Micronutrient-Fortified Rice Can Increase Hookworm Infection Risk: A Cluster Randomized Trial

BACKGROUND: Fortification of staple foods is considered an effective and safe strategy to combat micronutrient deficiencies, thereby improving health. While improving micronutrient status might be expected to have positive effects on immunity, some studies have reported increases in infections or inflammation after iron supplementation. OBJECTIVE: To study effects of micronutrient-fortified rice on hookworm infection in Cambodian schoolchildren. METHODS: A double-blinded, cluster-randomized trial was conducted in 16 Cambodian primary schools partaking in the World Food Program school meal program. Three types of multi-micronutrient fortified rice were tested against placebo rice within the school meal program: UltraRice_original, UltraRice_improved and NutriRice. Four schools were randomly assigned to each study group (placebo n = 492, UltraRice_original n = 479, UltraRice_improved n = 500, NutriRice n = 506). Intestinal parasite infection was measured in fecal samples by Kato-Katz method at baseline and after three and seven months. In a subgroup (N = 330), fecal calprotectin was measured by ELISA as a marker for intestinal inflammation. RESULTS: Baseline prevalence of hookworm infection was 18.6%, but differed considerably among schools (range 0%- 48.1%).Micronutrient-fortified rice significantly increased risk of new hookworm infection. This effect was modified by baseline hookworm prevalence at the school; hookworm infection risk was increased by all three types of fortified rice in schools where baseline prevalence was high (>15%), and only by UltraRice_original in schools with low baseline prevalence. Neither hookworm infection nor fortified rice was related to fecal calprotectin. CONCLUSIONS: Consumption of rice fortified with micronutrients can increase hookworm prevalence, especially in environments with high infection pressure. When considering fortification of staple foods, a careful risk-benefit analysis is warranted, taking into account severity of micronutrient deficiencies and local prevalence of parasitic infections. TRIAL REGISTRATION: ClinicalTrials.gov NCT01706419