Probiotics for treating acute infectious diarrhoea. 2020

Shelui Collinson, and Andrew Deans, and April Padua-Zamora, and Germana V Gregorio, and Chao Li, and Leonila F Dans, and Stephen J Allen
Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.

Probiotics may be effective in reducing the duration of acute infectious diarrhoea. To assess the effects of probiotics in proven or presumed acute infectious diarrhoea. We searched the trials register of the Cochrane Infectious Diseases Group, MEDLINE, and Embase from inception to 17 December 2019, as well as the Cochrane Controlled Trials Register (Issue 12, 2019), in the Cochrane Library, and reference lists from studies and reviews. We included additional studies identified during external review. Randomized controlled trials comparing a specified probiotic agent with a placebo or no probiotic in people with acute diarrhoea that is proven or presumed to be caused by an infectious agent. Two review authors independently applied inclusion criteria, assessed risk of bias, and extracted data. Primary outcomes were measures of diarrhoea duration (diarrhoea lasting ≥ 48 hours; duration of diarrhoea). Secondary outcomes were number of people hospitalized in community studies, duration of hospitalization in inpatient studies, diarrhoea lasting ≥ 14 days, and adverse events. We included 82 studies with a total of 12,127 participants. These studies included 11,526 children (age < 18 years) and 412 adults (three studies recruited 189 adults and children but did not specify numbers in each age group). No cluster-randomized trials were included. Studies varied in the definitions used for "acute diarrhoea" and "end of the diarrhoeal illness" and in the probiotic(s) tested. A total of 53 trials were undertaken in countries where both child and adult mortality was low or very low, and 26 where either child or adult mortality was high. Risk of bias was high or unclear in many studies, and there was marked statistical heterogeneity when findings for the primary outcomes were pooled in meta-analysis. Effect size was similar in the sensitivity analysis and marked heterogeneity persisted. Publication bias was demonstrated from funnel plots for the main outcomes. In our main analysis of the primary outcomes in studies at low risk for all indices of risk of bias, no difference was detected between probiotic and control groups for the risk of diarrhoea lasting ≥ 48 hours (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.91 to 1.09; 2 trials, 1770 participants; moderate-certainty evidence); or for duration of diarrhoea (mean difference (MD) 8.64 hours shorter, 95% CI 29.4 hours shorter to 12.1 hours longer; 6 trials, 3058 participants; very low-certainty evidence). Effect size was similar and marked heterogeneity persisted in pre-specified subgroup analyses of the primary outcomes that included all studies. These included analyses limited to the probiotics Lactobacillus rhamnosus GG and Saccharomyces boulardii. In six trials (433 participants) of Lactobacillus reuteri, there was consistency amongst findings (I² = 0%), but risk of bias was present in all included studies. Heterogeneity also was not explained by types of participants (age, nutritional/socioeconomic status captured by mortality stratum, region of the world where studies were undertaken), diarrhoea in children caused by rotavirus, exposure to antibiotics, and the few studies of children who were also treated with zinc. In addition, there were no clear differences in effect size for the primary outcomes in post hoc analyses according to decade of publication of studies and whether or not trials had been registered. For other outcomes, the duration of hospitalization in inpatient studies on average was shorter in probiotic groups than in control groups but there was marked heterogeneity between studies (I² = 96%; MD -18.03 hours, 95% CI -27.28 to -8.78, random-effects model: 24 trials, 4056 participants). No differences were detected between probiotic and control groups in the number of people with diarrhoea lasting ≥ 14 days (RR 0.49, 95% CI 0.16 to 1.53; 9 studies, 2928 participants) or in risk of hospitalization in community studies (RR 1.26, 95% CI 0.84 to 1.89; 6 studies, 2283 participants). No serious adverse events were attributed to probiotics. Probiotics probably make little or no difference to the number of people who have diarrhoea lasting 48 hours or longer, and we are uncertain whether probiotics reduce the duration of diarrhoea. This analysis is based on large trials with low risk of bias.

UI MeSH Term Description Entries
D007223 Infant A child between 1 and 23 months of age. Infants
D002648 Child A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL. Children
D002675 Child, Preschool A child between the ages of 2 and 5. Children, Preschool,Preschool Child,Preschool Children
D003967 Diarrhea An increased liquidity or decreased consistency of FECES, such as running stool. Fecal consistency is related to the ratio of water-holding capacity of insoluble solids to total water, rather than the amount of water present. Diarrhea is not hyperdefecation or increased fecal weight. Diarrheas
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000208 Acute Disease Disease having a short and relatively severe course. Acute Diseases,Disease, Acute,Diseases, Acute
D000293 Adolescent A person 13 to 18 years of age. Adolescence,Youth,Adolescents,Adolescents, Female,Adolescents, Male,Teenagers,Teens,Adolescent, Female,Adolescent, Male,Female Adolescent,Female Adolescents,Male Adolescent,Male Adolescents,Teen,Teenager,Youths
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D015982 Bias Any deviation of results or inferences from the truth, or processes leading to such deviation. Bias can result from several sources: one-sided or systematic variations in measurement from the true value (systematic error); flaws in study design; deviation of inferences, interpretations, or analyses based on flawed data or data collection; etc. There is no sense of prejudice or subjectivity implied in the assessment of bias under these conditions. Aggregation Bias,Bias, Aggregation,Bias, Ecological,Bias, Statistical,Bias, Systematic,Ecological Bias,Outcome Measurement Errors,Statistical Bias,Systematic Bias,Bias, Epidemiologic,Biases,Biases, Ecological,Biases, Statistical,Ecological Biases,Ecological Fallacies,Ecological Fallacy,Epidemiologic Biases,Experimental Bias,Fallacies, Ecological,Fallacy, Ecological,Scientific Bias,Statistical Biases,Truncation Bias,Truncation Biases,Bias, Experimental,Bias, Scientific,Bias, Truncation,Biase, Epidemiologic,Biases, Epidemiologic,Biases, Truncation,Epidemiologic Biase,Error, Outcome Measurement,Errors, Outcome Measurement,Outcome Measurement Error
D016032 Randomized Controlled Trials as Topic Works about clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table. Clinical Trials, Randomized,Controlled Clinical Trials, Randomized,Trials, Randomized Clinical

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