Leptospirosis (Weil’s disease) refers to the 10% of infections with Leptospira interrogans (previously termed Leptospira icterohaemorrhagiae) that result in clinical hepatitis (see also Chapter 6). It is endemic in the tropics but, in the west, is mainly carried by rats. Infection occurs through direct contact with contaminated soil, water, or urine. It enters the skin through cuts or abrasions. Diagnosis requires a careful history to elicit possible exposures. Occupational and recreational risk factors include:
• Farmworkers, veterinarians, and abattoir workers.
• Sewage workers.
• Military and naval personnel.
• Sports, including caving and those involving water contact.
Causes of Leptospirosis (Weil’s disease)
Leptospirosis is caused by infection with the spirochaete Leptospira interrogans, of which there are many subtypes (serovars). Leptospira are spiral-shaped aerobic spirochaetes, best visualized by darkfield microscopy, silver stain, or fluorescent microscopy. L. interrogans can be grown from clinical specimens, including blood, urine, and cerebrospinal fluid (CSF), but special media are required for isolation, so you should discuss this with the laboratory before samples are sent. Growth may take up to 3 months.
The commonest cause of leptospirosis in the UK is contact with rat urine, although cases have been seen in pig farmers and fisheries.
Investigations of Leptospirosis (Weil’s disease)
These should include FBC, U&E, LFTs, PT, CPK, CXR, urinalysis and cultures, Leptospira serology and blood cultures with a specific request to culture Leptospira.
There may be a leucocytosis, sterile pyuria, severe jaundice (bilirubin >1,000 micromoles/L), with other liver function tests being virtually normal (transaminases, especially AST, may increase up to 200 U/L), increased serum creatinine indicative of renal failure, increased creatinine kinase (CPK) due to muscle injury (50%), hyponatraemia, and abnormal CXR with a ground-glass appearance.
Treatment of Leptospirosis (Weil’s disease)
Patients should be treated with either benzylpenicillin or doxycycline, although these probably do not affect outcome.
Presentation of Leptospirosis (Weil’s disease)
Following a 7–14-day (up to a month) incubation period, Leptospirosis tends to present with an abrupt onset of a 4–7-day septicaemic phase, characterized by flu-like symptoms, including fever, rigours, muscle aches, dyspnoea and headache in 75–100% of patients. Sometimes patients are suspected of having meningitis and undergo lumbar puncture which is then attributed to viral meningitis since there tends to be a CSF lymphocytosis, a small or modest increase in CSF protein, and no organisms seen (aseptic meningitis). As organisms are cleared, there is a period of clinical improvement. Within the next 1–2 weeks, there follows the second phase of illness, which is immune-mediated. Features include recurrence of fever, meningeal irritation, iritis, skin haemorrhagic lesions (e.g. petechiae, purpura, and ecchymoses), renal failure with acute tubular necrosis, and jaundice with hepatomegaly, as part of the biphasic illness. The pathogenesis of jaundice remains unexplained: neither haemolysis nor hepatocellular necrosis are prominent, and it is difficult to demonstrate many organisms within the affected tissue.
Approximately 25% have a non-productive cough, and 50% have nausea, vomiting, and diarrhoea. Abdominal pain is rare.
Physical examination may reveal jaundice and a rash, as well as conjunctival suffusion, at least in the early stages and sometimes later stages too. Patients may also have hepatomegaly (60%), muscle tenderness, splenomegaly, lymphadenopathy, and pharyngitis.
Leptospirosis has a variable clinical course. Most cases are mild to moderate with subclinical or self-limited systemic infection. However, severe, potentially fatal illness complicated by multiorgan failure, including renal failure, jaundice, haemorrhage, uveitis, ARDS, myocarditis, and rhabdomyolysis may occur. Liver failure and death are rare but do occur. Vasculitis with necrosis of extremities is also rare.
FBC (usually Hb and platelets low, with neutrophilia), U&E (K+ often low due to renal wasting), LFTs (elevated bilirubin and ALT/AST more than ALP), and clotting (prolonged PT). The degree of jaundice has no prognostic significance. CK and aldolase are elevated during the first week in >50%, with liver disease as a consequence of coexistent muscle damage. Blood cultures give a high yield in the first phase. Serology is highly sensitive and specific.
Urinalysis is frequently positive for protein, WBCs, and RBCs. Darkfield microscopy of serially diluted urines for spirochaetes becomes positive in the second phase and remains so for several weeks. Yield is high, but culture usually takes too long to be beneficial.
Look for pleocytosis and the presence of leptospires. There is a high yield during the first week in the presence of meningitic symptoms. This becomes negative in the second phase.
The CXR may show patchy snowflake-like infiltrates in the periphery.
Antibiotics are highly effective if administered early. Give doxycycline 100 mg twice daily (bd) orally or amoxicillin 500 mg–1 g four times daily (qds) orally or IV (depending on severity) for 1 week. Jarisch–Herxheimer reaction may occur, which should be managed supportively.
• Pulmonary haemorrhage. Consider prompt intubation and ventilation.• Renal failure. Usually secondary to hypovolaemia that responds rapidly to intravenous fluids but interstitial nephritis can develop. May require renal replacement therapy, as renal failure is the commonest cause of death.• Coagulopathy. Bleeding principally occurs into the skin or lung.• Meningitis. Immune-mediated. Clinically evident in up to 50%.• Myopathy.• Myocarditis. First-degree heart block is common and reversible.
This is excellent if treated early, although overall mortality remains 5–10%, usually due to renal or cardiorespiratory failure. Liver involvement is rarely fatal, and patients demonstrate no residual liver dysfunction or pathological structural changes. Meningeal involvement is typically fully reversible.