Oral Zinc for the Treatment of Acute Diarrhea in US Children

In developing countries, diarrheal diseases are a leading cause of childhood morbidity and mortality. In the United States an estimated 4.67 million children per year suffer from gastroenteritis with a diarrheal component, impacting the delivery and cost of healthcare. Seventy-five percent of these children are brought to physician care across a range of settings from clinics to emergency departments. Children less than five years of age average 1.3 - 2.5 episodes per year, with 1.4% of those children requiring hospitalization annually. This results in an estimated 209,000 hospitalizations yearly for gastroenteritis. The impact of acute gastrointestinal disease can be felt in the developed world, including the United States, as cost attributed to hospitalization and productivity lost. Attempts at treating gastroenteritis have included Oral Rehydration Solution (ORS), introduced 30 years ago by the WHO, which continues to provide a safe and effective way to maintain hydration during acute illness. ORS, however, does not reduce the volume or frequency of stool output in diarrhea. The anti-diarrheal medication loperamide (Imodium®) was commonly used in children until reports of serious adverse reactions caused its use to fall out of favor. There are no other medications or supplements available to specifically treat the diarrheal component of gastroenteritis and studies have shown that adherence to treatment recommendations regarding fluid therapy is poor because care givers want to reduce duration of illness as opposed to supporting children through the natural course of the disease. The desire to relieve diarrheal symptoms often leads care givers to seek antibiotics during a time of rising antibiotic resistance, as well as other treatments with no proven efficacy.

Zinc is an essential trace element for humans. Its physiologic roles are seen throughout the body as a critical cofactor for enzymatic reactions; most notable are its actions in the gastrointestinal (GI) tract. Zinc is an important component of brush border enzymatic activity which promotes gastrointestinal absorption, it regulates water/electrolyte transport at the cellular level, and it enhances the repair of the intestinal mucosa by bolstering immune function. Over the past 10-15 years, there have been more than a dozen randomized controlled trials of zinc supplementation performed in children living in developing countries that have reported improvements in the duration and severity of diarrhea when compared to placebo in a variety of in- and outpatient settings. The majority of zinc trials were conducted in countries at high risk of zinc deficiency, but those conducted at medium risk showed similar effect on duration and severity. When stratified across all nutritional groups based on serum zinc levels a significant effect was seen compared to placebo despite baseline zinc level, with no occurrence of serious adverse reaction in any group. Given these results, the WHO has endorsed zinc supplementation for all children with acute diarrhea, despite the lack of data from similarly designed studies in industrialized/developed settings.