- 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:
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|
|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)|
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
- 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
- Incubation period: 2–14 days
- Prodromal symptoms:
- Fever, headache, myalgia/arthralgia: mimics a viral infection
- 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
- Pulmonary edema
- Acute respiratory distress syndrome
- Cardiac arrhythmias
- 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)
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
- Fever, cough, headache, malaise, nausea, myalgias
- Can be confused with typhoid fever in tropical zones
- 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)
- Recurrence of typhus symptoms years after initial infection
- Usually mild illness associated with fever, headache, malaise, and rash
- 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.
- Control body lice by washing clothes and bedding in hot water or dry-cleaning clothes.
- Use permethrin or other insecticides as needed.
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
- 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
- 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
- Petri, W.A. (2020). Overview of rickettsial and related infections. Merck Manuals Professional Edition. Retrieved January 17, 2021, from https://www.merckmanuals.com/professional/infectious-diseases/rickettsiae-and-related-organisms/overview-of-rickettsial-and-related-infections
- Riedel, S., Hobden, J.A. (2019). Rickettsia and Related Gener. In Riedel, S, Morse, S.A., Mietzner, T., Miller, S. (Eds.), Jawetz, Melnick, & Adelberg’s Medical Microbiology (28th ed, pp. 357-363).
- 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
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