What disease causes fever, headache, and calf pain?

Leptospirosis

The triad of fever, headache, and calf pain is highly characteristic of leptospirosis, a zoonotic infection caused by Leptospira spirochetes transmitted through contact with urine-contaminated water or soil from infected animals. 1

Clinical Presentation

The classic presentation occurs during the bacteremic phase (4-7 days after exposure) and includes: 1, 2

• High fever (typically ≥39°C) 2
• Severe myalgia, particularly of the calves - this is a distinguishing feature 1, 2, 3
• Headache (often severe) 1, 2
• Conjunctival suffusion (redness without discharge) - highly suggestive when present 1, 2, 3

Additional features that support the diagnosis include: 1

• Abdominal pain
• Nausea and vomiting
• Photophobia
• Chills and rigors

Epidemiological Clues

Critical history to elicit: 1, 3

• Fresh-water exposure (swimming in lakes/rivers) within 2-30 days, typically 7-12 days before symptom onset 1, 3
• Occupational exposure to animals (rats, dogs, cattle) or contaminated water 1, 3
• Recent flooding or recreational water sports 1
• Contact with animal urine 2

Severe Disease (Weil's Disease)

Approximately 5-10% progress to severe leptospirosis characterized by: 1, 2

• Jaundice with hepatorenal syndrome 1, 2, 3
• Acute renal failure (elevated creatinine >2 mg/dL) 3
• Hemorrhagic complications (due to capillary fragility, not coagulopathy) 1
• Pulmonary hemorrhage/ARDS (mortality >50%) 4
• Thrombocytopenia 1, 3

Diagnostic Approach

Initial Laboratory Findings 1, 2, 3

• Urinalysis: Proteinuria and hematuria 1, 2
• CBC: Polymorphonuclear leukocytosis (>11,000/mm³ strongly suggests leptospirosis), thrombocytopenia, anemia if hemorrhage present 1, 3
• Chemistry: Elevated bilirubin with mild transaminase elevation (distinguishes from viral hepatitis), elevated creatinine 1, 2, 3
• Normal coagulation studies despite bleeding 1

Confirmatory Testing 1, 2

• Serology (IgM ELISA): Most common confirmatory method 1, 2

  • Titers >1:320 are diagnostic 1, 2
  • Titers 1:80-1:160 suggest early infection 1, 2
  • Earliest positives appear 6-10 days after symptom onset 1, 3
  • Convalescent serology (>10 days) with microscopic agglutination test (MAT) confirms diagnosis 1, 2

• Blood cultures: Should be obtained within first 5 days before antibiotics, kept at room temperature 1, 3

• PCR/NAAT: Turnaround time 1-2 hours 2

• CSF testing: May have higher bacterial load than serum; important if meningeal signs present 5

Treatment

Empiric Therapy - Critical 1, 2, 3

Treatment must be initiated immediately upon clinical suspicion without waiting for laboratory confirmation, as delay beyond 5 days significantly increases mortality. 1, 2

Start empiric antibiotics if patient has: 3

• Fever with jaundice
• Conjunctival suffusion
• Fresh-water exposure history with fever and myalgia
• Calf pain with fever and headache

Antibiotic Regimens 1, 2

Mild-to-moderate disease:

• Doxycycline or penicillin 1, 2, 3
• Duration: 7 days (extend to 10 days if slow response) 2

Severe disease (Weil's disease):

• Intravenous penicillin, third-generation cephalosporins, or macrolides 2, 6
• Must initiate within first hour of recognition 2
• Continue full 7-10 day course even with clinical improvement 2

Supportive Care 2, 6

• Fluid resuscitation: Target systolic BP >90 mmHg, monitor for fluid overload 2
• Renal support: Early dialysis for oliguric renal failure is life-saving 4
• ICU monitoring: Required for persistent hypoperfusion, multiorgan dysfunction, or pulmonary hemorrhage 2, 3

Differential Diagnosis

The combination of fever, headache, and calf pain distinguishes leptospirosis from: 3

• Dengue fever: Presents with retro-orbital pain, rash, leukopenia, and thrombocytopenia with rising hematocrit (plasma leakage), but lacks jaundice, conjunctival suffusion, and calf tenderness 3
• Meningitis: May have similar fever/headache but lacks calf pain and conjunctival suffusion 1
• Rocky Mountain spotted fever: Has rash involving palms/soles, but calf pain is not a prominent feature 1

Common Pitfalls

• Do not wait for serological confirmation - early serology may be negative as seroconversion takes 6-10 days 1, 3
• Do not misdiagnose as viral hepatitis - leptospirosis causes jaundice with mild transaminase elevation, unlike viral hepatitis 2, 3
• Do not overlook CSF testing - may have higher bacterial load than blood and yield diagnosis when blood tests are negative 5
• Do not delay antibiotics - treatment after day 5 significantly increases mortality 1, 2