Leptospirosis (Weil's Disease)

Leptospirosis is an infection of worldwide distribution caused by spirochaetes of the genus Leptospira, which infect many species of both wild and domestic animals.¹

• The principal source of human infection is the rat but other sources include dogs, livestock and other wild animals.
• Infection occurs as two syndromes: anicteric (which is self-limiting) and icteric leptospirosis (Weil's disease).
• Disease is acquired through contact with contaminated water or soil, or through contact with urine or tissues of infected animals.
• The spirochaetes are shed from the urine and can survive in the environment for several months in moist, warm conditions.
• They enter the bloodstream through abraded skin or the mucosa from contaminated water or soil.
• Water-borne transmission has also been documented.

• Reported to be the most widespread zoonosis in the world (having an incidence greater in warm-climate areas than in temperate regions).²
• A large proportion of the population is antibody positive in areas such as rural Belize and Vietnam. Leptospirosis is a significant human disease in eastern and southern Europe, Australia and New Zealand.
• Most often affects teenagers and adults and is more common in men.
• Risk factors include sewage workers, travellers (e.g. swimming in contaminated water), farmers, veterinarians, abattoir workers, rodent control workers, and other occupations with animals.

• Incubation period is usually 7-14 days but can range from 2 to 25 days. Onset is usually abrupt.
• Many infections are mild with fever, headache, myalgia, anorexia, nausea and vomiting, dry cough and lethargy. Affected patients may not seek medical attention.
• The anicteric form may cause pneumonitis, arthritis, orchitis, cholecystitis, myocarditis, coronary arteritis, aortitis, aseptic meningitis and uveitis.
• Approximately 10% of those infected become jaundiced (with hepatocellular necrosis) and have a severe and rapidly progressive form of the disease with liver failure and renal failure.
• The jaundice appears during days 5-9 of illness and is most intense 4-5 days later, continuing for about 1 month.
• The degree of jaundice itself is not indicative of prognosis but leptospirosis without jaundice is very rarely fatal.
• Purpura, petechiae, epistaxis, minor haemoptysis and other signs of bleeding are common.
• Other symptoms include fever, vomiting, abdominal pain, skin rashes, conjunctival haemorrhage, uveitis. There is often a severe headache, retro-orbital pain, and photophobia. A severe myalgia (lower back, and legs) is common. Leptospirosis may present as aseptic meningitis.
• Pulmonary symptoms vary from cough, dyspnoea, and haemoptysis to adult respiratory distress syndrome and massive pulmonary haemorrhage.
• Hepatomegaly: hepatic percussion tenderness is a useful indicator of continuing disease activity.³
• Kidney dysfunction (Leptospiral nephropathy) is usual, sometimes with life threatening renal failure with signs of uraemia and disturbance of consciousness.

Possible alternative diagnoses to consider will include:

• Viral hepatitis
• Meningitis
• Influenza
• Malaria
• Typhoid fever
• Yellow fever
• Relapsing fever
• Scrub typhus
• Dengue fever
• Legionnaires' disease
• Toxic shock syndrome

• Liver function tests: increased serum bilirubin, transaminases
• Prolonged prothrombin time
• Full blood count: thrombocytopenia, leucocytosis and anaemia
• Renal function and electrolytes (renal failure); serum amylase levels are raised in acute renal failure
• Raised creatine kinase (muscle involvement, rhabdomyolysis)
• MSU usually shows sediment and proteinuria
• Chest x-ray: may be normal or show patchy shadowing in alveolar haemorrhage
• Diagnosis is based on serology (paired), either using microscopic slide agglutination test or new rapid sero-diagnostic kits
• Enzyme-linked immunosorbent assay (ELISA); has greater sensitivity and comparable specificity to microscopic slide agglutination test.

• First-choice drug is oral doxycycline, starting within 48 hours of illness (starting antibiotics can lead to a Jarisch-Herxheimer reaction).
• Oral amoxicillin, ampicillin and doxycycline are effective in mild-to-moderate infections.
• Intravenous penicillin G is the drug of choice for severely ill patients.
• A recent clinical trial showed that third-generation cephalosporins are as effective as doxycycline and penicillin in the treatment of acute disease.⁴
• Chloramphenicol is also active against Leptospira but should be reserved for critically ill patients.
• Supportive care and treatment of the hypotension, haemorrhage, renal failure and liver failure.
• Vitamin K should be administered for hypoprothrombinaemia.
• Immunity to leptospirosis is incomplete and so patients should be advised to adopt lifestyle changes to avoid re-exposure if possible.

• Spontaneous abortion in pregnant women
• Acute renal failure
• Thrombocytopenia
• Liver failure
• Gastrointestinal haemorrhage
• Pulmonary haemorrhage
• Rhabdomyolysis
• Eye problems, e.g. chronic or recurrent uveitis, iridocyclitis, chorioretinitis
• Adult respiratory distress syndrome
• Hypotension; vascular collapse may develop abruptly and can be fatal in the absence of aggressive supportive care
• CVA and subarachnoid haemorrhage, cerebral arteritis
• Kawasaki disease
• Erythema nodosum
• Myocarditis
• Congestive heart failure is rare but non-specific ECG changes are common

• Leptospirosis is usually self-limiting. Most cases without jaundice recover spontaneously but without treatment may progress to icteric leptospirosis.
• Liver and renal dysfunction are usually reversible, with resolution over 1-2 months.
• Leptospirosis with jaundice is fatal in 5-15%. Death is often caused by gastrointestinal and pulmonary haemorrhage, renal failure and adult respiratory distress syndrome.
• Mortality is increased in the elderly.

• Reduce direct contact with infected animals and indirect contact with animal urine. Avoid ponds, lakes, and sources known to be contaminated.
• Washing surfaces with detergents and wearing protective clothing for workers in high-risk occupations.
• Immunisation of animals with Leptospira vaccines.
• Doxycycline prophylaxis may be appropriate for people participating in high-risk water sports activities in known endemic areas or living or working in areas after natural disasters that have resulted in flooding.