Robyn Stoddard, Sean V. Shadomy

Infectious Agent

Leptospirosis is caused by obligate aerobic spirochete bacteria in the genus Leptospira, with optimal growth occurring at 28º C–30º C.

Mode of Transmission

Infection occurs through abrasions or cuts in the skin or through the conjunctiva and mucous membranes. Humans may be infected by direct contact with urine or reproductive fluids from infected animals or with water or soil contaminated with those fluids. Prolonged immersion in contaminated water increases the risk for infection. Infection rarely occurs through animal bites or human-to-human contact.

Occurrence

• Leptospirosis has worldwide distribution, with a higher incidence in tropical climates.
• Domestic, peridomestic, and wild animals serve as maintenance hosts of the bacteria and excrete the bacteria in their urine, amniotic fluid, or placental tissue, which can contaminate the soil and water.
• Most Leptospira species proliferate in fresh water, damp soil, or mud.
• The occurrence of flooding after hurricanes or heavy rainfall facilitates the spread of the organism, contributing to outbreaks. This is especially true in regions with high endemic rates of infection.
• Leptospirosis is associated with animal husbandry.
• Rodent-borne leptospirosis may be a risk to persons exposed to rat urine in infested urban areas.

Risk for Travelers

• Travelers participating in recreational water activities, such as whitewater rafting, adventure racing, kayaking, or triathlon events may be at increased risk for leptospirosis, particularly following periods of heavy rainfall or flooding.
• Outbreaks of leptospirosis have occurred in the United States after flooding in both Hawaii and Puerto Rico. Leptospirosis has also been reported in international travelers to regions experiencing epidemics following heavy rainfall or flooding (CDC, unreported data).

Clinical Presentation

• The incubation period is 2 days to 3 weeks.
• The symptoms of leptospirosis are broad and often biphasic. The acute or bacteremic phase lasts a week, followed by the immune phase that is characterized by both antibody production and the presence of leptospires in the urine.
• The acute, generalized illness mimics other acute febrile illnesses such as dengue fever, malaria, or typhus. Common symptoms include headache, fever, chills, myalgia, nausea, diarrhea, abdominal pain, uveitis, adenopathy, conjunctival suffusion without purulent discharge, and occasionally a skin rash. The headache is often severe and includes retro-orbital pain and photophobia. Aseptic meningitis occurs in up to 25% of cases.
• The icteric or severe form of the disease (Weil’s disease) occurs in 5%–10% of patients with leptospirosis. Symptoms include jaundice, renal failure, hemorrhage, cardiac arrhythmias, pneumonitis, and hemodynamic collapse. The mortality rate in patients with severe leptospirosis ranges from 5% to 15%.

Diagnosis

• Diagnosis of leptospirosis is usually based on serology. Antibodies may be detected in the blood within 5–7 days of symptom onset. Culture or demonstration of the organism under darkfield microscopy are both relatively insensitive. No PCR assay has been validated with clinical specimens.
• Confirmation of leptospirosis requires seroconversion between acute- and convalescent-phase serum specimens, as demonstrated by the microscopic agglutination test (MAT); culture of the organism from clinical specimens; or demonstration of Leptospira in a clinical specimen by immunofluorescence.
• MAT, the recognized standard reference test for serologic diagnosis of leptospirosis, is performed only in reference laboratories. Although MAT is not specific for diagnosis of acute cases, a single elevated MAT titer in a patient with a compatible febrile illness and suspected exposure suggests acute leptospirosis. Seroconversion with a four-fold or greater rise in titer between acute- and convalescent-phase serum specimens obtained ≥2 weeks apart confirms the diagnosis.
• Several rapid, reliable serologic assays are commercially available for diagnostic screening for an acute infection. A recent evaluation of four of these assays concluded that both a microplate IgM ELISA and an IgM dot-ELISA dipstick test exhibited high sensitivity and specificity on acute samples.

Treatment

• Missed or delayed diagnosis of leptospirosis is common due to its nonspecific clinical presentation and a low index of suspicion among health-care providers seeing returned travelers.
• Antimicrobial therapy should be initiated early in the course of the disease if leptospirosis is suspected.
• Intravenous penicillin is the drug of choice for patients with severe leptospirosis. As with other spirochete infections, a Jarisch–Herxheimer reaction (an acute febrile reaction that can range from rash to anaphylaxis) can develop after initiation of penicillin therapy. Various methods have been described to prevent or control Jarisch–Herxheimer reactions, and management should follow the appropriate standards for patient care.
• Oral doxycycline is effective in decreasing the severity and duration of leptospirosis and the occurrence of leptospiruria in acute or mild disease. Doxycycline should not be used in pregnant women or children younger than 8 years of age because of the risk for dental staining.
• Parenteral third-generation cephalosporins (e.g., ceftriaxone or cefotaxime), doxycycline, or azithromycin may also be used for the treatment of severe leptospirosis.
• Due to the risk for potential complications, including cardiac arrhythmia, renal failure, pulmonary involvement and respiratory distress, or myocarditis, patients with leptospirosis may require hospitalization, supportive therapy, and close monitoring.

Preventive Measures for Travelers

• No vaccine is available in the United States.
• Travelers who might be at an increased risk for infection due to recreational water activities or exposure to contaminated surface waters and soil should be advised to consider preventive measures such as wearing protective clothing, especially footwear, and covering cuts and abrasions with occlusive dressings. They should avoid contact with, submersion in, or swallowing potentially contaminated water.

Antibiotic Chemoprophylaxis

• Travelers at risk because of destination or activities during travel may benefit from chemoprophylaxis. Until further data become available, CDC recommends that adult travelers who might be at increased risk for leptospirosis be advised to consider chemoprophylaxis with doxycycline (200 mg orally, weekly), begun 1–2 days before and continuing through the period of exposure. Indications for prophylactic doxycycline use for children have not been established.
• Travelers at increased risk for leptospirosis and in need of malaria chemoprophylaxis should consider using doxycycline for both indications.

References

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