Renee L. Galloway, Ilana J. Schafer, Robyn A. Stoddard
Leptospira spp., the causative agents of leptospirosis, are obligate aerobic, gram-negative spirochete bacteria.
The infection route is 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, through contact with urine-contaminated water or soil, or by consuming contaminated food or water. Infection rarely occurs through animal bites or human-to-human contact.
Leptospirosis has worldwide distribution; incidence is higher in tropical climates. The estimated worldwide annual incidence is >1 million cases, including approximately 59,000 deaths. Regions with the estimated highest morbidity include South and Southeast Asia, Oceania, the Caribbean, parts of sub-Saharan Africa, and parts of Latin America. Outbreaks can occur after heavy rainfall or flooding in endemic areas, especially in urban areas of developing countries, where housing conditions and sanitation are poor. Outbreaks of leptospirosis have occurred in the United States after flooding in Hawaii, Florida, and Puerto Rico. Travelers participating in recreational freshwater activities, such as swimming or boating, are at increased risk, particularly after heavy rainfall or flooding. Prolonged exposure to contaminated water and activities that involve head immersion or swallowing water increase the risk of infection.
The incubation period is 2–30 days, and illness usually occurs 5–14 days after exposure. While most infections are thought to be asymptomatic, clinical illness can present as a self-limiting acute febrile illness, estimated to occur in approximately 90% of clinical infections, or as a severe, potentially fatal illness with multiorgan dysfunction in 5%–10% of patients. In patients who progress to severe disease, the illness can be biphasic, with a temporary decrease in fever between phases. The acute, septicemic phase (approximately 7 days) presents as an acute febrile illness with symptoms including headache (can be severe and include retroorbital pain and photophobia), chills, myalgia (characteristically involving the calves and lower back), conjunctival suffusion (characteristic of leptospirosis but not occurring in all cases), nausea, vomiting, diarrhea, abdominal pain, cough, and rarely, a skin rash. The second or immune phase is characterized by antibody production and the presence of leptospires in the urine. In patients who progress to severe disease, symptoms can include jaundice, renal failure, hemorrhage, aseptic meningitis, cardiac arrhythmias, pulmonary insufficiency, and hemodynamic collapse. The classically described syndrome, Weil disease, consists of renal and liver failure and has a case-fatality ratio of 5%–15%. Severe pulmonary hemorrhagic syndrome is a rare but severe form of leptospirosis that can have a case-fatality ratio >50%. Poor prognostic indicators include older age and development of altered mental status, respiratory insufficiency, or oliguria.
Diagnosis of leptospirosis is usually based on serology; microscopic agglutination test (MAT), the reference standard, is best performed on paired acute and convalescent serum samples, and can only be performed at certain reference laboratories. Detection of the organism in blood or cerebrospinal fluid (for patients with meningitis) using real-time PCR can provide a more timely diagnosis during the acute, septicemic phase, and PCR can also be performed on urine after the first week of illness. Various serologic screening tests are available, including ELISA and multiple rapid diagnostic tests; the use of IgM-specific serologic screening tests is recommended, and positive screening tests should be confirmed with MAT. Culture is insensitive and slow and therefore not recommended as the sole diagnostic method. The Zoonoses and Select Agent Laboratory at CDC performs MAT and PCR for diagnosis of leptospirosis as well as culture identification and genotyping of isolates: www.cdc.gov/ncezid/dhcpp/bacterial_special/zoonoses_lab.html. Leptospirosis is a nationally notifiable disease—the Council for State and Territorial Epidemiologists’ case definition can be found at wwwn.cdc.gov/nndss/conditions/leptospirosis/case-definition/2013.
Early antimicrobial therapy can be effective in decreasing the severity and duration of leptospirosis and should be initiated as soon as possible, without waiting for diagnostic test results, if leptospirosis is suspected. For patients with mild symptoms, doxycycline is a drug of choice (100 mg orally, twice daily), unless contraindicated; alternative options include ampicillin and amoxicillin. Intravenous penicillin (1.5 MU every 6 hours) is a drug of choice for patients with severe leptospirosis, and ceftriaxone was shown to be equally effective (1 g IV, once daily). As with other spirochetal diseases, antibiotic treatment of patients with leptospirosis may cause a Jarisch-Herxheimer reaction; however, this is rarely fatal. Patients with severe leptospirosis may require hospitalization and supportive therapy, including intravenous hydration and electrolyte supplementation, dialysis in the case of oliguric renal failure, and mechanical ventilation in the case of respiratory failure.
No vaccine is available in the United States. Travelers who might be at an increased risk for infection should be educated on exposure risks and advised to consider preventive measures such as chemoprophylaxis; wearing protective clothing, especially footwear; and covering cuts and abrasions with occlusive dressings. Limited studies have shown that chemoprophylaxis with doxycycline (200 mg orally, weekly), begun 1–2 days before and continuing through the period of exposure, might be effective in preventing clinical disease in adults and could be considered for people at high risk and with short-term exposures. The best way to prevent infection is to avoid exposure: travelers should avoid contact with potentially contaminated bodies of water, walking in flood waters, and contact with potentially infected animals or their body fluids.
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