What is the pathogenesis of typhoid (Typhoid) fever?

From the Guidelines

Typhoid fever pathogenesis follows a systematic progression beginning with ingestion of Salmonella Typhi through contaminated food or water, leading to invasion of the small intestinal mucosa, survival and replication within macrophages, and eventual dissemination to lymphoid tissues, liver, spleen, and bone marrow, causing clinical manifestations and potential complications. The bacteria's virulence factors, such as the Vi capsular antigen and type III secretion systems, play a crucial role in evading host immune responses 1. After entering the gastrointestinal tract, S. Typhi survives stomach acid and invades the small intestinal mucosa, particularly through M cells in Peyer's patches. The infected macrophages transport bacteria to lymphoid tissues, liver, spleen, and bone marrow during the primary bacteremia phase, occurring 1-2 weeks after infection. In these organs, S. Typhi continues multiplying, eventually causing secondary bacteremia with clinical manifestations including fever, headache, abdominal pain, and rose spots.

The clinical presentation of typhoid fever can be non-specific, with symptoms such as fever, headache, constipation, and dry cough, making diagnosis challenging 1. The sensitivity of blood cultures for diagnosing typhoid fever is reported to be 40-80%, while stool and urine cultures become positive after the first week. Bone marrow cultures have a higher sensitivity than blood culture. The use of ciprofloxacin discs to determine Salmonella typhi and Salmonella paratyphi sensitivity is unreliable, and only if the organism is also sensitive on disc testing to nalidixic acid should the isolate be considered sensitive to fluoroquinolones.

The treatment of typhoid fever typically involves the use of antibiotics, with intravenous ceftriaxone being the preferred first-line agent in patients returned from Asia due to increasing reports of fluoroquinolone-resistant isolates 1. Azithromycin is a suitable oral alternative for uncomplicated disease, with resistance being currently rare in the UK. The addition of steroids may be helpful in severe cases, and treatment should be continued for 14 days to reduce the risk of relapse.

Some key points to consider in the pathogenesis and treatment of typhoid fever include:

• The importance of prompt diagnosis and treatment to prevent complications and reduce mortality
• The need for careful consideration of antibiotic resistance patterns when selecting treatment
• The potential for typhoid fever to present with non-specific symptoms, making diagnosis challenging
• The role of virulence factors, such as the Vi capsular antigen and type III secretion systems, in evading host immune responses
• The potential for complications, such as intestinal perforation, to arise from bacterial invasion of various organs.

From the Research

Pathogenesis of Typhoid Fever

The pathogenesis of typhoid fever is a complex process involving the interaction of the bacterium Salmonella Typhi with the human host. The following steps are involved in the pathogenesis of typhoid fever:

• Ingestion of contaminated food or water containing S. Typhi bacteria 2
• Colonization of the intestinal mucosa and invasion of the epithelial cells 3
• Survival and replication within the host cells, including macrophages and monocytes 4
• Dissemination of the bacteria to other parts of the body, including the bloodstream, liver, and spleen 2
• Evasion of the host immune response, including the innate immune response 3

Key Factors Involved in Pathogenesis

Several key factors are involved in the pathogenesis of typhoid fever, including:

• Virulence genes and proteins that enable the bacteria to invade and survive within host cells 2
• The ability of the bacteria to evade the host immune response, including the innate immune response 3
• The presence of antimicrobial resistance genes, which can make treatment more difficult 5, 6
• The host's immune status and ability to respond to the infection 4

Clinical Manifestations

The clinical manifestations of typhoid fever can vary, but typically include:

• Fever, which can be prolonged and severe 5, 6
• Headache, abdominal pain, and other non-specific symptoms 6
• Diarrhea or constipation, which can be bloody 3
• Rash, which can occur in some cases 4

Treatment and Outcomes

Treatment of typhoid fever typically involves the use of antibiotics, such as azithromycin or ciprofloxacin 5, 6. The outcomes of treatment can vary, depending on the severity of the infection and the presence of antimicrobial resistance 5, 6. In some cases, treatment may be complicated by the emergence of antimicrobial resistance, which can make treatment more difficult 5.