Tick- and louse-borne relapsing fever

• Infections caused by Borrelia spp.
  • Tick-borne relapsing fever (TBRF) is caused by non-Lyme Borrelia species
  • Louse-borne relapsing fever (LBRF) is caused by B. recurrentis

Microbiology

• Tick-borne relapsing fever is caused by multiple non-Lyme Borrelia species with global distribution
• Louse-borne relapsing fever is caused by B. recurrentis
• 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
TBRF
B. hermsii	Ornithodoros hermsii	Western US and Canada (most common)	Rodent
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
LBRF
B. recurrentis	Pediculus humanus	Ethiopia/Eastern Africa (previously worldwide)
Other
B. miyamotoi	Ixodes dammini and I. scapularis	US, Russia, and Japan	Deer
B. lonestari	Amblyomma americanum	Southern US	Deer & lizards

Epidemiology

• TBRF is transmitted by Ornithodoros species 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
• LBRF was present nearly worldwide prior to World War II, but is now present in Ethiopia
  • Associated with homelessness and refugee camps

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 fevers: febrile for 3 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, myalgia, arthralgia, dizziness, and vomiting
  • Each relapse is usually less severe
• Some patients will have lymphadenopathy, hepatosplenomegaly, and a rash
• Rare complications include lymphocytic meningitis, Bell palsy and other cranial nerve palsies, paralysis, seizure, uveitis, endophthalmitis, ARDS, and myocarditis
• Can cause spontaneous abortion in pregnant women
• May be septic, with multiple organ involvement
• May have a Jarisch-Herxheimer reaction following empiric antibiotics

Differential Diagnosis

Tick-borne relapsing fever

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

Louse-borne relapsing fever

• Typhus
• Malaria
• Typhoid fever
• Leptospirosis
• Hepatitis
• Dengue

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

Tick-borne relapsing fever

• 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

Louse-borne relapsing fever

• First-line: Doxycycline 200 mg po once
• Alternatives:
  • Penicillin G 400-800 kU IM once
  • Erythromycin 500 mg po once

Prevention

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