Leptospirosis

Infectious Agent

Obligate aerobic, gram-negative spirochete bacteria in the genus Leptospira .

Transmission

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. Indirect infection can occur through contact with contaminated water or wet soil or consuming contaminated food or water. Infection rarely occurs through animal bites or human-to-human contact.

Epidemiology

Leptospirosis has worldwide distribution; incidence is higher in tropical climates, and the estimated worldwide annual incidence is >1 million cases. 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 and Puerto Rico. Travelers participating in recreational freshwater activities, such as swimming or boating, are at increased risk, particularly after heavy rainfall or flooding and after prolonged immersion in, or swallowing, contaminated water.

Clinical Presentation

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

Diagnosis of leptospirosis is usually based on serology; microscopic agglutination test is the gold standard and can only be performed at certain reference laboratories. Culture is insensitive, but 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. Various serologic screening tests are available, including ELISA and multiple rapid diagnostic tests; positive screening tests should be confirmed with the microscopic agglutination test. Leptospirosis is a nationally notifiable disease.

Treatment

Early antimicrobial therapy can be effective in decreasing the severity and duration of leptospirosis and should be initiated early, without waiting for confirmatory test results, if leptospirosis is suspected. For patients with mild symptoms, doxycycline is a drug of choice (100 mg orally, twice daily) but is not recommended for pregnant women or children aged <8 years; 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. 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.

Prevention

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.

CDC website: www.cdc.gov/leptospirosis

Bibliography

  1. Costa F, Hagan JE, Calcagno J, Kane M, Torgerson P, Martinez-Silveira MS, et al. Global Morbidity and Mortality of Leptospirosis: A Systematic Review. PLoS Negl Trop Dis. 2015;9(9):e0003898.  [PMID:26379143]
  2. Galloway RL, Hoffmaster AR. Optimization of LipL32 PCR assay for increased sensitivity in diagnosing leptospirosis. Diagnostic microbiology and infectious disease. 2015 Jul;82(3):199–200.  [PMID:25912810]
  3. Haake DA, Dundoo M, Cader R, Kubak BM, Hartskeerl RA, Sejvar JJ, et al. Leptospirosis, water sports, and chemoprophylaxis. Clin Infect Dis. 2002 May 1;34(9):e40–3.  [PMID:11941571]
  4. Haake DA, Levett PN. Leptospira Species (Leptospirosis). In: Bennett JE, Dolin R, Blaser MJ, editors. Principles and Practice of Infectious Diseases. 8th ed. Philadelphia, PA: Saunders 2015. p. 2714–20.
  5. Haake DA, Levett PN. Leptospirosis in humans. Current topics in microbiology and immunology. 2015;387:65–97.  [PMID:25388133]
  6. Jensenius M, Han PV, Schlagenhauf P, Schwartz E, Parola P, Castelli F, et al. Acute and potentially life-threatening tropical diseases in western travelers—a GeoSentinel multicenter study, 1996–2011. Am J Trop Med Hyg. 2013 Feb;88(2):397–404.  [PMID:23324216]
  7. Pappas G, Cascio A. Optimal treatment of leptospirosis: queries and projections. Int J Antimicrob Agents. 2006 Dec;28(6):491–6.  [PMID:17084067]
  8. Picardeau M, Bertherat E, Jancloes M, Skouloudis AN, Durski K, Hartskeerl RA. Rapid tests for diagnosis of leptospirosis: current tools and emerging technologies. Diagnostic microbiology and infectious disease. 2014 Jan;78(1):1–8.  [PMID:24207075]
  9. van de Werve C, Perignon A, Jaureguiberry S, Bricaire F, Bourhy P, Caumes E. Travel-related leptospirosis: a series of 15 imported cases. J Travel Med. 2013 Jul-Aug;20(4):228–31.  [PMID:23809072]

Authors

Renee L. Galloway, Robyn A. Stoddard, Ilana J. Schafer