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BackgroundChronic aflatoxin (AF) exposure has been shown to occur at high levels in children from sub-Saharan Africa (SSA), and has been associated with growth retardation and immune dysfunction. Our objective was to investigate the impact of AF exposure on immune development in early infancy using thymic size and antibody (Ab) response to vaccination as indicators of immune function.MethodsA total of 374 infants born between May 2011 and December 2012 were enrolled into the current study. These infants were recruited from a larger, randomised trial examining the impact of nutritional supplementation of 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 diphtheria–tetanus–pertussis (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.ResultsThe 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 (pConclusionsHigh levels of AF exposure during early infancy may impact on infant immune development.Trial registration numberISRCTN49285450.

Background In rural Gambia, rates of malnutrition and infection are higher during the annual rainy/‘hungry’ season (June–October) in comparison to the dry/‘harvest’ season (November–May). The effects of this seasonal pattern on an infant’s immune development and their capacity to respond to childhood vaccinations remain unclear. The aim of the current analysis was to determine whether antibody responses to diphtheria-tetanus-pertussis (DTP) vaccinations in infants differ between seasons. Methods Infants received the DTP vaccine at 8, 12 and 16 weeks of age and antibody titres were measured in blood samples collected at 12 (n = 710) and 24 (n = 662) weeks of age. Mean DTP antibody titres, adjusted for maternal and infant confounders, were compared by t-tests and the effect sizes of the mean differences were calculated between seasons at mid-gestation (20 weeks gestation) and first vaccination (8 weeks of infant age). Results A smaller number of infants received their first vaccination during the rainy/hungry season months compared to the dry/harvest season (n = 224 vs. n = 486). At 12 weeks, infants vaccinated during the rainy/hungry season had lower weight-for-length Z-scores (p = 0.01) and were more likely to be anaemic (p p p p p Conclusions Infant antibody response to the primary dose of the DTP vaccine was influenced by both season of pregnancy and infancy, although effects were diminished following three doses. Environmental exposures, including nutrition, to both the mother and infant are hypothesised as likely drivers of these seasonal effects.

Background A nutritionally deficient environment during fetal life may impair an infant's ability to mount an optimal immune response to vaccination. We examined the impact of supplementation during pregnancy with multiple micronutrients (MMN) and/or protein-energy (PE) on infant antibody responses to diphtheria-tetanus-pertussis (DTP) vaccination. Methods The Early Nutrition and Immune Development Trial (ISRCTN49285450) randomized 875 pregnant women from rural Gambia to receive one of four nutritional interventions (iron-folate (FeFol) as standard of care), MMN, PE and PE MMN) daily from enrolment (mean gestational age = 13·7±3·3 weeks) until delivery. Antibody responses to DTP administered to infants at 8, 12 and 16 weeks of age were measured in blood collected from a total of 670 and 563 infants at 12 and 24 weeks, respectively. The main outcome was the impact of maternal supplementation on log-transformed antibody titres in infants analysed using regression models with adjustment for confounders. Results At 12 weeks, adjusted mean (95% CI) anti-diphtheria titres were higher in infants born to mothers in the MMN (0·15 (0·13-0·18) IU/ml, p=0·002) and PE MMN (0·14 (0·12-0·16) IU/ml, p=0·028) groups, compared with the FeFol group (0·10 (0·09-0·12) IU/ml). This resulted in 72·2% (96/133) and 64·9% (87/134) of infants with protective anti-diphtheria titres (>0·1IU/ml) from the MMN and PE MMN groups, respectively, compared with 48·1% (64/133) from the FeFol group (p=0·001). Additionally, supplementation with PE MMN enhanced anti-tetanus titres (β=0·12, 95% CI 0·01-0·23, p=0·028) at 12 weeks; and anti-pertussis titres (β=0·26, 95% CI 0·02-0·50, p=0·035) at 24 weeks. Conclusions This study demonstrates that supplementation during pregnancy with MMN or a combination of MMN and PE enhances infant antibody responses to vaccination in rural Gambia. Overall, this research supports interventions that improve nutritional status in pregnancy and promote infant immune development, especially in settings with high rates of infection. Funding: Medical Research Council (UK). Declaration of Interest: No conflict of interest was declared. Ethical Approval: The ENID trial was approved by the joint Gambian Government/MRC Unit the Gambia ethics committee (SCC1126v2). Written informed consent was obtained from all participants. The trial observed Good Clinical Practice Standards and the current version of the Helsinki Declaration. The ENID trial was registered as ISRCTN49285450.

Supplemental Digital Content is available in the text., Background: Bordetella pertussis can cause severe respiratory disease and death in children. In recent years, large outbreaks have occurred in high-income countries; however, little is known about pertussis incidence in sub-Saharan Africa. Methods: We evaluated antibody responses to pertussis toxin (Ptx) from individuals aged between 2 and 90 years in rural Gambia. IgG-Ptx was measured using luminex xMAP technology. IgG-Ptx geometric mean concentrations (GMC) and their 95% confidence intervals were calculated. The proportion seropositive (>20 EU/mL or ≥62.5 EU/mL) and GMCs were compared by age, sex, ethnic group, vaccination status, birth order and number of siblings per household using logistic and linear regression. Results: 76.3% had anti-Ptx levels