BACKGROUND
Environmental enteric dysfunction (EED) is an enigmatic disorder of the small intestine
postulated to play a role in childhood undernutrition, a pressing global health problem.
Defining the incidence of EED, its pathophysiology, and its contribution to impaired
linear and ponderal growth has been hampered by the difficulty in directly sampling the
small intestinal mucosa and microbial community (microbiota).
METHODS
Slum-dwelling Bangladeshi children aged 18±2 months, with linear
growth-faltering (stunting) who failed a nutritional intervention underwent endoscopy to
obtain duodenal biopsies and aspirates. Levels of 4077 plasma proteins and 2619 duodenal
proteins were quantified in 80 children with histopathologic evidence of EED, and the
abundances of bacterial strains in their duodenal microbiota were determined using
culture-independent methods. Young germ-free mice, fed a Bangladeshi diet, were
colonized with bacterial strains cultured from the duodenal aspirates.
RESULTS
The absolute abundances of a shared group of 14 bacterial strains recovered from the
duodenums of children with EED and not typically classified as enteropathogens were
negatively correlated with linear growth (length-for-age
Z-score;β=-0.38±0.12(SEM);ρ=-0.49;p=0.003), and positively
correlated with duodenal proteins involved in immunoinflammatory responses.
Representation of these 14 duodenal taxa was significantly different in fecal microbiota
from EED versus healthy children (p<0.001;PERMANOVA). Gnotobiotic mice colonized
with cultured EED-donor duodenal strains develop a small intestinal enteropathy.
CONCLUSIONS
These results provide evidence of a causal relationship between components of the small
intestinal microbiota, enteropathy and stunting and offer a rationale for developing
therapeutics that target what must no longer remain terra incognita-the small intestinal
microbiota. ClinicalTrials.gov identifier: NCT02812615
IntroductionEnvironmental enteric dysfunction (EED) is a subacute inflammatory condition of the small intestinal mucosa with unclear aetiology that may account for more than 40% of all cases of stunting. Currently, there are no universally accepted protocols for the diagnosis, treatment and ultimately prevention of EED. The Bangladesh Environmental Enteric Dysfunction (BEED) study is designed to validate non-invasive biomarkers of EED with small intestinal biopsy, better understand disease pathogenesis and identify potential therapeutic targets for interventions designed to control EED and stunting.Methods and analysisThe BEED study is a community-based intervention where participants are recruited from three cohorts: stunted children aged 12–18 months (length for age Z-score (LAZ) <−2), at risk of stunting children aged 12–18 months (LAZ <−1 to −2) and malnourished adults aged 18–45 years (body mass index <18.5 kg/m2). After screening, participants eligible for study provide faecal, urine and plasma specimens to quantify the levels of candidate EED biomarkers before and after receiving a nutritional intervention. Participants who fail to respond to nutritional therapy are considered as the candidates for upper gastrointestinal endoscopy with biopsy. Histopathological scoring for EED will be performed on biopsies obtained from several locations within the proximal small intestine. Candidate EED biomarkers will be correlated with nutritional status, the results of histochemical and immunohistochemical analyses of epithelial and lamina propria cell populations, plus assessments of microbial community structure.Ethics and disseminationEthics approval was obtained in all participating institutes. Results of this study will be submitted for publication in peer-reviewed journals.Trial registration numberClinicalTrials.gov ID: NCT02812615. Registered on 21 June 2016.
The usefulness of nutritional indices and classifications in predicting the death of children under 5 years old was evaluated by comparing measurements of 34 children with diarrhoea who died in a Dhaka hospital with those of 318 patients who were discharged in a satisfactory condition. In a logistic regression analysis mid-upper arm circumference was found to be as effective as other nutritional indices in predicting death. Combinations of different indices did not improve the prediction.Arm circumference might be preferable to more complex criteria for predicting the death of malnourished children.
During August 2008–June 2009, an estimated 95,531 suspected cases of cholera and 4,282 deaths due to cholera were reported during the 2008 cholera outbreak in Zimbabwe. Despite the efforts by local and international organizations supported by the Zimbabwean Ministry of Health and Child Welfare in the establishment of cholera treatment centres throughout the country, the case-fatality rate (CFR) was much higher than expected. Over two-thirds of the deaths occurred in areas without access to treatment facilities, with the highest CFRs (>5%) reported from Masvingo, Manicaland, Mashonaland West, Mashonaland East, Midland, and Matabeleland North provinces. Some factors attributing to this high CFR included inappropriate cholera case management with inadequate use of oral rehydration therapy, inappropriate use of antibiotics, and a shortage of experienced healthcare professionals. The breakdown of both potable water and sanitation systems and the widespread contamination of available drinking-water sources were also considered responsible for the rapid and widespread distribution of the epidemic throughout the country. Training of healthcare professionals on appropriate cholera case management and implementation of recommended strategies to reduce the environmental contamination of drinking-water sources could have contributed to the progressive reduction in number of cases and deaths as observed at the end of February 2009.
Sixty-nine children age 2-5 y, convalescing from shigellosis in a randomized clinical trial were fed either a high-protein diet containing 628 kJ.kg-1.d-1 with 15% of total energy as protein, or a standard-protein diet that was isoenergetic but with 7.5% of total energy as protein for 21 d. Children fed the high-protein diet showed a significant increase in height (1.02 +/- 0.44 cm; mean +/- SD) compared with the children who were fed the standard-protein diet (0.69 +/- 0.34 cm; P < 0.001). Similarly, increases in body weight were 1.25 +/- 0.48 vs 0.86 +/- 0.48 kg for the high-protein and the standard-protein diet, respectively (P < 0.001). The mean increases of serum proteins were also significantly higher in the high-protein group (P < 0.01). These results indicate that increasing the protein content of the diet during convalescence from shigellosis in children leads to more rapid catch-up growth.
The DRD technique can detect changes in total body stores of vitamin A in response to different daily vitamin A supplements. However, abrupt changes in dietary vitamin A intake can affect estimates of total-body vitamin A stores.
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