Epidemiology

Etiology

• Pathogen
  • Salmonella enterica serotype Typhi: typhoid fever
    • Gram-negative rod
    • Facultative anaerobe with peritrichous flagella
    • Produces hydrogen sulfide (H2S) on TSI agar
    • Oxidase-negative
    • Cannot ferment lactose
  • Salmonella enterica serotype Paratyphi: paratyphoid fever
• Reservoir
  • Salmonella enterica serotype Typhi: humans
  • Other Salmonella species: humans and animals
• Transmission: fecal-oral

Pathophysiology

Lifecycle

1. 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.
2. 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.
3. Infection of macrophages → nonspecific symptoms
4. Spread from macrophages to the bloodstream → septicemia → systemic disease
5. 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 faint, salmon-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

Diagnostics

Treatment