Hypoallergenic and anti-inflammatory feeds in children with complicated severe acute malnutrition: an open randomised controlled 3-arm intervention trial in Malawi

Abstract

Intestinal pathology in children with complicated severe acute malnutrition (SAM) persists despite standard management. Given the similarity with intestinal pathology in non-IgE mediated gastrointestinal food allergy and Crohn’s disease, we tested whether therapeutic feeds effective in treating these conditions may benefit children with complicated SAM. After initial clinical stabilisation, 95 children aged 6–23 months admitted at Queen Elizabeth Central Hospital, Blantyre, Malawi between January 1st and December 31st, 2016 were allocated randomly to either standard feeds, an elemental feed or a polymeric feed for 14 days. Change in faecal calprotectin as a marker of intestinal inflammation and the primary outcome was similar in each arm: elemental vs. standard 4.1 μg/mg stool/day (95% CI, −29.9, 38.15; P = 0.81) and polymeric vs. standard 10 (−23.96, 43.91; P = 0.56). Biomarkers of intestinal and systemic inflammation and mucosal integrity were highly abnormal in most children at baseline and abnormal values persisted in all three arms. The enteropathy in complicated SAM did not respond to either standard feeds or alternative therapeutic feeds administered for up to 14 days. A better understanding of the pathogenesis of the gut pathology in complicated SAM is an urgent priority to inform the development of improved therapeutic interventions.

The synergistic interaction of systemic inflammation, dysbiosis and antimicrobial resistance promotes growth restriction in children with acute severe malnutrition: An emphasis on Escherichia coli

“…Overall, the pro-inflammatory events triggered by the upregulation of Th1-related cytokines in SAM follow the same trend seen in other cell-mediated inflammatory diseases of the intestine, including inflammatory bowel disease (IBD) (Attia et al, 2016). Interestingly, at the histological and immune levels, SAM changes resemble those seen in IBD, Crohn's disease and in food allergy, and just like in patients suffering those conditions, the use of hypoallergenic elemental formula composed of single amino acids has been demonstrated to be tolerated in SAM children as well, who additionally gain weight upon this approach (Bartels et al, 2019). With nutritional rehabilitation, the total leukocyte counts in these children increase as well (Njunge et al, 2020).…”

“…Under normal conditions and appropriate nutrient intake, the submucosal layer of the intestine is enriched with infiltrated Foxp3 + T regulatory (Treg) cells that maintain a homeostatic state through permanent communication with healthy microbiota, and together, both ensure a low inflammatory environment (Cosovanu and Neumann, 2020). In SAM children, this immune equilibrium is disrupted to favor Th1 immune pro-inflammatory conditions in the intestine, driving environmental enteropathy, Figure 1, especially in the small intestine (Bartels et al, 2019).…”

“…The persistence of inflammatory infiltrates, such as IFN-g derived from Th1 lymphocytes, promotes crypt hyperplasia and villous atrophy, which could induce loss of the intestinal barrier to increase the permeability of the intraepithelial layer (Attia et al, 2016;Bartels et al, 2019). Additionally, the intestinal damage in SAM children enables the chronic exposure to bacterial products such as LPS, thus enhancing the state of systemic inflammation in a progressive positive cycle (Patterson et al, 2021).…”

“…Certain biomarkers can be measured to evaluate the severity of inflammation in SAM, such as the intestinal inflammation marker fecal calprotectin, which is an acute phase protein upregulated in these children (Bartels et al, 2019) that is significantly associated with both the presence of multiple intestinal pathogens and with death (Attia et al, 2016). In a recent multi-center, randomized, controlled case-control study in SAM children from Kenya and Malawi, it was reported that circulating proteomic and metabolomic profiles were different between children who survived from those who died, the latter being enriched in calprotectin and C-reactive protein (CRP), and in the inflammatory intermediates interleukin (IL)-8 and TNF-a (Njunge et al, 2020).…”

“…This condition dramatically predisposes children to increased rates of morbimortality, particularly due to infectious diseases. In fact, over the past 70 years, case-fatality rates of hospitalized SAM children in underdeveloped countries have been maintained at 20-30% (Collins et al, 2006), and up to 7.4-7.8% of all child deaths are associated to SAM (Bartels et al, 2019). Furthermore, SAM is linked to negative economic consequences due to loss of lifeproductivity and to high costs for the health system (Moyer et al, 2020), which can rise up to US$453 per child in their ambulatory community-based treatment alone (Bachmann, 2010).…”