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Diarrheal diseases remain the third most common cause of death worldwide for children under the age of five, with most of these deaths occurring in low- and middle-income countries. While diarrhea is rarely fatal in high-income countries, such as Canada, it remains a leading cause of child hospitalizations.

Previous studies have independently shown varying benefits and harms of a number of treatments, such as zinc, vitamin A, micronutrients, probiotics, diluted milk, and others. Fortunately, researchers at St. Joseph’s Healthcare Hamilton and McMaster University have conducted what is believed to be the first study to assess which of these is the most effective intervention for acute diarrhea and gastroenteritis (ADG), and which treatments should be avoided by physicians.

The study found that two combination treatments, zinc plus Saccharomyces boulardii (a yeast probiotic), and zinc plus smectite (a medicinal clay), are the most effective interventions used to treat ADG in hospitalized children. These findings are expected to inform future clinical guidelines for the treatment of ADG in children, mostly in low- and middle-income countries.

Dr. Ivan Florez“Our research has identified what works best to treat ADG in children,” said Dr. Ivan Florez, the lead author of the study (pictured left). Dr. Florez is a pediatrician from Colombia and a PhD student in the Department of Health Research Methods, Evidence and Impact (HEI) at McMaster University.

“This is going to have an enormous impact, particularly in low- and middle-income countries where these diseases can be more dangerous for children,” said Dr. Lehana Thabane, senior author of the study. Thabane is a biostatistician in the Father Sean O’Sullivan Research Centre at St. Joseph’s Healthcare Hamilton, and professor of clinical epidemiology and biostatistics in HEI at McMaster University.

The main goal of ADG treatment is to prevent dehydration, according to the World Health Organization. To find the most effective medicine for ADG, a systematic review and network meta-analysis was conducted by a team of interdisciplinary researchers, including several from McMaster University.

Dr. Lehana Thabane

“We brought together a team of researchers with a wide spectrum of expertise — pediatrics, public health, nutrition, general medicine, knowledge translation, research methods and biostatistics — to tackle the issue of determining the best evidence-based therapeutic option for treating ADG in children,” said Dr. Thabane (pictured right).

ADG infections are caused by a variety of microorganisms, particularly rotavirus, but also norovirus, Salmonella, E. coli, and others. Nearly every child in the world is infected by rotavirus at least once by the age of 5. As the body builds immunity with each subsequent infection, adults tend to be largely unaffected by rotavirus.

The findings were published in the journal PLOS ONE, which is known for its high ethical standards and rigorous methodology of its research publications.

The research also showed that the best single interventions used to treat ADG were symbiotics (which contain both a prebiotic and probiotic), loperamide, and zinc, respectively. However, loperamide was shown to be the most unsafe of these treatments, in terms of side effects.

Further analysis found that the therapeutic effect of zinc was higher in low- and middle-income countries, and was not present in high-income countries. The disparity is likely associated with a higher prevalence of a dietary zinc deficiency in low- and middle-income countries.

“Our findings confirm that zinc remains among the most effective treatment options for ADG in low- and middle-income countries because zinc is one of the least expensive treatments available to physicians,” said Dr. Florez. “Furthermore, based on the available evidence, symbiotics can be considered the best single intervention to reduce the diarrhea duration in high-income countries.”

According to the National Institutes of Health, dietary zinc is most prevalent in a variety of protein foods. This includes seafood, lean meats, poultry, legumes, whole grains, and more. As some plant-based foods contain phytates, which decreases zinc absorption, vegetarians may require up to fifty percent more of the recommended dietary allowance for zinc compared to non-vegetarians.

Though zinc deficiency is common in low- and middle-income countries, short-term zinc supplementation as treatment for ADG in children has been shown to be an effective and inexpensive option for hospitals in these countries.

These results agree with the recommendation by the World Health Organization to use zinc in all children with ADG, in low- and middle-income countries. However, practice guidelines from organizations in high-income countries should consider this evidence to update their recommendations for treatment of ADG in children.

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