Typhoid, or typhoid fever, is one of the oldest documented diseases known to have afflicted mankind. However, the reason for its lethality was not discovered until recently. There is currently no cure for typhoid, but it can be managed by a myriad of antibiotics, as it is caused by bacteria. However, identification of which bacteria, and why it is so lethal, will make treatments more specific and effective.

A new study by Yale scientists has identified a toxin, possessed by Salmonella typhi, S. Typhi, the bacterium that causes typhoid, as the major cause of typhoid symptoms.

Salmonella enterica, commonly called Salmonella and related to S. Typhi, typically causes food poisoning, as it can only effect the stomach and digestive tract. S. Typhi, on the other hand, causes a body-wide and life-threatening disease because its toxin can enter all of the body's cells and cause infection. Bacterial infections can easily be treated by antibiotics, but toxins cannot. There is currently no specific cure for typhoid, other than a bevy of antibiotics that may or may not work. The symptoms of S. Typhi infection worsen as time passes, as does the level of infection by the toxin. Salmonella infection, or food poisoning, tends to only last five to 10 days at most and can be debilitating, but not for as long as typhoid can be.

According to the Mayo Clinic, typhoid patients, in their first week after infection, experience fevers, loss of appetite, rashes, and weakness. In the second week, they continue to have a fever, lose much weight, and face diarrhea or constipation. In the third week, they enter what is known as "typhoid state" and become delirious and unable to sit up or open their eyes as their fever has persisted for three weeks. By the fourth week after infection, life-threatening complications may occur, or small improvements are seen in health.

Infections can come from exposure to food or water, contaminated with S. Typhi from a person carrying the disease or fecal matter from a person with the disease. The Centers for Disease Control and Prevention estimate that five percent of people who survive the disease become carriers, meaning they no longer exhibit symptoms, but can still give others typhoid.

The study, performed on mice, has indicated that the difference between S. Typhi and Salmonella is the toxin that S. Typhi makes. Researchers found that the toxin had an affinity for many cells and would negatively affect them once it associated with a cell to which it was attracted. The toxin can infect healthy cells and make them kill themselves, but it can also prevent the body's immune response, which would act to kill off the bacteria, destroy toxins, and restore health. If a toxin is blocking immune response, then the body has no choice but to remain infected by the bacteria and its toxins. Herein lies the difference between the lengths of infection of typhoid versus food poisoning.

Researchers also established the conformation and characteristics of the toxin. This is important because the existence of the toxin appears to be what makes typhoid so dangerous. Even if one kills the S. Typhi bacteria, the toxin's effects can still endure.

While typhoid and food poisoning seem to be caused by similar strains of bacteria, their effects are quite different. Typhoid still affects about 21.5 million people each year. While many survive after long periods of antibiotic treatment, scientists and doctors will soon be able to treat the root cause of typhoid, its toxin, and finally make its characteristic life-threatening month-long infection a thing of the past.

Source: Song J, Gao X, Galan JE. Conferring Virulence: Structure and Function of the chimeric A2B5 Typhoid Toxin. Nature. 2013.