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Rickettsial diseases (rickettsioses) and related diseases (ehrlichiosis, Q fever) are caused by a group of gram-negative, obligately intracellular coccobacilli. Most 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 chloramphenicol.

Although rickettsiae require living cells for growth, they are true bacteria because they have metabolic enzymes and cell walls, use O₂, and are susceptible to antibiotics. Rickettsiae (except Coxiella burnetii, the causative agent of Q fever, which is no longer classified with the Rickettsiae) have an animal reservoir and usually an arthropod vector that infects humans (see Table 1: Rickettsiae and Related Organisms: Diseases Caused by Rickettsia, Ehrlichia, and Coxiella Sp ).

Table 1
Diseases Caused by Rickettsia, Ehrlichia, and Coxiella Sp  Disease Organism Rash or Eschar Vector Endemic Region Typhus Epidemic typhus Brill-Zinsser disease Rickettsia prowazekii Trunk to extremities May be absent in Brill-Zinsser disease No eschar Body lice Worldwide Murine (endemic) typhus R. typhi (formerly R. mooseri) Trunk to extremities No eschar Rat flea, cat flea Worldwide Scrub typhus Scrub typhus (tsutsugamushi disease) R. tsutsugamushi Trunk to extremities Eschar present Trombiculid mite larvae (chiggers) Asiatic-Pacific area bounded by Japan, India, and Australia Spotted fever Rocky Mountain spotted fever R. rickettsii Extremities to trunk No eschar Ixodid ticks, including Dermacentor andersoni (wood tick) principally in western US and D. variabilis (dog tick) principally in eastern and southern US) Western Hemisphere, including most of the US (except Maine, Hawaii, and Alaska); Central and South America North Asian tick-borne rickettsiosis R. sibirica Trunk, extremities, face Eschar present Ixodid ticks Armenia, central Asia, Siberia, Mongolia Queensland tick typhus R. australis Trunk, extremities, face Eschar present Ixodid ticks Australia African tick bite fever R. africae Eschar on extremities (tache noir) at the site of the tick bite Ixodid ticks South Africa, Zimbabwe Mediterranean spotted fever (boutonneuse fever)* R. conorii Trunk, extremities, face Eschar present Rhipicephalus sanguineus (brown dog tick) Africa; India; Europe; the Middle East adjacent to the Mediterranean, Black, and Caspian Seas Rickettsialpox R. akari Vascular Trunk, extremities, face Eschar present Mites US, Russia, Korea, Africa Ehrlichioses Monocytic ehrlichiosis Ehrlichia chaffeensis None No eschar Ticks Southeastern and south central US Granulocytic ehrlichiosis Anaplasma phagocytophila, E. ewingii None No eschar Ticks   Q Fever Q fever Coxiella burnetii None No eschar No vector needed Worldwide *Often known by the area in which it occurs (eg, Indian tick typhus, Marseilles fever).

Rickettsiae multiply at the site of arthropod attachment and often produce a local lesion (eschar). They penetrate the skin or mucous membranes; some (Rickettsia rickettsii) multiply in the endothelial cells of small blood vessels, causing vasculitis, and others (Ehrlichia sp) replicate in WBCs. The endovasculitis of R. rickettsii produces a rash, encephalitic signs, and gangrene of skin and tissues. Patients seriously ill with a rickettsial disease of the typhus or spotted fever group or with ehrlichiosis may have ecchymotic skin necrosis, digital gangrene, circulatory collapse, shock, oliguria, anuria, azotemia, anemia, hyponatremia, hypochloremia, edema, delirium, and coma.

Diagnosis

• Clinical features
• Biopsy of rash
• Serology not useful acutely
• PCR for Ehrlichia sp

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. 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.

Meningococcemia

Rubeola (Confluent Diffuse Macular Rash)

Rubella

Differentiating among rickettsial diseases: Rickettsial and related 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.
• Epidemic typhus: The rash of 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.

Rocky Mountain Spotted Fever

Scrub Typhus

Testing: 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.

Treatment

• 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 Some Trade Names
PERIOSTAT
VIBRAMYCIN
Click for Drug Monograph
200 mg po once followed by 100 mg bid until the patient improves and has been afebrile for 24 to 48 h but continued 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 Some Trade Names
PERIOSTAT
VIBRAMYCIN
Click for Drug Monograph
is warranted. Chloramphenicol Some Trade Names
CHLOROMYCETIN
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500 mg po or IV qid for 7 days is 2nd-line treatment. Both drugs are rickettsiostatic, not rickettsicidal. Ciprofloxacin Some Trade Names
CILOXAN
CIPRO
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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 Some Trade Names
HEPFLUSH-10
Click for Drug Monograph
is not recommended in patients who develop disseminated intravascular coagulation.

Last full review/revision November 2007 by William A. Petri, Jr., MD, PhD

Content last modified November 2007