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Randomized Controlled Trial
. 2017 Oct 9;12(10):e0185177.
doi: 10.1371/journal.pone.0185177. eCollection 2017.

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

Jeffrey M Pernica  1 , Andrew P Steenhoff  2   3 , Margaret Mokomane  4 , Banno Moorad  3 , Kwana Lechiile  3 , Marek Smieja  5 , Loeto Mazhani  6 , Ji Cheng  7 , Matthew S Kelly  8 , Mark Loeb  5 , Ketil Stordal  9 , David M Goldfarb  10
Affiliations
Randomized Controlled Trial

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

Jeffrey M Pernica et al. PLoS One. .

Erratum in

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.

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Conflict of interest statement

Competing Interests: BioGaia donated and shipped the probiotic preparations and Copan Italia donated the swabs. Neither of these companies provided cash for the conduct of the trial or for any other reason to any of the study investigators. Neither of these entities had any role in the study design, data collection, data analysis or interpretation, or writing of the report. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. CONSORT diagram.
See this image and copyright information in PMC

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