Rickettsia rickettsii

Background

• Causes Rocky Mountain spotted fever (RMSF)

Microbiology

• Obligate intracellular bacterium
• Structurally Gram-negative, but difficult to stain
  • Needs Gimenez method or acridine orange stain
• Contain lipopolysaccharide (LPS) as well as OmpA and OmpB autotransporters

Life Cycle

• Transmitted by ticks
  • Dermacentor variabilis (American dog tick) in the eastern two-thirds of the US
  • Dermacentor andersoni (Rocky Mountain wood tick) in the western states
  • Rhipicephalus sanguineus in Mexico and Arizona
  • Amblyomma cajennense and Amblyomma aureolatum in South America
  • Amblyomma imitator in Mexico
• Has a deleterious effect on ticks
• Transmitted trans-stadially (stage to stage) and trans-ovarially in ticks, as well as horizontally through vertebrate hosts
  • Trans-ovarial transmission uncommon for D. variabilis
• Only the adult ticks feed on humans, during prolonged feeding of 1 to 2 weeks
  • Infection requires a minimum of 8 hours of tick attachment, though can theoretically be as quick as 10 minutes
  • Can also be infected during tick removal, when it is crushed between the fingers
• As few as a single bacillus can cause disease

Pathophysiology

• From cutaneous inoculation, bacilli spread via lymphatics and small blood vessels to the larger blood vessels
• There, the OmpA, OmpB, Sca1, and Sca2 proteins induce phagocytosis by vascular endothelial cells
• From there, they replicate and spread to adjacent cells

Epidemiology

• Wide global distribution
  • Most cases in the US are in the south Atlantic and south-central regions
    • Highly endemic in North Carolina
  • Also occurs in Argentina, Brazil, Colombia, Panama, Costa Rica, and Mexico
• Most cases occur in late spring and summer
• Higher with occupational tick exposures
• Other spotted fever species include R. conorii (Europe, Africa, and South Asia), R. sibirica (eastern Russia and Asia), R. africae (sub-Saharan African and West Indies), R. parkeri (North and South America), and R. slovaca (Europe), as well as R. felis (worldwide)

Clinical Manifestations

• Incubation period of 7 days (range 2 to 14 days)
• Most common presenting symptoms are high fever, headache, and myalgias
• Rash starts after a few days, on the wrists and ankles and spreading inward as well as outward to include palms and soles
• GI symptoms are common: nausea/vomiting and abdominal pain, sometimes diarrhea
• Can see papilledema from retinal vasculitis without raised intracerebral pressure
• Can also have conjunctivitis, lymphadenopathy, stupor, edema, meningismus, hepatosplenomegaly, pneumonitis, myocarditis, gangrene
  • Neurologic involvement has a poor prognosis
• Often have increased AST and thombocytopenia (from consumption), occasionally anemia, hyponatremia, hypoalbuminemia, and AKI
  • Normal or low WBCs
• Death occurs within 7 to 15 days without appropriate treatment
  • Mortality is high without treatment (30%) and still elevated if treated early (1-5%)

Rash

• Begins as small (1–5 mm in diameter), blanching, pink macules on the ankles, wrists, or forearms that subsequently spread to the arms, legs, and trunk
  • Often involves the palms and soles
  • Usually spares the face
• Classic spotted or generalized petechial rash, including involvement of the palms and soles, usually appears by day 5 or 6
• Rash may not occur in black patients and elderly patients

Comparison to Other Spotted Fevers

• Probably the most severe spotted fever
  • Mortality likey above 20%
  • Others typically less severe disease course
• Others often have eschar at tick bite site

Differential Diagnosis

• Typhoid fever, measles, rubella, respiratory tract infection, gastroenteritis, acute surgical abdomen, enteroviral infection, meningococcemia, disseminated gonococcal infection, secondary syphilis, leptospirosis, immune complex vasculitis, immune thrombocytopenic purpura, thrombotic thrombocytopenic purpura, infectious mononucleosis, adverse drug reaction, ehrlichiosis, anaplasmosis, and other rickettsial diseases
• Other spotted fevers

Diagnosis

• Microscopy and Culture
  • Can be isolated from blood, though it's not commonly done
• Serology
  • Enables retrospective diagnosis, since antibodies are only detectable in convalescent phase
  • Indirect immunofluorescence and enzymes immunoassay
    • Titre of 1:64 is diagnostic, but does not distinguish between spotted fevers
    • Takes 7 to 10 days for IgM
    • Usually wait 2 to 3 weeks after onset for convalescent
• Molecular Testing
  • PCR possible but not sensitive

Management

• Supportive management, with aggressive fluid resuscitation
• Antimicrobials
  • Doxycycline 100 mg po bid
  • Tetracycline 25-50 mg/kg/day or chloramphenicol 50-75 mg/kg/day divided qid
  • Duration is 7 days and at least 2 days afebrile
  • Can use doxycycline in children <8 years for the durations required to treat rickettioses