Probiotics for treating acute infectious diarrhoea

Stephen J Allen; Elizabeth G Martinez; Germana V Gregorio; Leonila F Dans

doi:10.1002/14651858.CD003048.pub3

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Figure 1

Funnel plot of comparison: 1 Primary diarrhoea outcomes, outcome: 1.1 Mean duration of diarrhoea.

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Figure 2

Funnel plot of comparison: 1 Primary diarrhoea outcomes, outcome: 1.2 Diarrhoea lasting ≥ 4 days.

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Figure 3

Funnel plot of comparison: 1 Primary diarrhoea outcomes, outcome: 1.3 Mean stool frequency on day 2.

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Analysis 1.1

Comparison 1 Primary diarrhoea outcomes, Outcome 1 Mean duration of diarrhoea.

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Analysis 1.2

Comparison 1 Primary diarrhoea outcomes, Outcome 2 Diarrhoea lasting ≥4 days.

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Analysis 1.3

Comparison 1 Primary diarrhoea outcomes, Outcome 3 Mean stool frequency on day 2.

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Analysis 2.1

Comparison 2 Secondary diarrhoea outcomes, Outcome 1 Diarrhoea lasting ≥3 days.

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Analysis 2.2

Comparison 2 Secondary diarrhoea outcomes, Outcome 2 Mean stool frequency on day 3.

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Analysis 3.1

Comparison 3 Strain of probiotic organisms, Outcome 1 Mean duration of diarrhoea.

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Analysis 3.2

Comparison 3 Strain of probiotic organisms, Outcome 2 Diarrhoea lasting ≥4 days.

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Analysis 3.3

Comparison 3 Strain of probiotic organisms, Outcome 3 Mean stool frequency on day 2.

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Analysis 4.1

Comparison 4 Single organism versus combinations, Outcome 1 Mean duration of diarrhoea.

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Analysis 4.2

Comparison 4 Single organism versus combinations, Outcome 2 Diarrhoea lasting ≥4 days.

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Analysis 4.3

Comparison 4 Single organism versus combinations, Outcome 3 Mean stool frequency on day 2.

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Analysis 5.1

Comparison 5 Live versus killed organisms, Outcome 1 Mean duration of diarrhoea.

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Analysis 6.1

Comparison 6 Dose of probiotic; live organisms, Outcome 1 Mean duration of diarrhoea.

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Analysis 6.2

Comparison 6 Dose of probiotic; live organisms, Outcome 2 Diarrhoea lasting ≥4 days.

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Analysis 6.3

Comparison 6 Dose of probiotic; live organisms, Outcome 3 Mean stool frequency on day 2.

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Analysis 7.1

Comparison 7 Children with rotavirus diarrhoea, Outcome 1 Mean duration of diarrhoea.

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Analysis 7.2

Comparison 7 Children with rotavirus diarrhoea, Outcome 2 Mean stool frequency on day 2.

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Analysis 8.1

Comparison 8 Severity of diarrhoea; studies of outpatients, Outcome 1 Mean duration of diarrhoea.

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Analysis 9.1

Comparison 9 Mortality stratum for children and adults in the countries where trials were undertaken (children/adults), Outcome 1 Mean duration of diarrhoea.

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Analysis 9.2

Comparison 9 Mortality stratum for children and adults in the countries where trials were undertaken (children/adults), Outcome 2 Diarrhoea lasting ≥4 days.

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Analysis 9.3

Comparison 9 Mortality stratum for children and adults in the countries where trials were undertaken (children/adults), Outcome 3 Mean stool frequency on day 2.

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Comparison 1. Primary diarrhoea outcomes

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mean duration of diarrhoea Show forest plot	35	4555	Mean Difference (IV, Random, 95% CI)	‐24.76 [‐33.61, ‐15.91]

2 Diarrhoea lasting ≥4 days Show forest plot	29	2853	Risk Ratio (M‐H, Random, 95% CI)	0.41 [0.32, 0.53]

3 Mean stool frequency on day 2 Show forest plot	20	2751	Mean Difference (IV, Random, 95% CI)	‐0.80 [‐1.14, ‐0.45]

Comparison 1. Primary diarrhoea outcomes

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Comparison 2. Secondary diarrhoea outcomes

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Diarrhoea lasting ≥3 days Show forest plot	30	3022	Risk Ratio (M‐H, Random, 95% CI)	0.62 [0.56, 0.70]

2 Mean stool frequency on day 3 Show forest plot	14	2367	Mean Difference (IV, Random, 95% CI)	‐0.63 [‐1.18, ‐0.07]

Comparison 2. Secondary diarrhoea outcomes

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Comparison 3. Strain of probiotic organisms

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mean duration of diarrhoea Show forest plot	11		Mean Difference (IV, Random, 95% CI)	Subtotals only

1.1 Live Lactobacillus casei strain GG	11	2072	Mean Difference (IV, Random, 95% CI)	‐26.69 [‐40.50, ‐12.88]
2 Diarrhoea lasting ≥4 days Show forest plot	14		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Live Lactobacillus casei strain GG	4	572	Risk Ratio (M‐H, Random, 95% CI)	0.59 [0.40, 0.87]
2.2 LIve Enterococcus LAB SF68	4	333	Risk Ratio (M‐H, Random, 95% CI)	0.21 [0.08, 0.52]
2.3 Saccharomyces boulardii	6	606	Risk Ratio (M‐H, Random, 95% CI)	0.37 [0.21, 0.65]
3 Mean stool frequency on day 2 Show forest plot	6		Mean Difference (IV, Random, 95% CI)	Subtotals only

3.1 Live Lactobacillus casei strain GG	6	1335	Mean Difference (IV, Random, 95% CI)	‐0.76 [‐1.32, ‐0.20]

Comparison 3. Strain of probiotic organisms

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Comparison 4. Single organism versus combinations

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mean duration of diarrhoea Show forest plot	35		Mean Difference (IV, Random, 95% CI)	Subtotals only

1.1 Single organism	22	3196	Mean Difference (IV, Random, 95% CI)	‐23.95 [‐35.57, ‐12.32]
1.2 Two or more organisms	13	1375	Mean Difference (IV, Random, 95% CI)	‐21.23 [‐30.38, ‐12.09]
2 Diarrhoea lasting ≥4 days Show forest plot	29		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Single organism	22	2136	Risk Ratio (M‐H, Random, 95% CI)	0.45 [0.33, 0.60]
2.2 Two or more organisms	7	717	Risk Ratio (M‐H, Random, 95% CI)	0.29 [0.12, 0.73]
3 Mean stool frequency on day 2 Show forest plot	20		Mean Difference (IV, Random, 95% CI)	Subtotals only

3.1 Single organism	14	2040	Mean Difference (IV, Random, 95% CI)	‐0.79 [‐1.21, ‐0.38]
3.2 Two or more organisms	6	711	Mean Difference (IV, Random, 95% CI)	‐0.77 [‐1.53, 0.00]

Comparison 4. Single organism versus combinations

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Comparison 5. Live versus killed organisms

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mean duration of diarrhoea Show forest plot	32		Mean Difference (IV, Random, 95% CI)	Subtotals only

1.1 Live organisms	29	3990	Mean Difference (IV, Random, 95% CI)	‐26.55 [‐36.95, ‐16.16]
1.2 Killed organisms	3	243	Mean Difference (IV, Random, 95% CI)	‐10.39 [‐30.75, 9.97]

Comparison 5. Live versus killed organisms

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Comparison 6. Dose of probiotic; live organisms

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mean duration of diarrhoea Show forest plot	26		Mean Difference (IV, Random, 95% CI)	Subtotals only

1.1 Low dose (≤10,000 million organisms/day)	16	2683	Mean Difference (IV, Random, 95% CI)	‐25.88 [‐39.04, ‐12.72]
1.2 High dose (>10,000 million organisms/day)	10	980	Mean Difference (IV, Random, 95% CI)	‐27.02 [‐38.64, ‐15.39]
2 Diarrhoea lasting ≥4 days Show forest plot	17		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Low dose (≤10,000 million organisms/day)	13	1325	Risk Ratio (M‐H, Random, 95% CI)	0.43 [0.29, 0.62]
2.2 High dose (>10,000 million organisms/day)	4	374	Risk Ratio (M‐H, Random, 95% CI)	0.37 [0.12, 1.17]
3 Mean stool frequency on day 2 Show forest plot	15		Mean Difference (IV, Random, 95% CI)	Subtotals only

3.1 Low dose (≤10,000 million organisms/day)	7	1455	Mean Difference (IV, Random, 95% CI)	‐1.01 [‐1.61, ‐0.41]
3.2 High dose (>10,000 million organisms/day)	8	861	Mean Difference (IV, Random, 95% CI)	‐0.99 [‐1.39, ‐0.60]

Comparison 6. Dose of probiotic; live organisms

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Comparison 7. Children with rotavirus diarrhoea

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mean duration of diarrhoea Show forest plot	12	701	Mean Difference (IV, Random, 95% CI)	‐29.14 [‐42.07, ‐16.20]

2 Mean stool frequency on day 2 Show forest plot	3	164	Mean Difference (IV, Random, 95% CI)	‐1.25 [‐2.09, ‐0.41]

Comparison 7. Children with rotavirus diarrhoea

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Comparison 8. Severity of diarrhoea; studies of outpatients

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mean duration of diarrhoea Show forest plot	31		Mean Difference (IV, Random, 95% CI)	Subtotals only

1.1 Studies of inpatients	26	3507	Mean Difference (IV, Random, 95% CI)	‐20.90 [‐31.44, ‐10.35]
1.2 Studies of outpatients	5	506	Mean Difference (IV, Random, 95% CI)	‐42.81 [‐55.07, ‐30.56]

Comparison 8. Severity of diarrhoea; studies of outpatients

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Comparison 9. Mortality stratum for children and adults in the countries where trials were undertaken (children/adults)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mean duration of diarrhoea Show forest plot	32		Mean Difference (IV, Random, 95% CI)	Subtotals only

1.1 Child and adult mortality low or very low	21	2075	Mean Difference (IV, Random, 95% CI)	‐24.83 [‐34.42, ‐15.23]
1.2 Either child or adult mortality high	11	2032	Mean Difference (IV, Random, 95% CI)	‐24.75 [‐43.40, ‐6.10]
2 Diarrhoea lasting ≥4 days Show forest plot	26		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Child and adult mortality low or very low	19	1559	Risk Ratio (M‐H, Random, 95% CI)	0.35 [0.23, 0.51]
2.2 Either child or adult mortality high	7	846	Risk Ratio (M‐H, Random, 95% CI)	0.45 [0.26, 0.76]
3 Mean stool frequency on day 2 Show forest plot	19		Mean Difference (IV, Random, 95% CI)	Subtotals only

3.1 Child and adult mortality low or very low	14	1456	Mean Difference (IV, Random, 95% CI)	‐0.99 [‐1.35, ‐0.63]
3.2 Either child or adult mortality high	5	1231	Mean Difference (IV, Random, 95% CI)	0.00 [‐0.78, 0.78]

Comparison 9. Mortality stratum for children and adults in the countries where trials were undertaken (children/adults)

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