contains a high quantity, about 142 meq/l, of sodium. a healthy individual secretes 2000–3000 milligrams of sodium per day into the intestinal lumen. nearly all of this is reabsorbed so that sodium levels in the body remain constant. in a diarrheal illness, sodium-rich intestinal secretions are lost before they can be reabsorbed. this can lead to life-threatening dehydration or electrolyte imbalances within hours when fluid loss is severe. the objective of therapy is the replenishment of sodium and water losses by ort or intravenous infusion. sodium absorption occurs in two stages. the first is via intestinal epithelial cells (enterocytes). sodium passes into these cells by co-transport with glucose, via the sglt1 protein. from the intestinal epithelial cells, sodium is pumped by active transport via the sodium-potassium pump through the basolateral cell membrane into the extracellular space. the sodium–potassium atpase pump at the basolateral cell membrane moves three sodium ions into the extracellular space, while pulling into the enterocyte two potassium ions. this creates a "downhill" sodium gradient within the cell. sglt proteins use energy from this downhill sodium gradient to transport glucose across the apical membrane of the cell against the glucose gradient. the co-transporters are examples of secondary active transport. the glut uniporters then transport glucose across the basolateral membrane. both sglt1 and sglt2 are known as symporters, since both sodium and glucose are transported in the same direction across the membrane. the co-transport of glucose into epithelial cells via the sglt1 protein requires sodium. two sodium ions and one molecule of glucose (or galactose) are transported together across the cell membrane via the sglt1 protein. without glucose, intestinal sodium is not absorbed. this is why oral rehydration salts include both sodium and glucose. for each cycle of the transport, hundreds of water molecules move into the epithelial cell to maintain osmotic equilibrium. the resultant absorption of sodium and water can achieve rehydration even while diarrhea continues. history definition in the early 1980s, "oral rehydration therapy" referred only to the preparation prescribed by the world health organization (who) and unicef. in 1988, the definition changed to encompass recommended home-made solutions, because the official preparation was not always readily available. the definition was again amended in 1988 to include continued feeding as an appropriate associated therapy. in 1991, the definition became, "an increase in administered hydrational fluids" and in 1993, "an increase in administered fluids and continued feeding". development crane and his sketch of the sodium-glucose symporter refugee camp. dehydration was a major cause of death during the 1829 cholera pandemic in russia and western europe. in 1831, william brooke o'shaughnessy noted the changes in blood composition and loss of water and salt in the stool of people with cholera and prescribed intravenous fluid therapy (iv fluids), first administered by latta. the prescribing of hypertonic iv therapy by rogers decreased the mortality rate of cholera from 70 to 40 percent. in the west, iv therapy became the "gold standard" for the treatment of moderate and severe dehydration. in 1953, indian physician hemendra nath chatterjee published his results in the lancet of treating people with mild cholera with ort. he gave the solution orally and rectally along with coleus extract, antihistimines and antiemetics without controls. the formulation of the fluid replacement solution was 4 g of sodium chloride, 25 g of glucose and 1000 ml of water. he did not publish any balance data and his exclusion of patients with severe dehydration did not lead to any confirmatory study; his report remained anecdotal. robert allan phillips attempted to create an effective ort solution based on his discovery that, in the presence of glucose, sodium and chloride could be absorbed in patients with cholera. however, phillips' efforts failed because the solution he used was excessively hypertonic, and he used to try to stop the diarrhea rather than to rehydrate patients. in the early 1960s, biochemist robert k. crane described the sodium-glucose co-transport mechanism and its role in intestinal glucose absorption. this, combined with evidence that the intestinal mucosa appears undamaged in cholera, suggested that intestinal absorption of glucose and sodium might continue during the illness. this supported the notion that oral rehydration might be possible even during severe diarrhea due to cholera. in 1967–1968, norbert hirschhorn and nathaniel f. pierce, working in dhaka, bangladesh and calcutta, india, respectively, showed that people with severe cholera can absorb glucose, salt and water and that this can occur in sufficient amounts to maintain hydration. in 1968, david r. nalin and richard a. cash, assisted by rafiqul islam and majid molla, reported that in adults with cholera, given an oral glucose-electrolyte solution in volumes equal to that of the diarrhea losses, reduced the need for iv fluid therapy by eighty percent. in 1971, fighting during the bangladesh liberation war displaced millions and an epidemic of cholera ensued among the refugees. when iv fluid ran out in the refugee camps, dilip mahalanabis, a physician working with the johns hopkins international center for medical research and training in calcutta, instructed to prepare and distribute an oral rehydration solution prepared from individual ingredients to family members and caregivers. over 3,000 people with cholera received ort in this way. the mortality rate was 3.6 percent among those given ort compared with 30 percent in those given iv fluid therapy. after the independence of bangladesh, a wide circulation campaign was conducted on the use of saline in the treatment of diarrhea. in the year 1980, the world health organization recognized ort and began a global program for its dissemination. in the 1970s, norbert hirschhorn used oral rehydration therapy on the white river apache indian reservation with a grant from the national institute of allergy and infectious diseases. he made the important observation that children would voluntarily drink as much of the solution as needed to restore hydration, and that rehydration and early re-feeding would protect their nutrition. this led to increased use of ort for children with diarrhea, especially in developing countries. in 1980, the bangladeshi nonprofit brac created a door-to-door and person-to-person sales force to teach ort for use by mothers at home. a task force of fourteen women, one cook and one male supervisor traveled from village to village. after visiting with women in several villages, they hit upon the idea of encouraging the women in the village to make their own oral rehydration fluid. they used available household equipment, starting with a "half a seer" (half a quart) of water and adding a fistful of sugar and a three-finger pinch of salt. later on, the approach was broadcast over television and radio and a market for oral rehydration salts packets developed. three decades later, national surveys have found that almost 90% of children with severe diarrhea in bangladesh are given oral rehydration fluids at home or in a health facility. ort is known in bangladesh as orosaline or orsaline. from 2006 to 2011, unicef estimated that worldwide about a third of children under 5 who had diarrhea received an oral rehydration solution, with estimates ranging from 30% to 41% depending on the region. ort is one of the principal elements of the unicef "gobi fff" program (growth monitoring; ort; breast feeding; immunization; female education; family spacing and food supplementation). the program aims to increase child survival in developing nations through proven low-cost interventions. mozambique civil war refugees, 1990 people had fled from civil war in mozambique to southern malawi. in november 1990, cholera broke out in a refugee camp in southern malawi where approximately 74,000 persons were temporarily living. david swerdlow of the u.s.'s cdc epidemic intelligence service (eis) wrote about the situation. he recommended setting up a tent just for children who would be assisted by some of the best nurses. he recommended against over-reliance on iv tubes, which often were left attached to persons for a week or more and which could lead to infections and septic shock. and he noticed that sick persons were not drinking enough rehydration solution. he assigned so-called "ors officers" whose job was to encourage persons to drink more solution. it was a minor mystery how persons were getting sick since deep-bore wells provided clean water and refugees were encouraged to wash their hands. it was then discovered that the only place for persons to wash hands were in the same buckets in which water was transported and stored. swerdlow wrote in his report, "use of narrow mouthed water containers would probably decrease the likelihood of contamination." awards centre for health and population research, dhaka, bangladesh, 2001 gates award for global health. norbert hirschhorn, dilip mahalanabis, david nalin, and nathaniel pierce, 2002 inaugural pollin prize for pediatric research. richard a. cash, david nalin, dilip mahalanabis and stanley schultz, 2006 prince mahidol award.