Trace elements, inflammation, and rotavirus vaccine response among a cohort of infants in El Alto, Bolivia Public

Abstract

Rotavirus infection is the most common cause of fatal diarrhea in infants despite the existence of effective rotavirus vaccines. Over 90% of rotavirus deaths occur in low- and middle-income countries (LMIC’s). One such LMIC, Bolivia, experiences the highest under-5 mortality rate in Spanish speaking South America, with numerous deaths attributable to rotavirus infection. Yet, in LMIC’s like Bolivia, rotavirus vaccines are less effective than in high-income countries. The Nutrition, Immunology, Diarrhea in Infants (NIDI) study in El Alto, Bolivia was created to explore the factors related to reduced immune response to the rotavirus vaccine in Bolivia. NIDI investigators enrolled 461 infants in the study. Blood was drawn up to three times – once pre-vaccination, at approximately 2 months, and twice post-vaccination, at approximately 6 months and 12-18 months – and analyzed for several biomarkers, including: serum concentrations of calcium, copper, iron, magnesium, and zinc; concentrations of systemic inflammatory markers α-1-acid glycoprotein (AGP) and C-reactive protein (CRP); and rotavirus-specific IgA antibodies. There is a need to understand how micronutrient levels play a role in the rotavirus vaccine’s reduced performance in low income settings. To meet this need, a secondary analysis was completed on the NIDI data. Spearman’s correlation analyses revealed moderate positive correlations between serum copper and both AGP (ρ = 0.51-0.71, p <0.01) and CRP (ρ = 0.46-0.55, p<0.01). The distributions of values for trace element concentrations were described, with many values falling outside of reference ranges in the literature, especially values for serum magnesium and zinc (up to 55% and 67% of the time, respectively). There were no significant relationships between any serum element and rotavirus-specific IgA seroconversion using logistic regression analyses, but Spearman’s analyses revealed inverse relationships between both serum copper (ρ = -0.14, p=0.01) and CRP (ρ = -0.16, p<0.01) and the fold-change in rotavirus-specific IgA following vaccination. These results indicate a need to account for inflammation when assessing copper status, as well as a need to refine the reference ranges for serum element concentrations in infants. Furthermore, the findings suggest that higher inflammatory burden may blunt the strength of the immune response to rotavirus vaccination.

Table of Contents

Table of Contents

Rotavirus Infection & Vaccination: A literature review of the role of trace elements and inflammation in vaccine response. 3

I. Rotavirus. 3

I.a. The Virus. 3

I.b. Transmission and Pathogenesis. 4

I.c. Clinical Symptoms, Diagnosis, and Treatment 4

II. Immunity and Vaccination. 5

II.a. Immunity. 5

II.b. Rotavirus Vaccination. 7

II.c. Reduced Vaccine Effectiveness in Low and Middle-Income Countries. 8

III. Nutrition and Trace Elements. 8

IV.a. Copper 10

IV.b. The Copper/Zinc Ratio. 12

IV.c. Magnesium, Calcium, and Iron. 13

IV.d. Inflammation and Elemental Micronutrient Concentrations. 15

IV.a. Bolivia. 17

IV.b. Rotavirus Vaccination in Bolivia. 17

IV.c. El Alto. 17

IV.d. Nutrition, Immunology, Diarrhea in Infants Study. 18

V. Conclusion. 18

VI. Significance. 19

Analysis. 21

VII. Methods. 21

VII.a. The NIDI Study Population and Design. 21

VII.b. Statistical Methods. 22

VII.c. Linear Regression to Correct Copper for AGP and CRP. 23

VIII. Results. 25

IX. Discussion. 31

X. Conclusion. 37

XI. Public Health Implications. 38

XII. Tables. 40

XIII. Appendices. 47

References. 50

About this Master's Thesis

Rights statement

• Permission granted by the author to include this thesis or dissertation in this repository. All rights reserved by the author. Please contact the author for information regarding the reproduction and use of this thesis or dissertation.

School	Rollins School of Public Health
Department	Epidemiology
Degree	M.P.H.
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Public Health
Mot-clé	Inflammation Bolivia Health Nutrition Elements Rotavirus Copper Vaccine Public Global
Committee Chair / Thesis Advisor	Leon, Juan, Emory University
Committee Members	Rebolledo, Paulina, Emory University
Partnering Agencies	Emory University schools, faculty or affiliated programs

Dernière modification

Primary PDF

Thumbnail	Title	Date Uploaded	Actions
	Trace elements, inflammation, and rotavirus vaccine response among a cohort of infants in El Alto, Bolivia ()	2018-04-24 17:59:29 -0400	Press to Select an action Download

Supplemental Files

Thumbnail	Title	Date Uploaded	Actions