Tick-borne relapsing fever

• Tick-borne relapsing fever (TBRF) is caused by a number of non-Lyme Borrelia species

Background

Microbiology

• Tick-borne relapsing fever is caused by multiple non-Lyme Borrelia species with global distribution, usually carried by Ornithodorus ticks
• Other non-Lyme Borrelia species include B. miyamotoi and B. lonestari, although B. lonestari may also be able to cause TBRF
• Borrelia are spirochetes
• Serotypes are determined by the outer membrane variable major proteins (vmp)
• Grow in modified Kelly medium and stained by Wright stain (in peripheral blood film)

Species	Vector	Distribution	Reservoir
B. hermsii	O. hermsii	Western US and Canada (most common)	squirrels and chipmucks
B. turicatae	O. turicata	Southwestern US	Rodent
B. parkeri	O. parkeri	Western US and Baja California	Rodent
B. mazzottii	O. talaje	Mexico and Central America	Rodent
B. venezuelensis	O. rudis	South America	Rodent
B. crocidurae	O. erraticus	Middle East	Rodent
B. hispanica	O. marocanus	Iberian peninsula and North Africa

Epidemiology

• TBRF is transmitted by Ornithodoros ticks, with rodent reservoirs
• Present on every continent except Australia and Antarctica
• In North America, it is mostly in the Rocky Mountain regions above 1500 feet elevation
  • Most have exposure to woodpiles or cabins with rodents
• Spirochetes can survive in the tick for years, and can be transmitted vertically within ticks
  • Doesn't need its mammalian host to complete its life cycle
• Ticks feed for short periods (20 min) and are painless, so is often not noticed
• Can be transmitted vertically, by transfusion, and from laboratory exposure

Pathophysiology

• During febrile periods, spirochetes divide rapidly and cause a spirochetemia
• This is followed by an immune response to the vmp proteins, which clears the spirochetemia and the patient becomes afebrile
• The vmp proteins undergo rearrangement, evading the immune system and allowing another spirochetemia
  • This is the cause of the relapsing fever

Clinical Presentation

• Incubation period of 7 days (range 2 to 18 days)
• Relapsing fever: febrile for 3 days (range 12 hours to 17 days), afebrile for 7 days
• TBRF can relapse up to 30 times, whereas LBRF is usually self-limited after a single relapse
  • Febrile periods may be associated with headache, myalgias, chills, arthralgias, dizziness, and vomiting
  • Sometimes abdominal pain, confusion, non-productive cough, eye pain, diarrhea, photophobia, and neck pain
  • Each relapse is usually less severe
  • A minority of patients will have lymphadenopathy, hepatosplenomegaly, a rash, dysuria, jaundice
• Rare complications include lymphocytic meningitis, Bell palsy and other cranial nerve palsies, paralysis, seizure, uveitis, endophthalmitis, ARDS, and myocarditis
• Thrombocytopenia on bloodwork
• May be septic, with multiple organ involvement
• Can cause spontaneous abortion in pregnant women
• May have a Jarisch-Herxheimer reaction following antibiotics

Differential Diagnosis

• Colorado tick fever (Coltivirus)
• Brucellosis
• Tularemia
• Juvenile rheumatoid arthritis
• Leptospirosis
• Occult malignancy
• Lyme disease

Diagnosis

• Often seen on blood film
  • Giemsa or Wright stains
  • 70% sensitive during febrile period for TBRF, lower for LBRF
• Acute-convalescent serology with IFA/EIA
  • May cross-react with Lyme disease
• Can cause a false-positive VDRL
• Can be cultured with modified Kelly medium

Management

• First-line: doxycycline 100 mg po bid for 7 to 10 days
• Alternatives: erythromycin 500 mg qid for 10 days
• If CNS involvement:
  • Penicillin G 3 mU IV q4h for 10-14 days, or
  • Ceftriaxone 2 g IV q24h for 10-14 days

Prevention

• Can do post-exposure prophylaxis with doxycycline 200 mg po once followed by 100 mg daily for 4 days