Typhus

Aka: Typhus, Epidemic Typhus, Louse-Borne Typhus, Murine Typhus, Endemic Typhus, Flea-Borne Typhus, Scrub Typhus, Brill-Zinsser Disease, Rickettsia prowazekii, Rickettsia typhi, Orientia tsutsugamushi

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II. Epidemiology

  1. Epidemic Typhus
    1. Rare outbreaks that kill hundreds of thousands or more
  2. Endemic Typhus
    1. Uncommon in U.S. (300 cases/year, primarily in California, Hawaii, Texas)
    2. Likely under-reported due to relatively mild presentations (outside of Immunocompromised patients)
  3. Scrub Typhus
    1. One million cases per year worldwide (in endemic regions, esp. Asia)
    2. Considered a major health concern

III. Pathophysiology

  1. Vector-borne illnesses caused by Rickettsial or Oriential infection
  2. Typhus is divided into 3 distinct diseases (epidemic, endemic, Scrub Typhus)
    1. Differ in transmission and mortality
    2. Similar in presentations and treatment
  3. Rickettsiaceae family of Bacteria
    1. Tiny Gram Negative Cocci
    2. Obligate intracellular Parasites

IV. Types

  1. Epidemic Typhus, Louse-Borne Typhus, or Sylvatic Typhus (Rickettsia prowazekii)
    1. Louse-borne transmission of Rickettsia prowazekii
    2. Typically occurs during war or over-crowded conditions, transmitted by Body Lice
    3. May recur years after initial infection (Brill-Zinsser Disease)
      1. Occurs in Immunocompromised patients
      2. Similar to the Shingles reactivation of Chicken Pox
      3. Rash is typically absent on reactivation
    4. Rare in developed countries
      1. Outbreaks still occur in areas of poor sanitation or overcrowding
      2. Isolated cases in U.S. are associated with Flying Squirrel exposure
      3. Historically, large outbreaks of Epidemic Typhus have occurred with high mortality
        1. Last major outbreak occurred in 1997, Burundi (Russia)
        2. Caused 3 million deaths in Russian soldiers during World War 1
        3. Caused up to 300,000 deaths in Napolean's advance on Russia in 1813
        4. English outbreak in 1557 killed 10% of the population
  2. Endemic Typhus or Murine Typhus (Rickettsia typhi)
    1. Found in tropical and subtropical climates, as well as in U.S. (California, Hawaii, Texas)
    2. Flea-borne transmission of Rickettsia typhi from rats (or mice, cats)
    3. Vectors include rat flea (Xenopsylla) and squirrel flea (Orchospea)
  3. Scrub Typhus (Orientia tsutsugamushi)
    1. Endemic to Southeast Asia, Indonesia, China, Japan, India, northern Australia
    2. Common cause of undifferentiated acute febrile illness in endemic regions
    3. Mite-borne transmission of Orienta tsutsugamushi (esp. during wet season)
    4. Vector
      1. Mites (Leptotrombidium) live on rodents
      2. Larval mite Chiggers living in soil are the primary vector

V. Findings

  1. Typhus or Epidemic Typhus
    1. Incubation Period: 2 weeks
    2. Findings
      1. Presents with abrupt onset of high fever (104 F) and intractable Headache
      2. Nonproductive cough may also be present
      3. Rash is a late sign, seen in two-thirds of patients
        1. Small pink Macules starting on trunk and then spreading to extremities
        2. Spares the face, palms and soles (contrast with Rocky Mountain Spotted Fever)
    3. Serious complications follow
      1. Myocarditis, Pneumonia, Pancreatitis, Encephalitis, Acute Renal Failure, Sepsis
      2. Untreated mortality 10-60%
        1. While early treatment within first week drops mortality to 0%
  2. Murine Typhus or Endemic Typhus
    1. Flea exposure is often unrecognized
    2. Findings
      1. Presents with viral syndrome 3 to 14 days after flea exposure
        1. Fever
        2. Headache
        3. Myalgias and Arthralgias
        4. Nausea and Vomiting
      2. Maculopapular Rash in half of patients, onset 6 days after initial symptoms
      3. Neurologic symptoms (confusion, imbalance, Seizures) may occur in up to 45% of patients (Vasculitis related)
      4. Thrombocytopenia in 48% of patients
    3. Prognosis
      1. Less severe than Epidemic Typhus (but may be fatal in elderly, Immunocompromised)
  3. Scrub Typhus
    1. Presents with flu-like illness 7-10 days (up to 21 days) after Chigger Bite
      1. High fever
      2. Headache
      3. Malaise
      4. Myalgias
    2. Skin
      1. Black eschar variably develops at the bite site
      2. Macular rash in 50% of patients (may be associated with eschar)
      3. Regional Lymphadenopathy may be present
    3. Neurologic findings
      1. Encephalitis, encephalomyelitis or Meningitis
      2. Tinnitus and Hearing Loss (or Deafness) may occur
      3. Cranial Nerve palsy
    4. Vascular Findings
      1. Disseminated Vasculitis
      2. Disseminated Intravascular Coagulation (DIC)
      3. Thrombotic complications
    5. Labs
      1. Thrombocytopenia in most patients
    6. Prognosis
      1. Untreated mortality may be as high as 4 to 40%
      2. Low mortality with prompt treatment

VI. Differential Diagnosis

  1. Brucellosis
  2. Dengue
  3. Infectious Mononucleosis
  4. Leptospirosis
  5. Malaria
  6. Measles
  7. Rocky Mountain Spotted Fever (or other Rickettsial Diseases)
  8. Rubella
  9. Typhoid Fever

VII. Management

  1. Typhus or Epidemic Typhus
    1. High mortality without prompt treatment in the first 8 days of illness
    2. Eliminate vector (e.g. kill lice)
    3. Doxycycline 100 mg twice daily for 5 days (or 200 mg once) OR
    4. Chloramphenicol 500 mg oral or IV four times daily for 5 days
  2. Murine Typhus or Endemic Typhus
    1. Spontaneously resolves without treatment in 14 days in healthy patients
      1. However, deaths may occur in elderly and Immunocompromised patients
    2. Antibiotic response is prompt
      1. Doxycycline 100 mg twice daily for 7 days OR
      2. Chloramphenicol 500 mg oral or IV four times daily for 7 days
  3. Scrub Typhus
    1. High mortality without prompt treatment
    2. Doxycycline 100 mg twice daily for 7 days (if resistance suspected, add Rifampin) OR
    3. Chloramphenicol 500 mg oral or IV four times daily for 7 days OR
    4. Azithromycin 500 mg oral or IV for 1 dose (if resistance suspected, extend for 3 days)

VIII. Prevention

  1. See Prevention of Vector-borne Infection

IX. Resources

  1. CDC Yellow Book
    1. http://wwwnc.cdc.gov/travel/yellowbook/2016/infectious-diseases-related-to-travel/rickettsial-spotted-typhus-fevers-related-infections-anaplasmosis-ehrlichiosis

X. References

  1. Sexton in Calderwood (2016) Epidemic Typhus, UpToDate, IOS app accessed 4/14/2016
  2. (2016) Sanford Guide to Antibiotics, IOS app accessed 4/14/2016
  3. Blanton (2019) Infect Dis Clin North Am 33(1):213-29 +PMID: 30712763 [PubMed]
  4. Huntington (2016) Am Fam Physician 94(7): 551-7 [PubMed]

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