Oral rehydration therapy

From Wikipedia, the free encyclopedia
  (Redirected from Oral Rehydration Solution)
Jump to: navigation, search
Oral rehydration therapy
Intervention
Cholera rehydration nurses.jpg
A cholera patient drinking oral rehydration solution (ORS).
MeSH D005440
eMedicine 906999-treatment

Oral rehydration therapy (ORT) involves drinking water with modest amounts of sugar and salt, as well as supplemental zinc for two weeks, continuing to eat if some appetite is present as this helps to speed recovery of normal intestinal functioning, and having family members and caretakers learn the signs of worsening dehydration.[1] The aim of ORT is to prevent or treat dehydration. A key element of ORT is that water is still absorbed from the gastrointestinal tract into the body, even with loss of fluid through diarrhea or vomiting. In the case of vomiting, the WHO recommends a pause of 5-10 minutes, then continuing to slowly administer the fluid. In the case of diarrhea, the WHO recommends giving children under two a quarter- to a half-cup of fluid following each loose bowel movement, and older children a half- to a full cup. ORT is often given by parents or other family members in a home setting. ORT is also be given by aid workers and health care workers in refugee camps, health clinics and hospital settings.[2]

ORT adjunctive treatments include the administration of zinc supplements, and the encouragement of the patient with diarrhea and vomiting to continue to eat in order to speed up the recovery of normal intestinal function. Often, more frequent smaller meals are better tolerated. Most children with watery diarrhea regain their appetites soon after dehydration is remedied, whereas children with bloody diarrhea often eat poorly until their illness resolves.[1] A number of fluids may be used in ORT, these include: salted and unsalted rice water, salted and unsalted vegetable broth, weak unsweetened tea, salted and unsalted yoghurt drink, green coconut water, and unsweetened fresh fruit juice. A 2005 manual published by the World Health Organisation (WHO) suggests, "Plain clean water should also be given."[1]

Health organisations offer a number of differing recipes for making ORT at home using plain clean water as its base. Some publications recommend one teaspoon of salt and six teaspoons of sugar added to one litre of water, although others recommend half a teaspoon of salt and six teaspoons of sugar added to one litre of water.[3][4][5][6] Rehydration Project states, " Making the mixture a little too diluted (with more than 1 litre of clean water) is not harmful."[7] Commercial preparations are also available as either pre-prepared fluids or packets of oral rehydration salts (ORS) ready for mixing with water.[8][9] Since its introduction and development for widespread use in the latter part of the 20th century, oral rehydration therapy has decreased human deaths from dehydration in vomiting and diarrheal illnesses, especially in cholera epidemics occurring in children. It represents a major advance in global public health.

Effectiveness[edit]

Prior to the introduction of ORT, death from diarrhea was the leading cause of infant mortality in developing nations. Between 1980 and 2006, the introduction of ORT is estimated to have decreased the number of deaths, worldwide, from 5 to 3 million per year.[10][11] However, in 2008, diarrhea remained the second most common cause of death in children under five years (17 percent), (after pneumonia (19 percent)).[12] Moreover, by the same year, the use of ORT in children under five had declined.[13]

Physiological basis[edit]

Intestinal epithelium (H&E stain)

Fluid from the body enters the intestinal lumen during digestion. This fluid is isosmotic with the blood because it contains a high concentration of sodium (approx. 142 mEq/L). A healthy individual secretes 20–30 grams 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 a life-threatening hyponatraemia within hours. This is the motivation for sodium and water replenishment in ORT.[14]

Sodium absorption from the intestine occurs in two stages. The first is via intestinal epithelial cells. Sodium passes into these cells by co-transport via the SGLT1 protein. From the intestinal epithelia cells, sodium is pumped by active transport via the sodium potassium pump through the basolateral membrane into the extracellular space.[15][16] The sodium–potassium ATPase pump at the basolateral membrane of the cell moves three sodium ions into the extracellular space, whilst pulling into the cell 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 (as galactose) are transported together across the cell membrane via the SGLT1 protein. Without sodium, intestinal glucose is not absorbed. This is why oral rehydration salts (ORS) include both sodium and glucose. For each cycle of the transport, hundreds of water molecules move into the epithelial cell, slowly rehydrating the patient.[14]

Low-osmolarity oral rehydration salts[edit]

An ORS sachet is poured into a bottle

WHO and UNICEF jointly maintain official guidelines for the manufacture of oral rehydration salts (ORS). In 2003, clinical trials and comparisons with rice water led to a reduction in the recommended osmolarity of ORS.[17] The guidelines were also updated in 2006. The reduced osmolarity ORS has a total osmolarity of 245 mmol/L. It decreases vomiting; decreases stool volume by about twenty-five percent; and the need for IV therapy by about thirty percent. When the recommended osmolarity of ORS was reduced from 311 mmol/L to 245 mmol/L, the concentration of glucose and sodium chloride were reduced, while that of potassium and citrate remained the same.[18][19][20][21][22][23]

Basic ORT solutions[edit]

A basic oral rehydration therapy solution is composed of salt, sugar, and water in solution, made using a standard ratio[24][25] For example,

  • 30 ml sugar : 2.5 ml salt : 1 liter water
  • 6 tsp. sugar : 0.5 tsp. salt : 1 liter water
  • 2 tbl. sugar : 0.5 tsp. salt : 1 quart water

The WHO and UNICEF jointly maintain the official guidelines[26] for the contents of manufactured, reduced osmolarity ORS packets. These guidelines are used by commercial manufacturers of ORS packets and were last updated in 2006.[20] The reduced osmolarity ORS has a total osmolarity of 245 mmol/L.[27]

The WHO and UNICEF guidelines suggest home-made ORT should begin at the first sign of diarrhea in order to prevent dehydration.[28][29] Recommendations for home-made ORT fluid recipes vary. However, there are some consistent principles.

The molar ratio of sugar to salt should be 1:1 and the solution should not be hyperosmolar.[30] The Mayo clinic suggests half a teaspoon of salt, six level teaspoons of sugar and 1 litre (34 US fl oz) water.[31] The British Columbia health service suggests sugar free fruit juice mixed with water in a ratio of 1:4.[32]

Babies are given ORT fluid from a dropper or a syringe. Infants under two are given a teaspoon of ORT fluid every one to two minutes. Older children and adults take sips from a cup. If the patient vomits, the carer waits a short time then persists with the ORT.[1](Section 4.2)

Ideally, water for mixing with ORS is boiled or treated with chlorine. However, ORS is not withheld on the basis of potentially unsafe water. Rehydration takes precedence.[1]

Associated therapies[edit]

Zinc[edit]

As part of oral rehydration therapy, WHO recommends supplemental zinc (10 to 20 mg daily) for ten to fourteen days, to reduce the severity and duration of the illness and make recurrent illness in the following two to three months less likely. Preparations are available as a zinc sulfate solution for adults, a modified solution for children and in tablet form.[33]

Feeding[edit]

Continuing to feed the patient, when some appetite is present, speeds the recovery of normal intestinal function, as well as supporting continued nutrition, growth and weight gain in children. Small frequent meals are best tolerated (offering the child food every three to four hours). Mothers should continue to breastfeed.[1][34][35] A child with watery diarrhea typically regains his or her appetite as soon as dehydration is corrected, whereas a child with bloody diarrhea often eats poorly until the illness resolves. Such children should be encouraged to resume normal feeding as soon as possible. Once diarrhea is corrected, WHO recommends giving the child one more meal a day for two weeks, and longer if the child is malnourished.[1]

Children with malnutrition[edit]

Dehydration may be overestimated in wasted children and underestimated in edematous children.[36] Care of these children must also include careful management of their malnutrition and treatment of other infections. Useful signs of dehydration remain eagerness to drink, lethargy, cool and moist extremities, weak or absent radial pulse (wrist), and reduced or absent urine flow. In children with severe malnutrition it is often impossible to reliably distinguish between some dehydration and severe dehydration. A severely malnourished child who has signs of severe dehydration but who does not have a history of watery diarrhea should be treated for septic shock.[1]

Since the previous ORS (90 mmol sodium/L) and the current standard reduced-osmolarity ORS (75 mmol sodium/L) both have too much sodium and too little potassium for the typical severely malnourished child, the Bangladesh Institute of Public Health Nutrition recommends Rehydration Solution for Malnutrition (ReSoMal). An exception is if the severely malnourished child also has severe diarrhea (in which case ReSoMal may not provide enough sodium), then standard reduced-osmolarity ORS (75 mmol sodium/L) is recommended.[36]

The Bangladesh Institute of Public Health Nutrition further recommends that the IV route not be used for rehydration except in cases of shock and then only with care, infusing slowly to avoid flooding the circulation and overloading the heart. In addition, with severe acute malnutrition, the usual signs of infection, such as fever, are often absent, and infections are often hidden, and it's therefore recommended that all severely malnourished children be treated with broad-spectrum antibiotics on admission.[36]

The World Health Organization's THE TREATMENT OF DIARRHOEA: A manual for physicians and other senior health workers also recommends rehydrating malnourished children slowly. Specifically, WHO recommends 10 milliliters of ORS per kilogram body weight for each of the first two hours (for example, a 9-kilogram child should be given 90 ml of ORS over the course of the first hour, and another 90 ml for the second hour) and then continuing at this same rate or slower based on the child's thirst and ongoing stool losses, keeping in mind that a severely dehydrated child may be lethagic. If the child drinks poorly, a nasogastric tube should be used. IV infusion should only be used for the treatment of shock and then slowly to avoid over-hydration and heart failure. Increasing edema is a sign of over-hydration.[1]

WHO also states that standard reduced-osmolarity ORS (75 mmol sodium/L) contains too much sodium and too little potassium. And therefore, WHO recommends modifying the solution by adding one packet to two liters of water, adding 45 ml of potassium chloride solution from a stock solution containing 100g KCl/liter, and adding 50 grams of sucrose to the two liters. This will result in a solution with less sodium, more potassium, and more sugar, each of which is appropriate for severely malnourished children with diarrhea. This is best mixed by a medical professional in a clinic setting. If this is not available, refer to the previous recommendations about starting promptly with available home remedies such as salted rice water, unsalted rice water, salted vegetable broth, unsalted vegetable broth, weak unsweetened tea, plain water, etc.[1]

Feeding should usually resume within 2-3 hours of starting rehydration, and food should be given every 2-3 hours, day and night. Mothers should remain with their children if at all possible. WHO recommends continuing breastfeeding and perhaps even re-lactating if circumstances realistically allow. As an example of an initial cereal diet before a child regains his or her full appetite, WHO recommends combining 25 grams skimmed milk powder, 20 grams vegetable oil, 60 grams sugar, and 60 grams rice powder or other cereal into 1,000 milliliters water and boiling gently for five minutes. A child should be feed 130 ml per kilogram of body weight during one day (for example, a 9-kilogram child should be given 1,170 ml of this initial food over the course of a day). A child who cannot or will not eat this minimum amount should be given the diet by nasogastric tube divided into six feedings. Later on, the child should be given cereal made with a greater amount of skimmed milk product and vegetable oil and slightly less sugar. As appetite fully returns, a child will be eating 200 ml per kilogram of body weight during a day (a 9-kilogram child should be given 1,800 ml of this modified cereal over the course of a day). Zinc, potassium, vitamin A, and other vitamins and minerals should be added to both recommended cereal products, or to the oral rehydration solution itself. Some mothers exclusively breastfeed for the first six months of an infant's life, and this has health advantages. WHO states, "In general, foods suitable for a child with diarrhoea are the same as those required by healthy children."[1]

WHO recommends that all severely malnourished children admitted to hospital should receive broad spectrum antibiotics (for example, gentamicin and ampicillin). In addition, hospitalized children should be checked daily for other specific infections.[1]

History[edit]

Definition[edit]

In the early 1980s, the term oral rehydration therapy referred only to the solution 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".[2]

Development[edit]

Refugee camp.

Over 2,500 years ago, the Indian physician Sushruta described the treatment of acute diarrhea with rice water, coconut water, and carrot soup.[37]

Until 1960, ORT was not known in the West. 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 loss of water and salt in the stool of cholera patients and prescribed intravenous fluid therapy (IV fluids). The prescribing of hypertonic IV therapy 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.[37]

In 1957, Hemendra Nath Chatterjee, a physician of India, published his results of treating patients with cholera with ORT.[38] However, he had not performed a controlled trial. Robert A. Phillips attempted to create an effective ORT solution based on his discovery that, in the presence of glucose, sodium and chloride become absorbable during diarrhea in patients with cholera. Phillips did not succeed due to inadequate methodology.[39]

In the early 1960s, Robert K. Crane, a biochemist, discovered the sodium-glucose co-transport mechanism and its role in intestinal glucose absorption.[40] This strengthened belief in the concept that the intestinal mucosa is not disrupted in cholera and led to understanding of the physiological basis of the effectiveness of ORT. In 1960, David R. Nalin found that in adults, ORT given in volumes equal to that of the diarrhea, reduces the need for IV fluid therapy by eighty percent.[37][41]

In 1971, the Bengali people fought for independence from Pakistan. The fighting displaced many people and an epidemic of cholera ensued. When IV fluid ran out in the refugee camps, Dilip Mahalanabis, a physician, instructed his staff to distribute oral rehydration salts (ORS) to family members and carers. Over 3,000 patients with cholera received ORT in this way. The mortality rate was 3.6 percent with ORT and 30 percent with IV fluid therapy.[37][39]

As an example of the implementation of ORT, in 1980 the Bangladeshi nonprofit BRAC essentially developed a door-to-door and person-to-person sales force to teach ORT. A task force of fourteen women, one cook, and one male supervisor traveled from village to village, figuring the supervisor would protect them from others, and the women’s numbers would protect them from the supervisor. After visiting with women in the village, each evening they got together and talked about what worked and what didn’t. They hit upon the method of encouraging the women in the village to themselves go through the steps of making oral rehydration fluid. And 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, these changes were sustained with television and radio and the development of a market for oral rehydration salt packets. Three decades later, national surveys have found that almost 90% of children with severe diarrhea in Bangladesh are given oral rehydration fluid.[42]

From 2006 to 2011, UNICEF estimated that worldwide about a third of children under 5 who had diarrhea received oral rehydration solution, with estimates ranging from 30% to 41% depending on the region of the world.[43][44]

ORT is one of the principle elements of the UNICEF "GOBI FFF" program (growth monitoring; ORT; breast feeding; immunisation; female education; family spacing and food supplementation). The program aims to increase child survival in developing nations through low-cost interventions.[45]

Awards[edit]

Controversy and ongoing investigations[edit]

The ORS formulation has been criticised for not providing enough sodium for adults with cholera.[49][50]

In Rwanda, a charity supplied the sports drink Gatorade, which is not indicated in ORT in children and was accused of making them worse.[51] The president of AmeriCares, the said charity, responded, "We stand by our decision to ship Gatorade to Rwandan refugees. In the absence of potable water, Gatorade, with its electrolytes and water, saved countless lives in a true triage situation."[52]

References[edit]

  1. ^ a b c d e f g h i j k l "The treatment of diarrhea, a manual for physicians and other senior health workers." World Health Organization, 2005.
  2. ^ a b "WHO position paper on oral rehydration salts to reduce mortality from cholera." WHO 2014. Accessed 1 January 2014.
  3. ^ "The treatment of diarrhoea: a manual for physicians and other senior health workers." World Health Organization, Department of Child and Adolescent Health and Development, 2005, page 9 (13 in PDF): "A home-made solution containing 3g/l of table salt (one level teaspoonful) and 18g/l of common sugar (sucrose) is effective but is not generally recommended because the recipe is often forgotten."
  4. ^ "A guide on safe food for travellers: Welcome to South Africa, host to the 2010 FIFA world Cup." (bottom left on page 1): "If ORS are not available, mix 6 teaspoons of sugar plus one level teaspoon of salt in one litre of safe water ("taste of tears") and drink as indicated in the table."
  5. ^ "Guidelines for the control of shigellosis, including epidemics due to Shigella dysenteriae type 1". World Health Organization, 2005, Annex 12 - Preparation of Home Made Oral Rehydration Solution, page 51 (57 in PDF): "Ingredients: Half a teaspoon of salt (2.5 grams), six level teaspoons of sugar (30 grams) and one litre of safe drinking water".
  6. ^ "Dehydration, treatments and drugs." Mayo Clinic 7 January 2011. "In an emergency situation where a pre-formulated solution is unavailable, you can make your own oral rehydration solution by mixing half teaspoon salt, six level teaspoons of sugar and one litre (about 1 quart) of safe drinking water."
  7. ^ Rehydration Project, home page, updated August 2, 2013. "The Rehydration Project web site is funded by The Mother and Child Health and Education Trust, a Hong Kong registered charity no 91/10374. . . This site complies with the HONcode standard for trustworthy health information."
  8. ^ "Oral rehydration salts and solutions and rice-based solutions worldwide manufacturers and suppliers." Rehydration Project website. Accessed 3 January 2014.
  9. ^ "Oral rehydration therapy (ORT) in children." US Department of Health and Human Services. Accessed 1 January 2014.
  10. ^ Gerline, A. (8 October 2006). "A simple solution". Time. 
  11. ^ "Water with sugar and salt". Lancet 312 (8084): 300–1. August 1978. doi:10.1016/S0140-6736(78)91698-7. 
  12. ^ The state of the world's children: child survival (PDF). UNICEF. December 2007. p. 8. ISBN 978-92-806-4191-2. 
  13. ^ Ram PK, Choi M, Blum LS, Wamae AW, Mintz ED, Bartlett AV (March 2008). "Declines in case management of diarrhoea among children less than five years old". Bull. World Health Organ. 86 (3): E–F. PMC 2647400. PMID 18368194. 
  14. ^ a b Guyton, A.C.; Hall, J.E. (2006). Textbook of Medical Physiology. Philadelphia: Elsevier Saunders. p. 840. ISBN 0-7216-0240-1. 
  15. ^ Guyton & Hall 2006, p. 330
  16. ^ "Oral rehydration therapy and early refeeding in the management of childhood gastroenteritis." Paediatrics and Child Health, Canadian Paediatric Society, nutrition committee 2006 11(8) p527–531. Accessed 17 February 2009.
  17. ^ "New formulation of oral rehydration salts (ORS) with reduced osmolarity." UNICEF. Dead URL December 2012.
  18. ^ "New ORS." UNICEF. Accessed 16 February 2009.
  19. ^ "Pharmacopoeia library: oral rehydration salts." WHO Accessed 16 February 2009.
  20. ^ a b "Improved formula for oral rehydration salts to save children's lives". UNICEF. Retrieved 2008-07-15. 
  21. ^ Kim Y, Hahn S, Garner P (2001). "Reduced osmolarity oral rehydration solution for treating dehydration caused by acute diarrhoea in children". Cochrane Database Syst Rev (2): CD002847. doi:10.1002/14651858.CD002847. PMID 11406049. 
  22. ^ Murphy C, Hahn S, Volmink J (2004). "Reduced osmolarity oral rehydration solution for treating cholera". Cochrane Database Syst Rev (4): CD003754. doi:10.1002/14651858.CD003754.pub2. PMID 15495063. 
  23. ^ Musekiwa A, Volmink J (2011). "Oral rehydration salt solution for treating cholera: ≤ 270 mOsm/L solutions vs ≥ 310 mOsm/L solutions". Cochrane Database Syst Rev (12): CD003754. doi:10.1002/14651858.CD003754.pub3. PMID 22161381. 
  24. ^ , "WHO position paper on Oral Rehydration Salts to reduce mortality from cholera." World Health Organization, Global Task Force on Cholera Control.
  25. ^ "How to Make an Oral Rehydration Salts Drink (ORS)." Wikihow. Accessed 26 February 2011.
  26. ^ "Oral rehydration salts." WHO Pharmacopoeia Library. Accessed 16 February 2009.
  27. ^ "UNICEF: New formulation of Oral Rehydration Salts (ORS) with reduced osmolarity." UNICEF. Accessed 16 February 2009. Dead link December 2012.
  28. ^ "Oral rehydration salts: production of the new ORS" (PDF). WHO UNICEF. 2006. 
  29. ^ "The selection of fluids and food for home therapy to prevent dehydration from diarrhoea: guidelines for developing a national policy" (PDF). Programme for the Control of Diarrhoeal Diseases. WHO. 1993. 
  30. ^ Churgay CA, Aftab Z (1 June 2012). "Gastroenteritis in children: part II, prevention and management". Am Fam Physician 85 (11): 1066–70. PMID 22962878. 
  31. ^ "Dehydration, treatments and drugs." Mayo Clinic. Accessed 1 January 2014.
  32. ^ "Oral rehydration therapy." Parent education and resources, British Columbia Guidelines, Canada. Accessed 1 January 2014.
  33. ^ "Pediatric zinc sulfate oral solution" (PDF). WHO. 15 July 2008. 
  34. ^ Victora CG, Bryce J, Fontaine O, Monasch R (2000). "Reducing deaths from diarrhoea through oral rehydration therapy" (PDF). Bull. World Health Organ. 78 (10): 1246–55. PMC 2560623. PMID 11100619. 
  35. ^ "Community health worker training materials for cholera prevention and control." CDC.
  36. ^ a b c National Guidelines for the Management of Severely Malnourished Children in Bangladesh, Institute of Public Health Nutrition, Directorate General of Health Services, Ministry of Health and Family Welfare, Government of the People’s Republic of Bangladesh, May 2008, "Step 3. Treat/prevent dehydration" and "Step 4. Correct electrolyte imbalance," pages 21–23 (22-24 in PDF).
  37. ^ a b c d Guerrant R. L. et al."Cholera, diarrhea, and oral rehydration therapy: triumph and indictment." Clinical Infectious Diseases, Infectious Diseases Society of America 2003, vol 37(3) p398 -405. PMID 12884165. Accessed 2 January 2014 and at "Oxford Journals".
  38. ^ Chatterjee HN (June 1957). "Reduction of cholera mortality by the control of bowel symptoms and other complications". Postgrad Med J 33 (380): 278–84. doi:10.1136/pgmj.33.380.278. PMC 2501333. PMID 13431557. 
  39. ^ a b Ruxin JN (October 1994). "Magic bullet: the history of oral rehydration therapy". Med Hist 38 (4): 363–97. PMC 1036912. PMID 7808099. 
  40. ^ Crane R. K. et al. "The restrictions on possible mechanisms of intestinal transport of sugars." Membrane Transport and Metabolism, proceedings of a symposium held in Prague, August 22 – 27, 1960. Kleinzeller A. and Kotyk A. Czech Academy of Sciences, Prague, 1961, p439– 449.
  41. ^ Nalin DR, Cash RA, Islam R, Molla M, Phillips RA (August 1968). "Oral maintenance therapy for cholera in adults". Lancet 2 (7564): 370–3. doi:10.1016/S0140-6736(68)90591-6. 
  42. ^ Gawande, Atul (29 July 2013). "SLOW IDEAS, Some innovations spread fast. How do you speed the ones that don’t?". The New Yorker. "They found that, although boiled water was preferable, contaminated water was better than nothing." 
  43. ^ Oral rehydration therapy / oral rehydration solution, PATH, "PATH is an international nonprofit organization that transforms global health through innovation."
  44. ^ Source: UNICEF.Pneumonia and Diarrhoea: Tackling the Deadliest Diseases for the World’s Poorest Children. New York: UNICEF; 2012.
  45. ^ 1946–2006, sixty years for children (PDF). UNICEF. November 2006. ISBN 92-806-4053-4. 
  46. ^ "Centre for Health and Population Research — 2001 Gates Award for Global Health Recipient." Bill and Melinda Gates Foundation. Accessed 21 February 2009.
  47. ^ "First Pollin prize in pediatric research recognizing developers of revolutionary oral rehydration therapy." NewYork-Presbyterian Hospital Accessed 22 February 2009.
  48. ^ "Prince Mahidol Award 2006." Prince Mahidol Award Foundation. Accessed 22 February 2009.
  49. ^ Nalin DR, Hirschhorn N, Greenough W 3rd, Fuchs GJ, Cash RA (2 June 2004). "Clinical concerns about reduced osmolarity oral rehydration solution". JAMA 291 (21): 2632–5. PMID 15173156. 
  50. ^ "UNICEF: new formulation of oral rehydration salts (ORS) with reduced osmolarity." dead url December 2012.
  51. ^ Pendergrast, Mark (2010). Inside the Outbreaks: The Elite Medical Detectives of the Epidemic Intelligence Service. Houghton Mifflin Harcourt. pp. 289–91. ISBN 0-547-48723-1. 
  52. ^ Johnson, S.M. (24 December 1994). "AmeriCares relief reached Rwanda first". New York Times.