Rapid enteric testing to permit targeted antimicrobial therapy, with and without Lactobacillus reuteri probiotics, for paediatric acute diarrhoeal disease in Botswana: A pilot, randomized, factorial, controlled trial

PLoS One. 2017 Oct 9;12(10):e0185177. doi: 10.1371/journal.pone.0185177. eCollection 2017.

Abstract

Introduction: Diarrhoeal disease is the second-leading cause of death in young children. Current guidelines recommend treating children with acute non-bloody diarrhea with oral rehydration solutions and zinc, but not antimicrobials. However, in many resource-limited settings, infections with treatable enteric bacterial and protozoan pathogens are common. Probiotics have shown promise as an adjunct treatment for diarrhoea but have not been studied in sub-Saharan Africa.

Methods: We conducted a pilot, factorial, randomized, placebo-controlled trial of children aged 2-60 months hospitalized in Botswana for acute non-bloody diarrhoea. A rapid test-and-treat intervention, consisting of multiplex PCR testing of rectal swabs taken at enrolment, accompanied by targeted antimicrobial therapy if treatable pathogens were detected, was compared to the reference standard of no stool testing. Additionally, Lactobacillus reuteri DSM 17938 x 60 days was compared to placebo treatment. The main objective of this pilot study was to assess feasibility. The primary clinical outcome was the increase in age-standardized height (HAZ) at 60 days adjusted for baseline HAZ.

Results: Seventy-six patients were enrolled over a seven-month study period. We judged that the recruitment rate, lab processing times, communication protocols, provision of specific antimicrobials, and follow-up rates were acceptable. Compared to the reference arm (no stool testing and placebo treatment), the combination of the rapid test-and-treat strategy plus L. reuteri DSM 17938 was associated with an increase of 0.61 HAZ (95% CI 0.09-1.13) and 93% lower odds of recurrent diarrhoea (OR 0.07, 95%CI 0.01-0.61) at 60 days.

Discussion: We demonstrated that it was feasible to evaluate the study interventions in Botswana. Despite the small sample size, we observed a statistically significant increase in HAZ at 60 days and significantly lower odds of recurrent diarrhoea in children receiving both rapid test-and-treat and L. reuteri. There is sufficient evidence to warrant proceeding with a larger follow-up trial in a similar setting.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Anti-Bacterial Agents / therapeutic use*
  • Anti-Infective Agents
  • Bacteria / genetics
  • Bacteria / isolation & purification*
  • Bacterial Infections / diagnosis
  • Bacterial Infections / epidemiology
  • Bacterial Infections / microbiology*
  • Bacterial Infections / therapy*
  • Botswana / epidemiology
  • Child, Preschool
  • Diarrhea / diagnosis
  • Diarrhea / epidemiology
  • Diarrhea / microbiology*
  • Diarrhea / therapy*
  • Female
  • Humans
  • Infant
  • Limosilactobacillus reuteri* / physiology
  • Male
  • Pilot Projects
  • Probiotics / therapeutic use*
  • Treatment Outcome

Substances

  • Anti-Bacterial Agents
  • Anti-Infective Agents

Grants and funding

This study (S4-0192) was funded by the Stars in Global Health program of Grand Challenges Canada (http://www.grandchallenges.ca), funded by the Government of Canada. The study would not have been possible without support from the Penn Center for AIDS Research (CFAR). Dr. Pernica is also supported by a Hamilton Health Sciences Foundation Early Career Award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.