Recent Advances in Cholera Pathophysiology and Therapeutics

Abstract

In recent years it has been found that cholera pathophysiology is highly complex even though the Vibrio is not a tissue-invasive organism. Of necessity at the present stage of understanding of this complex process this outline will include some as yet hypothetical steps. The sequence of events leading to clinical disease includes infection, colonization of the host, adherence to the intestinal mucosa, elaboration of cholera toxin and binding of toxin to a receptor. Following toxin-receptor binding the complex is probably transported to an active site where changes in existing mechanisms of electrolyte transport, currently thought to be related to the adenyl cyclase-cyclic — AMP system, alter the movement of water and salts from plasma to lumen and lumen to plasma. These in turn lead to a decrease in mt absorption followed by net secretion. Eventually cumulative losses of water, sodium, potassium and bicarbonate become large enough to induce hypovolemic shock, acidosis and muscular weakness. These stages are summarized as follows:

• Infection

• Colonization

• Adhesion

• Toxin-elaboration

• Toxin-binding

• Cyclase-activation

• Flux changes

• Fluid accumulation

• Dehydration

To illustrate the complexity of this process, I shall follow a hypothetical Vibrio from infection of a patient until the development of clinical symptoms.