Lactoferrin and lysozyme to promote nutritional, clinical, and enteric recovery: A factorial placebo-controlled randomized trial among children with diarrhea and malnutrition

PROJECT SUMMARY/ABSTRACT Diarrhea kills more than half a million children each year and is the third largest contributor to lost disability adjusted life years. While rehydration addresses the acute consequences of diarrhea, there are no interventions for diarrhea convalescence during which children are at high risk of malnutrition, lower-respiratory tract

infections, and recurring diarrhea episodes. Safe and effective interventions to address the long-term consequences of diarrheal disease are urgently needed. Lactoferrin and lysozyme are milk-derived nutritional supplements that may reduce the duration of diarrheal episodes, treat or prevent underlying enteric infections, improve enteric function, and accelerate nutritional

recovery. However, it remains unclear whether their antimicrobial action will translate into significant improvements in the long-term clinical and nutritional outcomes of childhood diarrhea. We propose a factorial, double-blind, placebo-controlled, randomized trial to determine the efficacy and mechanisms of lactoferrin and

lysozyme supplementation in minimizing the incidence of diarrhea and promoting nutritional recovery among children recovering from diarrhea and wasting. Kenyan children aged 6-24 months who have been discharged from an inpatient or outpatient hospital stay for diarrhea, and have a mid-upper arm circumference [MUAC] <12.5

cm will be randomized to 16-weeks of lactoferrin, lysozyme, a combination of the two, or placebo. This trial will provide much efficacy, mechanistic, and feasibility data from populations most likely to benefit from these interventions.