title: Micronutrient-Fortified Rice Can Increase Hookworm Infection Risk: A Cluster Randomized Trial.
abstract: 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.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01706419.
authors.affiliation: Section Health and Life Sciences, Athena Institute, Faculty of Earth and Life Sciences, VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Brechje
authors.initials: B
authors.lastname: de Gier
authors.affiliation: Section Infectious Diseases, department of Health Sciences, Faculty of Earth and Life Sciences, VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Maiza
authors.initials: M
authors.lastname: Campos Ponce
authors.affiliation: UMR-204, NutriPass IRD-UM-SupAgro, Institut de Recherche pour le Développement, Montpellier, France.
authors.forename: Marlene
authors.initials: M
authors.lastname: Perignon
authors.affiliation: UMR-204, NutriPass IRD-UM-SupAgro, Institut de Recherche pour le Développement, Montpellier, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Fiorentino
authors.affiliation: Department of Fisheries Post-Harvest Technologies and Quality control, Fisheries Administration, Phnom Penh, Cambodia.
authors.forename: Kuong
authors.initials: K
authors.lastname: Khov
authors.affiliation: Department of Fisheries Post-Harvest Technologies and Quality control, Fisheries Administration, Phnom Penh, Cambodia.
authors.forename: Chhoun
authors.initials: C
authors.lastname: Chamnan
authors.affiliation: Section Methodology and Applied Biostatistics, Department of Health Sciences, Faculty of Earth and Life Sciences, VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Michiel R
authors.initials: MR
authors.lastname: de Boer
authors.affiliation: PATH, Seattle, Washington, United States of America.
authors.forename: Megan E
authors.initials: ME
authors.lastname: Parker
authors.affiliation: United Nations World Food Programme, Phnom Penh, Kingdom of Cambodia.
authors.forename: Kurt
authors.initials: K
authors.lastname: Burja
authors.affiliation: Department of Nutrition, Exercise and Sports, Copenhagen University, Copenhagen, Denmark.
authors.forename: Marjoleine A
authors.initials: MA
authors.lastname: Dijkhuizen
authors.affiliation: UMR-204, NutriPass IRD-UM-SupAgro, Institut de Recherche pour le Développement, Montpellier, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Berger
authors.affiliation: Section Infectious Diseases, department of Health Sciences, Faculty of Earth and Life Sciences, VU University Amsterdam, Amsterdam, The Netherlands.|Department of Biomedical Sciences, Institute for Tropical Medicine, Antwerp, Belgium.
authors.forename: Katja
authors.initials: K
authors.lastname: Polman
authors.affiliation: UMR-204, NutriPass IRD-UM-SupAgro, Institut de Recherche pour le Développement, Montpellier, France.
authors.forename: Frank T
authors.initials: FT
authors.lastname: Wieringa
mesh_terms: D000723:Ancylostomatoidea / Q000502:physiology*; D000818:Animals; D002648:Child; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005243:Feces / Q000469:parasitology; D005260:Female; D005527:Food, Fortified; D006801:Humans; D007411:Intestinal Diseases, Parasitic / Q000453:epidemiology / Q000209:etiology*; D019266:Iron, Dietary / Q000008:administration & dosage; D039841:Leukocyte L1 Antigen Complex / Q000032:analysis; D008137:Longitudinal Studies; D008297:Male; D018977:Micronutrients / Q000008:administration & dosage* / Q000737:chemistry; D012275:Oryza / Q000737:chemistry*; D015990:Placebo Effect; D015995:Prevalence
chemical_list: D019266:Iron, Dietary; D039841:Leukocyte L1 Antigen Complex; D018977:Micronutrients