PRoRota

The challenge

Diarrhoeal diseases are responsible for almost one in ten deaths of young children – more than a thousand deaths a day globally. Diarrhoeal diseases are caused by a wide range of pathogens, but the greatest disease burden is associated with rotavirus infections.

This burden has been significantly reduced over the past decade through the widespread introduction of rotavirus vaccination. However, the performance of rotavirus vaccines is markedly lower in countries in sub-Saharan Africa. 

There is some evidence that this effect may be related to the composition of bacterial communities in the gut (the gut microbiota), which appears to affect responses to oral vaccines in low-income countries. ‘Healthy’ gut bacteria may prevent colonisation by pathogenic bacteria, protecting against gut damage, and may also stimulate gut immune responses.

These findings have led to speculation that supplementary probiotics – live, non-pathogenic bacterial cultures – might temporarily shift the gut microbiota and boost immune responses when given alongside rotavirus vaccines. However, limited data are available.

Probiotics may also have other benefits. There is some evidence that they enhance recovery from diarrhoeal disease when used as a treatment. When given prophylactically, they may also limit the diarrhoea linked to antibiotic use. And they may reduce the risk of colonisation with antibiotic-resistant strains of gut bacteria.

The project

The PRoRota project is generating rigorous data on the benefits of probiotic supplementation in young babies, as part of a holistic disease-prevention approach that also incorporates vaccination and improved water, sanitation and hygiene (WASH) practices.

In Côte d’Ivoire, Malawi and Tanzania, the project is recruiting 4,000 newborns and comparing a combined intervention against the usual standard of care. The intervention includes four four-weekly courses of a commercially available probiotic supplement, at birth, 6, 10 and 14 weeks, plus rotavirus vaccination and WASH advice (based on a pre-trial study examining current WASH practices). 

The babies are being followed for six months. A wide range of data is being collected, including the number of episodes of diarrhoeal disease, cases of rotavirus diarrhoea, hospital visits and hospitalisations due to diarrhoeal disease. The strength of immune responses following vaccination will be monitored, as will changes in weight and growth, and the presence of drug-resistant gut bacteria and microbiota diversity.

Data on the impacts of probiotic supplementation on these outcomes will be used to estimate the intervention's cost-effectiveness and the costs of implementation.

In addition, the project is collecting data on a wide range of climate-related variables at study sites. These will be used to explore associations between various climate factors and the risk of diarrhoeal disease, to support the development of a predictive model to identify diarrhoeal disease hotspots based on environmental context.

Impact

The PRoRota project will generate robust data on a potentially impactful intervention to prevent diarrhoeal disease in babies. It will:

• Reveal whether probiotic supplementation leads to improved immune responses to rotavirus vaccines.
• Show whether supplementation leads to a reduction in the risk of diarrhoeal disease.
• Identify the likely cost-effectiveness of supplement use.
• Develop a model for identifying diarrhoeal disease hotspots and the potential impacts of climate change on diarrhoeal disease risk in different locations.

If shown to be effective, probiotic supplementation is a relatively simple intervention that could have immediate benefits in preventing episodes of potentially severe diarrhoeal disease, while also reducing the long-term impacts on childhood growth and development caused by repeated gut infections.