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Overview of Rickettsial and Related Infections


William A. Petri, Jr

, MD, PhD, University of Virginia School of Medicine

Reviewed/Revised Mar 2022 | Modified Sep 2022
Topic Resources

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 polymerase chain reaction (PCR). First-line treatment is with doxycycline, a tetracycline.

Rickettsia, Orientia, Ehrlichia, Anaplasma, and Coxiella species 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. For some organisms (eg, R. rickettsii and other spotted fever rickettsia, and R. akari, R. felis, and Orientia), the vector is also the reservoir and the geographic distribution of these rickettsia is determined by that of the infected arthropod. Specific vectors, reservoirs, and endemic regions differ widely (see table ).

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

  • R. rickettsii

  • R. prowazekii

  • R. typhi


Symptoms and Signs of Rickettsial Infections

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 white blood cells (Ehrlichia species in monocytes, Anaplasma species in granulocytes).

Regional lymphadenopathy is common with infection by Orientia species 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.

Diagnosis of Rickettsial and Related Infections

  • Clinical features

  • Biopsy of rash with fluorescent antibody staining to detect organisms

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

  • Polymerase chain reaction (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, Rubeola, and Rubella

Differentiating among rickettsial diseases

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


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 polymerase chain reaction (PCR) of a biopsy specimen of the rash. Culture is difficult and not clinically useful. For Ehrlichia species, PCR of blood is the best test. Serologic tests are not useful for acute diagnosis because they usually become positive only during convalescence.

Treatment of Rickettsial and Related Infections

  • 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 orally once followed by 100 mg twice a day in adults until the patient improves, has been afebrile for 24 to 48 hours, and has received treatment for at least 7 days. IV preparations are used in patients too ill to take oral drugs. Although some tetracyclines can cause tooth staining in children < 8 years of age, experts think that a course of doxycycline 2.2 mg/kg orally or IV twice a day is warranted. The Centers for Disease Control and Prevention (CDC) has found 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 (1 Treatment reference Rickettsial diseases (rickettsioses) and related diseases (anaplasmosis, ehrlichiosis, Q fever, scrub typhus) are caused by a group of gram-negative, obligately intracellular coccobacilli. All... read more Treatment reference ).

Chloramphenicol 500 mg orally or IV 4 times a day for 7 days is 2nd-line treatment when doxycycline cannot be used. Oral chloramphenicol is not available in the US, and IM administration is not effective. Chloramphenicol can cause adverse hematologic effects, which require monitoring of blood indices.

Both drugs are rickettsiostatic, not rickettsicidal.

Ciprofloxacin and other fluoroquinolones are effective in vitro against certain rickettsiae, but very little clinical experience supports the use of fluoroquinolones for RMSF.

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 blood pressure while avoiding worsening pulmonary and cerebral edema.

Treatment reference

  • 1. Todd SR, Dahlgren FS, Traeger MS, et al: No visible dental staining in children treated with doxycycline for suspected Rocky Mountain Spotted Fever. J Pediatr 166(5):1246-51, 2015. doi: 10.1016/j.jpeds.2015.02.015. Epub 2015 Mar 17. PMID: 25794784.

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 other 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 with doxycycline.

Drugs Mentioned In This Article

Drug Name Select Trade
Acticlate, Adoxa, Adoxa Pak, Avidoxy, Doryx, Doxal, Doxy 100, LYMEPAK, Mondoxyne NL, Monodox, Morgidox 1x, Morgidox 2x , Okebo, Oracea, Oraxyl, Periostat, TARGADOX, Vibramycin, Vibra-Tabs
Emtet-500, Panmycin, Sumycin
AK-Chlor, Chloromycetin, Chloroptic, Chloroptic S.O.P., Ocu-Chlor
Cetraxal , Ciloxan, Cipro, Cipro XR, OTIPRIO, Proquin XR
NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
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