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
- Spotted fever group:
R. rickettsii: photomicrograph of a yolk sac smear, showing many intracellular bacteria stained in red by Giemsa stain
Image: “10955” by CDC/ Billie Ruth Bird. License: Public DomainGiemsa-stained R. rickettsii in the cells of a tick
Image: “Rickettsia rickettsii” by CDC. License: Public Domain
Transmission and geography
- Transmitted by arthropod vectors
- A summary of the major clinically relevant species is outlined in the table below.
R. rickettsii | R. prowazekii | R. typhi | R. akari | |
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Vector | Hard ticks (Ixodidae family): Dermacentor (dog tick), Amblyoma (wood tick) | Human lice (Pediculus humanus corporis):
| Rat and cat flea bites | Mites from mice |
Disease | Rocky Mountain spotted fever (the most serious rickettsial disease) | Epidemic (louse-borne) typhus | Endemic typhus | Rickettsialpox (the least serious rickettsial disease) |
Geographic variations |
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Related videos
Clinical Relevance (R. rickettsii)
Rocky Mountain spotted fever
Epidemiology:
- 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
Pathophysiology:
- 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.
Prognosis:
- Pre-antibiotic era: 20%–25% mortality (range: 20%–80%)
- Currently 3%–5%, mostly due to delayed diagnosis and treatment
Identification:
- 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: hand and wrist of an affected child
Image: “Rocky Mountain spotted fever PHIL 1962 lores” by CDC. License: Public DomainClinical Relevance (R. prowazekii, R. typhi, R. acari)
Epidemic (louse-borne) typhus (R. prowazekii)
Epidemic (louse-borne) typhus is now a rare disease.
Pathogenesis:
- 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
Image: “Epidemic typhus Burundi” by D. Raoult, V. Roux, J.B. Ndihokubwayo, G. Bise, D. Baudon, G. Martet, and R. Birtles. License: Public DomainEndemic (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, 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 DomainReferences
- Sexton D.J., McClain M.T. (2020). Biology of Rickettsia rickettsii infection. Retrieved January 6, 2021, from https://www.uptodate.com/contents/biology-of-rickettsia-rickettsii-infection
- Sexton D.J., McClain M.T. (2020). Clinical manifestations and diagnosis of Rocky Mountain spotted fever. Retrieved January 6, 2021, from https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-rocky-mountain-spotted-fever
- Sexton D.J., McClain M.T. (2019). Epidemic typhus. Retrieved January 6, 2021, from https://www.uptodate.com/contents/epidemic-typhus
- Sexton D.J., McClain M.T. (2020). Murine typhus. Retrieved January 6, 2021, from https://www.uptodate.com/contents/murine-typhus
- Sexton D.J., McClain M.T. (2020). Rickettsialpox. Retrieved January 6, 2021, from https://www.uptodate.com/contents/rickettsialpox
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- CDC. Rocky Mountain spotted fever (RMSF) | tick-borne diseases | ticks | cdc. (2020, October 1). Retrieved on Jan. 18, 2021, from https://www.cdc.gov/ticks/tickbornediseases/rmsf.html
- Walker, D.H., Dumler, J.S., Blanton, L.S., Marrie, T. (2018). Diseases Caused by Rickettsiae, Mycoplasmas, and Chlamydia. In Jameson, J.L., et al. (Ed.), Harrison’s Principles of Internal Medicine (20th ed. Vol 1, pp. 1303–1309).