Typhoid fever

Typhoid fever or just typhoid is an infectious disease caused by the Salmonella enterica serovar Typhi bacterium, usually spread by the orofecal route. The condition is characterized by severe fever, acute systemic symptoms, with occasionally serious enterocolic complications.

Terminology

Do not confuse typhoid with typhus which is a different disease, caused by an entirely different organism. Typhoid fever and paratyphoid fever are both enteric fevers. Paratyphoid fever is caused by a related serotype of Salmonella enterica, and is very similar to typhoid fever clinically, but usually less severe.

Epidemiology

Most hospital presentations with typhoid fever are in those aged 5 to 25 years. Evidence from the primary care setting, however, shows that many patients, especially infants under 5 years old, may not be medically-recognized as typhoid due to the non-specific nature of their presentation. From 60-90% of typhoid sufferers are either managed wholly as outpatients, or do not engage with medical services at all.

It is usually contracted by consuming contaminated food or water and therefore the provision of safe food sources and clean water in the developed world means that typhoid is now unusual. On the other hand, the absence of safe food and water in the developing world means that typhoid prevalence remains high.

Clinical presentation

• incubation period lasts 7 to 14 days after the Salmonella enterica serotype Typhi bacterium is ingested
  • as little as 3 days and as much as 60 days has been seen
• prodrome of fever and malaise: indicates the start of bacteremia 
  • typically quotidian, i.e. daily
  • starts as low-grade but by week 2 tends to be high (39-40°C)
• within a week of the onset of symptoms:
  • flu-like illness
    • chills (rigors rare)
    • frontal headache
    • malaise
    • loss of appetite
    • generalized abdominal ache
      • may mimic right iliac fossa pain of appendicitis
    • dry cough
    • myalgia
• confusion
• relative bradycardia is classic, but is not often seen
• constipation 
  • diarrhea more common in infants and adults with HIV
• absence of bowel symptoms in sick patients is atypical
• hepatosplenomegaly
• rose spot rash is classic, but <30% of patients
  • occasional 2-4 mm red maculopapular blanching spots
  • chest and abdomen predominantly

Laboratory tests

• hemoglobin, leukocyte and platelet counts are usually normal or low
• disseminated intravascular coagulation (DIC) may be present
  • usually not clinically significant
• abnormal liver function tests: up to 3x normal range

Complications

Complications are seen in up to 15% affected patients. Acute GI bleeding is the most common serious sequela, in as many as 10% cases; its pathogenesis is necrotic adenopathy in a Peyer patch eroding through a small bowel blood vessel ¹. Generally fortunately it is mild, but in 2% it is massive, and potentially fatal without rapid resuscitation.

Perforation of the bowel, usually ileal, is the gravest sequela and may be seen in up to 3% hospital inpatients with typhoid. 

• gastrointestinal
  • bowel perforation
  • bowel hemorrhage
  • hepatitis
  • cholecystitis
• cardiac
  • myocarditis
  • cardiogenic shock
• central nervous system
  • encephalopathy
  • acute confusional state
  • psychosis
  • leptomeningitis
  • ataxia
• respiratory
  • acute bronchitis
  • pneumonia
• miscellaneous
  • abscess, e.g. intestinal
  • pharyngitis
  • anemia
  • miscarriage

Pathology

Typhoid fever is caused by Salmonella enterica serotype Typhi and most patients are infected by the consumption of contaminated food or water. Unlike all the other Salmonella species, serovar Typhi is not a zoonosis, and humans are their only host. Once it has invaded the GI epithelium it spreads to the regional nodes, where it multiplies before dispersing throughout the reticuloendothelial system. 

Radiographic features

CT

Gastrointestinal and hepatobiliary manifestations are the commonest findings on imaging of typhoid fever.

• enteritis: usually ileitis
  • concentric diffuse/focal ileal mural thickening
• colitis
  • much less common than enteritis
  • toxic megacolon rarely
• mesenteric adenopathy common
• GI bleeding
• GI perforation
• ascites
• acute acalculous cholecystitis
  • usually subclinical ¹
  • empyema rare
• ascending cholangitis
• splenomegaly +/- splenic abscess
  • splenic rupture post-trauma in context of typhoid fever is seen ³

Cardiac, pulmonary, genitourinary and central nervous system imaging abnormalities may also be seen ³.

Treatment and prognosis

• fluoroquinolone antibiotics are the mainstay of successful treatment, e.g. ciprofloxacin
  • if resistance is a problem, third-generation cephalosporins, e.g. ceftriaxone, may be tried
• supportive measures

Complications

Chronic asymptomatic carriage of typhoid is a well-recognized sequela, 10% excreting the bacteria in their feces for three months and as many as 4% do so for over a year.

Prognosis

With effective treatment, the mortality rate is <1%.