Weil Disease

Weil disease is the severe form of leptospirosis, with jaundice, acute kidney injury and haemorrhage, caused by Leptospira species (mainly Leptospira interrogans). Pulmonary haemorrhage and multi-organ failure may follow.

Epidemiology. Leptospirosis affects over 1 million people each year, with about 60,000 deaths, mostly in tropical regions after floods. About 5 to 15% of cases become severe, with mortality of 5 to 15% in Weil disease and up to 50% with pulmonary haemorrhage.

Exposure. Contact with water or soil contaminated by the urine of rodents (rats), cattle, pigs and dogs, during flooding, agriculture (rice paddies, sugar cane), sewer and abattoir work, recreation (swimming, kayaking), and slum dwelling.

Pathophysiology. Spirochaetes penetrate skin and mucous membranes, disseminate through blood, and cause vasculitis, endothelial injury and capillary leakage. Kidney disease is interstitial nephritis and tubular injury. Jaundice is caused by cholestasis and hepatocyte dysfunction, without extensive necrosis. Pulmonary haemorrhage is caused by capillary injury.

The first (septicaemic) phase of 4 to 7 days has high fever, headache, severe myalgia (calves), conjunctival suffusion, nausea and rash. The second (immune) phase has jaundice, renal failure, haemorrhage, meningitis and uveitis. Features of severe disease: jaundice with oliguria, haemoptysis, dyspnoea, hypotension, arrhythmia, myocarditis and thrombocytopenia.

Red flags.

• Jaundice with oliguria or rising creatinine.
• Haemoptysis, dyspnoea or hypoxia (pulmonary haemorrhage).
• Hypotension, arrhythmia or bleeding.

Blood tests: full blood count (neutrophilia, thrombocytopenia), bilirubin (raised, with only modestly raised transaminases), creatinine, creatine kinase, potassium (often low, with non-oliguric renal failure), coagulation, gas and lactate. Microscopic agglutination test (paired sera 7 to 10 days apart), IgM enzyme linked immunosorbent assay, and nucleic acid amplification testing on blood in the first week or urine later. Chest radiograph (patchy alveolar infiltrates), ECG and urinalysis.

Differential diagnosis. Viral hepatitis, malaria, dengue, hantavirus infection, typhoid, rickettsial infection, sepsis, acute cholangitis and hepatorenal syndrome.

Antibiotics (start at once, even before confirmation).

• Benzylpenicillin 1.5 million units (0.9 g) IV every 6 hours, or ceftriaxone 1 to 2 g IV daily, or cefotaxime 1 g IV every 6 hours, for 7 days. Adjust in renal impairment.
• Doxycycline 100 mg orally or IV twice daily for 7 days is an alternative, and may be given in less severe disease (avoid in pregnancy and young children).
• Expect a Jarisch-Herxheimer reaction (fever, rigors, hypotension) within hours of the first dose, which needs supportive care.

Fluids and renal care. Careful fluid resuscitation with isotonic crystalloid, early renal replacement therapy for oliguria, hyperkalaemia, acidosis or fluid overload (peritoneal dialysis and haemodialysis give similar results, and early dialysis improves survival), potassium replacement for hypokalaemia in non-oliguric phase, and avoidance of nephrotoxins.

Pulmonary haemorrhage. Lung protective ventilation (6 mL/kg predicted body weight), PEEP, and early intubation. Methylprednisolone 500 mg to 1 g IV daily for 3 days may be tried in specialist hands, though evidence is weak. Consider ECMO for refractory hypoxaemia.

Bleeding. Platelet and plasma replacement for bleeding, and vitamin K 10 mg IV for jaundice.

Circulatory shock. Fluids and noradrenaline 0.05 to 1 microgram/kg/min.

Chemoprophylaxis. Doxycycline 200 mg orally once weekly during high risk exposure, or 200 mg once after a single high risk exposure.

Monitoring. Urine output, creatinine, potassium, bilirubin, platelets, oxygen saturation and chest imaging.

Referral and escalation. Intensive care and nephrology for renal failure or pulmonary haemorrhage, with infectious disease specialists. Notify public health.

Special groups. In pregnancy, use benzylpenicillin or ceftriaxone, and avoid doxycycline. In children under 8 years, avoid long courses of doxycycline.