Seroprevalence Study of Conserved Enterotoxigenic Escherichia coli Antigens in Globally Diverse Populations.

Enterotoxigenic Escherichia coli (ETEC) are common causes of infectious diarrhea among young children of low-and middle-income countries (LMICs) and travelers to these regions. Despite their significant contributions to the morbidity and mortality associated with childhood and traveler's diarrhea, no licensed vaccines are available. Current vaccine strategies may benefit from the inclusion of additional conserved antigens, which may contribute to broader coverage and enhanced efficacy, given their key roles in facilitating intestinal colonization and effective enterotoxin delivery. EatA and EtpA are widely conserved in diverse populations of ETEC, but their immunogenicity has only been studied in controlled human infection models and a population of children in Bangladesh. Here, we compared serologic responses to EatA, EtpA and heat-labile toxin in populations from endemic regions including Haitian children and subjects residing in Egypt, Cameroon, and Peru to US children and adults where ETEC infections are sporadic. We observed elevated IgG and IgA responses in individuals from endemic regions to each of the antigens studied. In a cohort of Haitian children, we observed increased immune responses following exposure to each of the profiled antigens. These findings reflect the wide distribution of ETEC infections across multiple endemic regions and support further evaluation of EatA and EtpA as candidate ETEC vaccine antigens.

Choline, DHA, and Diarrheal Disease Associated with Growth Faltering in a Case-Control Study.

Background: Children with recurrent infectious diarrhea are susceptible to growth faltering. DHA and choline may play a role in this relationship due to their involvement in lipid metabolism, gut immunity, and inflammatory pathways. Objectives: This study aimed to characterize the contributions made by DHA and choline status and enteric damage in young children in the association between diarrheal illness and child growth. Methods: A longitudinal case-control study was conducted among children aged 6-36 mo (N = 195) in Cap-Haitien, Haiti. Mother-child dyads were recruited from community health posts and outpatient clinics. Cases were defined as children experiencing acute diarrhea within the last 3 d and matched to healthy controls. Child anthropometry, dietary intake, and blood and stool samples were collected at baseline and follow-up. Plasma DHA, choline, and betaine were determined by LC-MS/MS methods (n = 49) and intestinal fatty acid-binding protein (I-FABP) by ELISA (n = 183). Multivariate regression models were applied with mediation analyses to examine associations and adjust for confounding factors. Results: At baseline, mean plasma DHA concentrations (1.03 µg/mL; 95% CI: 0.91, 1.15) were not significantly different between cases and controls, nor was there a difference in mean plasma choline concentrations (4.5 µg/mL; 95% CI: 3.8, 5.1). Mean plasma I-FABP concentrations were significantly higher at follow-up in cases (3.34; 95% CI: 3.28, 3.40) than controls (3.20; 95% CI: 3.13, 3.27; P = 0.002). In adjusted multilinear regression models, higher plasma DHA concentrations at follow-up were associated with a negative change in weight-age z score (P = 0.016), and follow-up I-FABP was inversely associated with height-age z score (P = 0.035). No interaction or mediation effects were found. Conclusions: I-FABP concentrations were significantly higher in cases as compared with controls at follow-up, suggesting ongoing enteric damage and increased risk for malnutrition. Plasma DHA and I-FABP may have a role in childhood growth outcomes.

Grandi Byen-supporting child growth and development through integrated, responsive parenting, nutrition and hygiene: study protocol for a randomized controlled trial.

BACKGROUND: Poor child growth and development outcomes stem from complex relationships encompassing biological, behavioral, social, and environmental conditions. However, there is a dearth of research on integrated approaches targeting these interwoven factors. The Grandi Byen study seeks to fill this research gap through a three-arm longitudinal randomized controlled trial which will evaluate the impact of an integrated nutrition, responsive parenting, and WASH (water, sanitation and hygiene) intervention on holistic child growth and development. METHODS: We will recruit 600 mother-infant dyads living in Cap-Haitien, Haiti and randomize them equally into one of the following groups: 1) standard well-baby care; 2) nutritional intervention (one egg per day for 6 months); and 3) multicomponent Grandi Byen intervention (responsive parenting, nutrition, WASH + one egg per day for 6 months). Primary outcomes include child growth as well as cognitive, language, motor, and social-emotional development. The study also assesses other indicators of child health (bone maturation, brain growth, diarrheal morbidity and allergies, dietary intake, nutrient biomarkers) along with responsive parenting as mediating factors influencing the primary outcomes. An economic evaluation will assess the feasibility of large-scale implementation of the interventions. DISCUSSION: This study builds on research highlighting the importance of responsive parenting interventions on overall child health, as well as evidence demonstrating that providing an egg daily to infants during the complementary feeding period can prevent stunted growth. The multicomponent Grandi Byen intervention may provide evidence of synergistic or mediating effects of an egg intervention with instruction on psychoeducational parenting and WASH on child growth and development. Grandi Byen presents key innovations with implications for the well-being of children living in poverty globally. TRIAL REGISTRATION: NCT04785352 . Registered March 5, 2021 at https://clinicaltrials.gov/.

Differences in factors associated with anemia in Haitian children from urban and rural areas.

BACKGROUND: In Haiti, differences in the prevalence of anemia between urban and rural areas have been observed. OBJECTIVE: To identify moderating factors that may help explain the difference in the prevalence of anemia in children from poor urban vs. rural areas of Haiti. METHODS: This cross-sectional study used secondary data from urban and rural school-based trials that assessed the effectiveness of a nutrition intervention. The study was registered at ClinicalTrials.gov as NCT02747524. A total of 300 rural- and 981 urban- children between 2.5-13 years of age were included in this analysis. Effect modification in a binary logistic generalized linear mixed model was conducted using sample weights in SPSS® version 26. Models were adjusted for age and income. School cluster was included as random effect. RESULTS: In rural areas, stunting was more prevalent in children with anemia vs. no anemia, (16.6%, and 6.3%, P = 0.008), respectively. Also, rural children with anemia lived with fewer adults vs. rural children with no anemia, ([Formula: see text] = 2.83±1.29, and 3.30±1.54, P = 0.005), respectively. In poor urban areas, helminth morbidities were more frequent in children with anemia vs. no anemia, (21.9% vs. 13.9, P = 0.011), respectively. In the combined sample, stunting, [AOR = 2.05; 95%CI (1.32-3.18)], age [AOR = 0.89; 95%CI (0.85-0.93)], and households with more adults [AOR = 0.77; 95%CI (0.67-0.87)] were associated with anemia. Effect modification by place of residence was observed in households with more adults (t = 3.83, P<0.001). No other nutritional, dietary, sanitation or morbidity factors or effect modifiers were observed. CONCLUSIONS: In this sample, factors associated with anemia differed in poor urban and rural children from Haiti including family structure and helminth morbidities. Stunting and lower age increased the odds of anemia in the combined sample. Family structure appears to have an important role in anemia, and further research understanding the influence of family structures in anemia is needed.

Economic determinants of breastfeeding in Haiti: The effects of poverty, food insecurity, and employment on exclusive breastfeeding in an urban population.

There is limited and inconsistent empirical evidence regarding the role of economic factors in breastfeeding practices, globally. Studies have found both negative and positive associations between low income and exclusive breastfeeding (EBF). Employment, which should improve household income, may reduce EBF due to separation of mother and infant. In the context of a randomized controlled study of lipid-based complementary feeding in an urban slum in Cap Haitien, Haiti, we examined the economic factors influencing breastfeeding practices using mixed methods. Findings demonstrate relationships between urban context, economic factors, and breastfeeding practices. Poverty, food insecurity, time constraints, and limited social support create challenges for EBF. Maternal employment is associated with lower rates of EBF and less frequent breastfeeding. Extreme food insecurity sometimes leads to increased exclusive breastfeeding among Haitian mothers, what we call "last resort EBF." In this case, women practice EBF because they have no alternative food source for the infant. Suggested policies and programs to address economic constraints and promote EBF in this population include maternal and child allowances, quality child care options, and small-scale household urban food production.

Fortified Snack Reduced Anemia in Rural School-Aged Children of Haiti: A Cluster-Randomized, Controlled Trial.

BACKGROUND: Nutrition in the school-aged child matters for brain development and public policy investments globally. Our group previously conducted a trial in urban schools of Haiti to examine the effects of a fortified peanut butter snack, Vita Mamba, with limited findings for anemia. OBJECTIVE: We aimed to test the hypothesis that Vita Mamba, with systematic deworming in both study arms, would significantly reduce anemia among rural, school-aged children. METHODS: A cluster, randomized longitudinal study was conducted in two rural communities of the North-East Department of Haiti, 2014-2015. Healthy children ages 3-16 years were enrolled (n = 321) and assigned by school to intervention (Vita Mamba and deworming) and control (deworming). Vita Mamba contains 260 kcal and meets >75% of the Recommended Dietary Allowance for critical micronutrients. Multivariate regression analyses including propensity score matching techniques to correct for potential group imbalance (Kernel-based Matching and Propensity Score Weighting) were applied to examine difference-in-difference intervention effects. RESULTS: At baseline, 51% of the children were anemic with no significant differences between study groups. Vita Mamba supplementation showed a consistent, positive effect across regression models on increasing Hb concentration and reducing the odds of anemia compared to the control group after adjusting for child age, vitamin A supplementation, milk consumption, and height-for-age z score. The average treatment effect for the treated in the Propensity Score Weighting models was 0.62±0.27 grams per 100 milliliters (g/dL) for Hb concentration (F = 4.64, P = 0.001), and the odds of anemia were reduced by 88% (Wald χ² = 9.77, P = 0.02). No differences in change in anthropometric markers were evident. CONCLUSIONS: School feeding programs that integrate fortified foods with deworming could reduce anemia burden with important implications for learning, health, and well-being. The rural-urban differences in anemia require further study.

Linear growth increased in young children in an urban slum of Haiti: a randomized controlled trial of a lipid-based nutrient supplement.

BACKGROUND: Haiti has experienced rapid urbanization that has exacerbated poverty and undernutrition in large slum areas. Stunting affects 1 in 5 young children. OBJECTIVE: We aimed to test the efficacy of a daily lipid-based nutrient supplement (LNS) for increased linear growth in young children. DESIGN: Healthy, singleton infants aged 6-11 mo (n = 589) were recruited from an urban slum of Cap Haitien and randomly assigned to receive: 1) a control; 2) a 3-mo LNS; or 3) a 6-mo LNS. The LNS provided 108 kcal and other nutrients including vitamin A, vitamin B-12, iron, and zinc at ≥80% of the recommended amounts. Infants were followed monthly on growth, morbidity, and developmental outcomes over a 6-mo intervention period and at one additional time point 6 mo postintervention to assess sustained effects. The Bonferroni multiple comparisons test was applied, and generalized least-squares (GLS) regressions with mixed effects was used to examine impacts longitudinally. RESULTS: Baseline characteristics did not differ by trial arm except for a higher mean age in the 6-mo LNS group. GLS modeling showed LNS supplementation for 6 mo significantly increased the length-for-age z score (±SE) by 0.13 ± 0.05 and the weight-for-age z score by 0.12 ± 0.02 compared with in the control group after adjustment for child age (P < 0.001). The effects were sustained 6 mo postintervention. Morbidity and developmental outcomes did not differ by trial arm. CONCLUSION: A low-energy, fortified product improved the linear growth of young children in this urban setting. The trial was registered at clinicaltrials.gov as NCT01552512.