In a patient with recent exposure to contaminated water or rodents presenting with acute fever, myalgias, headache, conjunctival suffusion, or jaundice, how should leptospirosis be diagnosed?

Testing for Leptospirosis

Immediate Clinical Action

Start antibiotic treatment immediately upon clinical suspicion without waiting for laboratory confirmation, as each hour of delay increases mortality. 1, 2

Key Clinical Features to Elicit

Exposure History (Past 2-20 Days)

• Contact with flood water or contaminated fresh water 1
• Recreational water sports in fresh water 3
• Occupational exposure to animals or contaminated water 3
• Contact with rats, dogs, cattle, or other domestic/wild animals 3

Characteristic Clinical Presentation

Biphasic illness pattern:

• Initial bacteremic phase (days 1-7): Sudden high fever (≥39°C), severe myalgias (especially calves, thighs, lumbar region), frontal headache, chills 1, 3
• Conjunctival suffusion (non-purulent redness without discharge) is highly suggestive and should immediately raise suspicion 1, 3

Severe disease indicators (Weil's disease):

• Jaundice with modest transaminase elevation but marked hyperbilirubinemia 1, 3
• Signs of hemorrhage (petechiae, ecchymoses, gingival bleeding, epistaxis, hematemesis, melena) 1
• Hepatomegaly 1
• Signs of respiratory distress or hypoxemia 1
• Acute kidney injury 1

Diagnostic Testing Algorithm

For Patients Presenting ≤7 Days After Symptom Onset

Immediate laboratory workup:

• Blood cultures (ideally within first 5 days, before antibiotics) 1, 3
• Complete blood count 1
• Comprehensive metabolic panel 1
• Urinalysis (looking for proteinuria and hematuria) 1, 3

Molecular testing (preferred in early phase):

• Nucleic acid amplification testing (NAAT/PCR) on serum should be performed first, as it can confirm diagnosis before antibodies develop 1, 4
• PCR turnaround time is typically 1-2 hours 3
• PCR is positive during the bacteremic phase when serology is still negative 5, 4

Serology (if NAAT unavailable or negative):

• IgM ELISA on serum 1
• IgM titer >1:320 is diagnostic 1
• IgM titers of 1:80-1:160 suggest early infection 3
• Critical caveat: Antibodies are often absent in the first week, so negative serology does not exclude leptospirosis 1, 5, 6

For Patients Presenting >7 Days After Symptom Onset

• IgM ELISA is more reliable after day 7 1
• Convalescent serology with microscopic agglutination test (MAT) should be repeated >10 days after symptom onset 1, 3
• A fourfold or greater increase in titer between acute and convalescent specimens confirms diagnosis 3

Supportive Laboratory Findings

• Leukocytosis with polymorphonuclear predominance 3
• Thrombocytopenia 1
• Elevated bilirubin with mild transaminase elevation 1, 3
• Elevated creatinine indicating renal dysfunction 1, 3
• Proteinuria and hematuria on urinalysis 1, 3

Clinical Diagnostic Criteria

Faine's criteria can be used for clinical diagnosis with 95.45% sensitivity and 56.86% specificity, though the high negative predictive value (98.6%) makes it most useful for screening out leptospirosis 1, 7

Critical Pitfalls to Avoid

• Do not wait for serological confirmation before starting antibiotics 1, 3
• Do not rely on darkfield microscopy—it is unreliable and not recommended 5
• Do not use urine for culture—it is not suitable for leptospira isolation 1
• Do not mistake leptospirosis for viral hepatitis in patients with fever and jaundice 1, 3
• Do not rely on normal coagulation studies (PT, PTT, fibrinogen) to exclude hemorrhagic complications, as these are typically normal despite active bleeding due to capillary fragility rather than consumptive coagulopathy 1

Differential Diagnosis to Consider

Other infectious etiologies include chikungunya, malaria, dengue, Zika virus, rubella, measles, hepatitis A, parvovirus, adenovirus, enterovirus, rickettsiosis, group A streptococcal infections, hantavirus (if pulmonary hemorrhage), and aseptic meningitis from other causes 8, 1