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Overview of Rickettsial and Related Infections

By William A. Petri, Jr, MD, PhD, Wade Hampton Frost Professor of Medicine and Chief, Division of Infectious Diseases and International Health, University of Virginia School of Medicine

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Rickettsial diseases (rickettsioses) and related diseases (anaplasmosis, ehrlichiosis, Q fever, scrub typhus) are caused by a group of gram-negative, obligately intracellular coccobacilli. All, except for Coxiella burnetii, have an arthropod vector. Symptoms usually include sudden-onset fever with severe headache, malaise, prostration, and, in most cases, a characteristic rash. Diagnosis is clinical, confirmed by immunofluorescence assay or PCR. Treatment is with tetracyclines or, except for anaplasmosis and ehrlichiosis, chloramphenicol.

Rickettsia, Orientia, Ehrlichia, Anaplasma, and Coxiella spp were once thought to belong to the same family but now, based on genetic analysis, are considered distinct entities. Although this group of organisms require living cells for growth, they are true bacteria because they have metabolic enzymes and cell walls, use oxygen, and are susceptible to antibiotics.

These organisms typically have an animal reservoir and an arthropod vector; exceptions are R. prowazekii,for which humans are the primary reservoir, and C. burnetii, which does not require an arthropod vector. Specific vectors, reservoirs, and endemic regions differ widely (see Table: Diseases Caused by Rickettsia, Orientia, Ehrlichia, Anaplasma, and Coxiella Spp).

There are many rickettsial species, but 3 cause most human rickettsial infections:

  • R. rickettsii

  • R. prowazekii

  • R. typhi

Diseases Caused by Rickettsia, Orientia, Ehrlichia, Anaplasma, and Coxiella Spp



Rash or Eschar


Endemic Region


Rickettsia prowazekii

Trunk to extremities

May be absent in Brill-Zinsser disease

No eschar

Body lice


R. typhi, R. felis

Trunk to extremities

No eschar

Rat flea, cat flea


Scrub typhus

Scrub typhus (tsutsugamushi disease)

Orientia tsutsugamushi (formerly R. tsutsugamushi)

Trunk to extremities

Eschar present

Trombiculid mite larvae (chiggers)

Asia-Pacific area bounded by Japan, Korea, China, India, and northern Australia

Spotted fever

R. rickettsii

Extremities to trunk

No eschar

Ixodid (hard) ticks, including Dermacentor andersoni (wood tick), principally in the western US, and D. variabilis (dog tick), principally in the eastern and southern US

Western Hemisphere, including most of the US (except Maine, Hawaii, and Alaska); Central and South America

R. sibirica

Trunk, extremities, face

Multiple eschars present

Ixodid ticks

Armenia, central Asia, Siberia, Mongolia, China

Queensland tick typhus

R. australis

Trunk, extremities, face

Eschar present

Ixodid ticks


African tick bite fever

R. africae

Multiple eschars on extremities at the sites of the tick bites

Ixodid ticks

Sub-Saharan Africa, West Indies

Mediterranean spotted fever (boutonneuse fever)*

R. conorii

Trunk, extremities, face

Eschar present

Rhipicephalus sanguineus(brown dog tick)

Africa; India; southern Europe; the Middle East adjacent to the Mediterranean, Black, and Caspian Seas

R. akari

Trunk, extremities, face

Eschar present


US, Russia, Korea, Africa

R. parkeri rickettsiosis

R. parkeri

Eschar present

Gulf Coast tick (Amblyomma maculatum)

Southern US, South America

Monocytic ehrlichiosis

Ehrlichia chaffeensis

Uncommon but more common among children

No eschar

Ticks (A. americanum, also known as the lone star tick)

Southeastern and south central US

Granulocytic anaplasmosis

Anaplasma phagocytophilum


No eschar

Ticks (Ixodes scapularisin the eastern and Midwest US, I. pacificus in the western US, possibly I. ricinus in Europe)

In the US, the Northeast, mid-Atlantic, upper Midwest, and West Coast; Europe

Q Fever

Coxiella burnetii

Rare but more common among children

No eschar

No vector needed


*Often known by the area in which it occurs (eg, Indian tick typhus, Marseilles fever).

Symptoms and Signs

Rickettsiae multiply at the site of arthropod attachment and often produce a local lesion (eschar). They penetrate the skin or mucous membranes; some (R. rickettsii) multiply in the endothelial cells of small blood vessels, causing vasculitis, and others replicate in WBCs (Ehrlichia sp in monocytes, Anaplasma sp in granulocytes).

Regional lymphadenopathy is common with infection by Orientia sp or members of the spotted fever group (except for R. rickettsii).

The endovasculitis of R. rickettsii causes a petechial rash (due to focal areas of hemorrhage), encephalitic signs, and gangrene of skin and tissues.

Patients seriously ill with a rickettsial disease of the typhus or spotted fever group may have ecchymotic skin necrosis, edema (due to increased vascular permeability), digital gangrene, circulatory collapse, shock, oliguria, anuria, azotemia, anemia, hyponatremia, hypochloremia, delirium, and coma.


  • Clinical features

  • Biopsy of rash with fluorescent antibody staining to detect organisms

  • Acute and convalescent serologic testing (serologic testing not useful acutely)

  • PCR

Differentiating rickettsial from other infections

Rickettsial and related diseases must be differentiated from other acute infections, primarily meningococcemia, rubeola, and rubella. A history of louse or flea contact, tick bite, or presence in a known endemic area is helpful, but such history is often absent. Clinicians should specifically ask about travel to an endemic region within the incubation period of the disease.

Clinical features may help distinguish diseases:

  • Meningococcemia: The rash may be pink, macular, maculopapular, or petechial in the subacute form and petechially confluent or ecchymotic in the fulminant form. The rash develops rapidly in acute meningococcal disease and, when ecchymotic, is usually tender when palpated.

  • Rubeola: The rash begins on the face, spreads to the trunk and arms, and soon becomes confluent.

  • Rubella: The rash usually remains discrete. Postauricular lymph node enlargement and lack of toxicity suggest rubella.

Differentiating among rickettsial diseases

Rickettsial diseases must also be differentiated from each other. Clinical features allow some differentiation, but overlap is considerable:

  • Rocky Mountain spotted fever (RMSF): The rash usually appears on about the 4th febrile day as blanching macules on the extremities and gradually becomes petechial as it spreads to the trunk, palms, and soles over several days. Some patients with RMSF never develop a rash. Vasculitis often develops; it may affect the skin, subcutaneous tissues, CNS, lungs, heart, kidneys, liver, or spleen.

  • Epidemic typhus: The rash usually appears initially in the axillary folds and on the trunk. Later, it spreads peripherally, rarely involving the palms, soles, and face. Severe physiologic and pathologic abnormalities similar to those of RMSF occur.

  • Murine typhus: The rash is nonpurpuric, nonconfluent, and less extensive, and renal and vascular complications are uncommon.

  • Scrub typhus: Manifestations are similar to those of RMSF and epidemic typhus. However, scrub typhus occurs in different geographic areas, and frequently, an eschar develops with satellite adenopathy.

  • Rickettsialpox: This disease is mild, and the rash, in the form of vesicles with surrounding erythema, is sparse and may resemble varicella.

  • African tick bite fever (due to R. africae): Symptoms are similar to those of other rickettsial diseases. The rash is characterized by multiple black eschars on the distal extremities with regional adenopathy.


Knowledge of residence and recent travel often helps in diagnosis because many rickettsiae are localized to certain geographic areas. However, testing is usually required.

The most useful tests for R. rickettsii are indirect immunofluorescence assay (IFA) and PCR of a biopsy specimen of the rash. Culture is difficult and not clinically useful. For Ehrlichia sp, PCR of blood is the best test. Serologic tests are not useful for acute diagnosis because they usually become positive only during convalescence.


  • Tetracyclines

Because diagnostic tests can take time and may be insensitive, antibiotics are usually begun presumptively to prevent significant deterioration, death, and prolonged recovery.

Tetracyclines are first-line treatment: doxycycline 200 mg po once followed by 100 mg bid until the patient improves, has been afebrile for 24 to 48 h, and has received treatment for at least 7 days. IV preparations are used in patients too ill to take oral drugs. Although tetracyclines can cause tooth staining in children, experts think that a course of doxycycline is warranted.

Chloramphenicol 500 mg po or IV qid for 7 days is 2nd-line treatment.

Both drugs are rickettsiostatic, not rickettsicidal.

Ciprofloxacin and other fluoroquinolones are effective against certain rickettsiae, but extensive clinical experience is lacking.

Because severely ill patients with RMSF or epidemic typhus may have a marked increase in capillary permeability in later stages, IV fluids should be given cautiously to maintain BP while avoiding worsening pulmonary and cerebral edema.

Heparin is not recommended in patients who develop disseminated intravascular coagulation.

Key Points

  • Rickettsial diseases and related diseases (anaplasmosis, ehrlichiosis, Q fever, scrub typhus) are caused by a group of gram-negative, obligately intracellular coccobacilli; all, except for Coxiella burnetii, have an arthropod vector.

  • Rickettsial diseases cause fever and, depending on the disease, sometimes a local lesion (eschar), petechial rash, regional lymphadenopathy, encephalitic signs, vasculitis, gangrene of skin and tissues, organ dysfunction, and vascular collapse.

  • Distinguish rickettsial and related diseases from other acute infections and from each others based on history, clinical features, and results of tests (eg, biopsy with indirect immunofluorescence assay, serologic tests, PCR).

  • Treat with antibiotics presumptively, without waiting for diagnostic test results, to prevent significant deterioration, death, and prolonged recovery.

  • First-line treatment is tetracyclines.

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