatment and prevention strategies in malaria-endemic areas. However, it is unclear whether iron supplementation is unsafe, as improved iron status may result in a long-term increase in malaria risk.

There have been few observational studies that investigated the effect of iron status on malaria risk. Previous studies that have investigated the effect of iron status on malaria risk suggest that iron deficiency is associated with a reduced risk for malaria, but little is known about whether other indicators of iron status (including hepcidin, hemoglobin, soluble transferrin receptors, and transferrin saturation) influence malaria risk. Therefore, this observational study aimed to determine whether a child’s iron status influences their subsequent risk for malaria infection in sub-Saharan Africa.

Community-based cohorts of 1309 Kenyan and 1374 Ugandan children aged 0 to 7 years were assayed for iron and inflammatory biomarkers, and prospective surveillance for episodes of malaria were conducted. To determine the effect of iron status on the incidence rate ratio of malaria, Poisson regression models were fitted using longitudinal data covering a 6-month period and were adjusted for age, sex, inflammation, parasitemia, and study site. A malaria episode was defined as a parasitemia and temperature >37.5°C.

The prevalence of iron deficiency at baseline was 36.9% and 34.6% in Kenyan and Ugandan children, respectively. Iron deficiency anemia affected 23.6% and 17.6% of Kenyan and Ugandan children, respectively. The prevalence of iron deficiency based on transferrin saturation (measured in the Kenya cohort only) was 52.4%; the prevalence of malaria parasitemia was 20.1% in the Kenyan cohort and 6.7% in the Ugandan cohort. At least 1 episode of malaria infection was experienced in 31.1% of Kenyan and 14.3% of Ugandan children during the 6-month follow-up.

Results showed that iron deficiency defined by low ferritin, iron deficiency defined by low transferrin saturation, and anemia were associated with 40%, 20%, and 30% reduced risk for malaria, respectively. There was a lower malaria risk in children with iron deficiency (incidence rate ratio [IRR], 0.7; P <.001) than iron deficiency anemia (IRR, 0.7; P =.006). Low transferrin saturation was also associated with a lower malaria risk (IRR, 0.8; P =.016). However, results suggested that variation in hepcidin, soluble transferrin receptors, and anemia (or hemoglobin concentration) did not influence subsequent malaria risk.

Overall, the study authors concluded that, “Since [iron deficiency] prevents children from reaching their developmental potential it is important to establish causality in the iron-malaria relationship. Thus, these data warrant further large-scale studies, including studies which utilize genetic variants associated with iron status to infer causality (Mendelian randomization), and prospective interventional trials.”

Reference

Muriuki JM, Mentzer AJ, Kimita W, et al. Iron status and associated malaria risk among african children [published September 14 2018]. Clin Infect Dis. doi: 10.1093/cid/ciy791/5096852