Optimizing Management of Paediatric Diarrhoeal Disease: A Pilot, Factorial, Randomized, Placebo-Controlled Trial of Rapid Enteric Diagnostics and Probiotics

摘要

Background: Diarrhoeal disease is the second-leading cause of under-five mortality in the world, as well as a major cause of both growth failure and delayed cognitive development in children. The objective of this study was to verify the feasibility of a randomized controlled trial (RCT) designed to measure the benefit of rapid enteric diagnostic testing and Lactobacillus reuteri therapy for children admitted to hospital in Botswana with acute gastroenteritis. Methods: Children with acute diarrhoea aged 2-60 mos. admitted to hospital were eligible if they did not have bloody stools or signs of sepsis. Participants received standard fluid rehydration plus zinc and were randomized to one of: 1) rapid diagnostic testing (plus targeted antimicrobial therapy if indicated) plus Lactobacillus reuteri therapy x 60 days 2) rapid diagnostic testing (plus targeted antimicrobial therapy if indicated) plus placebo therapy x 60 days 3) standard care (no diagnostic testing) plus L. reuteri therapy x 60 days 4) standard care plus placebo therapy x 60 days. Multiplex PCR assays were used to detect Shigella, Campylobacter, enterotoxigenic E. coli, and Cryptosporidium. For this pilot study, achievement of feasibility outcomes was primary; these included validation of trial protocols, ensuring that testing and treatment could be integrated into clinical care, and verifying recruitment rates. Clinical outcomes included height-for-age (HAZ) at 60 days adjusted for baseline HAZ and recurrence of Results: In a 6-month study period, 76 participants without severe acute malnutrition were enrolled, with a median age of 10.8 months. Compared to standard care plus placebo therapy, rapid diagnostics plus placebo therapy was associated with a 0.28 SD (95% CI -0.26,0.81) increase in 60-day adjusted HAZ and less recurrent diarrhoea in the follow-up period (OR 0.45, 95% CI 0.12,1.79). Rapid diagnostics plus L. reuteri therapy was associated with a significant 0.63 SD (95%CI 0.12- 1.13, p=0.02) increase in 60-day adjusted HAZ and significantly less recurrent diarrhoea (OR 0.07, 95%CI 0.01- 0.61, p=0.02). Conclusion: Our results suggest that a multicentre trial is feasible. Rapid diagnostics and Lactobacillus reuteri therapy hold promise for the treatment of gastroenteritis and the prevention of stunting in children living in high-burden settings.