Impact of dietary aflatoxin on immune development in Gambian infants: a cohort study.

BACKGROUND: Chronic 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. METHODS: A 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. 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 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

Impact of nutritional supplementation during pregnancy on antibody responses to diphtheria-tetanus-pertussis vaccination in infants: A randomised trial in The Gambia.

BACKGROUND: Exposure to a nutritionally deficient environment during fetal life and early infancy may adversely alter the ontogeny of the immune system and affect an infant's ability to mount an optimal immune response to vaccination. We examined the effects of maternal nutritional supplementation during pregnancy on infants' antibody responses to the diphtheria-tetanus-pertussis (DTP) vaccine included in the Expanded Programme on Immunisation (EPI). METHODS AND FINDINGS: The Early Nutrition and Immune Development (ENID) trial was a randomised, partially blinded trial conducted between April 2010 and February 2015 in the rural West Kiang region of The Gambia, a resource-poor region affected by chronic undernutrition. Pregnant women (<20 weeks' gestation) with a singleton pregnancy (n = 875) were randomised to receive one of four supplements: iron-folic acid (FeFol; standard of care), multiple micronutrient (MMN), protein-energy (PE), or PE + MMN daily from enrolment (mean [SD] 13.7 [3.3] weeks' gestation) until delivery. Infants were administered the DTP vaccine at 8, 12, and 16 weeks of age according to the Gambian Government protocol. Results for the primary outcome of the trial (infant thymic size) were described previously; here, we report on a secondary outcome, infant antibody response to vaccination. The effects of supplementation on mean DTP antibody titres measured in blood samples collected from infants at 12 weeks (n = 710) and 24 weeks (n = 662) were analysed with adjustment for confounders including maternal age, compliance to supplement, and infant sex and season. At 12 weeks, following a single dose of the vaccine, compared with FeFol (mean 95% confidence interval [CI]; 0.11 IU/mL, 0.09-0.12), antenatal supplementation with MMN or MMN + PE resulted in 42.4% (95% CI 20.1-64.6; p < 0.001) and 29.4% (6.4-52.5; p = 0.012) higher mean anti-diphtheria titres, respectively. Mean anti-tetanus titres were higher by 9.0% (5.5-12.5), 7.8% (4.3-11.4), and 7.3% (4.0-10.7) in MMN, PE, and PE + MMN groups (all, p < 0.001), respectively, than in the FeFol group (0.55 IU/mL, 0.52-0.58). Mean anti-pertussis titres were not significantly different in the FeFol, MMN, and PE + MNN groups but were all higher than in the PE group (all, p < 0.001). At 24 weeks, following all three doses, no significant differences in mean anti-diphtheria titres were detected across the supplement groups. Mean anti-tetanus titres were 3.4% (0.19-6.5; p = 0.038) higher in the PE + MMN group than in the FeFol group (3.47 IU/mL, 3.29-3.66). Mean anti-pertussis titres were higher by 9.4% (3.3-15.5; p = 0.004) and 15.4% (9.6-21.2; p < 0.001) in PE and PE + MMN groups, compared with the FeFol group (74.9 IU/mL, 67.8-82.8). Limitations of the study included the lack of maternal antibody status (breast milk or plasma) or prevaccination antibody measurements in the infants. CONCLUSION: According to our results from rural Gambia, maternal supplementation with MMN combined with PE during pregnancy enhanced antibody responses to the DTP vaccine in early infancy. Provision of nutritional supplements to pregnant women in food insecure settings may improve infant immune development and responses to EPI vaccines. TRIAL REGISTRATION: ISRCTN49285450

Seasonal modulation of antibody response to diphtheria-tetanus-pertussis vaccination in infants: a cohort study in rural Gambia

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 < 0.001). Their mothers, however, were pregnant mostly during the dry/harvest season, had higher weight gain (p < 0.001) and were less likely to be anaemic during pregnancy (p < 0.001). At 12 weeks, infants vaccinated during the rainy/hungry season had significantly higher mean diphtheria, tetanus and pertussis antibody titres; by 62.3, 16.9 and 19.7%, respectively (all, p < 0.001). However, at 24 weeks, they had lower mean anti-diphtheria titres (by 20.6%, p < 0.001) compared with infants vaccinated during the dry/harvest season, and no differences were observed in mean tetanus and pertussis antibody titres by vaccination season. 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

SARS-CoV-2 seroprevalence in pregnant women during the first three COVID-19 waves in The Gambia

OBJECTIVES: SARS-CoV-2 transmission in Sub-Saharan Africa has probably been underestimated. Population-based seroprevalence studies are needed to determine the extent of transmission in the continent. METHODS: Blood samples from a cohort of Gambian pregnant women were tested for SARS-CoV-2 total receptor binding domain (RBD) IgM/IgG before (Pre-pandemic: October-December 2019), and during the pandemic (Pre-wave1: February-June 2020; Post-wave1: October-December 2020, Post-wave2: May-June 2021; and Post-wave3: October-December 2021). Samples reactive for SARS-CoV-2 total RBD IgM/IgG were tested in specific S1- and nucleocapsid (NCP) IgG assays. RESULTS: SARS-CoV-2 total RBD IgM/IgG seroprevalence was 0.9% 95%CI (0.2, 4.9) in Pre-pandemic; 4.1% (1.4, 11.4) in Pre-wave1; 31.1% (25.2, 37.7) in Post-wave1; 62.5% (55.8, 68.8) in Post-wave2 and 90.0% (85.1, 93.5) in Post-wave3. S-protein IgG and NCP-protein IgG seroprevalence also increased at each Post-wave period. Although S-protein IgG and NCP-protein IgG seroprevalence was similar at Post-wave1, S-protein IgG seroprevalence was higher at Post-wave2 and Post-wave3, [prevalence difference (PD) 13.5 (0.1, 26.8) and prevalence ratio (PR) 1.5 (1.0, 2.3) in Post-wave2; and 22.9 (9.2, 36.6) and 1.4 (1.1, 1.8) in Post-wave3 respectively, p<0.001]. CONCLUSION: SARS-CoV-2 transmission in The Gambia during the first three COVID-19 waves was high, differing significantly from official numbers of COVID-19 cases reported. Our findings are important for policy makers in managing the near-endemic COVID-19

Low seroprevalence of brucellosis in humans and small ruminants in the Gambia

Background Brucellosis is a worldwide zoonosis with significant impact on rural livelihoods and a potentially underestimated contributor to febrile illnesses. The aim of this study was to estimate the seroprevalence of brucellosis in humans and small ruminants in The Gambia. Methods The study was carried out in rural and urban areas. In 12 rural villages in Kiang West district, sera were collected from humans (n = 599) and small ruminants (n = 623) from the same compounds. From lactating small ruminants, milk samples and vaginal swabs were obtained. At the urban study sites, sera were collected from small ruminants (n = 500) from slaughterhouses and livestock markets. Information on possible risk factors for seropositivity was collected through questionnaires. Sera were screened for antibodies against Brucella spp. with the Rose Bengal Test, ELISA and Micro Agglutination Test (human sera only). PCR was performed on 10 percent of the milk samples and vaginal swabs from small ruminants. Results One human and 14 sheep sera were positive by the Rose Bengal Test. The rest were negative in all serological tests used. The PCR results were all negative.Conclusions The results suggest that brucellosis is currently not a generalized problem in humans or small ruminants in The Gambia.</p

Seroprevalence of pertussis in the Gambia : evidence for continued circulation of bordetella pertussis despite high vaccination rates

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 <20 EU/mL, 17.5% had concentrations between 20 and 62.5 EU/mL, 4.4% had concentrations between 62.5 and 125 EU/mL and 1.8% had concentrations ≥125 EU/mL. The overall Ptx antibody GMC was 6.4 EU/mL (95% confidence interval: 5.8-6.9). Higher antibody concentrations were observed in older populations with evidence for an increase in infection risk with increasing age (1.9% yearly increase, 95% confidence interval: 1.3-2.5). No child under 6 years of age had GMC above 62.5 EU/mL but 29.5% had concentrations between 20 and 62.5 EU/mL. CONCLUSIONS: These data provide evidence that B. pertussis is being transmitted within this population despite high vaccination coverage. Re-infection may occur implying that immunity from childhood vaccination may not be lifelong. In the absence of data on actual clinical cases of pertussis, seroprevalence studies remain valuable tools to assess the transmission dynamics of B. pertussis

Coxiella burnetii (Q fever) prevalence in associated populations of humans and small ruminants in The Gambia

Objectives To simultaneously estimate the prevalence of antibodies against Coxiella burnetii (Q fever) among adults and small ruminants, and C. burnetii shedding prevalence among small ruminants in households in the Kiang West district of The Gambia; and to assess associated risk factors. Methods Sera of 599 adults and 615 small ruminants from 125 compounds within 12 villages were tested for antibodies against C. burnetii using ELISA. Vaginal swabs and milk samples of 155 small ruminants were tested using PCR to investigate shedding of C. burnetii. Results 3.8% to 9.7% of adults, depending on ELISA test cutoff, and 24.9% of small ruminants in Kiang West were seropositive. Having at least one seropositive animal in one's compound was a risk factor for human seropositivity (OR 3.35, 95% CI: 1.09-14.44). A grazing area within a village was a risk factor for seropositivity in small ruminants (OR 2.07, 95% CI: 1.26-3.50); others were having lambed (OR 2.75, 95% CI: 1.37-5.76), and older age of the animals (OR 2.75, 95% CI: 1.37-5.76 for 1-3 years and OR 5.84, 95% CI: 3.10-11.64 for >3 years). 57.4% of sampled small ruminants were shedding C. burnetii. Conclusion C. burnetii infection is endemic among both humans and small ruminants in this area of The Gambia. Human and animal exposure to C. burnetii were related at compound-level. Further research into the clinical relevance of C. burnetii infection in West Africa is needed

SARS-CoV-2 Seroprevalence in The Gambia dataset

A quantitative dataset containing information on COVID seroprevalence in pregnant women, based upon an analysis of samples collected from 803 women between October 2019 – March 2022 in Farafenni, North Bank Region of The Gambia. This is a sub-set of women in the PRECISE Study where pregnant women were recruited to the cohort and followed up during their pregnancy

Coxiella burnetii (Q fever) prevalence in associated populations of humans and small ruminants in The Gambia

Objectives: To simultaneously estimate the prevalence of antibodies against Coxiella burnetii (Q fever) among adults and small ruminants, and C. burnetii shedding prevalence among small ruminants in households in the Kiang West district of The Gambia, and to assess associated risk factors. Methods: Sera of 599 adults and 615 small ruminants from 125 compounds within 12 villages were tested for antibodies against C. burnetii using ELISA. Vaginal swabs and milk samples of 155 small ruminants were tested using PCR to investigate shedding of C. burnetii. Results: A total of 3.8–9.7% of adults, depending on ELISA test cut-off, and 24.9% of small ruminants in Kiang West were seropositive. Having at least one seropositive animal in one's compound was a risk factor for human seropositivity (OR: 3.35, 95% CI: 1.09–14.44). A grazing area within a village was a risk factor for seropositivity in small ruminants (OR: 2.07, 95% CI: 1.26–3.50); others were having lambed (OR: 2.75, 95% CI: 1.37–5.76) and older age of the animals (OR: 2.75, 95% CI: 1.37–5.76 for 1–3 years and OR 5.84, 95% CI: 3.10–11.64 for >3 years); 57.4% of sampled small ruminants were shedding C. burnetii. Conclusion: Coxiella burnetii infection is endemic among both humans and small ruminants in this area of The Gambia. Human and animal exposure to C. burnetii were related at compound level. Further research into the clinical relevance of C. burnetii infection in West Africa is needed

Coxiella burnetii (Q fever) prevalence in associated populations of humans and small ruminants in The Gambia.

To simultaneously estimate the prevalence of antibodies against Coxiella burnetii (Q fever) among adults and small ruminants, and C. burnetii shedding prevalence among small ruminants in households in the Kiang West district of The Gambia, and to assess associated risk factors