From the Guidelines
Typhoid fever is caused by the bacterium Salmonella enterica serotype Typhi, which invades the intestinal epithelium and survives within macrophages to cause a systemic illness. The pathogenesis of typhoid fever involves several key steps, including ingestion of contaminated food or water, survival in the acidic environment of the stomach, and invasion of the intestinal epithelium, particularly through specialized M cells in Peyer's patches 1.
Key Steps in Pathogenesis
- Ingestion of contaminated food or water
- Survival in the acidic environment of the stomach
- Invasion of the intestinal epithelium
- Entry into the bloodstream through the lymphatic system, causing primary bacteremia
- Survival within macrophages using virulence factors like the Vi capsular antigen to evade immune detection
- Multiplication in the reticuloendothelial system (liver, spleen, bone marrow) before reentering the bloodstream in a secondary bacteremia phase
- Onset of clinical symptoms, including the characteristic step-ladder fever pattern
- Eventual reach of the gallbladder, where the bacteria can establish persistent infection, leading to a chronic carrier state in some individuals
Clinical Implications
The complex pathogenesis of typhoid fever explains why it is a systemic illness rather than primarily an intestinal infection. Patients with enteric fever treated early in their clinical courses have better outcomes than patients treated later 1.
Treatment Considerations
Time to loss of fever was longer and case fatality ratio was higher among series of patients receiving supportive treatment only and patients receiving low doses of appropriate antimicrobial therapy compared with patients receiving recommended doses 1.
Important Considerations
It is essential to note that the treatment of typhoid fever should be guided by the most recent and highest quality evidence, taking into account the evolving resistance patterns of S. Typhi 1.
From the Research
Pathogenesis of Typhoid Fever
- The causative organism of typhoid fever, Salmonella enterica subsp. enterica serovar Typhi, is transmitted via the faecal-oral route, crossing the intestinal epithelium and disseminating to systemic and intracellular sites, causing an undifferentiated febrile illness 2.
- The pathogenesis of typhoid fever involves the adherence to and invasion of gut epithelial cells, dissemination to systemic sites, and survival and replication within host cells 3.
- Salmonella enterica serovar Typhi has a monophyletic population structure, indicating that typhoid in humans is a relatively new disease, and antimicrobial usage is reshaping the current S. Typhi global population 4.
Disease Mechanism
- The disease mechanism of typhoid fever is complex and involves the interaction of the bacteria with the host's immune system, leading to the production of inflammatory cytokines and the activation of immune cells 2.
- The bacteria can survive and replicate within host cells, including macrophages and epithelial cells, which allows them to evade the host's immune response and cause persistent infection 3.
Treatment and Resistance
- The emergence of multidrug resistance and decreased ciprofloxacin susceptibility in Salmonella enterica serovar Typhi has rendered older drugs ineffective or suboptimal for typhoid fever 5.
- Azithromycin has been shown to be effective in treating typhoid fever, but its use is associated with prolonged bacteraemia and fever clearance times compared to ciprofloxacin 6.
- The development of novel diagnostic modalities and effective vaccination programmes is crucial for the control and prevention of typhoid fever 2.