Rickettsia

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.

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)

Clinical 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.

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