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 animals¹. 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. 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 activity³.
• 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, Legionnaire's disease and 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 creatinine 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 48h 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
• 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, chorioretinits
• 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
• Immunization 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