Leptospirosis

A zoonotic bacterial infection caused by pathogenic Leptospira species, spirochaete bacteria maintained in the renal tubules of a wide range of animal reservoirs (most notably rodents, though also livestock and domestic animals).

It is transmitted to humans through direct or, more commonly, indirect contact with water or soil contaminated by infected animal urine.

It presents on a spectrum from a mild, self limiting febrile illness to severe, potentially fatal disease with hepatic and renal failure together with pulmonary haemorrhage (Weil disease and severe pulmonary haemorrhagic leptospirosis respectively).

Occupational and recreational freshwater exposure is the key epidemiological association informing clinical suspicion.

Pathophysiology and risk factors

• The organism penetrates through breaks in the skin or through intact mucous membranes. It disseminates haematogenously with a particular tropism for the kidney, liver, and, in severe disease, the pulmonary vasculature and central nervous system.
• Vasculitic endothelial injury underlies the characteristic pattern of multi organ involvement in severe presentations.
• Risk factors include occupational exposure (farming, sewage work, veterinary work, abattoir work) and recreational freshwater activity (swimming, kayaking, particularly in tropical and subtropical regions).
• Exposure to flood water is also a risk factor, particularly relevant following natural disasters in endemic regions where outbreak clusters are well recognised.

• A biphasic illness pattern is classically described. The initial acute septicaemic phase lasts four to seven days. Features are fever, headache, severe myalgia particularly affecting the calves and lower back, and conjunctival suffusion without discharge (a relatively specific and useful clinical sign).
• In a proportion of patients, a second immune phase follows, with recurrence of fever together with the more severe organ specific manifestations if progression occurs.
• Severe disease (Weil disease) presents with jaundice, acute kidney injury and haemorrhagic manifestations.
• Severe pulmonary haemorrhagic leptospirosis presents with rapidly progressive respiratory failure from diffuse alveolar haemorrhage. It is the most rapidly fatal presentation of this infection if not promptly recognised and treated.
• Conjunctival suffusion (diffuse conjunctival redness without purulent discharge), together with the characteristic severe calf and lumbar myalgia and a relevant freshwater or occupational exposure history, provides the most useful combination of clinical features raising suspicion for this diagnosis.
• Aseptic meningitis can occur during the immune phase, and uveitis is a recognised, sometimes delayed, ophthalmological complication.

• Polymerase chain reaction testing on blood is most sensitive during the first week of illness (the leptospiraemic phase).
• Microscopic agglutination testing (the serological reference standard) and other antibody based assays become more reliably positive from the second week onward as the immune phase develops. The optimal diagnostic test therefore depends on the timing of presentation relative to illness onset.
• Culture of blood (first week) or urine (from the second week onward, once renal shedding of the organism begins) can confirm the diagnosis. It requires specialised media and prolonged incubation, limiting its practical utility for acute clinical decision making.
• Full blood count, renal and liver function, creatine kinase (frequently elevated, reflecting the characteristic myalgia) and coagulation studies support assessment of severity.
• Progression toward severe disease is indicated by thrombocytopenia, rising creatinine, and deranged liver function with disproportionately modest transaminase elevation relative to the degree of jaundice.
• A detailed exposure history covering occupational activity, freshwater recreational exposure and any recent flood water contact within the preceding one to two weeks (the typical incubation period) should be actively sought in any compatible febrile presentation.

• Mild to moderate disease is treated with oral doxycycline 100 mg twice daily for seven days, or, as an alternative, azithromycin 500 mg once daily for three days. Both are generally well tolerated with rapid symptomatic improvement when started promptly.
• Severe disease requires intravenous benzylpenicillin 1.5 million units every six hours, or intravenous ceftriaxone 1 g once daily, continued for seven days. Both demonstrate comparable efficacy to each other for severe disease.
• A Jarisch Herxheimer reaction can occur following initiation of antibiotic therapy, similar to that seen with spirochaetal infections generally, requiring anticipation and appropriate supportive management.
• Intensive supportive care is essential for severe presentations:
  • Renal replacement therapy for significant acute kidney injury, which is frequently reversible with adequate supportive management even when severe.
  • Respiratory support for pulmonary haemorrhage, which may require mechanical ventilation. In severe cases it has been managed with adjunctive high dose corticosteroid therapy in some protocols, though evidence remains limited.
  • Blood product support for significant coagulopathy or haemorrhage.
• Prevention is through avoidance of potentially contaminated freshwater exposure where possible, protective clothing and footwear for relevant occupational activities, and rodent control.
• For specific high risk occupational or travel scenarios, doxycycline chemoprophylaxis (200 mg once weekly) may be considered. It is particularly relevant for short term, high risk exposure such as military personnel or adventure travellers in highly endemic settings.