A 28-year-old male farmer from rural Maharashtra presents with a 5-day history of high-grade fever, severe headache, myalgia, and vomiting. On examination, he is febrile (39.5°C), alert but restless, with mild neck stiffness. He reports wading through flooded rice fields 10 days ago. Laboratory findings show WBC 12,000/μL with left shift, platelet count 80,000/μL, and serum creatinine 2.1 mg/dL. Cerebrospinal fluid analysis reveals lymphocytic pleocytosis with normal glucose and protein. Blood culture is sterile. What is the most likely diagnosis?

Explanation

## Clinical Diagnosis: Leptospirosis with Renal Involvement ### Key Clinical Features **Key Point:** Leptospirosis is a biphasic zoonotic disease caused by *Leptospira interrogans*, transmitted through contact with water or soil contaminated with infected animal urine — classically in agricultural/monsoon settings. This patient presents with the classic **leptospiremic phase** (days 3–7): - High fever, severe headache, myalgia, vomiting — hallmark systemic features - **Occupational exposure**: wading through flooded rice fields 10 days prior (incubation 2–30 days, typically 5–14 days) - **Thrombocytopenia** (80,000/μL) and **renal dysfunction** (creatinine 2.1 mg/dL) → consistent with **Weil's disease** (severe leptospirosis) - **Lymphocytic CSF pleocytosis with normal glucose and protein** — aseptic meningitis pattern seen in leptospirosis > **SME Note:** CSF protein in leptospirosis is typically mildly elevated (20–100 mg/dL), not strictly normal. The stem states "normal protein," which represents the lower end of the leptospirosis spectrum; this does not exclude the diagnosis and is consistent with early or mild meningeal involvement. ### Why NOT the Other Options? | Feature | Leptospirosis | Bacterial Meningitis | Dengue | JEV | |---------|---------------|----------------------|--------|-----| | **CSF Glucose** | Normal | **Low (<40 mg/dL)** | Normal | Normal | | **CSF Protein** | Normal–mildly ↑ | **High (>100 mg/dL)** | Normal | Elevated | | **Blood culture** | Sterile (leptospires need special media) | **Positive** | Sterile | Sterile | | **Water/occupational exposure** | ✅ Yes | ❌ No | Mosquito vector | Mosquito vector | | **Renal involvement** | ✅ Common (Weil's) | Rare | Rare | Rare | | **Thrombocytopenia** | Moderate | Rare | Marked | Moderate | - **Bacterial meningitis** (A): Excluded by sterile blood culture, normal CSF glucose, and normal CSF protein — bacterial meningitis shows low glucose and high protein. - **Dengue** (B): Dengue causes thrombocytopenia but does NOT cause renal failure or CSF pleocytosis; no mosquito bite history; dengue is not associated with flooded field exposure. - **Japanese Encephalitis** (C): JEV causes encephalitis with altered sensorium and seizures; CSF protein is typically elevated; renal involvement is NOT a feature; requires Culex mosquito vector, not water contact. Maharashtra is endemic for JEV, but the combination of **renal failure + water exposure + sterile blood culture + aseptic meningitis** is far more consistent with leptospirosis. ### Pathophysiology *Leptospira interrogans* (serovar *icterohaemorrhagiae*) penetrates through skin abrasions or mucous membranes during water exposure. During leptospiremia: 1. **Renal tubular necrosis** → acute kidney injury (creatinine ↑) 2. **Thrombocytopenia** — bone marrow suppression + platelet consumption 3. **Meningeal inflammation** → lymphocytic pleocytosis (aseptic meningitis) 4. Hepatic involvement (jaundice in full Weil's triad) **Clinical Pearl:** Weil's disease (severe leptospirosis) = triad of **jaundice + renal failure + hemorrhage**. This patient demonstrates renal failure and thrombocytopenia, consistent with severe/Weil's leptospirosis even without overt jaundice. ### Confirmation - **Microscopic Agglutination Test (MAT)** — gold standard serology; results in 5–7 days - **Leptospira culture** — blood (early/leptospiremic phase), urine (after day 7); takes 6–8 weeks - **PCR** — rapid (24–48 hrs), sensitive in early phase; increasingly preferred in endemic settings ### Management 1. **Mild–moderate:** Doxycycline 100 mg BD × 7 days (also used for chemoprophylaxis: 200 mg once weekly) 2. **Severe (Weil's disease):** IV Penicillin G 1.5 MU 6-hourly OR IV Ceftriaxone 1 g 6-hourly × 7 days 3. Supportive: fluid management, renal replacement therapy if needed [cite: Park's Textbook of Preventive and Social Medicine, 26th ed., Ch. 7; Harrison's Principles of Internal Medicine, 21st ed., Ch. 178]