Optimising the management of childhood acute diarrhoeal disease using a rapid test-and- treat strategy and/or Lactobacillus reuteri DSM 17938: A multicentre, randomised, controlled, factorial trial in Botswana

Introduction The study aim was to determine if rapid enteric diagnostics followed by the provision of targeted antibiotic therapy ( test-and-treat') and/or Lactobacillus reuteri DSM 17938 would improve outcomes in children hospitalised in Botswana with acute gastroenteritis. Methods This was a multicentre, randomised, factorial, controlled, trial. Children aged 2-60 months admitted for acute non-bloody diarrhoea to four hospitals in southern Botswana were eligible. Participants were assigned to treatment groups by web-based block randomisation. Test-and-treat results were not blinded, but participants and research staff were blinded to L. reuteri/placebo assignment; this was dosed as 1×10 8 cfu/mL by mouth daily and continued for 60 days. The primary outcome was 60-day age-standardised height (HAZ) adjusted for baseline HAZ. All analyses were by intention to treat. The trial was registered at Clinicaltrials.gov. Results Recruitment began on 12 June 2016 and continued until 24 October 2018. There were 66 participants randomised to the test-and-treat plus L. reuteri group, 68 randomised to the test-and-treat plus placebo group, 69 to the standard care plus L. reuteri group and 69 to the standard care plus placebo group. There was no demonstrable impact of the test-and-treat intervention (mean increase of 0.01 SD, 95% CI -0.14 to 0.16 SD) or the L. reuteri intervention (mean decrease of 0.07 SD, 95% CI -0.22 to 0.08 SD) on adjusted HAZ at 60 days. Conclusions In children hospitalised for acute gastroenteritis in Botswana, neither a test-and-treat algorithm targeting enteropathogens, nor a 60-day course of L. reuteri DSM 17938, were found to markedly impact linear growth or other important outcomes. We cannot exclude the possibility that test-and-treat will improve the care of children with significant enteropathogens (such as Shigella) in their stool. Trial registration number NCT02803827.