ProbiSAM

Diarrhoea and mortality

The study found no effect of probiotics on days with diarrhoea during inpatient treatment of children with SAM. However, during outpatient treatment, the number of days with diarrhoea reduced by 2.2 days (95% CI 0.6 – 3.5), equivalent to a 26% reduction in the probiotic group compared to placebo.

There were no effects of probiotics on incidence of diarrhoea, pneumonia or weight gain during in- or outpatient treatment. (Grenov et al. 2017). Diarrhea was associated with increased mortality in children with SAM (Nabukeera-Barungi et al 2018, Grenov et al 2019)

Microbiota

Children with SAM had a dysbiotic microbiota. During treatment, their microbiota approached the composition of non-malnourished children from the same community.

Probiotic intake resulted in a modest increase in microbiota diversity (alpha-diversity) during both in- and outpatient treatment, however did not change the overall composition of bacteria (beta-diversity).

In addition, the cumulative incidence of diarrhoea was lower among children where the probiotic bacteria could be detected, compared to placebo and children receiving probiotics where the probiotics could not be detected. (Castro-Mejira et al 2020)

Thymus and gut function

Severely malnourished children also had poor gut function and small thymus size, indicating poor immune function compared to non-malnourished children.

Thymus size improved during treatment, however thymus size did not reach normal size within the follow-up period. There were no effects of probiotics on thymus size. (Lanyero et al 2019, Nabukeera-Barungi et al 2018).

Conclusion

Complete recovery from SAM takes time and exceeds standard nutritional rehabilitation. Probiotics may be useful in prevention or treatment of diarrhoea among children with SAM in the outpatient treatment phase.

1. Kamugisha JGK, Lanyero B, Nabukeera-Barungi N, Ritz C, Mølgaard C, Michaelsen KF, Briend A, Mupere E, Friis H, Grenov B. Weigth-for-Height Z-score Gain during Inpatient Treatment and Subsequent Linear Growth during Outpatient treatment of Young Children with Severe Acute Malnutrition: A Prospective Study from Uganda. Curr Dev Nutr 2021; 00: nzab118
2. Kamugisha JGK, Lanyero B, Nabukeera-Barungi N, Nambuya-Lacor H, Ritz C, Mølgaard C, Michaelsen KF, Briend A, Mupere E, Friis H, Grenov B. Weight and mid-upper arm circumference gain velocities during treatment and the role of edema, a prospective study of young children admitted with severe acute malnutrition. BMC Nutrition, 2021, 7, article number 26.
3. Nabukeera-Barungi N, Lanyero B, Grenov B, Friis H, Namusoke H, Mupere E, Michaelsen KF, Mølgaard C, Wiese M, Nielsen DS, Mohammed MK, Christensen VB, Rytter M. Thymus size and its correlates among children admitted with severe acute malnutrition: a cross-sectional study in Uganda. BMC Ped., 2021, org/10.1186/s12887-020-02457-3
4. Castro-Mejia JL, O’Ferrall S, Krych L, O’Mahony E, Namusoke H, Lanyero B, Kot W, Nabukeera-Barungi N, Michaelsen KF, Mølgaard C, Friis H, Grenov B*, Nielsen DS*. Restitution of gut microbiota in Ugandan children administered with probiotics (Lactobacillus rhamnosus GG and Bifidobacterium animalis lactis BB-12) during treatment for severe acute malnutrition. Gut Microbes, 2020, doi.org/10.1080/19490976.2020.1712982 *shared last authorship
5. Lanyero B, Grenov B, Barungi NN, Namusoke H, Michaelsen KF, Mupere E, Mølgaard C, Jiang P, Frøkjær H, Wiese M, Muhammed MK, Pesu H, Nielsen DS, Friis H, Rytter MJ, Christensen VB. Correlates of gut function in children hospitalized for severe acute malnutrition, a cross-sectional study in Uganda. J Paediatr Gastroenterol Nutr, 2019, 69(3), 292-298.
6. Grenov B, Lanyero B, Nabukeera-Barungi N, Namusoke H, Ritz C, Friis H, Michaelsen KF, Mølgaard C. Diarrhea, dehydration, and the associated mortality in children with complicated severe acute malnutrition: A prospective cohort study in Uganda. J Peds, 2019, 210:26-33. DOI: 10.1016/j.peds.2019.03.014.
7. Nabukeera-Barungi N, Grenov B, Friis H, Lanyero B, Namusoke H, Mupere E, Michaelsen KF, Mølgaard C, Christensen VB, Rytter MJ. Thymus gland size during recovery from complicated severe acute malnutrition: a prospective study of the role of probiotics. Paediatr Int Child Health, 2018, DOI: 1080/20469047.2018.1535871
8. Nabukeera-Barungi N, Grenov B, Lanyero B, Namusoke H, Mupere E, Christensen VB, Michaelsen KF, Mølgaard C, Rytter MJ, Friis H. Predictors of mortality among hospitalized children with severe acute malnutrition: a prospective study from Uganda. Pediatr Res, 2018, 84(1):92-98.
9. Lanyero B, Namusoke H, Nabukeera-Barungi N, Grenov B, Mupere M, Michaelsen KF, Mølgaard C, Christensen VB, Friis H, Briend A. Transition from F-75 to ready-to-use therapeutic food in children with severe acute malnutrition, an observational study in Uganda. Nutr J 2017, 16:52
10. Grenov B, Namusoke H, Nabukeera-Barungi N, Lanyero B, Ritz C, Carlsson A, Vinter CK, Michaelsen KF, Holm-Larsen T. Validation of a simple stool diary used by caregivers to document diarrhea among young children in a low-income country. J Pediatr Gastroenterol Nutr. 2017, 65(2):156-64
11. Grenov B, Namusoke H, Lanyero B, Nabukeera-Barungi N, Ritz C, Mølgaard C, Friis H, Michaelsen KF. Effect of probiotics on diarrhea in children with severe acute malnutrition: A randomized controlled study in Uganda. J Pediatr Gastroenterol Nutr, 2017;64:396-403

2022: Ponderal and linear growth in malnourished Children, Jolly General Katebarirwe Kamugisha.

2019 Gut function in children hospitalized with severe acute malnutrition - Cohort study in Uganda , Betty Lanyero.

2018 Thymus gland size and mortality among children admitted with severe acute malnutrition, Dr. Nicolette Nabukeera-Barungi.

2016 The effect of probiotics of diarrhea in children with severe acute malnutrition – an intervention study in Uganda, Benedikte Grenov.

2017, Nutritional Recovery and its Determinants among children aged 6-59 Months with Severe Acute Malnutrition at Mwanamugimu Nutrition Unit, Mulago Hospial, Nabaasa Gloria, Makerere University.

2016, Exploring the Gut Microbiome of Ugandan children suffering from Severe Acute Malnutrition, Sinead O’Ferrall.

2016, The Effects of Probiotic Supplementation on the Gut Microbiota of Malnourished Children aged 6-59 Months, Elaine O’Mahony.

2015 Intestinal parasites and diarrhoea in severely malnourished children <5 years old: Cross-sectional study at Mulago Hospital, Uganda, Mia V Lübbert.

2015, The association between weight gain and linear growth during nutritional rehabilitation of severely malnourished children, Simona Laurinaviciute.

ESPGHAN conference 2018: Effect of probiotics on the gut microbiota composition of children suffering from severe acute malnutrition in Uganda.

The Rank Prize Funds mini-symposium 2018 on malnutrition for invited junior researchers ProbiSAM: The effect of probiotics on diarrhoea and other outcomes in children with severe acute malnutrition: A randomized, double-blind, placebo-controlled study in Uganda.

CAPGAN conference 2017: Correlates of gut function in children admitted with severe acute malnutrition, a cross-sectional study in Uganda.

Nutrition & Growth conference 2017: The effect of probiotics on diarrhea in children with severe acute malnutrition: A randomized, double-blind, placebo-controlled study in Uganda.

WSPGHAN conference 2016: The effect of probiotics on diarrhea in children with severe acute malnutrition: A randomized, double-blind, placebo-controlled study in Uganda.

Although childhood mortality is decreasing globally, undernutrition still accounts for approximately 3 million annual deaths among children below 5 years of age.

Children that are hospitalized with severe acute malnutrition are some of the most vulnerable patients, and in many sub-Saharan hospitals, 20% or more of these patients die. Diarrhea is one a common complication and cause of death in these patients.

As probiotics may have an effect on diarrhea and perhaps other outcomes, we conducted the ProbiSAM project to assess the effect of two probiotic strains on diarrhoea, pneumonia, weight gain and markers of gut function, immune function and gut microbiota in children with severe acute malnutrition in Uganda.

The project was conducted between 2013 - 2016.

Background

• 5 -1 million child die annually due to SAM
• Diarrhoea is a common cause of death
• Probiotics have been shown to reduce the duration of acute diarrhoea mainly in well-nourished children

Aim & Objective

• To assess the effect of probiotics on diarrhoea in children with SAM
• Intervention 10 billion CFU/day, combination of
  • Bifidobacterium animalis subsp lactis (BB-12)
  • Lactobacillus rhamnosus GG (LGG)

Outcomes

• Primary
  • Days with diarrhoea during inpatient treatment
• Secondary
  • Days with diarrhoea during outpatient treatment
  • Diarrhea incidence and severity
  • Pneumonia incidence and duration
  • Weight gain and recovery
• Exploratory
  • Gut function, gut microbiota, thymus size

The study was conducted as a randomized, double-blind, placebo-controlled study at Mwanamugimu Nutrition Unit, Mulago Hospital, Kampala, Uganda, between March 2014 and October 2015.

The study enrolled 400 children between 6 and 59 months of age with SAM. The children either received one daily dose of 10 billion colony-forming units in total of two probiotic strains BB-12 and LGG (ratio 1:1) or placebo. Probiotics or placebo was administered during hospitalization and during a subsequent 8-12 week outpatient treatment period.

The primary outcome was number of days with diarrhea during hospitalization.

Secondary outcomes included number of days with diarrhea during outpatient treatment, diarrhea incidence, diarrhea severity according to the Vesikari scale, fever, vomitus, pneumonia, weight gain and nutritional recovery.

All outcomes were analyzed separately for in- and outpatient treatment.

University of Copenhagen, Department of Nutrition, Exercise and Sports.

Makerere University, Department of Paediatrics and Child Health, Kampala, Uganda.

Chr. Hansen A/S, Denmark.