15.1.3.5: Rickettsia rickettsii

 

Gimenez stain of tick hemolymph cells infected with Rickettsia rickettsii, the causative agent of Rocky Mountain spotted fever. R. rickettsii is a small bacterium that grows inside the cells of its hosts. These bacteria range in size from 0.2 x 0.5 micrometers to 0.3 x 2.0 micrometers. They are difficult to see in tissues by using routine histologic stains and generally require the use of special staining methods. The genus Rickettsia is included in the bacterial tribe Rickettsieae, family Rickettsiaceae, and order Rickettsiales. This genus includes many other species of bacteria associated with human disease, including those in the spotted fever group and in the typhus group. (1979; CDC; Public Domain)

Organism

• Members of the genus Rickettsia are very small coccobacilli
• Use aerobic respiration
• All are obligate intracellular parasites or symbionts (they must live inside another cell)
• Lack glycolysis and the ability to synthesize many required biomolecules including ADP and NAD+
  • Use products of glycolysis taken from the host cell as their carbon and energy source
  • Obtain ADP and NAD+ from host cell
• The ancestor of eukaryotic mitochondria was closely related to the genus Rickettsia

Habitat

• In the cytoplasm of animal cells

Source

• Zoonotic disease
• Transmitted through arthropod biological vectors (insects and arachnids)
• In the case of Rickettsia rickettsii, the bacteria are transferred to the bloodstream through a tick bite, specifically ixodid (hard) ticks

Epidemiology

• The disease caused by R. rickettsii is called Rocky Mountain Spotted Fever (RMSF) based on its discovery in Idaho in 1896, but it is found throughout North America and parts of South America
  • Actually more prevalent in the southeast and midwest (Figure \(\PageIndex{1}\) A)
• Incidence has been increasing over the past 20 years or so, likely due to an increase in contact between people and ticks with the spread of suburbs into previously undeveloped areas (similar to the increase in Lyme disease which is also a tick-transmitted infection) (Figure \(\PageIndex{1}\) B)

Figure \(\PageIndex{1}\): Incidence of Rocky Mountain Spotted Fever.  Annual cases per 1 million people by state (A) and total number of reported cases in the US by year (B) (2020; CDC; https://www.cdc.gov/rmsf/stats/index.html)

• Anyone who may come in contact with ticks (such as dog owners or hikers) is susceptible to infection, although there are some with higher risk for severe disease:
  • men develop disease more frequently than women
  • people over forty
    • children under 10, however, account for the highest number of deaths
  • people with glucose-6-phosphate dehydrogenase (G6PD) deficiency, an X-linked genetic disorder and therefore more prevalent in men
  • people with weakened immune systems
• 20-25% mortality without treatment; 3-5% with treatment, primarily due to delayed diagnosis

Clinical Disease

• Symptoms of Rocky Mountain Spotted Fever (RMSF) begin about a week after the infective tick bite
• Infection of endothelium and inflammation of blood vessels lead to most of the observed symptoms
• Early symptoms:
  • fever
  • severe headache
  • muscle pain
  • gastrointestinal symptoms
  • rash (2-4 days after fever onset): small, flat, pink, macules (non-raised discolorations) on the wrists, forearms, and ankles and spreads to include the trunk and sometimes the palms of hands and soles of feet (Figure \(\PageIndex{2}\)).

Figure \(\PageIndex{2}\): Rocky Mountain Spotted Fever rash. (public domain; CDC)

• Late symptoms:
  • Rash becomes maculopapular (raised) due to leakage from blood vessels; can develop petechiae (small hemorrhages) in the center of lesions
  • Altered mental status, possibly coma, due to cerebral edema
  • Pulmonary edema
  • Necrosis (tissue death) in areas of body with decreased blood flow
    • often requires amputation
  • Multiorgan system damage
• Prompt treatment with doxycycline is required for best outcomes
  • treatment with doxycycline is recommended even if RMSF is just suspected
  • delayed treatment or treatment with other antibiotics increases chances of poor outcome

Primary Virulence Factors

• Specific virulence factors are not well understood
• Progression of infection is similar to Listeria is many ways, although the genes/proteins involved are different
  • Once R. rickettsii is in the bloodstream, it attached to and enters endothelial cells through induced phagocytosis
  • R. rickettsii escapes the phagosome and multiplies in the cytoplasm
  • R. rickettsii  moves between cells by polymerizing the actin of the host cell to propel it to neighboring cells
• Infection of the endothelium results in inflammation of the blood vessels and subsequent symptoms

Additional Information:

• http://textbookofbacteriology.net/Rickettsia.html
• https://www.cdc.gov/rmsf/healthcare-...ers/index.html