Lactoferrin and lysozyme for Kenyan children presenting with wasting and diarrhea: A 2 x 2 factorial randomized controlled trial

IntroductionLactoferrin and lysozyme are milk derived proteins with antimicrobial and anti-inflammatory properties. We tested if these supplements improved time-to-nutritional-recovery and reduced the incidence of new moderate or severe diarrhea (MSD) among children presenting to hospital with wasting and diarrhea. MethodsMedically-stable children aged 6-24 months with diarrhea and wasting were randomized to a 16-week course of lactoferrin, lysozyme, a combination of both, or placebo. Time-to-nutritional-recovery (mid-upper arm circumference [≥] 12.5cm) and incidence of new onset MSD were the primary outcomes observed over 6-months follow-up. Subgroup analyses included efficacy by wasting status (severe vs. moderate), stunting, age, inpatient/outpatient, and adherence. ResultsAmong the 600 children randomized, 531 (88.5%) nutritionally recovered within 16-weeks; 63% among severely wasted children and 95% in children with moderate wasting. The wasting recovery rate in the combination arm was non significantly higher (HR: 1.23, 95%CI: 0.97, 1.57; p=0.083) than the placebo group. Children randomized to lactoferrin alone and lysozyme alone had nutritional recovery rates similar to placebo (HR: 0.94, 95% CI 0.74, 1.20; p=0.607 and HR: 0.91, 95% CI: 0.71, 1.17; p=0.462, respectively). Among severely wasted children, the combination arm had a higher recovery rate than placebo (HR: 2.76, 95% CI 1.49, 5.09; p=0.001), but not the individual lactoferrin (HR: 1.29, 95% CI 0.69, 2.41; p=0.427) and lysozyme (HR: 0.80, 95% CI: 0.40, 1.60; p=0.530) arms. Children randomized to intervention arms had comparable incidence of MSD (82.3-97.0 per 100 child-years) to the placebo arm (75.3 per 100 child-years). ConclusionsThe combination of lactoferrin and lysozyme for 16 weeks modestly improved nutritional recovery time particularly among severely wasted children. If confirmed, there may be a role for enteric-targeted therapeutics as adjuvants to severe wasting management. Additional strategies are needed for the post-acute diarrhea recovery period.