title: Effect of preventive supplementation with zinc and other micronutrients on non-malarial morbidity in Tanzanian pre-school children: a randomized trial.
abstract: BACKGROUND
  The efficacy of preventive zinc supplementation against diarrhea and respiratory illness may depend on simultaneous supplementation with other micronutrients. We aimed to assess the effect of supplementation with zinc and multiple micronutrients on diarrhea and other causes of non-malarial morbidity.
  
  
  RESULTS
  Rural Tanzanian children (n = 612) aged 6-60 months and with height-for-age z-score < -1.5 SD were randomized to daily supplementation with zinc (10 mg) alone, multi-nutrients without zinc, multi-nutrients with zinc, or placebo. Children were followed for an average of 45 weeks. During follow-up, we recorded morbidity episodes. We found no evidence that concurrent supplementation with multi-nutrients influenced the magnitude of the effect of zinc on rates of diarrhea, respiratory illness, fever without localizing signs, or other illness (guardian-reported illness with symptoms involving skin, ears, eyes and abscesses, but excluding trauma or burns). Zinc supplementation reduced the hazard rate of diarrhea by 24% (4%-40%). By contrast, multi-nutrients seemed to increase this rate (HR; 95% CI: 1.19; 0.94-1.50), particularly in children with asymptomatic Giardia infection at baseline (2.03; 1.24-3.32). Zinc also protected against episodes of fever without localizing signs (0.75; 0.57-0.96), but we found no evidence that it reduced the overall number of clinic visits.
  
  
  CONCLUSIONS
  We found no evidence that the efficacy of zinc supplements in reducing diarrhea rates is enhanced by concurrent supplementation with other micronutrients. By reducing rates of fever without localizing signs, supplementation with zinc may reduce inappropriate drug use with anti-malarial medications and antibiotics.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00623857.
authors.affiliation: Cell Biology and Immunology Group, Wageningen University, Wageningen, The Netherlands.
authors.forename: Jacobien
authors.initials: J
authors.lastname: Veenemans
authors.forename: Laura R A
authors.initials: LR
authors.lastname: Schouten
authors.forename: Maarten J
authors.initials: MJ
authors.lastname: Ottenhof
authors.forename: Theo G
authors.initials: TG
authors.lastname: Mank
authors.forename: Donald R A
authors.initials: DR
authors.lastname: Uges
authors.forename: Erasto V
authors.initials: EV
authors.lastname: Mbugi
authors.forename: Ayşe Y
authors.initials: AY
authors.lastname: Demir
authors.forename: Rob J
authors.initials: RJ
authors.lastname: Kraaijenhagen
authors.forename: Huub F J
authors.initials: HF
authors.lastname: Savelkoul
authors.forename: Hans
authors.initials: H
authors.lastname: Verhoef
mesh_terms: D002675:Child, Preschool; D003967:Diarrhea / Q000401:mortality / Q000517:prevention & control; D019587:Dietary Supplements; D005260:Female; D006801:Humans; D007223:Infant; D008288:Malaria; D008297:Male; D018977:Micronutrients / Q000008:administration & dosage*; D012140:Respiratory Tract Diseases / Q000401:mortality / Q000517:prevention & control; D012423:Rural Health; D012424:Rural Population; D013636:Tanzania; D015032:Zinc / Q000008:administration & dosage*
chemical_list: D018977:Micronutrients; D015032:Zinc