The dataset analysed within this paper is available in the corresponding author on reasonable request, and with appropriate additional ethical approvals, where required
The dataset analysed within this paper is available in the corresponding author on reasonable request, and with appropriate additional ethical approvals, where required. Competing interests: non-e declared. Patient and open public involvement: Sufferers and/or the TAPI-1 general public were not mixed up in design, or carry out, or reporting, or dissemination programs Mouse monoclonal to WDR5 of the extensive analysis. Provenance and peer review: Not commissioned; peer reviewed externally. Data availability statement Data not contained in the manuscript can be found upon reasonable demand. Ethics statements Patient consent for publication Not required. Ethics approval Ethical approval for the ENID trial and the aflatoxin substudy was obtained from the joint Gambian Government/Medical Research Council Unit The Gambia ethics committee (SCC1126v2 and L2013.40).. mothers and infants on infant immune development (the Early Nutrition and Immune Development Trial). Thymic size (Thymic Index, TI) was measured by sonography at 1 week, 8 weeks, 24 weeks and 52 weeks of infant age. Infants were given the diphtheriaCtetanusCpertussis (DTP) vaccine at 8 weeks, 12 weeks and 16 weeks of age, and Ab responses to each vaccine measured at 12 weeks and 24 weeks of age. AF-albumin (AF-alb) adduct levels in infant blood were measured by ELISA as the biomarker of AF exposure. Results The geometric mean (GM) level of AF-alb increased with age. Only half of infants had detectable AF-alb with a GM of 3.52?pg/mg at 24 weeks, increasing to 25.39?pg/mg at 52 weeks, when 98% of infants had AF-alb limit of detection. Significant negative association of AF-alb level with TI was seen in infants during the first 24 weeks, especially at 8 weeks of age (p 0.001), which is the time point of fastest thymus growth. There were no associations between AF exposure level and Ab response to pertussis and tetanus, but a significant positive correlation was observed between AF-alb TAPI-1 level and Ab titre to diphtheria (p 0.005). Conclusions High levels of AF exposure during early infancy may impact on infant immune development. Trial registration number ISRCTN49285450. and fungi that frequently contaminate crops in tropical and subtropical areas. It poses a great health risk to populations living in sub-Saharan Africa (SSA), especially in regions where groundnuts and/or maize are the staple foods.1 Exposure to AF can begin in utero through transplacental exposure, continue in early infancy through breast feeding and increase as children are weaned onto family foods, such as maize porridge or peanut sauces.2 Populations in the Gambia are at a high risk of AF exposure through food consumption.3C7 AF is a human liver carcinogen,8 and has also been associated with childhood growth faltering.9 10 An inverse relationship has been reported between AF-albumin adduct (AF-alb) levels in pregnant women and subsequent infant growth5 as well as between AF-alb and growth in infants below 2 years old,7 10 and high levels of AF lysine were associated with stunting and severe malnutrition in children in Nigeria,11 and with underweight children in Kenya.12 Data from animal studies suggests that AF modulates the immune response at the level of innate cell functions, antibody (Ab) production, lymphocyte activation and proliferation and regulation of cytokine/chemokine expression, but there have been few studies on the impact of AF on immune function in humans.13 14 A reduction of salivary IgA expression15 and lower percentage of lymphocytes16 17 in children with high AF exposure have been reported. A greater understanding of the impact of chronic AF exposure during infancy and early childhood on immune system development is required. The thymus is a primary lymphoid organ, essential for the development and differentiation of T lymphocytes. Thymic Index (TI; a derived estimate of thymic volume) measured sonographically has been used as an indicator of immune development in infants. Impaired thymic development in infancy has been associated with morbidity and mortality in childhood in Guinea-Bissau and Bangladesh,18C20 indicating a functional consequence of poor early thymic development. The effect of chronic AF exposure on humoral immunity is less consistent in animal and human studies.21 22 A study conducted in infants in the Gambia reported a weak but significant positive association between the level of AF-alb and pneumococcal Ab titres.15 Combined DTP (diphtheria, tetanus and pertussis) vaccine has been involved in the Expanded Programme on Immunisation (EPI), which was established in 1977 by the WHO and is estimated to prevent 2C3 million deaths in children every year. The aim of the current study was to determine the impact of TAPI-1 AF exposure in early infancy on thymus growth and altered Ab response to combined DTP vaccination. Methods Study subjects The current substudy into the effects of AF exposure on immune parameters was embedded within the Early Nutrition and Immune Development (ENID) trial. Full details of the ENID trial protocol have been published.23 The primary objective of the ENID trial was to investigate whether combined prenatal (protein energy and/or micronutrients) and infant (micronutrient) nutritional supplements could improve.