2012 Annual Report
1a.Objectives (from AD-416):
Determine if 50,000 IU vitamin A supplementation within 48 hours of birth will (1) improve thymus function; (2) enhance vaccine responses; and (3) decrease incidence of infections.
1b.Approach (from AD-416):
A community-based intervention trial in Dhaka, Bangladesh.
The agreement supports the goal of objective 4 to examine the effect of vitamin A on immune function and provides funding from the World Health Organization to the Agricultural Research Service to conduct an intervention trial in Dhaka, Bangladesh at the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b). The principal investigator is from the WHNRC and other investigators are staff scientists at icddr,b. The goal of our study is to determine if supplementation of newborn infants with 50,000 IU of vitamin A (vs. a placebo) improves aspects of immune function that may be impaired by vitamin A deficiency. The total sample size will be 300 infants with 150 infants in each group. Objective 1: Determine if vitamin A supplementation improves morphological features of thymus, as indicated by ultrasonic analysis of thymus size, and functional properties of thymus by the analysis of thymic output of naïve T-cells, using flow cytometric analysis of peripheral blood T-cells and by quantification of T-cell-receptor excision circles in peripheral blood. Objective 2: Determine if vitamin A supplementation at birth alters the T-cell response to tuberculosis and oral polio virus immunization assessed at 6 and 15 weeks of age; the B-cell response to polio immunization, assessed at 15 weeks of age, and the secretory IgA response to polio assessed at 6, 11 and 15 weeks of age; and the T- and B-cell response to tetanus toxoid and hepatitis B virus immunization, assessed at 15 weeks of age. Objective 3: Determine if vitamin A supplementation at birth will decrease bacterial lipopolysaccharide (LPS) concentrations in capillary blood, a marker of bacterial translocation.
Preparations for initiation of study: In Dhaka, one study physician, three research officers and four field workers have been hired. The research officers will conduct the laboratory work and the physician and field workers will carry out the clinical aspects of the study. Laboratory and clinical supplies have been shipped from Davis to Dhaka for initiation of lab work. Some supplies are purchased locally in Dhaka. The study physician received refresher training on the evaluation of infant thymus size measurement by ultrasound. All field workers have trained on three different days regarding their understanding of the study questionnaires as well as administrating them in the field site. Laboratory staff with basic immunology expertise were trained in specific methods by the study investigators at icddr,b.
Recruitment of study participants: Recruitment began in late 2011 and, as of June 14, 2012, 87 newborn infants have been recruited and randomized to treatment. Recruitment will continue throughout 2012. Lab work on blood samples is in progress and will continue throughout the recruitment and follow-up period.
Database: A database for clinical and laboratory data has been established using the REDCap software system, with the assistance of the Clinical and Translational Sciences Center at the University of California, Davis. Data are entered via the web from Dhaka and stored on a secure server in Davis.
Study Coordination: The principal investigator travelled to the study site twice to oversee study activities. Bi-weekly conference calls and regular e-mail contact are also used to coordinate research activities from Davis. An ARS SharePoint site has been established to share study material.