Recent Advances in Discovery and Development of Medicines for the Treatment of Secretory Diarrhea in the Developing World

Abstract

Secretory diarrhea remains a global health challenge in the developing and developed countries. Secretory or infectious diarrhea is caused by infection of the gastrointestinal tract with a bacterial, viral, or parasitic pathogen. Acute diarrheal diseases have a major impact on morbidity and mortality across the world, with as many as four billion cases occurring annually. Diarrheal disease is responsible for the approximately 1.7 million deaths in children under 5 years old annually. Preventative healthcare measures include safe and effective vaccines and improved water, sanitation, hygiene systems, and nutritional practices. Treatment options in developing countries are usually supportive, replacing intestinal fluid losses with oral rehydration solution (ORS). Oral rehydration therapy (ORT) is well accepted as the most effective treatment for rehydration of children with acute diarrhea and is recommended by the World Health Organization for the prevention and management of dehydration. Its use has resulted in a significant reduction in diarrhea-related mortality. ORT has been recently complemented by zinc supplementation therapy. Rehydration has little effect on stool volume or frequency; therefore, the World Health Organization has recommended that anti-secretory drug treatment be added to rehydration therapy as long as the treatment has proven safe and efficacious in the pediatric population. In the developing countries, Hydrasec™ (racecadotril) is the most widely used antisecretory antidiarrheal, particularly in children. This review focuses on recent advances in the discovery and development of medicines and pharmacological mechanisms that modulate the secretory component of diarrhea that could be efficacious in the treatment of infectious diarrhea in the developing countries, particularly in the pediatric population.

Engineering novel beneficial therapeutic microorganisms for Vibrio cholerae therapy using synthetic biology

“…Apart from antibiotics, another big group of medical compounds has its use in cholera treatment -drugs which reduce secretion from the gastrointestinal tract (GI). In this group of drugs one can find compounds such as inhibitors of enkephalinase enzymes, inhibitors of cystic fibrosis transmembrane regulator and agonists of peripheral opioid receptors (these are not exactly anti-secretory, but rather they reduce GI motility) [14]. When administered, drugs from those subgroups reduce the diarrhea, effectively reducing loss of fluids, which is lifesaving in many cases [14].…”

“…In this group of drugs one can find compounds such as inhibitors of enkephalinase enzymes, inhibitors of cystic fibrosis transmembrane regulator and agonists of peripheral opioid receptors (these are not exactly anti-secretory, but rather they reduce GI motility) [14]. When administered, drugs from those subgroups reduce the diarrhea, effectively reducing loss of fluids, which is lifesaving in many cases [14]. The main disadvantage of these drugs are their high cost and low availability in affected areas.…”