Rickettsiae are a diverse collection of obligate intracellular, gram-negative bacteria that have a tropism for vascular endothelial cells. The vectors for transmission vary by species but include ticks, fleas, mites, and lice. The most clinically relevant pathogens are R. rickettsii, which causes Rocky Mountain spotted fever; R. prowazekii, which causes epidemic (louse-borne) typhus; R. typhi, which causes endemic typhus; and R. akari, which causes rickettsialpox. All of these diseases are a form of inflammatory vasculitis and commonly present with fever, headache, and rash. Treatment is with doxycycline.

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General Characteristics

General characteristics

  • Obligate intracellular organisms
  • Pleomorphic (cocci, bacilli, threads)
  • Weakly gram negative (poor Gram staining)
  • Can be visualized with special stains such as Giemsa and by direct fluorescent antibody staining techniques
  • Lack enzymes for amino acid, sugar, lipid, and nucleotide metabolism
  • Depend on the host cells for nutritional needs
  • Have the ability to acquire host ATP (adenosine triphosphate)
  • Have a tropism for vascular endothelial cells:
    • Cause direct vascular injury
    • Also produce prostaglandins and activate clotting factors, which can lead to systemic clinical manifestations
  • Clinically relevant species:
    • Spotted fever group:
      • R. rickettsii (Western hemisphere)
      • R. akari (United States, Russia, Korea, South Africa)
      • Multiple other species (primarily in Asia and Africa)
    • Typhus group:
      • R. prowazekii
      • R. typhi

Transmission and geography

  • Transmitted by arthropod vectors
  • A summary of the major clinically relevant species is outlined in the table below.
Table: Summary of major clinically relevant species
R. rickettsiiR. prowazekiiR. typhiR. akari
VectorHard ticks (Ixodidae family): Dermacentor (dog tick), Amblyoma (wood tick)Human lice (Pediculus humanus corporis):
  • Defecate on skin
  • Host scratches area.
  • Bacteria enter the skin.
Eastern flying squirrels along with their lice and fleas maintain a zoonotic cycle.
Rat and cat flea bitesMites from mice
DiseaseRocky Mountain spotted fever (the most serious rickettsial disease)Epidemic (louse-borne) typhusEndemic typhusRickettsialpox (the least serious rickettsial disease)
Geographic variations
  • North America (in the United States, especially south-central, south-eastern states)
  • South and Central America
  • Rare nowadays
  • In some areas of Africa, Asia, and South America, especially where there are ongoing wars/disasters/refugee camps, etc.
  • Worldwide
  • Southeastern states/Gulf of Mexico
  • United States (often, New York City)
  • Russia
  • Korea
  • South Africa

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Clinical Relevance (R. rickettsii)

Rocky Mountain spotted fever


  • More common in rural and suburban settings
  • Risk factors include living near the woods, walking in high grass, or through exposure to dogs
  • Seasonal variation: highest incidence in spring and early summer
  • Highest incidence in people 40–64 years of age
  • Higher incidence in Native Americans
  • Increased severity/lethality:
    • Male gender
    • Increasing age
    • Glucose-6-phosphate dehydrogenase deficiency
    • Chronic alcohol abuse
    • African American origin


  • Virulence:
    • Factors are not well understood.
    • Dose of inoculum plays a role.
  • Inoculation from a feeding tick
  • Lipopolysaccharides, rickettsial outer membrane proteins (rOmps), and surface-exposed proteins (SEPs) act as adhesins for endothelial cells.
  • Bacteria get inside the cells via endocytosis.
  • Once in the cytosol, express proteins that lead to polymerization of actin filaments
  • This process allows passage into neighboring cells via filopodia derived from the host membrane.
  • Subsequent spread via bloodstream and lymphatics
  • Endothelial cell damage/necrosis
  • Accumulation of macrophages/lymphocytes → lymphocytic vasculitis

Clinical presentation:

  • Incubation period: 2–14 days
  • Prodromal symptoms:
    • Fever, headache, myalgia/arthralgia: mimics a viral infection
    • Nausea/vomiting
    • Abdominal pain common in children
  • Rash: variably present
    • Appears on days 3–5 in 50% of cases, and may never appear in about 10% of patients
    • Typically starts at wrists/ankles and spreads centrally; rash does not spare palms and soles, but often never develops in these areas (18%–64% of cases)
    • Blanching erythematous macular rash that becomes petechial over time
  • Complications:
    • Encephalitis
    • Pulmonary edema
    • Acute respiratory distress syndrome
    • Cardiac arrhythmias
    • Coagulopathy
    • Gastrointestinal bleeding
    • Skin necrosis
  • Preferred treatment is doxycycline.


  • Pre-antibiotic era: 20%–25% mortality (range: 20%–80%)
  • Currently 3%–5%, mostly due to delayed diagnosis and treatment


  • Skin biopsy (3-mm punch): immunofluorescence testing/immunoperoxidase staining (70% sensitive, 100% specific)
  • Culture is difficult, dangerous, and reserved mostly for research purposes.
  • Serology: not useful for diagnosis, as it establishes diagnosis only post-factum
  • Polymerase chain reaction (PCR) tests of blood specimens not useful (low sensitivity)
Characteristic spotted rash of Rocky Mountain spotted fever

Characteristic spotted rash of Rocky Mountain spotted fever: hand and wrist of an affected child

Image: “Rocky Mountain spotted fever PHIL 1962 lores” by CDC. License: Public Domain

Clinical Relevance (R. prowazekii, R. typhi, R. acari)

Epidemic (louse-borne) typhus (R. prowazekii)

Epidemic (louse-borne) typhus is now a rare disease.


  • Direct injury to endothelial cells followed by immune response
  • Results in vascular permeability, edema, activation of coagulation and inflammation
  • Lymphocytic vasculitis, thrombosis, microscopic hemorrhage

Clinical presentation:

  • Fever, cough, headache, malaise, nausea, myalgias
  • Can be confused with typhoid fever in tropical zones
  • Rash:
    • Macular or maculopapular, petechial, and confluent without treatment; starts on trunk and spreads to the extremities
    • Starts several days after the onset of symptoms; often not present
  • Neurologic symptoms (confusion, coma, seizures) are common.
  • Pulmonary involvement in 35% of patients (interstitial pneumonia, edema, pleural effusions)

Brill-Zinsser disease:

  • Recurrence of typhus symptoms years after initial infection
  • Usually mild illness associated with fever, headache, malaise, and rash
  • Diagnosis: 
    • Skin biopsy (3-mm punch): immunohistochemical stain
    • Can also test louse found on patient 
  • Treatment: doxycycline
  • Prognosis: Untreated disease is fatal in 7%–40% of cases.
  • Prevention:
    • Control body lice by washing clothes and bedding in hot water or dry-cleaning clothes.
    • Use permethrin or other insecticides as needed.
Rash in a patient with epidemic typhus

Rash in a patient with epidemic typhus

Image: “Epidemic typhus Burundi” by D. Raoult, V. Roux, J.B. Ndihokubwayo, G. Bise, D. Baudon, G. Martet, and R. Birtles. License: Public Domain

Endemic (murine) typhus (R. typhi)

  • Worldwide distribution
  • More frequent in areas with rat accumulations
  • In temperate regions, more common in late summer and early fall
  • Inflammatory vasculitis
  • Symptoms are usually mild, fatality is low
  • Fever, headache, myalgias, and rash
  • In severe cases, may present with neurologic, renal, cardiac, pulmonary, or hepatic dysfunction
  • Treatment: doxycycline
  • Prognosis: severe disease associated with old age, comorbidities; case-fatality rate is 1%

Rickettsialpox (R. acari)

  • Mice serve as natural reservoirs.
  • Mice mites rarely bite humans, unless the mouse population is reduced.
  • Incubation period: 10–14 days
  • Initial lesion: a small papule that vesiculates and then forms an eschar
  • Constitutional symptoms: fever, malaise, and headache
  • Rash
    • Generalized
    • Maculopapular that becomes papulovesicular, followed by eschar crust
    • Lesions scab (crust) and fall off without scarring.
  • Diagnosis: clinical symptoms and signs, epidemiologic data, and convalescent sera
  • Treatment and prognosis: doxycycline; without treatment, fever lasts 6–10 days
Painless black, crusted eschar of Rickettsialpox

Painless, black, crusted eschar of rickettsialpox, which develops as the last stage of the typical rash (macules → papules → vesicles → crusts/eschars that heal without scarring).

Image: “Rickettsialpox lesion” by Krusell A, Comer JA, Sexton DJ. License: Public Domain


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