Emerging treatments

Probiotics

The use of probiotics, such as various species of lactobacilli, Bifidobacterium bifidum, Streptococcus thermophilus, and Saccharomyces boulardii, early in the course of the diarrhea may reduce the stool frequency and shorten the duration of the diarrhea and even reduce rotavirus shedding in affected patients.[65][66][67][68][69][70][71][72] The mechanism of action is not fully understood but may involve a complex interaction among epithelial, molecular, metabolic, and immune responses.[73] Presumably, probiotics work by competitively blocking receptor sites, enhancing the immune response, and producing substances that inactivate viral particles.[74]

Zinc supplementation

Zinc supplementation in children with diarrhea in developing countries leads to reduced duration and severity of diarrhea.[75][76][77] Zinc is an essential micronutrient and a cofactor for several enzymes involved in intermediary metabolism. It acts as a scavenger against free oxygen radicals, protecting cell membranes from oxidative damage. Zinc has a direct effect on intestinal villus and brush border disaccharidase activity and intestinal transport of water and electrolytes.[78] Zinc also helps to enhance cellular and humoral immunity leading to increased clearance of pathogen(s) responsible for the diarrhea from the intestinal tract.[79] Given the benefits of zinc supplementation in a large number of studies, the World Health Organization and UNICEF recommend daily 20 mg zinc supplements for 10 to 14 days for children with acute diarrhea (10 mg/day for infants <6 months of age).[80] Another way of giving zinc during acute diarrhea is to mix it with oral rehydration solution (ORS). Patients who benefit most from zinc supplementation are perhaps malnourished children and those children with deficiency. The role of zinc supplementation during diarrheal episodes in developed countries awaits further evaluation. Because of the effectiveness of traditional ORS and the increased cost of zinc supplementation, zinc supplementation is not routinely recommended in developed countries.

Racecadotril

Racecadotril is an antidiarrheal drug with an intestinal antisecretory mode of action. One meta-analysis of 9 randomized controlled trials compared the efficacy of racecadotril as an adjunct to ORS versus ORS alone versus ORS plus placebo in children with acute gastroenteritis. It found that when racecadotril was used as an adjunct to ORS it reduced diarrhea (duration, stool output, and stool number) in inpatient, outpatient, and different cultural settings, despite variable baseline conditions (level of dehydration, different ages, and presence of rotavirus).[81]

Neonatal rotavirus vaccine (RV3-BB)

RV3-BB vaccine has been developed from the human neonatal virus strain RV3 (serotype G3P6), which appears to be naturally attenuated and adapted to the newborn gut, and therefore replicates well. Wild-type infection results in strong serologic responses to community rotavirus strains and provides protection from severe rotavirus gastroenteritis in infants up to the age of 3 years.[82] One randomized placebo-controlled trial of RV3-BB in Indonesia found the vaccine to be efficacious, immunogenic, and well tolerated when given to neonates. It had an efficacy of 94% to 12 months in the neonatal vaccine group and 99% in the infant vaccine group.[82] Current vaccines are licensed for use in infants 6 weeks of age and older. In the future, this new vaccine may offer a prevention strategy that can be given from birth.

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