> Table of Contents > Typhus Fevers
Typhus Fevers
Douglas W. MacPherson, MD, MSc-CTM, FRCPC
image BASICS
Typhus is an infectious disease syndrome caused by several rickettsial bacterial organisms resulting in acute, chronic, and recurrent disease (1)[C].
  • Acute infection caused by three species of Rickettsia
    • Epidemic typhus: human-to-human transmission by body louse; primarily in setting of refugee camps, war, famine, and disaster. Recurrent disease occurs years after initial infection and can be a source of human outbreak. Flying squirrels are a reservoir.
    • Endemic (murine) typhus: spread to humans by rat flea bite
    • Scrub typhus: infection and infestation of chiggers and of rodents to humans by the chigger; primarily in Asia and western Pacific areas
  • System(s) affected: endocrine/metabolic; hematologic/lymphatic/immunologic; pulmonary; skin/exocrine
  • Synonym(s): louse-borne typhus; Brill-Zinsser disease; murine typhus
  • Epidemic and endemic typhus: rare in the United States (outside of South Texas)
  • Scrub typhus: travelers returning from endemic areas only (rare)
Endemic typhus: <100 cases annually, primarily in states around the Gulf of Mexico, especially South Texas; underreporting suspected
  • Epidemic typhus by Rickettsia prowazekii
  • Endemic typhus by Rickettsia typhi
  • Scrub typhus by Rickettsia tsutsugamushi
  • Vector exposure
  • Travel to endemic countries
Geriatric Considerations
Elderly may have more severe disease.
Vector control:
  • Scrub typhus: Wear protective clothing and use insect repellents.
  • Endemic typhus: Practice ectoparasite and rodent control.
  • Epidemic typhus: delousing and cleaning of clothing; vaccine for those at high risk of exposure (typhus vaccine production has been discontinued in the United States)
Typhus syndromes are rare in the United States. A high level of clinical suspicion is necessary.
  • General
    • Fever
    • Relative bradycardia (scrub typhus)
  • Epidemic typhus
    • Incubation period ˜ 1 week
    • Macular or maculopapular rash beginning on trunk ˜ 5th day of illness
    • Nonproductive cough
    • Pulmonary infiltrates
  • Endemic typhus
    • Incubation period 1 to 2 weeks
    • Macular or maculopapular rash beginning on trunk 3rd to 5th day of illness
  • Scrub typhus
    • Incubation period 1 to 3 weeks
    • Eschar at bite site
    • Regional lymphadenopathy
    • Generalized lymphadenopathy
    • Splenomegaly
    • Macular or maculopapular rash beginning on trunk approximately 5th day of illness
    • Relative bradycardia early in disease
    • Ocular pain
    • Conjunctival injection
  • Other rickettsial disease: Rocky Mountain spotted fever; ehrlichiosis; Mediterranean spotted fever (boutonneuse fever) (Rickettsia conorii)
  • Bacterial meningitis; meningococcemia
  • Measles, rubella
  • Toxoplasmosis
  • Leptospirosis
  • Typhoid fever
  • Dengue, malaria
  • Relapsing fever
  • Secondary syphilis
  • Viral syndromes: mononucleosis, acute retroviral syndrome
  • Specific serologies with rising antibody titer
  • If suspected, isolate Rickettsia in qualified laboratory to minimize the risk of laboratory-acquired infection.
  • CDC Rickettsial Zoonoses Branch 404-639-1075.
Initial Tests (lab, imaging)
  • CBC often normal
  • Weil-Felix serologic reaction may be positive; test value hampered by low sensitivity and nonspecificity; epidemic and endemic typhus, 4-fold titer rise or titer >1/320 to OX-19; scrub typhus, 4-fold rise in titer to OX-K
  • Hyponatremia in severe cases
  • Hypoalbuminemia in severe cases
  • Recent antibiotic exposure may alter lab results.
Test Interpretation
Diffuse vasculitis on skin biopsy
Initiate treatment based on epidemiologic risk and clinical presentation.
  • Skin and mouth care
  • Supportive care for the severely ill, directed at complications

First Line
  • Begin treatment when diagnosis is likely and continue until clinically improved and the patient is afebrile for at least 48 hours; usual course is 5 to 7 days.
  • Children ≥8 years of age and adults
    • Doxycycline IV/PO: adults 100 mg q12h, children ≤45 kg: 5 mg/kg/day divided twice daily (max of 200 mg/day); >45 kg: adult dosing
    • Children ≥8 years of age: Risk of dental staining from tetracyclines is minimal with short courses of therapy.
    • Tetracycline: 25 mg/kg PO initially, then 25 mg/kg/day in equally divided doses q6h
  • Children ≤8 years of age, pregnant women, or if typhoid fever is suspected
    • Chloramphenicol: 50 mg/kg PO initially, then 50 mg/kg/day in equally divided doses q6h
    • If severely ill, chloramphenicol sodium succinate: 20 mg/kg IV initially, infused over 30 to 45 minutes, then 50 mg/kg/day infused in equally divided doses q6h until orally tolerable
    • Azithromycin, fluoroquinolones, and rifampin may be alternatives depending on the clinical scenario.
  • Precautions: Refer to the manufacturer's profile for each drug.
  • Significant possible interactions: Refer to the manufacturer's profile for each drug.
Second Line
  • Doxycycline: single oral dose of 100 or 200 mg orally for those in refugee camps, victims of disasters, or in the presence of limited medical services
  • Isolated reports indicate that erythromycin and ciprofloxacin are effective.
  • Azithromycin 1,000 mg orally once a day for 3-day course is effective for scrub typhus; better tolerated than doxycycline but more expensive
  • Rifampin may be effective in areas where scrub typhus responds poorly to standard antirickettsial drugs.
Infectious disease consultation is recommended. Contact CDC and local public health authorities.
Admission Criteria/Initial Stabilization
  • Outpatient care unless severely ill
  • Severely ill or constitutionally unstable (e.g., shock)
Patient Monitoring
  • Admit severely ill patients.
  • If treated as an outpatient, ensure regular follow-up to assess clinical improvement and resolution.
As tolerated
Travel advice (minimize exposure risks, vector avoidance, vaccination as appropriate)
  • Recovery is expected with prompt treatment.
  • Relapses may follow treatment, especially if initiated within 48 hours of onset (this is not an indication to delay treatment). Treat relapses the same as primary disease.
  • Without treatment, the mortality rate of typhus is 40-60% for epidemic, 1-2% for endemic, and up to 30% for scrub disease.
  • Mortality is higher among the elderly.
1. Centers for Disease Control and Prevention. McQuiston J. Rickettsial (spotted and typhus fevers) and related infections (anaplasmosis and ehrlichiosis). http://wwwnc.cdc.gov/travel/yellowbook/2016/infectious-diseases-related-to-travel/rickettsial-spotted-typhusfevers-related-infections-anaplasmosis-ehrlichiosis. Accessed 2015.
Additional Reading
  • Botelho-Nevers E, Raoult D. Host, pathogen and treatment-related prognostic factors in rickettsioses. Eur J Clin Microbiol Infect Dis. 2011;30(10): 1139-1150.
  • Botelho-Nevers E, Rovery C, Richet H, et al. Analysis of risk factors for malignant Mediterranean spotted fever indicates that fluoroquinolone treatment has a deleterious effect. J Antimicrob Chemother. 2011;66(8):1821-1830.
  • Botelho-Nevers E, Socolovschi C, Raoult D, et al. Treatment of Rickettsia spp. infections: a review. Expert Rev Anti Infect Ther. 2012;10(12):1425-1437.
  • Chikeka I, Dumler JS. Neglected bacterial zoonoses. Clin Microbiol Infect. 2015;21(5):404-415.
  • Graham J, Stockley K, Goldman RD. Tick-borne illnesses: a CME update. Pediatr Emerg Care. 2011;27(2):141-147.
  • Green JS, Singh J, Cheung M, et al. A cluster of pediatric endemic typhus cases in Orange County, California. Pediatr Infect Dis J. 2011;30(2):163-165.
  • Hendershot EF, Sexton DJ. Scrub typhus and rickettsial diseases in international travelers: a review. Curr Infect Dis Rep. 2009;11(1):66-72.
  • Molina N. Borders, laborers, and racialized medicalization Mexican immigration and US public health practices in the 20th century. Am J Public Health. 2011;101(6):1024-1031.
  • Panpanich R, Garner P. Antibiotics for treating scrub typhus. Cochrane Database Syst Rev. 2002;(3):CD002150.
  • A75.9 Typhus fever, unspecified
  • A75.0 Epidemic louse-borne typhus fever d/t Rickettsia prowazekii
  • A75.2 Typhus fever due to Rickettsia typhi
Clinical Pearls
  • Consider typhus (along with malaria and dengue) in febrile travelers returning from endemic areas.
  • Rickettsial infections typically present within 2 to 14 days. Febrile illnesses presenting with onset >18 days after travel are unlikely to be rickettsial.
  • Routine blood cultures do not detect Rickettsia.
  • Prior vaccination does not exclude the diagnosis of typhus.