Orsaline a liquid formulation made by mixing salts (of which the important one is common salt) and sugar which is used to compensate for the loss of excessive fluid (water and salts) from the body that occurs during an episode of severe watery diarrhoea as exemplified by cholera. Large quantity of fluid loss over a short period of time in the form of watery stool causes rapid dehydration of the body which if left untreated may often be fatal. Of the several types of diarrhoea, one which is associated with this type of discharge of large quantities of watery stool with the consequent loss of electrolytes such as sodium and potassium, often leads to life threatening dehydration and has been the major cause of diarrhoeal mortality in the past. Replacement of the lost fluid or rehydration is the needed medical intervention in such cases.
The usual route to rehydration in cholera, for instance, has been injection through the vein of a fluid containing a mixture of electrolytes such as sodium, potassium and chloride together with glucose and a small quantity of bicarbonate, called intra-venous saline. But injection is not always a feasible treatment approach in many of the developing countries of the world where incidence of such illnesses is high due to poor personal hygiene and sanitation conditions and lack of safe drinking water, and hence the need for rehydration therapy is thus great. Therefore, the possibility of whether rehydration can be achieved through the oral route by administering all these ingredients as a drink has long been a subject of scientific interest because of its obvious practical utility.
In cholera which is the prototype of dehydrating diarrhoea, the causative bacteria Vibrio cholerae, enters the gut through contaminated food or water. There it multiplies and produces a toxic substance, the cholera toxin (CT). The toxin interferes with proper functioning of a particular absorption-secretion pathway in the gut resulting in vastly increased secretion of fluid by the gut wall into the gut cavity which is then lost as watery stool. The toxin also reduces absorption of fluid by the gut wall from the gut cavity. The result is rapid loss of water from blood with concomitant severe dehydration of the body.
An understanding of the mechanism of water loss or dehydration through this process led to the discovery of the rehydration mechanism. It was found that there are other absorption-secretion pathways operational in the gut that are not sensitive to the action of cholera toxin. One such CT-insensitive absorption-secretion pathway was found to be activated when glucose is present in the gut fluid. The discovery was exploited in the development oral replacement therapy (ORT) in the treatment of cholera - a treatment given through the oral route in order to replace the lost fluid. In other words, rehydration was achieved with the use of a rehydration salt-solution or saline, given orally and hence the solution generally referred to as oral saline or orsaline.
Laboratory studies on this approach to rehydration were initiated at the Oxford University in England during the late1940s and, by the early 1960s, the basic mechanism of this absorption-secretion pathway was understood. Clinical study of various formulations of such oral rehydration solution were soon undertaken on patients with severe cholera to validate its efficacy in correcting dehydration. In these studies, the then Pakistan-SEATO Cholera Research Laboratory (PSCRL) situated at Dhaka, played a pivotal role in rehydration studies in cholera that were carried out in the cholera ward of the laboratory. These studies demonstrated the efficacy of oral rehydration salts (ORS) formulations in correcting the dehydration caused by severe cholera in the hospitalised cholera cases. The study was then extended to cholera cases in the field during cholera epidemics to test efficacy of ORS in the field-setting with highly encouraging results.
The Matlab field station of PSCRL played a pivotal role in these studies during the late 1960s and, during the early 1970s the refugee camps in the Indian state of West Bengal that were set up during the Bangladesh war of liberation where several million refugees from Bangladesh were sheltered, provided a suitable setting for field trial of ORS. In these camps cholera soon broke out because of poor sanitation conditions and unsafe drinking water, and use of ORS proved to be an effective intervention. Success of PSCRL obviously led to its transformation in 1979 into an international research centre. By an Act of the Parliament of Bangladesh, the PSCRL was so transformed and given the name International Centre for Diarrhoeal Diseases Research, Bangladesh (ICDDR,B).
The ICDDR,B successfully promoted oral rehydration treatment in cholera and other watery diarrhoea for wider use at the community level. For this purpose, low cost formulations of ORS using commonly available household ingredients such as common salt and sugarcane molasses, which is rich in potassium, were made and tested for efficacy. This formulation was called in Bangla 'lobon-gur' or salt-molasses. Other formulations using powdered cereal cooked to the consistency of a liquid so as to be easily taken by patients were also made and given the descriptive connotation, cereal-based ORS. These different versions of oral rehydration treatment have been extensively promoted in filed studies carried out at the Matlab field station which was converted into a Demographic Surveillance System (DSS) after the creation of ICDDR,B. In the DSS area, 200,000 inhabitants are kept under surveillance round the year as to birth, death, disease, migration etc. This system proved to be an invaluable tool for field trials of biomedical interventions such as vaccine and drug trials and also various types of family planning interventions and a range of operations research. The DSS provides the best longitudinal data set to be found anywhere in the developing world.
The salt-molasses formulation or the cereal-based formulation of ORS proved to be useful in rehydration of the bulk of the severe watery diarrhoea cases in community if properly made and used. This intervention thus promised to reduce the need for hospital visits during severe episodes of diarrhoea. In this context, these formulations proved to carry great community value contributing significantly to reduction of morbidity and mortality due to diarrhoea in the villages. But the difficulty with these home formulations is that it is not easy to teach the proper procedure for making these at home because of low literacy level, extreme poverty and lack of even small gadgets such as teaspoons to be used in measuring the amount of salt needed for making a certain volume of 'lobon-gur'. Standard WHO recommended packets of glucose-based ORS were thus introduced in the market. It had the advantage that the preparation was standardised at the level of manufacturing. One packet is made for 500 ml of ORS solution, so when the content of a packet is dissolved in this volume of water, a standard solution with respect to all essential ingredients is readily made that can be saved without refrigeration for about 8 hours.
The packet-ORS gained rapid acceptance and its cost was subsidised by the government to facilitate its use as a convenient home treatment of diarrhoea. ORS or oral saline, is thus globally emerging as an easy home treatment of severe watery diarrhoea and bears the promise of saving and, indeed have actually saved in recent years, millions of lives all over the world. In the course of time it may find much wider application in achieving oral rehydration in conditions of clinical dehydration due to other diseases and may thus turn out to be the century's most potent discovery in community medicine. [Zia Uddin Ahmed]