Anaplasmosis Overview
Anaplasmosis (human granulocytic anaplasmosis, HGA) is a tick-borne rickettsial infection caused by Anaplasma phagocytophilum that requires immediate empiric treatment with doxycycline when suspected, as delay in treatment can lead to severe complications and death. 1
Epidemiology and Transmission
Anaplasmosis is transmitted primarily by Ixodes scapularis ticks in the Northeast and upper Midwest United States, and Ixodes pacificus in the Pacific Northwest 2. The disease is emerging in Canada due to expanding tick populations from climate change 3. Transmission can also occur through blood transfusion, particularly in immunocompromised patients (42% of immunocompromised cases acquired infection this way) 1, 4. The same tick vector transmits Lyme disease and babesiosis, making coinfection possible 2.
Clinical Presentation
Key Clinical Features to Recognize:
- Fever (88.5-90% of cases) - the dominant presenting symptom 5, 4
- Constitutional symptoms: headache, chills, myalgia (59% of cases) 5, 4
- Gastrointestinal symptoms: nausea, vomiting, abdominal pain (56% of cases) 4
- Notably, rash is uncommon (only 17% of cases), distinguishing it from Rocky Mountain spotted fever 4
Critical Laboratory Abnormalities:
- Thrombocytopenia (71.8-76% of cases) - most common finding 5, 4
- Elevated liver enzymes (66.7% of cases, particularly AST) 5, 4
- Leukopenia (49.8% of cases) 5
This triad of fever + thrombocytopenia + elevated transaminases in a patient with tick exposure should immediately trigger consideration of anaplasmosis. 2, 5
Severe Complications (occur in 40.5% of cases):
- Acute renal failure (9.8%)
- Multi-organ failure (7.5%)
- ARDS (6.3%)
- Neurological manifestations including stroke (rare but reported) 6
- Overall mortality: 3-5.7%, higher in immunocompromised patients (18.2%) 5, 4, 7
Diagnosis
Diagnostic Approach:
PCR testing of whole blood is the primary diagnostic method (used in 76% of confirmed cases) and should be ordered immediately when anaplasmosis is suspected 4
Peripheral blood smear may show morulae (intracytoplasmic inclusions in neutrophils), though this is less sensitive 2, 6
Serology (IgG/IgM antibodies) is useful for retrospective confirmation but should not delay treatment 2
Critical pitfall: Do not wait for diagnostic confirmation to initiate treatment. The clinical presentation with appropriate epidemiologic exposure (tick bite or endemic area travel within 3 weeks) is sufficient to start empiric therapy 2, 1.
Treatment
First-Line Treatment:
Doxycycline is the only recommended treatment for anaplasmosis in all patients, including children <8 years old and pregnant women. 1
Dosing:
- Adults: 100 mg orally or IV twice daily 1
- Children <45 kg (100 lbs): 2.2 mg/kg orally or IV twice daily (maximum 100 mg/dose) 1
Duration:
- Standard: Continue for at least 3 days after fever subsides and until clinical improvement; minimum 5-7 days total 1
- If Lyme disease coinfection suspected: Extend to 10 days 1
Expected Response:
Fever should subside within 24-48 hours of starting doxycycline. 2, 1 If fever persists beyond 48 hours, strongly consider:
- Alternative diagnosis
- Coinfection with Babesia microti or Borrelia burgdorferi 2, 1
- Severe disease requiring longer response time 1
Alternative Agents (Limited Use):
Rifampin may be considered ONLY for:
- Mild anaplasmosis in pregnancy
- Documented severe doxycycline allergy
- Dose: 300 mg orally twice daily (adults) or 10 mg/kg twice daily (children, max 300 mg/dose) 1
Critical warning: Before using rifampin, you must rule out Rocky Mountain spotted fever, as rifampin is ineffective for RMSF and the presentations overlap. Rifampin also does not treat Lyme coinfection 1.
Agents That Do NOT Work:
- Chloramphenicol: Ineffective for anaplasmosis 1
- Beta-lactams, macrolides, aminoglycosides, sulfonamides: No activity 1
- Fluoroquinolones: Not recommended; relapse reported with levofloxacin 1
Special Populations
Pregnancy:
Doxycycline at recommended doses for short duration (5-10 days) is unlikely to pose substantial teratogenic risk and is preferred over disease-related maternal and fetal mortality 1. Case reports document successful outcomes with doxycycline treatment during pregnancy and parturition 2, 5.
Children <8 years:
Doxycycline is the treatment of choice regardless of age. 1 The AAP and CDC explicitly recommend doxycycline for children <8 years with suspected tickborne rickettsial diseases, as delayed treatment contributes to higher mortality in young children 1.
Lactation:
Short-term doxycycline use is considered probably safe during breastfeeding 1.
Management Algorithm
Outpatient vs. Inpatient:
Hospitalize if:
- Organ dysfunction
- Severe thrombocytopenia
- Mental status changes
- Need for supportive therapy
- Multiple organ dysfunction 1
Outpatient management acceptable if:
- Early-stage disease
- Reliable caregiver available
- Patient can take oral medications
- Close follow-up ensured within 24-48 hours 1
Coinfection Considerations:
Coinfection rate is approximately 9% 4. Most common coinfections:
If coinfection suspected, the 10-day doxycycline course covers both anaplasmosis and Lyme disease. For babesiosis, add atovaquone plus azithromycin 2.
Key Clinical Pitfalls to Avoid
Do not delay doxycycline while awaiting diagnostic confirmation - mortality increases with treatment delay 1
Do not avoid doxycycline in children <8 years - this contributes to preventable deaths 1
Do not use broad-spectrum antibiotics alone (beta-lactams, fluoroquinolones) - they are ineffective and delay appropriate treatment 1
Do not provide prophylactic doxycycline after tick bite in asymptomatic patients 1
Do not treat asymptomatic seropositive patients - antibodies persist for months to years without active infection 1
Do not mistake drug rash for disease rash - patients treated with sulfonamides or beta-lactams may develop rash mistaken for drug eruption when it's actually disease progression 1