Oral uptake of pathogen: A relatively large number of organisms (∼ 105) is needed to cause infection (high infective dose), unlike, e.g., in Shigella infection, where as few as ∼ 10 organisms suffice to infect the host.
Migration into the Peyer patches of the distal ileum: If the pathogen manages to reach the distal ileum, it migrates via M cells through the epithelium and into the Peyer patches.
Infection of macrophages → nonspecific symptoms
Spread from macrophages to the bloodstream → septicemia → systemic disease
Migration back to intestine → excretion in feces
Clinical features
Week 1
Body temperature rises gradually.
Relative bradycardia (not seen in children)
Physiologically, the heart rate increases in proportion to body temperature (for every degree Fahrenheit, the heart rate should increase ∼ 10 beats/min). In typhoid fever, this physiological response is typically reduced. Thus, the heart rate is only moderately increased despite a high fever, which is known as relative bradycardia.
The Salmonella typhi bacteria releases endotoxins that affect the autonomic nervous system, specifically dampening the sympathetic response that would normally increase heart rate with fever.
Constipation or diarrhea
Week 2
Persistent fever, but no chills; mostly unresponsive to antipyretics
The lack of chills is interesting and relates to how the fever develops:
In most infections, bacteria multiply in the bloodstream, causing sudden spikes in endotoxin levels that trigger rapid temperature increases (accompanied by chills)
In typhoid, because the bacteria live inside cells and release endotoxins gradually, there isn’t the sudden change in temperature that would cause chills
Rose-colored spots: a small, speckled, rose-colored exanthem that appears on the lower chest and abdomen (most commonly around the navel) in approx. 30% of affected individuals
Nonspecific abdominal pain and headache
Yellow-green diarrhea, comparable to pea soup (caused by purulent, bloody necrosis of the Peyer patches), or obstipation and bowel obstruction (as a result of swollen Peyer patches in the ileum)
Neurological symptoms (delirium, coma)
Week 3
Clinical features of week 2
Additional possible complications include:
Gastrointestinal ulceration with bleeding and perforation
The pathogen induces necrotic intestinal inflammation (especially in the Peyer patches), which may result in a severe disease course with intestinal rupture and fecal peritonitis.
Hepatosplenomegaly
In rare cases: sepsis, meningitis, myocarditis, and renal failure
