What is the Typhoid?
Typhoid is not your everyday fever or cold; it is a serious and potentially fatal infectious disease brought on by a Gram-negative bacterium, Salmonella enterica serotype Typhi, or more simply put, the typhoid bacillus. This pathogen is responsible for causing typhoid fever, a systemic infection that results in an acute illness routinely connected with fever, caused by the consumption of food or water contaminated with feces from a carrier infected with typhoid.
The disease itself traces back to the 19th century, with the earliest cases being identified as typhoid dating back to the late 1800s. The bacteria were first discovered by Karl Eberth, a German pathologist in 1879. It wasn't until 1884, though, that microbiologist George Gaffky isolated the bacteria and elaborated on Eberth's findings. Despite these groundbreaking discoveries, the typhoid fever death rate remained at approximately 10% until the development of antibiotics in the mid-twentieth century.
In terms of its structure, the bacterium is rod-shaped, with a prominent flagellum enhancing its motility. The bacterial cell is engulfed by a cell wall, termed a capsule, composed of lipopolysaccharides, polysaccharides, and several proteins that contribute to its virulence.
What are the symptoms of Typhoid lead to?
The symptoms associated with typhoid fever typically start surfacing one to two weeks after exposure to the bacterium. Early indications may include sudden onset of fever, headache, weakness, and pain in various body parts. As the disease progresses, symptoms such as rose spots on the lower chest, distended abdomen, constipation or diarrhea, and delirium may occur. If left untreated, the disease can cause life-threatening complications such as intestinal perforation and/or hemorrhage.
Proteins and Antigens
Typhoid's ability to invade and thrive in humans is attributed to a variety of proteins produced by the bacterium. Some of these proteins, unique to the typhoid bacteria, serve as identifiers for the immune system and could be utilized as antigens. Two prime examples are the Vi (virulence) antigen and the O antigen, both of which make up the capsule of the bacterium.
The Vi antigen, a non-branched, partially acetylated homopolymer of α-1,4-N-acetylgalactosaminuronate, gives the bacterium its resistance against the immune system's defense mechanisms. The O antigen, comprising repeating units of sugars, has a role in resisting the bactericidal action of serum.
Apart from these, the 'H' or flagellar antigen, a protein found in the flagellum of the bacterium, is another potential antigen candidate. Each of these antigens triggers a unique immune response, leading to the production of different antibodies by the host's immune system.
Antigens related vaccines
Study of these antigens has led to the development of various vaccines. Two vaccines that are currently in use worldwide are the oral Ty21a vaccine and the injectable typhoid polysaccharide vaccine (TPV). The Ty21a vaccine uses a weakened strain of the S. typhi bacterium that still produces a protective immune response but doesn't cause the full-blown disease. This vaccine particularly targets the Vi antigen.
On the other hand, the TPV is based on the purified Vi antigen. It provokes a vigorous immune response targeted at the Vi antigen, thereby providing immunity against the disease. Immunization with these vaccines has substantially reduced the incidence and mortality rate of typhoid fever.
Research is ongoing to explore the typhoid antigen-related signaling pathways that these antigens employ to ascertain their roles in each vaccine's pathway. A notable pathway is the Toll-like Receptor (TLR) signaling pathway that recognizes bacterial proteins, kickstarting an immune response.
