From a pump handle to oral rehydration therapy: a model of translational research.

Few afflictions have attracted as much attention and impacted on as many societal and biomedical areas as cholera. Dr. John Snow's studies launched the field of epidemiology, were early applications of medical cartography, and promoted the use of statistical methods in medicine. The finding that cholera was due to the ingestion of contaminated water lent to the demise of the prevalent "miasmatic theory of contagion," set the platform for the "germ theory of disease," and promoted the growth of public health concerns for water purification and sanitation. More recent attention to this disease led to the notion of "secretory diarrhea" and the translation of basic principles to the development of oral rehydration therapy and its "spin-offs" (Gatorade and Pedilyte).

History of development of oral rehydration therapy.

PIP: Before oral rehydration therapy (ORT) was developed, intravenous fluid therapy was the mainstay of fluid therapy for diarrheal dehydration. The following early observations, however, formed the scientific basis for the discovery of ORT: a group of physiologists observed that glucose enhances the absorption of sodium and water across the intestinal brush-border membrane of experimental animals and that no morphological changes occur in the gut epithelium of cholera patients. Captain Phillips of the US Army in 1964 first successfully tried oral glucose saline on two cholera patients. Following this, scientists working at the Cholera Research Laboratory, Dhaka, and the Infectious Diseases Hospital, Calcutta, contributed to the development of modern oral rehydration salt (ORS) solution. The efficacy of standard ORS was first demonstrated by Pierce et al and others during 1965-69. During the Bangladesh liberation war, Dr. Dilip Mahalanabis showed the efficacy of ORS in cholera cases among Bangladeshi refugees (1971-72) and Sircar et al in 1978 demonstrated the efficacy of ORS in a cholera epidemic in Manipur. De et al in 1974 and Chatterjee et al in 1978 convincingly demonstrated the efficacy of ORS in children with diarrhea including cholera. Based upon this information, the World Health Organization in 1978 launched the global diarrheal diseases control program with ORS at its heart and the short-term objective of reducing mortality due to diarrhea. The safety and efficacy of WHO-ORS containing 90 mmol/liter of sodium for neonates was not demonstrated until 1979 at which time Dr. Daniel Pizarrow and colleagues showed the WHO-ORS was effective even for neonates with dehydrating diarrhea and safe if used along with plain water in a 2:1 regimen. To avoid confusing illiterate mothers in developing countries, Dutta et al and Roy et al in 1984 reported the safety and simplicity of uninterrupted breastfeeding together with breastfeeding. Further findings were produced on the optimal salt content of ORS for severely malnourished children. Studies with their corresponding findings have continued since then, with current efforts focused upon developing a treatment for diarrhea using the role of short chain fatty acids in acute watery diarrhea.^ieng