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Relapsing Fever

Chapter 190 | Part 5: Infectious Diseases

KEY CLINICAL POINTS

  • Relapsing fever is caused by Borrelia spirochetes, with three clinical forms: louse-borne (LBRF), soft tick (STRF), and hard tick (HTRF).
  • Clinical presentation includes recurrent fever episodes with intervals of afebrility, often accompanied by headache, myalgia, and splenomegaly.
  • Diagnosis relies on blood smear microscopy, PCR, and CSF analysis, with treatment guided by antibiotic selection based on patient age and allergy status.

1. DEFINITION & OVERVIEW

Relapsing fever is an acute febrile illness caused by infection with Borrelia spirochetes, transmitted by lice or ticks. It presents with recurrent fever episodes, systemic inflammation, and potential neurological complications. The disease is classified into three epidemiologic forms: louse-borne (LBRF), soft tick (STRF), and hard tick (HTRF).

Table 190-1: Relapsing Fever Borrelia Species by Type, Region, and Vector

SPECIES RELAPSING FEVER TYPE REGION(S) ARTHROPOD VECTOR(S)
B. crocidurae STRF West Africa Ornithodoros sonrai
B. duttonii STRF East Africa, southern and central Africa O. moubata
B. hermsii STRF Western North America O. hermsi
B. hispanica STRF North Africa, southern Europe O. erraticus
B. kalaharica STRF West Africa, southern Africa O. savignyi
B. lonestari HTRF Southern and eastern United States Amblyomma americanum
B. mazzotti STRF Mexico, Central America O. talaje
B. miyamotoi HTRF North America, Asia, Europe Ixodes pacificus, I. persulcatus, I. ricinus, I. scapularis
B. nietonii STRF Western North America O. hermsii
B. persica STRF Central Asia, Middle East O. tholozani
B. puertoricensis STRF Central America O. puertoricensis
B. recurrentis LBRF Africa, globala Pediculus humanus corporis
SPECIES RELAPSING FEVER TYPE REGION(S) ARTHROPOD VECTOR(S)
B. turicatae STRF Southwestern United States, northern Mexico O. turicata
B. venezuelensis STRF Central America, South America O. rudis

1.1 Clinical Forms

LBRF: Transmitted by body lice, common in areas of poverty, war, or homelessness. STRF: Spread by soft ticks, prevalent in rural areas. HTRF: Caused by hard ticks, more common in North America and Europe.

1.2 Pathogenesis

Spirochetes enter the bloodstream during tick feeding, proliferate in blood, and trigger systemic inflammation. Antigenic variation of surface proteins leads to relapsing fever. Immune response includes Jarisch-Herxheimer reaction.

2. EPIDEMIOLOGY

LBRF is endemic in Ethiopia, Eritrea, Somalia, and occurs in refugee camps. STRF is globally distributed, with high prevalence in Africa and Central Asia. HTRF is common in North America and Europe. Risk factors include poverty, homelessness, and exposure to ticks or lice. Mortality is highest in elderly patients and those with severe complications.

2.1 Demographics

LBRF: Common in war-torn regions and refugee camps. STRF: Endemic in rural areas of Africa, Central Asia, and the Americas. HTRF: Prevalent in North America, particularly in the western U.S. and southern Canada.

2.2 Transmission

LBRF: Spread by body lice. STRF: Transmitted by soft ticks (Ornithodoros spp.). HTRF: Spread by hard ticks (Amblyomma, Ixodes spp.).

3. ETIOLOGY & PATHOPHYSIOLOGY

Caused by Borrelia species, which are spirochetes with coiled, thin filaments. Pathogenesis involves spirochete proliferation in blood, systemic inflammation, and immune-mediated relapsing fever. Antigenic variation of surface proteins allows evasion of host immunity.

3.1 Spirochete Characteristics

Borrelia species are gram-negative, extracellular pathogens with lipoproteins that activate Toll-like receptors. They lack exotoxins but induce proinflammatory cytokines (TNF- α , IL-6, IL-8).

3.2 Immune Response

IgM antibodies target surface lipoproteins. Jarisch-Herxheimer reaction occurs due to release of bacterial products during antibiotic treatment.

4. CLINICAL FEATURES

Sudden onset of fever with intervals of afebrility, often accompanied by headache, myalgia, splenomegaly, and hepatomegaly. Neurological complications include meningitis, cranial neuritis, and Bell’s palsy. Severe cases may present with ARDS or renal failure.

4.1 Fever Patterns

Febrile episodes last 1–3 days, separated by afebrile intervals of 4–14 days. LBRF may have prolonged fever (3–6 days) with a single milder episode.

4.2 Complications

Renal failure, pulmonary hemorrhage, ARDS, meningitis, and coagulopathy. Neurological sequelae may include permanent visual impairment or cognitive deficits.

5. DIFFERENTIAL DIAGNOSIS

Differential diagnoses include malaria, typhus, leptospirosis, rickettsioses, ehrlichiosis, and Lyme disease. Co-infections with other pathogens (e.g., Rickettsia, Bartonella) are common in endemic areas.

5.1 Common Mimics

Rocky Mountain spotted fever, dengue, typhoid fever, and viral hemorrhagic fevers. In areas with co-endemic Borrelia and Lyme disease, STRF may be misdiagnosed as Lyme.

6. INVESTIGATIONS & DIAGNOSIS

Diagnosis confirmed by blood smear microscopy (spirochetes ≥ 105/mL), PCR, or CSF analysis. Serologic tests (ELISA, C6 peptide assay) are less reliable due to cross-reactivity. NAAT is more sensitive than blood smears for samples obtained between febrile episodes.

6.1 Diagnostic Tests

Blood smear (Giemsa-Wright stain), PCR (for B. miyamotoi, B. lonestari), CSF analysis (pleocytosis, elevated protein), and serology (limited utility).

6.2 Imaging

Chest X-ray for pulmonary edema or ARDS. MRI/CT for neurological complications.

7. MANAGEMENT & TREATMENT

Antibiotics (penicillin, doxycycline, erythromycin) are first-line. Supportive care includes fluid resuscitation, dialysis for renal failure, and mechanical ventilation for ARDS. Treatment duration is 7–14 days, with adjustments for pregnancy or allergies.

Table 190-1: Treatment Algorithm for Relapsing Fever

AGE/GROUP TREATMENT REGIMEN DURATION
‡9 years, not pregnant Single dose: doxycycline 200 mg PO, tetracycline 500 mg PO, or ceftriaxone 250 mg IM 7 days
<9 years or pregnant Erythromycin 12.5 mg/kg PO qid 7 days
AGE/GROUP TREATMENT REGIMEN DURATION
Penicillin allergy Erythromycin 500 mg PO qid 7 days
Severe cases Intravenous ceftriaxone 2 g qd or penicillin G 5 million U q6h 14 days

7.1 Antibiotic Regimens

Penicillin G (5 million U q6h), doxycycline (200 mg PO), or erythromycin (500 mg qid). Avoid tetracyclines in pregnancy. Ceftriaxone is an alternative for severe cases.

7.2 Supportive Care

Aggressive fluid resuscitation for renal failure, dialysis for oliguric renal failure, and mechanical ventilation for ARDS. Monitor for Jarisch-Herxheimer reaction.

8. PROGNOSIS & COMPLICATIONS

Most patients recover fully, but complications like renal failure, pulmonary hemorrhage, and meningitis can be life-threatening. Mortality is highest in elderly patients and those with severe disease. Long-term follow-up shows recovery of renal and hepatic function.

8.1 Complications

Renal failure, ARDS, coagulopathy, meningitis, and congenital infections in pregnancy. Neurological sequelae may include permanent visual impairment.

9. SPECIAL CONSIDERATIONS

Pregnancy: Avoid tetracyclines; use erythromycin. Pediatrics: Erythromycin is preferred. Elderly: Monitor for renal failure and ARDS. Co-infections with other pathogens (e.g., Rickettsia, Bartonella) require broader treatment.