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Typhoid Fever

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Typhoid Fever, Enteric Fever, Salmonella typhi, Paratyphoid Fever, Salmonella partyphi, Rose Spot

  • History
  1. Typhoid Mary was a cook who infected 51 patients
    1. Brooks (1996) CMAJ 154:915-6 [PubMed]
  1. World: 13-17 million cases per year
    1. Most cases occur in Asia (13 Million)
    2. Worldwide annual deaths approach 600,000
  2. U.S.: 400 cases per year (70% in travelers)
    1. Decreased from nearly 36,000 cases in 1920
  • Pathophysiology
  1. Systemic Bacterial Infection (Enteric Fever)
    1. Salmonella typhi (Typhoid Fever)
      1. Most common and more severe form
    2. Salmonella paratyphi (Paratyphoid Fever)
      1. Much more mild than Typhoid Fever
    3. SalmonellaCholeraesuis
  2. Transmission
    1. Humans are only hosts of Salmonella typhi and Salmonella paratyphi
    2. Asymptomatic chronic carriers can shed Bacteria in the stool
    3. Ingestion of contaminated food or water (via feces or urine) is primary source
      1. Raw fruits and vegetables (grown in fields fertilized by sewage)
      2. Street vendor food and drink
      3. Flooding
      4. Poor hand washing practices
    4. Other sources
      1. May also be transmitted by patient contact
      2. Male sexual partners may also transmit to each other
  • Risk factors
  1. Travel to developing country (Southeast Asia, as well as Africa, West Asia, Central and South America)
    1. High risk regions: Mexico, India, Pakistan, Philippines, El Salvador and Haiti
  2. Highly dense living conditions (e.g. Refugee camp)
  • Symptoms
  1. Incubation (first 5-21 days after ingestion depending on inoculum load, may be up to 60 days)
    1. Usually asymptomatic in incubation period
    2. Diarrhea may occur during incubation period
  2. Active infection
    1. Malaise
    2. Fever (75% of cases)
      1. Intermittent Fever initially
      2. Sustained Fever to high Temperatures later
      3. See Pulse-Temperature Dissociation described below
    3. Associated symptoms
      1. Severe Headache
      2. Myalgia
      3. Anorexia
      4. Nausea or Vomiting
      5. Generalized Abdominal Pain
      6. Change in stool consistency (<50% of cases)
        1. Child: Diarrhea most common
        2. Adult: Constipation most common
  • Signs
  1. Pulse-Temperature Dissociation (Fager Sign, uncommon)
    1. Paradoxical and Relative Bradycardia with fever spikes
  2. Rose Spots (Pathognomonic, present in up to 30% of cases)
    1. Represent Bacterial emboli to the skin
    2. Groups of blanching, faint pink Macular and papular spots 2-3 mm over trunk
    3. Onset at end of first week or into second week of infection
  3. Other findings
    1. Hepatosplenomegaly
    2. Epistaxis
  4. Severe Infection
    1. Gastrointestinal Bleeding
    2. Bowel perforation and peritonitis
    3. Septic Shock
    4. Altered Level of Consciousness
  • Labs
  1. Complete Blood Count
    1. Leukopenia
    2. Thrombocytopenia
    3. Increased liver transaminases
    4. Increased acute phase reactants (CRP, ESR)
  2. Cultures
    1. Blood Culture
      1. Best Test Sensitivity in first week (up to 40-60% Test Sensitivity)
    2. Bone Marrow culture (rarely used in clinical practice)
      1. Higher sensitivity than Blood Culture
    3. Fecal culture
      1. Low Test Sensitivity (~33%)
      2. Better Test Sensitivity after the first week
  3. Salmonella serology (Widal's Test)
    1. Poor Test Specificity
    2. Low Test Sensitivity (70%)
  • Management
  • Antibiotics
  1. Antibiotic Resistance is increasing (esp. in Asia to Fluoroquinolones)
  2. Severe or complicated infection
    1. Ceftriaxone 2 g IV/IM every 24 hours for 7-14 days OR
  3. Infection acquired outside Asia
    1. Ciprofloxacin 400 mg IV (or 500 mg orally) every 12 hours for 7-10 days OR
    2. Levofloxacin 750 mg IV (or 750 mg orally) every 24 hours for 7-10 days
  4. Infection acquired in Asia
    1. Ceftriaxone 2 g IV/IM every 24 hours for 7-14 days OR
    2. Azithromycin 1 g orally day 1, then 500 mg orally daily for 5-7 days
      1. Consider using Azithromycin combined WITH Ceftriaxone in ill hospitalized patients
  5. Alternative antibiotics (resistance is common)
    1. Chloramphenicol 500 mg IV or oral every 6 hours for 14 days
  6. Additional measures
    1. Consider adding Dexamethasone in seriously ill patients
  • Complications (occurs in 10-15% of cases)
  1. Typhoid encephalopathy
  2. Peyer patch necrosis (sites of Salmonella infiltration at Small Intestine lymphoid Nodules)
    1. Gastrointestinal Bleeding (2-10% of cases)
    2. Bowel perforation
  3. Mycotic aneurysm (10% of patients over age 50 years old)
  4. Septic Arthritis or Osteomyelitis
  5. Pneumonia
  • Prognosis
  1. Mortality in untreated, prolonged cases is 12-60%
  • Prevention
  1. See Foodborne Illness Prevention
  2. See Water Disinfection
  3. Typhoid Vaccine
    1. Adjunctive, but not complete protection
    2. Even when taken properly, still <75% effective
  4. Steam or boil shellfish at least 10 minutes
  5. All milk and dairy products should be pasteurized
  6. Control fly populations
  • References
  1. Anderson (2014) Crit Dec Emerg Med 28(7):11-9
  2. Black, Martin, DeVos (2018) Crit Dec Emerg Med 32(8): 3-12
  3. Butler in Goldman (2000) Cecil Medicine, p. 1681-3
  4. Pearson in Mandell (2000) Infectious Disease, p. 1136
  5. Feder (2013) Am Fam Physician 88(8): 524-30 [PubMed]
  6. Maskalyk (2003) CMAJ 169:132 [PubMed]
  7. Wain (2015) Lancet 385(9973): 1136-45 [PubMed]