Relapsing Fever¶
Chapter 190 | Part 5: Infectious Diseases · Part 5 – Infectious Diseases: Bacterial · Chapter 190
Key Clinical Points¶
- Relapsing fever is a recurrent febrile illness caused by Borrelia spirochetes.
- Three clinical forms exist: louse-borne (LBRF), soft tick-borne (STRF), and hard tick-borne (HTRF).
- Antigenic variation of surface proteins allows Borrelia to evade host immunity, causing the characteristic relapsing pattern.
- Diagnosis relies on blood microscopy (thin/thick smears), PCR/NAAT (preferred for HTRF), or GlpQ-based serology.
- First-line treatments include penicillin and tetracyclines; erythromycin is used for pregnant/nursing women and children.
- LBRF is limited to northeastern Africa; STRF and HTRF are found globally.
- Jarisch-Herxheimer reaction (JHR) occurs in ~50% of cases during treatment, requiring monitoring for fever, hypotension, and diaphoresis.
- Neurologic complications (e.g., Bell's palsy, meningitis) are more common in STRF than LBRF.
- Tick-borne forms may coexist with Lyme disease or other tick-borne infections.
- Borrelia spirochetes are resistant to rifampin, sulfonamides, and aminoglycosides.
1. DEFINITION & CLASSIFICATION¶
• Definition: Relapsing fever is a recurrent febrile illness caused by Borriella spirochetes. • Clinical Forms: ◦ Louse-borne relapsing fever (LBRF): Caused by Borrelia recurrentis, transmitted by human body lice (Pediculus humanus corporis). ◦ Soft tick relapsing fever (STRF): Transmitted by Ornithodoros ticks; caused by multiple species including B. turicatae and B. duttonii. ◦ Hard tick-borne relapsing fever (HTRF): Transmitted by Ixodes or Amblyomma ticks; includes B. miyamotoi and B. lonestari. • Pathophysiology: ◦ Antigenic variation of surface proteins prevents sustained immunity. ◦ CNS invasion is uncommon in LBRF (indicated by dashed line in Figure 190-3).
Clinical Forms & Table 190-1¶
• LBRF: Limited to northeastern Africa; associated with poverty and overcrowding. ◦ Note: CNS involvement is less common in this form. • STRF: Found on most continents except Arctic regions; transmitted via Ornithodoros ticks. • HTRF: Widespread in North America, Europe, and Asia; B. miyamotoi often coexists with Lyme disease.
Table 190-1 (Relapsing Fever Borrelia Species): ◦ STRF: Includes B. crocidurae, B. turicatae, B. duttonii, B. hermsii, B. mazzotti, B. nietonii, and B. puertoricensis. ◦ HTRF: Includes B. miyamotoi and B. lonestari. ◦ LBRF: Includes B. recurrentis.
2. EPIDEMIOLOGY¶
• LBRF: Limited to Ethiopia, Eritrea, and Somalia. • STRF: Global distribution (except Arctic); transmitted via Ornithodoror ticks in homes or caves. • HTRF: North America, Europe, Asia; B. miyamotoi coexists with Lyme disease. • Transmission Dynamics: ◦ Tick-borne forms involve transovarial transmission in ticks, sustaining infection risk even without a constant mammalian host.
3. ETIOLOGY & PATHOPHYSIOLOGY¶
• Entry: Spirochetes enter via tick saliva during feeding. • Proliferation: STRF spirochetes replicate rapidly (doubling every 6 hours); HTRF grow more slowly. • Hematologic Effects: Binding to erythrocytes causes sequestration in spleen/liver → hepatosplenomegaly and anemia. • Neurotropism: Some species (e.g., B. turicatae) cross the blood-brain barrier, causing meningitis or cranial neuritis. • Proinflammatory Response: Lipoproteins activate Toll-like receptors → cytokine release (TNF-α, IL-6).
4. CLINICAL FEATURES¶
• Fever Pattern: ◦ Sudden high fever (>39°C) with afebrile intervals of 4–14 days. ◦ LBRF: First episode (3–6 days) followed by 1 milder relapse. ◦ STRF: Multiple febrile episodes (1–3 days each), recurring at least twice. • Systemic Symptoms: ◦ Common: Headache, myalgia, arthralgia, vomiting. ◦ LBRF specific: Jaundice, epistaxis, subconjunctival hemorrhages. ◦ General: Splenomegaly and hepatomegaly. • Neurologic Manifestations: ◦ STRF: Bell's palsy (common), aseptic meningitis, cranial neuritis. ◦ LBRF: Altered mental state (likely due to systemic inflammation). • Cardiac Involvement: Gallop rhythm, prolonged QT interval in STRF/LBRF.
Laboratory Findings¶
• Hematology: Mild normocytic anemia, thrombocytopenia (<50,000/μL). ◦ Inflammatory markers: Elevated CRP and procalcitonin. ◦ Organ function: Elevated aminotransferases. ◦ CSF: Mononuclear pleocytosis, elevated protein.
5. DIFFERENTIAL DIAGNOSIS¶
• Tick-borne: Lyme disease (coexists with B. miyamotoi), Rocky Mountain spotted fever, ehrlichiosis, babesiosis. • Louse-borne: Typhus (Rickettsia prowazekii), trench fever (B. quintana). • Co-infections: Malaria, typhoid, leptospirosis.
6. DIAGNOSTIC APPROACH¶
- Microscopy: ◦ Thin blood smear: Detects spirochetes at ≥10^5/mL. ◦ Thick smear (acetic acid or citrated blood wet mount): Higher sensitivity for detection.
- Molecular Testing: ◦ PCR/NAAT: Preferred for detecting B. miyamotoi and B. lonestari in blood/CSF, especially between febrile episodes.
- Serology: ◦ GlpQ-based assays: Better specificity for STRF/LBRF than Lyme disease.
7. MANAGEMENT & TREATMENT¶
- Initial Assessment: Identify infection type (Tick vs Louse) and presence of CNS involvement.
- Treatment for Meningitis/Encephalitis (Both types): ◦ Ceftriaxone 2 g qd OR Na penicillin G, 5 million U q6h for 14 days.
- Treatment for Non-CNS cases: • Tick-borne: ◦ Age ≥ 9, not pregnant → Doxycycline 100 mg bid (10 days). ◦ Alternatives: Tetracycline 500 mg qid OR Erythromycin 500 mg qid. ◦ Age < 9 → Erythromycin 12.5 mg/kg per day. • Louse-borne: ◦ Penicillin Allergy → Erythromycin 500 mg qid (≥ 9) or 12.5 mg/kg per day (< 9) for 7 days. ◦ No Allergy (Sequential Therapy): ◦ Initial: Penicillin G 20M IM OR Ceftriaxone 800,000 U (Adults); 125 mg or 200,000–400,000 U (Children). ◦ Follow-up (4–12 h later): Doxycycline/Tetracycline (≥ 9) OR Erythromycin (< 9 or pregnant). ◦ Duration: 7 days.
- Monitoring: ◦ Jarisch-Herxheimer Reaction (JHR): Monitor for fever, hypotension, diaphoresis; manage with fluids and antipyretics.
Treatment Algorithm (Figure 190-3)¶
• Step 1: Identify Pathogen Type → Tick-borne vs. Louse-borne. • Step 2: Meningitis/Encephalitis? ◦ YES → Ceftriaxone 2 g qd OR Na penicillin G, 5 million U q6h for 14 days. ◦ NO → Proceed to specific type treatment. • Step 3: Path A (Tick-borne) - No Meningitis: ◦ Age ≥ 9, not pregnant → Doxycycline 100 mg bid (10 days). ◦ Alternative 1 → Tetracycline 500 mg qid. ◦ Alternative 2 → Erythromycin 500 mg qid. ◦ Age < 9 → Erythromycin 12.5 mg/kg per day. • Step 4: Path B (Louse-borne) - No Meningitis: ◦ Decision Node: Penicillin Allergy? ◦ YES → Erythromycin 500 mg qid (≥ 9) or 12.5 mg/kg per day (< 9) for 7 days. ◦ NO → Sequential Therapy (Initial dose + follow-up 4–12 h later). ◦ Initial: Penicillin G 20M IM OR Ceftriaxone 800,000 U (Adults); 125 mg or 200,000–400,000 U (Children). ◦ Follow-up (4–12 h later): Doxycycline/Tetracycline (≥ 9) OR Erythromycin (< 9 or pregnant). ◦ Duration: 7 days.
8. PROGNOSIS & COMPLICATIONS¶
• Prognosis: Rapid cure with antibiotics; mortality <1% with appropriate treatment. ◦ Higher risk in elderly or severe disease. • Jarisch-Herxheimer Reaction (JHR): Occurs in ~50% of cases during treatment. • Complications: Neurologic sequelae (e.g., permanent vision loss), myocarditis, acute respiratory distress syndrome.
9. SPECIAL CONSIDERATIONS¶
• Pregnancy/Pediatrics: Tetracyclines contraindicated; Erythromycin is the only safe option. • Prevention: Avoid tick exposure (insect repellent, protective clothing); louse control in endemic areas.
10. KEY PEARLS & CLINICAL TRAPS¶
• Diagnostic Pearls: PCR/NAAT is more sensitive than blood smear for B. miyamotoi. ◦ GlpQ-based assays are preferred for distinguishing STRF/LBRF from Lyme. • Treatment Pearls: Erythromycin is the only safe option for pregnant/nursing patients. ◦ Doxycycline 100 mg bid (Tick-borne) vs. Sequential Therapy (Louse-borne) is a key distinction. • Clinical Traps: JHR may mimic worsening illness; do not mistake it for treatment failure. ◦ Confusing STRF with Lyme disease in endemic areas.
Reference Tables¶
TABLE 189-1 Treatment and Chemoprophylaxis of Leptospirosis in Adults a INDICATION Treatment Mild leptospirosis¶
Harrison's 22e, p.1444
| INDICATION | REGIMEN |
|---|---|
| Treatment | |
| Mild leptospirosis | Doxycyclineb (100 mg PO bid) or Amoxicillin (500 mg PO tid) or Ampicillin (500 mg PO tid) |
| Moderate/severe leptospirosis |
Penicillin (1.5 million units IV or IM q6h) or Ceftriaxone (2 g/d IV) or Cefotaxime (1 g IV q6h) or Doxycyclineb (loading dose of 200 mg IV, then 100 mg IV q12h) |
| Chemoprophylaxis | |
| 190 | Relapsing Fever Alan G. Barbour |
TABLE 190-1 Relapsing Fever Borrelia Species, by RF Type, Geographic Region, and Vector SPECIES B. crocidurae B.…¶
Harrison's 22e, p.1445
| SPECIES | RELAPSING FEVER TYPE | REGION(S) | ARTHROPOD VECTOR(S) |
|---|---|---|---|
| B. crocidurae | Soft tick RF (STRF) | West Africa | Ornithodoros sonrai |
| STRF | East Africa, southern and central Africa | ||
| B. hermsii | STRF | Western North America | O. hermsi |
| STRF | North Africa, southern Europe | ||
| B. kalaharica | STRF | West Africa, southern Africa | O. savignyi |
| Hard tick RF (HTRF) | Southern and eastern United States | ||
| B. mazzotti | STRF | Mexico, Central America | O. talaje |
| HTRF | North America, Asia, Europe | ||
| B. nietonii | STRF | Western North America | O. hermsii |
| STRF | Central Asia, Middle East | ||
| B. puertoricensis | STRF | Central America | O. puertoricensis |
| Louse-borne RF | Africa, globala | ||
| B. turicatae | STRF | Southwestern United States, northern Mexico | O. turicata |
| STRF | Central America, South America |