Epidemic typhus is caused by Rickettsia prowazekii; most transmission is between humans, but zoonotic transmission from animals to humans via body lice as a vector is possible. Symptoms are prolonged high fever, intractable headache, and a maculopapular rash. Diagnosis is with serologic tests, immunohistochemistry of biopsied skin material, or polymerase chain reaction testing. Treatment is with doxycycline.
Epidemic typhus is a rickettsial disease (1).
Humans are the natural reservoir for R. prowazekii, which is prevalent worldwide and transmitted by body lice (Pediculus humanus var. corporis) when louse feces are scratched or rubbed into bite or other wounds (or sometimes the mucous membranes of the eyes or mouth).
Epidemic typhus occurs primarily in the rural highlands (elevated terrain) of Africa and Central and South America and prevalence has dramatically re-emerged since the late 1990s (2). Sporadic cases have been reported in Eastern Europe, North Africa, and France. Cooler climates and living situations that make hygiene difficult create ideal conditions for spread of body lice. Populations at risk include those subject to mass displacement due to war or famine, those in refugee camps or prisons, and those who are experiencing homelessness (1, 3). Infections are particularly prevalent in the colder months of the year because of factors that favor compromised personal hygiene.
In the United States, infection is rare, but humans occasionally contract epidemic typhus via a sylvatic reservoir (ie, after contact with wild flying squirrels) because fleas or lice on flying squirrels may be vectors. A sylvatic reservoir is a wild animal host population in which a pathogen is naturally maintained in a forest or wilderness (sylvan) environment, independent of human or domestic animal populations.
Fatalities are rare in children < 10 years old, but mortality increases with age. Epidemic typhus mortality is approximately 4% with appropriate antibiotic treatment but is higher if antibiotic treatment is not available (2).
Brill-Zinsser disease refers to a unique, mild, recrudescent form of epidemic typhus that can reactivate years or even decades after a primary infection in people who are under chronic stress or are immunosuppressed (1). It most commonly occurs in people who did not receive treatment during the primary infection.
Epidemic typhus is not a nationally notifiable condition in the United States (4).
General references
1. CDC. Clinical Overview of Epidemic Typhus. May 15, 2024. Accessed January 5, 2026.
2. Bechah Y, Capo C, Mege JL, Raoult D. Epidemic typhus. Lancet Infect Dis. 2008;8(7):417-426. doi:10.1016/S1473-3099(08)70150-6
3. Newton PN, Fournier PE, Tappe D, Richards AL. Renewed Risk for Epidemic Typhus Related to War and Massive Population Displacement, Ukraine. Emerg Infect Dis. 2022;28(10):2125-2126. doi:10.3201/eid2810.220776
4. CDC. Information for Public Health Officials. December 11, 2025. Accessed January 5, 2026.
Symptoms and Signs of Epidemic Typhus
After an incubation period of 8 to 16 days, fever, headache, and prostration suddenly occur (1). Temperature reaches 40° C in several days and remains high, with slight morning remission, for approximately 2 weeks. Headache is generalized and intense.
Small, pink macules, which appear on the fourth to sixth days, rapidly cover the body, usually in the axillae and on the upper trunk but not on the palms, soles, or face. Later, the rash becomes dark and maculopapular. In severe cases, the rash becomes petechial and hemorrhagic. Eschar is absent.
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CDC
Splenomegaly sometimes occurs. Hypotension occurs in most seriously ill patients. Vascular collapse, renal insufficiency, encephalitic signs, ecchymosis with gangrene, and pneumonia are poor prognostic signs.
Symptoms and signs reference
1. CDC. Clinical Overview of Epidemic Typhus. May 15, 2024. Accessed January 5, 2026.
Diagnosis of Epidemic Typhus
History and physical examination
Serologic testing
Biopsy of rash with antibody staining (eg, immunohistochemistry) to detect organisms
Molecular diagnostic testing (polymerase chain reaction [PCR]) of a blood or tissue sample
The diagnosis of epidemic typhus relies primarily on clinical recognition (abrupt high fever, headache, myalgia) in the appropriate epidemiologic context. Louse infestation is usually obvious and strongly suggests typhus if history (eg, living in or visiting an endemic area, contact with flying squirrels in the United States) suggests possible exposure.
Serologic testing (eg, indirect immunofluorescence test of serum samples) is considered the reference standard for confirmation (1) and is most commonly used (2); however, this testing is rarely helpful from a management perspective because serial measurements are required and results are often negative in acute illness.
Immunohistochemistry (direct immunofluorescence staining) of biopsied skin or other materials from rashes can detect rickettsial antigens (2), especially in infected cutaneous endothelial cells and macrophages.
This image shows a smear specimen of Rickettsia prowazekii bacteria cultivated in a chicken embryo's yolk sac and stained with Macchiavello staining (which is used for intracellular organisms).
CDC
Confirmatory PCR testing of whole blood is less sensitive than other rickettsial diseases and not as easily available (2). PCR testing of tissue samples may also be performed.
The diagnosis of suspected Brill-Zinsser disease is confirmed by detecting a rapid, predominant IgG (with absent IgM) antibody rise against R. prowazekii via serology (2). This rise in IgG is due to recruitment of previously formed, antigen-specific immune memory responses.
For details, see Diagnosis of Rickettsial and Related Infections: Testing.
Diagnosis references
1. Miller JM, Binnicker MJ, Campbell S, et al. A Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2018 Update by the Infectious Diseases Society of America and the American Society for Microbiology. Clin Infect Dis. 2018;67(6):e1-e94. doi:10.1093/cid/ciy381
2. CDC. Clinical Overview of Epidemic Typhus. May 15, 2024. Accessed January 5, 2026.
3. Bechah Y, Capo C, Mege JL, Raoult D. Epidemic typhus. Lancet Infect Dis. 2008;8(7):417-426. doi:10.1016/S1473-3099(08)70150-6
Treatment of Epidemic Typhus
Doxycycline
For both suspected acute epidemic typhus and Brill-Zinsser disease, doxycycline is the recommended first-line antibiotic for all ages until the patient improves, has been afebrile for 24 to 48 hours, and has received treatment for at least 7 to 10 days (1, 2). For patients who cannot tolerate doxycycline, desensitization is recommended.
Chloramphenicol is second-line treatment. Oral chloramphenicol is not available in the United States, only IV formulations of chloramphenicol are available. Chloramphenicol can cause adverse hematologic effects, which require monitoring of blood indices, and, in neonates, gray baby syndrome.
Although some tetracyclines can cause tooth staining in children < 8 years of age, the United States Centers for Disease Control and Prevention (CDC) advises that a course of doxycycline is warranted (1). Research indicates that short courses of doxycycline (5 to 10 days, as used for rickettsial disease) can be used in children without causing tooth staining or weakening of tooth enamel (3).
Severely ill patients with epidemic typhus may have a marked increase in capillary permeability in later stages; thus, IV fluids should be given cautiously to maintain blood pressure while avoiding worsening pulmonary and cerebral edema.
Treatment references
1. CDC. Clinical Overview of Epidemic Typhus. May 15, 2024. Accessed January 5, 2026.
2. Bechah Y, Capo C, Mege JL, Raoult D. Epidemic typhus. Lancet Infect Dis. 2008;8(7):417-426. doi:10.1016/S1473-3099(08)70150-6
3. CDC. Research: Doxycycline and Tooth Staining. May 15, 2024. Accessed January 2, 2026.
Prevention of Epidemic Typhus
Louse control is highly effective for prevention. Lice may be eliminated by dusting infested people with malathion or lindane. Bedding and clothing should be washed at least once a week in hot water (> 65° C or 149° F) and dried on high heat. Non-washable clothing and items can be dry-cleaned or sealed in a plastic bag and stored for 2 weeks. Bedding and clothing also can be treated with the insecticide permethrin.
Historically, an effective vaccine was available for use, particularly in military settings; however, it is no longer available because of the rarity of the disease and because effective alternatives (ie, insecticides, antibiotics) are available (1).
See also table .
Prevention reference
1. Bechah Y, Capo C, Mege JL, Raoult D. Epidemic typhus. Lancet Infect Dis. 2008;8(7):417-426. doi:10.1016/S1473-3099(08)70150-6
Key Points
Epidemic typhus is prevalent worldwide; humans are the natural reservoir.
Infection is transmitted among humans by body lice when louse feces are scratched or rubbed into louse bites, wounds, or mucous membranes.
Small, pink macules rapidly cover the body and later become dark and maculopapular.
Mortality increases with age; vascular collapse, renal insufficiency, encephalitic signs, ecchymosis with gangrene, and pneumonia are poor prognostic signs.
Suspect epidemic typhus based on clinical manifestations and signs of louse infestation and recent residence in or travel to an endemic region; confirm with serologic testing, immunohistochemistry, or PCR.
Treatment is with doxycycline.
Brill-Zinsser disease, a mild recrudescence of epidemic typhus, can occur years or decades after the primary infection in people who are under chronic stress or are immunosuppressed.
Brill-Zinsser Disease
Brill-Zinsser disease is a recrudescence of epidemic typhus, occurring years or decades after a primary episode.
Patients with Brill-Zinsser disease developed a primary infection with epidemic typhus earlier in life or lived in an endemic area. When patients are under chronic stress or are immunosuppressed, dormant yet viable organisms retained in the body may be reactivated, causing recurrent typhus; thus, disease is sporadic, occurring at any season or in any geographic area, and in the absence of infected lice. Lice that feed on patients may acquire and transmit the organism.
Symptoms and signs of Brill-Zinsser disease are almost always mild and resemble those of epidemic typhus, with similar circulatory disturbances and hepatic, renal, and central nervous system changes. The remittent febrile course lasts about 7 to 10 days. The rash is often evanescent or absent. The mortality rate is much lower than in an initial episode of epidemic typhus (1).
Treatment is with doxycycline; regimens are similar to those in acute epidemic typhus.
See also Diagnosis of Epidemic Typhus and Treatment of Epidemic Typhus for additional details.
Reference
1. Bechah Y, Paddock CD, Capo C, Mege JL, Raoult D. Adipose tissue serves as a reservoir for recrudescent Rickettsia prowazekii infection in a mouse model. PLoS One. 2010;5(1):e8547. Published 2010 Jan 1. doi:10.1371/journal.pone.0008547
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