From the Guidelines
Typhoid fever primarily affects the gastrointestinal tract, particularly the small intestine, where the causative organism, Salmonella enterica serotype Typhi, invades the intestinal mucosa, specifically targeting the Peyer's patches in the ileum, leading to complications like intestinal perforation or hemorrhage 1.
Relevant Anatomy and Physiology
The small intestine, especially the ileum, is the primary site of infection, where S. Typhi invades the intestinal mucosa and targets the Peyer's patches, leading to inflammation and ulceration of intestinal lymphoid tissue.
- The bacteria then enter the bloodstream and lymphatic system, where they are taken up by macrophages in the liver, spleen, and bone marrow, causing bacteremia and multi-organ manifestations.
- The gallbladder is also a common site for S. Typhi to establish chronic carriage, which can lead to further complications.
- The immune response to typhoid fever involves both cell-mediated and humoral components, with macrophages playing a crucial role in containing the infection.
Clinical Presentation and Complications
The clinical presentation of typhoid fever typically includes systemic symptoms like fever, headache, and abdominal pain, with complications like intestinal perforation or hemorrhage occurring in 10-15% of patients, especially if the duration of illness is >2 weeks 1.
- Intestinal perforation is a serious complication of typhoid fever, with a mortality rate of up to 60% in some areas, and is often caused by the perforation of the ileum or jejunum 1.
- Other complications, such as gastrointestinal bleeding and typhoid encephalopathy, can also occur, especially if the disease is left untreated or if treatment is delayed.
Diagnosis and Treatment
Diagnosis of typhoid fever is typically made through blood cultures, which have the highest yield within a week of symptoms onset, although stool and urine cultures can also be positive after the first week 1.
- Treatment of typhoid fever typically involves antibiotics that penetrate intracellular spaces, such as fluoroquinolones, third-generation cephalosporins, or azithromycin, with intravenous ceftriaxone being the preferred first-line agent in patients returned from Asia due to increasing reports of fluoroquinolone-resistant isolates 1.
From the Research
Relevant Anatomy
- The intestinal epithelium is the primary site where Salmonella enterica subsp. enterica serovar Typhi crosses and enters the body 2
- Peyer's patches, located in the small intestine, play a crucial role in the pathogenesis of typhoid fever, as the bacteria proliferate in the mucosal macrophages 3
- The liver is also affected in typhoid fever, with hepatomegaly and elevated liver enzymes commonly observed 4
Relevant Physiology
- The immune system, particularly the gut-associated lymphoid tissue (GALT), plays a vital role in responding to Salmonella Typhi infection 5
- The follicle-associated epithelium and immune cells in Peyer's patches interact to induce immune tolerance or defense against pathogens 5
- The pathogenesis of typhoid fever involves the dissemination of bacteria to systemic and intracellular sites, causing an undifferentiated febrile illness 2
- The infection can lead to intestinal pathology, including ulceration and perforation of Peyer's patches, resulting in peritonitis and mortality 6