title: Zinc supplementation fails to increase the immunogenicity of oral poliovirus vaccine: a randomized controlled trial.
abstract: BACKGROUND
  Polio eradication remains a challenge in Pakistan and the causes for the failure to eradicate poliomyelitis are complex. Undernutrition and micronutrient deficiencies, especially zinc deficiency, are major public health problems in Pakistan and could potentially affect the response to enteric vaccines, including oral poliovirus vaccine (OPV).
  
  
  OBJECTIVE
  To assess the impact of zinc supplementation among infants on immune response to oral poliovirus vaccine (OPV).
  
  
  METHODS
  A double-blind, randomized placebo-controlled trial was conducted in newborns (aged 0-14 days). Subjects were assigned to either receive 10mg of zinc or placebo supplementation daily for 18 weeks. Both groups received OPV doses at birth, at 6 weeks, 10 weeks and 14 weeks. Data was collected on prior immunization status, diarrheal episodes, breastfeeding practices and anthropometric measurements at recruitment and at 6 and 18 weeks. Blood samples were similarly collected to determine the antibody response to OPV and for micronutrient analysis. Logistic regression was used to determine the relationship between seroconversion and zinc status.
  
  
  RESULTS
  Overall, 404 subjects were recruited. At recruitment, seropositivity was already high for poliovirus (PV) serotype 1 (zinc: 91.1%; control: 90.5%) and PV2 (90.0%; 92.7%), with lower estimates for PV3 (70.0%; 64.8%). By week 18, the proportion of subjects with measured zinc levels in the normal range (i.e. ≥60 μg/dL) was significantly greater in the intervention group compared to the control group (71.9%; 27.4%; p<0.001). No significant difference in seroconversion was demonstrated between the groups for PV1, PV2, or PV3.
  
  
  CONCLUSIONS
  There was no effect of zinc supplementation on OPV immunogenicity. These conclusions were confirmed when restricting the analysis to those with measured higher zinc levels.
authors.affiliation: Aga Khan University, Karachi, Pakistan.
authors.forename: M A
authors.initials: MA
authors.lastname: Habib
authors.affiliation: Aga Khan University, Karachi, Pakistan.
authors.forename: S
authors.initials: S
authors.lastname: Soofi
authors.affiliation: Aga Khan University, Karachi, Pakistan.
authors.forename: A
authors.initials: A
authors.lastname: Sheraz
authors.affiliation: Aga Khan University, Karachi, Pakistan.
authors.forename: Z S
authors.initials: ZS
authors.lastname: Bhatti
authors.affiliation: WHO, Headquarters, 20 Avenue Appia, CH-1211 Geneva 27, Switzerland.
authors.forename: H
authors.initials: H
authors.lastname: Okayasu
authors.affiliation: National Institute of Health (NIH), Islamabad, Pakistan.
authors.forename: S Z
authors.initials: SZ
authors.lastname: Zaidi
authors.affiliation: WHO, Headquarters, 20 Avenue Appia, CH-1211 Geneva 27, Switzerland.
authors.forename: N A
authors.initials: NA
authors.lastname: Molodecky
authors.affiliation: Centers for Disease Control and Prevention (CDC), Atlanta, GA, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Pallansch
authors.affiliation: WHO, Headquarters, 20 Avenue Appia, CH-1211 Geneva 27, Switzerland.
authors.forename: R W
authors.initials: RW
authors.lastname: Sutter
authors.affiliation: Aga Khan University, Karachi, Pakistan. Electronic address: zulfiqar.bhutta@aku.edu.
authors.forename: Zulfiqar A
authors.initials: ZA
authors.lastname: Bhutta
mesh_terms: D000914:Antibodies, Viral / Q000097:blood*; D019587:Dietary Supplements; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016015:Logistic Models; D008297:Male; D010154:Pakistan; D011051:Poliomyelitis / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D017955:Poliovirus / Q000276:immunology; D011055:Poliovirus Vaccine, Oral / Q000008:administration & dosage* / Q000276:immunology; D014611:Vaccination; D015032:Zinc / Q000008:administration & dosage*
chemical_list: D000914:Antibodies, Viral; D011055:Poliovirus Vaccine, Oral; D015032:Zinc
keywords: Poliomyelitis; Randomized controlled trial; Vaccine response; Zinc supplementation