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Typhoid Fever

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

  • See Also
  1. Salmonellosis
  2. Foodborne Illness
  3. Waterborne Illness
  4. Fever in the Returning Traveler
  • 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. Salmonella Characteristics (same as non-typhoid Salmonella)
    1. Facultative Anaerobic Gram Negative Rod in Enterobacteriaceae family
      1. Grouped with SS Gram Negative Bacteria (Salmonella, Shigella)
    2. Salmonella is distinguished from other Enterobacteriaceae
      1. Motile with flagella (unlike Shigella)
      2. Does not ferment lactose (unlike E. coli)
      3. Produces Hydrogen Sulfide or H2S (unlike Shigella)
  2. Salmonellosis Pathogenesis
    1. Vi Antigen (Virulence Antigen)
      1. Also present in Non-Typhoid Salmonella
      2. Surrounds the SalmonellaBacterial cell surface
      3. Protects surface Antigen O from immune response (Opsonization, Phagocytosis)
    2. Salmonella invades intestinal epithelial cells
      1. Cellular invasion is similar to non-typhoid Salmonella
      2. However, typhoid Salmonella results in systemic infection
        1. Invades regional Lymph Nodes and then spreads to other organ systems
        2. Salmonella typhi can also survive within Phagocytes (Macrophages)
  3. 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
  4. 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. Contaminated water or ice ingestion
      4. Flooding
      5. Poor Hand Washing practices
    4. Other sources
      1. May also be transmitted by patient contact in healthcare workers
      2. Male sexual partners may also transmit to each other
  • Risk factors
  1. Highly dense living conditions (e.g. Refugee camp)
  2. Travel to developing country
    1. Highest risk in Southeast Asia
    2. Also high risk in Africa, West Asia, Central and South America
    3. High risk countries: Mexico, India, Pakistan, Philippines, El Salvador and Haiti
  • 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 or right lower quadrant (may mimic Appendicitis)
      6. Change in stool consistency (<50% of cases)
        1. Child: Diarrhea most common
        2. Adult: Constipation most common
  • Signs
  1. Pulse-Temperature Dissociation (Faget Sign, uncommon)
    1. Paradoxical and Relative Bradycardia with fever spikes
  2. Rose Spots (Pathognomonic, present in up to 30% of cases)
    1. Groups of blanching, faint pink Macular and papular spots 2-3 mm over trunk
    2. Onset at end of first week or into second week of infection
    3. Represent Bacterial emboli to the skin
  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%)
  • Differential Diagnosis
  1. See Fever in the Returning Traveler
  2. See Traveler's Diarrhea
  3. Malaria
  4. Mononucleosis
  5. Brucellosis
  6. Tularemia
  7. Influenza
  8. Psittacosis
  9. Dengue Fever
  10. Viral Hemorrhagic Fever
  11. Ricketssia
  12. Leptospirosis
  13. Amoebic Liver Abscess
  14. Amoebic Dysentery
  15. Acute Hepatitis (including Viral Hepatitis)
  16. Acute HIV Infection
  17. Cholera
  18. Giardia
  19. Cryptosporidium
  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 and peritonitis
  3. Mycotic aneurysm (10% of patients over age 50 years old)
  4. Septic Arthritis or Osteomyelitis
  5. Pneumonia
  6. Chronic Carrier state
    1. Affects 2-5% of Typhoid Fever survivors after acute infection
    2. Salmonella typhi may continue to survive chronically in the gallbladder
    3. May continue to spread Salmonella to others
    4. Gunn (2014) Trends Microbiol 22(11):648-55 +PMID: 25065707 [PubMed]
  • 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, and non-compliance with the oral Vaccine is common)
    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. Nordurft-Froman and DeVos (2022) Crit Dec Emerg Med 36(4): 4-15
  5. Pearson in Mandell (2000) Infectious Disease, p. 1136
  6. Feder (2013) Am Fam Physician 88(8): 524-30 [PubMed]
  7. Maskalyk (2003) CMAJ 169:132 [PubMed]
  8. Wain (2015) Lancet 385(9973): 1136-45 [PubMed]