ORS or Oral Rehydration Solution, also known as ORT or Oral Rehydration Therapy is a solution of definite proportion of glucose and a few other salts and water. The famous medical journal, The Lancethailed it as ‘potentially the most important medical advance of the 20th century’. The use of ORT has been estimated to decrease the risk of death from diarrheal diseases by up to 93%.
Dr Dilip Mahalanabis discovered ORS, but this life-saving discovery was doomed to be unutilised, unrecognised and forgotten forever, as its effectiveness as claimed by Dr Mahalanabis was looked upon with suspicion by the majority of global scientific communities. The indifference went to the extent that some publishers refused to publish his original papers, and recognition of the medicine by WHO was put in cold storage. It took seven more years, when Indian physician Dr Dhiman Barua, through his persistent efforts made the WHO authorities agree for a trial of ORS. Eventually, Dr Barua led the ORS trial in 105 countries against cholera and enteric diseases, leading to its global recognition as the primary medicine against cholera and enteric diseases by WHO. Dr Mahalanabis received international recognition but no honour from reputed Indian scientific committees and various governments of India in his lifetime. It is ironic that after his death on 16 October 2022, the government of India honoured him with the Padma Vibhushan posthumously in 2023.
the 1971 Liberation War of Bangladesh
However, without the relentless efforts of Dr Dhiman Barua of WHO, the skeptical medical fraternity worldwide probably would not have been convinced even today that the therapy is an effective substitute to IV saline in the primary stage and could be administered by people with little or no training, thereby saving millions of lives.
A NEW CHAPTER IN CHOLERA RESEARCH
In those days, since plastic bottles were not put in practice, IV saline was packed in glass bottles which became so heavy that transporting cost by air became much more than the medicine itself. In 1970, the cholera epidemic spread over almost all the countries in Africa. Intravenous saline was required in tonnes, which became impossible to supply. Patients died in huge numbers in front of the helpless doctors. That incident pressed the need for ORS afresh. In the meanwhile, a new chapter in cholera research was started in 1968 when SEATO Cholera Research Laboratory at Dacca and two labs at Calcutta, the Johns Hopkins University International Center for Medical Research and Training (JH-CMRT) and Cholera Research Center (renamed NICED later) intensified research for the development of ORS.
Very soon, scientists got the proof from laboratory and limited field trial experiments that glucose and a few other salts dissolved in definite proportion in water (even sugar and common salt from the kitchen) caused absorption of water in the intestine. Large scale trial could not be undertaken as Dr Robert Philips, Director, PSCRL was skeptical of the ORS treatment; in 1962, he had treated 30 patients with ORS of his own formulation, of whom 5 had died due to liquid overpressure. The opportunity of large-scale trial came soon in 1971 when cholera broke out in refugee camps in Bongaon, West Bengal, at the border of India-East Pakistan where lakhs of refugees took shelter due to the atrocities of the then Pakistan government. Dr Mahalanabis of JH-CMRT left his research and came to the refugee camps for the treatment of patients. There were only two cottages with a total of 16 beds in the cholera ward, while the number of patients was huge. IV saline and medical persons were in meagre numbers. Patients were dying in flocks. The atmosphere was reverberating with woe and wail all around. In desperation, Dr Mahalanabis resorted to ORS treatment (22 g Glucose, 3.5 g Sodium Chloride, 2.5 g Sodium Carbonate) without seeking permission of higher ups, and with the help of JH-CMRT. During the eight-week period in which he and his team administered the therapy, only 135 cases proved fatal out of a total of 3700 patients, translating to a case fatality rate (CFR) of 3.6% in comparison to the earlier CFR of 30%.
DR DHIMAN BARUA OF WHO VISITS THE CAMP
During that period, Dr Dhiman Barua of WHO, who was Dr Mahalanabis’s teacher in medical college, visited the camp and was amazed at the way Dr Mahalanabis was managing the whole episode, despite the shortage of staff and danger of liquid over pressure on the patients. ORS liquid in drums with a tap were put in designated places. Relatives, volunteers, friends, whoever was available, was asked to take glasses of liquid for patients to drink and to stop when the patient did not want to drink anymore. In this way, Dr Mahalanabis not only tackled the danger of liquid over pressure on patients(hypertonicity), but at the same time, he proved that diarrheal patients could be cured by family members without supervision of medical professionals.
WHO DG AGREES FOR ORS TRIAL
Dr Barua joined WHO Geneva office in 1966. Since then, he advocated for ORS as primary treatment against cholera. But his colleagues did not approve of the solution. Even the success of the ORS treatment in Bangladesh refugee camps by Dr Mahalanobis in 1971 could not change their opinion.
One day, Dr Barua met the Director General of WHO, Dr Halfdan Mahler, by chance, in the car garage. Though Dr Barua was a junior staffer, he boldly explained the utility of the application of ORS salts for recovery of cholera patients and gave Dr Mahler some packets of ORS ingredients. From that day onward, he had long discussions about the use of oral rehydration in place of intravenous fluid. Ultimately, Dr Mahler agreed with Dr Barua’s proposal. He arranged for him to go to Africa to run five training courses in different countries in treating cholera patients with ORS. Following its success,Dr Mahler decided to seek funding for the Diarrheal Disease Control (CDD) programme. The mainstay of the CDD programme for proper management of diarrheal disease was:
* Prevent or treat dehydration with ORS solution (IV only in serious case)
* Feeding and breastfeeding during the diarrhea episode to be continued,
* Use antibiotics only in cases of bloody diarrhea.
The programme was eventually led by Dr Barua
ORS TREATMENT SPREADS WORLDWIDE
Prior to the discovery of ORS, IV saline was the only treatment for cholera. Hospital doctors regarded oral rehydration therapy as a second-grade treatment. Moreover, pediatricians in developed countries feared that sodium concentration in the formula was too high for children.
For ORS treatment to spread worldwide, caking of ORS ingredients due to absorption of moisture leading to short lifespan was an obstacle. Moreover, it took a long time to convince the critics that experience in practice showed no ill effects from ORS treatment, and they were invited to try it for themselves.
(Left) An ORS sachet with the osmolarity of its components ; (Right): A student demonstrates mixing of Oral Rehydration Salts (ORS) with water, outside a classroom in a school in Bihar’s Madhubani district
Image Courtesy: Flickr via UNICEF/ Dhiraj Singh
Fortunately, towards the end of 1970, a Swiss company succeeded in packaging the ingredients in aluminium foil bags to prevent absorption of moisture and caking of the powder. This increased its shelf-life, the cost of transportation was reduced, and handling became easy. Thereby, the ORS trial programme attained speed.
The opinion of the detractors was set aside when UNICEF reported in 1987: ‘No other single breakthrough of the 20th century has had the potential to prevent so many deaths over such a short period of time and at such a little cost.’
Annual global mortality due to diarrhea in children aged under five years was 146 per 1000 in 1970 and 79 per 1000 in 2003, a big reduction. Oral rehydration therapy may not be solely responsible for this improvement, but it surely played a remarkable role in it.
Image Courtesy: Flickr via UNICEF/ Graham Crouch
HOW DOES ORT WORK?
Lumen refers to the cavity in the body which enables the function of the organ system. For example, the lumen of the intestines allows for free flow of digested food through the digestive system. Epithelial cells are a type of cell that cover the inside and outside surface of the body. They are found on skin, blood vessels, and organs, including urinary tract, intestine, etc. Intestinal epithelial cells (IECs) line the surface of intestinal epithelium, where they play an important role in the digestion and absorption of nutrients and protection of the body from microbial infections.
There are some transporter and ion channels in the intestine, such as Chloride-Bicarbonate exchanger which pumps chloride ions from the lumen of the intestine to epithelial cells of intestine, and pumps bicarbonate ions on the opposite side.
The Sodium-Hydrogen exchanger pumps sodium ions in the intestine to epithelial cells of the intestine and sends protons in the opposite direction.
The CFTR channel is an ion that helps to maintain the balance of salt and water in the body.
SGLT1: This is different from other pumps. It sends both the molecules in the same direction. It pumps Glucose and Sodium from the lumen of the intestine to the epithelial cells of intestine. Both the Sodium and Glucose cannot pass alone through SGLT1 without the company of the other.
Sodium-Potassium ATPase pump: It pumps from the epithelial cells of intestine 3 sodium ions to the flow of blood and 2 potassium ions in the opposite direction.
For a healthy person, 2000 to 3000 milligram sodium secretes in lumen of the intestine which is absorbed almost totally in the blood to maintain balance. When cholera toxin enters the epithelial cells of the intestine, it deposits cyclic Adenosine Monophosphate (cAmp) in high amounts continuously. This disturbs normal functioning of Chloride-bicarbonate exchanger, Sodium-hydrogen exchanger and CFTR channel. As a result, the secreted Sodium and Chloride ions in the lumen of intestine exit out of the body as stool before being absorbed in blood. Only SGLT1 transporter is not affected by cAmp. Hence, if Sodium chloride and glucose (or sugar) water solution in the right proportion is provided to the patient, then SGLT1 will supply Glucose/ sugar and water from the lumen to the epithelial cells of the intestine, leading to its absorption there. Sodium-Potassium ATPase pump transports Sodium and water to the blood flow. With each cycle, hundreds of water molecules enter epithelial cells and rehydrate it. In this way, a simple solution of Salt, Glucose/ Sugar and water saves patients from dehydration.
Image Courtesy: Shutterstock
Acute diarrhea normally lasts only a few days. Diarrhea is not stopped by ORT, it replaces the lost fluids and essential salts, thus dehydration is prevented, and it strengthens the patient with the supply of essential salts. ORT alone is an effective treatment for most of the patients suffering from acute watery diarrhoea. Except for serious cases, intravenous drip therapy is unnecessary.
LIFE DEDICATED TO HUMANITY
Dhiman Barua was born to a family of doctors and traditional medicine practitioners in Burma (now Myanmar), which was then a part of undivided British India. When he was four years old, his family moved to his ancestral village near Chittagong in undivided British India (in present-day Bangladesh_. The area was infested with cholera. He saw a cholera epidemic causing deaths in almost every household of the village. In 1930, he took admission in Chittagong Medical School on a scholarship. Following that, he took a short commission posting in the Army Medical Corps during the World War II and served in Burma, India and Malaysia. After the war, he studied and earned a medical degree from the Lake Medical College in Calcutta, which was under the control of the Army then. He followed it up with a doctorate from Lucknow University, post-doctorate from Pasteur Institute, Paris, and the London School of Tropical Medicine.
Dr Barua began working for the World Health Organization in 1965 with the cholera control team based in Manila, and in 1966, he moved to the WHO head office in Geneva as a medical officer working on cholera and other diarrhoeal diseases. Throughout his career at WHO, he trained health workers in many countries in oral rehydration therapy and other aspects of diarrheal diseases in many capacities. He passed away in Geneva on 19 August 2020, two months short of his 100th birthday.
Dr Mahalanabis bestowed full credit to his teacher Dr Dhiman Barua for the global recognition of ORS developed by him against cholera and enteric diseases. But Dr Barua himself received practically no recognition for his vision and efforts in spreading the life-saving treatment around the world.
Dr Barua deserves complete credit for converting the “most important medical advance” of the 20th century into a household medicine worldwide. It is a tragedy that Dr Dhiman Barua’s contribution to humanity remains unhonoured by scientific communities and even the governments, including that of India. Will the Government of India honour him posthumously?
*The writer is ex-governing council member, Vijnana Bharati, and Retired Scientist, CSIR-CIMFR, Dhanbad. He can be reached at ganguli.kalyan@gmail.com.
