Leptospirosis

Essentials of Diagnosis

• Clinical illness can vary from asymptomatic to fatal liver and kidney failure

• Anicteric leptospirosis is the more common and milder form of the disease

• Icteric leptospirosis (Weil syndrome) is more severe form of the disease

General Considerations

• Leptospirosis is an acute and sometimes severe infection caused by 21 species within the genus Leptospira

• Leptospirosis

  • Occurs worldwide

  • Transmitted to humans by the ingestion of food and drink contaminated by the urine of the infected animal

• The organism may also enter through minor skin lesions and probably via the conjunctiva

• Cases have occurred in international travelers after swimming or rafting in contaminated water

• Occupational cases occur among sewer workers, rice planters, abattoir workers, and farmers

• Sporadic urban cases have been seen in homeless persons exposed to rat urine

• The incubation period is 2–20 days

Symptoms and Signs

• Anicteric leptospirosis is often biphasic

• Initial or "septicemic" phase characterized by

  • Abrupt fever to 39–40°C

  • Chills

  • Abdominal pain

  • Severe headache

  • Myalgias

  • Marked conjunctival suffusion

• The second or "immune" phase begins after a 1- to 3-day period of improvement and is characterized by

  • Appearance of specific antibodies

  • Recurrence of symptoms with the onset of meningitis

  • Uveitis—unilateral or bilateral

  • Rash

  • Nausea, vomiting, diarrhea

  • Adenopathy

• However, in severe disease the phases may appear indistinct

• Icteric leptospirosis (Weil syndrome) is often continuous and is characterized by

  • Impaired kidney and liver function

  • Abnormal mental status

  • Hemorrhagic pneumonia

  • Hypotension

Differential Diagnosis

• Bacterial meningitis

• Influenza

• Viral hepatitis

• Yellow fever

• Dengue

• Rickettsial disease

• Hemorrhagic fever, eg, hantavirus

• Relapsing fever

Laboratory Tests

• Early in the disease, the organism may be identified by

  • Darkfield examination of the patient's blood (a test requiring expertise since false-positives are frequent in inexperienced hands)

  • Culture on a semisolid medium (eg, Fletcher medium); cultures may take 1–6 weeks to become positive but may remain negative if antibiotics were started prior

• Leptospires are excreted in the urine, and urine cultures may be positive from 10 days to 6 weeks

• Leukocyte count may be normal or as high as 50,000/mcL (0.05/L)

• Urine bile, protein, casts, and red cells

• Oliguria is common; uremia may occur in severe cases

• Elevated bilirubin and aminotransferases in 75%

• Elevated creatinine (> 1.5 mg/dL [> 132.6 mcmol/L]) in 50%

• Serum creatine kinase is usually elevated

• Diagnosis is usually made by serologic tests

• Agglutination tests show a fourfold or greater rise in titer

• Indirect hemagglutination, enzyme immunosorbent assay (EIA), and ELISA tests are also available. The IgM EIA is particularly useful (positive as early as 2 days into illness, extremely sensitive and specific [93%])

• Polymerase chain reaction methods

  • Appear to be sensitive, specific, positive early in disease

  • Able to detect leptospiral DNA in blood, urine, CSF, and aqueous humor

  • However, still investigational

Medications

• Many cases are self-limited without specific treatment

• Mild to moderate leptospirosis

  • Doxycycline, 100 mg orally twice daily for 7 days, is effective if started early

  • Amoxicillin, 50 mg/kg orally divided into three doses daily

  • Azithromycin is also active, but clinical experience is limited

• Severe leptospirosis

  • Drugs of choice: doxycycline (100 mg every 12 hours orally or intravenously), penicillin (1.5 million units intravenously every 6 hours intravenously) or ceftriaxone (1 g/day intravenously)

  • Especially effective if started within the first 4 days of illness

  • Jarisch–Herxheimer reactions may occur

Complications

• Myocarditis, aseptic meningitis, acute kidney injury, and pulmonary infiltrates with hemorrhage

• Iridocyclitis

Prognosis

• Anicteric leptospirosis

  • Usually self-limited

  • Lasts 4–30 days

  • Almost never fatal

  • Complete recovery is the rule

• Icteric leptospirosis: mortality rate for those under age 30 is 5%; for those over age 60, it is 40%

Prevention

• Avoidance of potentially contaminated food and water

• Prophylaxis with doxycycline (200 mg orally once a week) has been effective in trials and may be useful if a person is a high risk due to being in an area or season when exposure would be more likely

• Human vaccine is used in some limited settings but is not widely available

When to Admit

• Patients with jaundice or other evidence of severe disease