Episode 228: Tickborne Illnesses

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Lyme, Anaplasmosis, Ehrlichiosis & Babesiosis at a Glance

Background

• Ixodes scapularis (deer tick) = primary US vector for Lyme, anaplasmosis, and babesiosis; I. pacificus on the West Coast. Ehrlichiosis → lone star tick (Amblyomma americanum), not the deer tick (CDC MMWR 2016)
• Why attachment time matters: B. burgdorferi lives in the tick midgut → multiplies and migrates to the salivary glands only after feeding starts → built-in delay
  • Single infected nymph: 0 of ~90 animals infected at 24 h, ~10% by 48 h, ~70% by 72 h (Eisen 2018)
  • Anaplasma can transmit w/in 24 h. Babesia ≈ Lyme, not faster: earliest 36 h, mostly after 48 h. True speedster = Powassan virus (w/in 15 min). Attachment time by hx is often unreliable (IDSA Lyme 2020)
• Regional variation: US Lyme = B. burgdorferi; Europe = mostly B. afzelii, B. garinii → different clinical picture. Systemic sx w/ EM more common in the US: ~65% vs ~37% in Europe (IDSA Lyme 2020)

Lyme: The Rash and the Serology

Erythema Migrans

• EM in ~70–80% of infections; appears at the bite site 3–30 d post-bite (avg ~7 d) (CDC)
• Usually not a bull’s-eye → most early EM is uniformly red
• Expanding erythematous patch + endemic area = Lyme until proven otherwise

Serology

• 2-tier: EIA or IFA → IgM/IgG Western blot (or modified 2-tier: 2 EIAs, no blot)
• Early localized dz → often seronegative (as few as ~20% positive w/in 1 wk of noticing EM) → EM in an endemic area = clinical dx, per IDSA (IDSA Lyme 2020)

The Other Three: Labs and the Smear

Babesiosis

• Hunt for hemolytic anemia: ↓Hgb, ↑LDH, ↓haptoglobin, reticulocytosis; ↓plt and ↑LFTs common
• Smear: intraerythrocytic parasites. Maltese cross (tetrad) = pathognomonic but infrequent; ring forms more common. PCR more sensitive than smear (IDSA Babesiosis 2020)

Anaplasmosis & Ehrlichiosis

• Near-identical presentations. Classic triad: leukopenia, thrombocytopenia, transaminitis
• Smear: morulae → Anaplasma in neutrophils, Ehrlichia in monocytes. Smear is insensitive → whole-blood PCR confirms (CDC MMWR 2016)

Management

Post-Bite Prophylaxis (Lyme)

• High-risk bite only → all 3: Ixodes tick, highly endemic area, attached ≥36 h (by engorgement or hx); give w/in 72 h of removal (IDSA Lyme 2020)
• Doxycycline 200 mg PO × 1 (adults); 4.4 mg/kg PO × 1, max 200 mg (kids)
• Landmark RCT: 482 pts w/ I. scapularis bites → EM 0.4% doxy vs 3.2% placebo, efficacy 87% (Nadelman 2001)
• Kids <8: doxy traditionally avoided (tooth staining), but a relative CI only → benefit wins. No staining seen w/ short courses; CDC/AAP: doxy = drug of choice for tickborne rickettsial dz at any age (CDC MMWR 2016)

Active Disease

• Early localized Lyme: Doxycycline 100 mg PO BID × 10–14 d (CDC: shorter end preferred; IDSA: 10 d)
• No 1st-gen cephalosporins (e.g., cephalexin) → ineffective vs B. burgdorferi
• EM vs cellulitis unclear → cefuroxime 500 mg PO BID × 14 d covers both. If using amoxicillin-clavulanate, dose it TID (500/125 mg) to match the TID amoxicillin regimen (CDC EM Treatment)
• Anaplasmosis: same doxy dose × 10 d (covers incubating Lyme). Ehrlichiosis: same dose until ≥3 d afebrile, usually 5–7 d total (CDC MMWR 2016)
• Babesiosis: Atovaquone 750 mg PO BID + azithromycin 500 mg day 1, then 250 mg daily × 7–10 d (IDSA Babesiosis 2020)

Severe Babesiosis

• Inpatient: Atovaquone 750 mg PO BID + azithromycin 500 mg IV daily → all-PO once sx subside, 7–10 d total. Alternative: IV clindamycin + PO quinine (CDC Babesiosis)
• Consider RBC exchange transfusion for parasitemia >10% or severe hemolysis; IDSA also lists severe pulmonary, renal, or hepatic compromise (IDSA Babesiosis 2020)
• Asplenia → ↑ risk of severe dz, but not itself an exchange criterion

The Case

• 35M, no PMH → 1 wk nausea, severe myalgias, arthralgias, HA, fatigue, fevers. Hiked upstate NY 1 wk prior; multiple tick bites to legs, none reportedly attached >24 h
• VS: BP 144/76, HR 69, RR 16, T 98.7°F s/p acetaminophen, SpO2 98% RA
• Exam: pruritic, painful papular rash w/ healing vesicles on bilateral wrists + anterior chest; tender bilateral axillary LAD; diffuse muscle and leg-joint tenderness
• Labs: plt 87K, Hgb 12.3, transaminitis
• Dx: concurrent babesiosis + poison ivy
• Lessons: poison ivy = red herring while hunting for EM; antipyretic masked the fever; ↓plt in a febrile hiker → smear; reported “<24 h” attachment didn’t exclude Babesia (hx unreliable)

Pitfalls

• Waiting for a bull’s-eye → most EM is uniformly red
• Sending serology to rule out early EM → often neg; treat clinically
• Cephalexin for “cellulitis” in tick season → misses EM
• Trusting pt-reported attachment time → runs short
• Fever persisting on doxy → think Babesia (coinfection is common); doxy doesn’t treat it (IDSA Lyme 2020)

Take-Home Points

1. Don’t wait for the bull’s-eye. Most EM is solid red. An expanding erythematous patch in an endemic area is Lyme until proven otherwise.
2. Watch the clock and the tick. Lyme needs ~36–48 h of attachment; Anaplasma can transmit w/in 24 h. Pts underestimate how long the tick was on.
3. The smear is your friend. Thrombocytopenia in a febrile hiker → manual peripheral smear for morulae or a Maltese cross.
4. Doxycycline is your workhorse. Covers Lyme, Anaplasma, and Ehrlichia → first-line for most tickborne febrile syndromes. Babesia needs atovaquone + azithromycin.

Links & References

Guidelines

• Lantos PM, et al. Clinical practice guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 guidelines for the prevention, diagnosis and treatment of Lyme disease. Clin Infect Dis. 2021;72(1):e1–e48. — doi.org/10.1093/cid/ciaa1215
• Krause PJ, et al. Clinical practice guidelines by the Infectious Diseases Society of America (IDSA): 2020 guideline on diagnosis and management of babesiosis. Clin Infect Dis. 2021;72(2):e49–e64. — doi.org/10.1093/cid/ciaa1216
• Biggs HM, et al. Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain spotted fever and other spotted fever group rickettsioses, ehrlichioses, and anaplasmosis — United States. MMWR Recomm Rep. 2016;65(2):1–44. — doi.org/10.15585/mmwr.rr6502a1

Key Studies

• Eisen L. Pathogen transmission in relation to duration of attachment by Ixodes scapularis ticks. Ticks Tick Borne Dis. 2018;9(3):535–542. — doi.org/10.1016/j.ttbdis.2018.01.002
• Nadelman RB, et al. Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after an Ixodes scapularis tick bite. N Engl J Med. 2001;345(2):79–84. — doi.org/10.1056/NEJM200107123450201

CDC

• CDC. Signs and symptoms of untreated Lyme disease. — cdc.gov/lyme/signs-symptoms
• CDC. Clinical treatment of erythema migrans rash. — cdc.gov/lyme/hcp/clinical-care/erythema-migrans-rash
• CDC. Clinical care of babesiosis. — cdc.gov/babesiosis/hcp/clinical-care