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By Larry M. Bush, MD, Affiliate Professor of Clinical Biomedical Sciences; Affiliate Associate Professor of Medicine, Charles E. Schmidt College of Medicine, Florida Atlantic University; University of Miami-Miller School of Medicine ; Maria T. Perez, MD, Associate Pathologist, Department of Pathology and Laboratory Medicine, Wellington Regional Medical Center, West Palm Beach

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Leptospirosis is an infection caused by one of several pathogenic serotypes of the spirochete Leptospira. Symptoms are biphasic. Both phases involve acute febrile episodes; the 2nd phase sometimes includes hepatic, renal, and meningeal involvement. Diagnosis is by darkfield microscopy, culture, and serologic testing. Treatment is with doxycycline or penicillin.

The family Spirochaetales is distinguished by the helical shape of the bacteria. They are too thin to be visualized using routine microscopy but can be viewed using darkfield microscopy. There are 3 genera: Treponema, Leptospira, and Borrelia.

Leptospirosis, a zoonosis occurring in many domestic and wild animals, may cause inapparent illness or serious, even fatal disease. Human infections are rare in the US.

Leptospira are maintained in nature through chronic renal infection of carrier animals—commonly rats, dogs, cattle, horses, sheep, goat, and pigs. These animals can shed leptospires in their urine for years. Dogs and rats are probably common sources of human infection.

Human infections are acquired by direct contact with infected urine or tissue or indirectly by contact with contaminated water or soil. Abraded skin and exposed mucous membranes (conjunctival, nasal, oral) are the usual entry portals. Leptospirosis can be an occupational disease (eg, of farmers or sewer and abattoir workers), but in the US, most patients are exposed incidentally during recreational activities (eg, swimming in contaminated freshwater). Outbreaks have been reported outside the US after heavy rainfall or flooding.

Cases of leptospirosis must be reported to the CDC. The 40 to 100 known annual US cases occur mainly in late summer and early fall. Because distinctive clinical features are lacking, probably many more cases are not diagnosed and reported.

Symptoms and Signs

The incubation period ranges from 2 to 20 (usually 7 to 13) days.

Leptospirosis is characteristically biphasic.

The septicemic phase starts abruptly, with headache, severe muscular aches, chills, fever, cough, pharyngitis, chest pain, and, in some patients, hemoptysis. Conjunctival suffusion usually appears on the 3rd or 4th day. Splenomegaly and hepatomegaly are uncommon. This phase lasts 4 to 9 days, with recurrent chills and fever that often spikes to > 39° C. Defervescence follows.

The 2nd, or immune, phase occurs between the 6th and 12th day of illness, correlating with appearance of antibodies in serum. Fever and earlier symptoms recur, and meningitis may develop. Iridocyclitis, optic neuritis, and peripheral neuropathy occur infrequently.

If acquired during pregnancy, leptospirosis, even during the convalescent period, may cause abortion.

Weil syndrome (icteric leptospirosis) is a severe form with jaundice and usually azotemia, anemia, diminished consciousness, and continued fever. Onset is similar to that of less severe forms. However, hemorrhagic manifestations, which are due to capillary injury and include epistaxis, petechiae, purpura, and ecchymoses, then develop and rarely progress to subarachnoid, adrenal, or GI hemorrhage. Thrombocytopenia may occur. Signs of hepatocellular and renal dysfunction appear from the 3rd to 6th day. Renal abnormalities include proteinuria, pyuria, hematuria, and azotemia. Hepatocellular damage is minimal, and healing is complete.

Mortality is nil in anicteric patients. With jaundice, the mortality rate is 5 to 10%; it is higher in patients > 60 yr.


  • Blood cultures

  • Serologic testing

  • Sometimes PCR

Similar symptoms can result from viral meningoencephalitis, hemolytic fever with renal syndrome due to hantaviruses, other spirochetal infections, influenza, and hepatitis. The history of biphasic illness may help differentiate leptospirosis.

Leptospirosis should be considered in any patient with FUO if they might have been exposed to leptospires.

Patients with suspected leptospirosis should have blood cultures, acute and convalescent (3- to 4-wk) antibody titers, CBC, serum chemistries, and liver function tests.

Meningeal findings mandate lumbar puncture; the CSF cell count is between 10 and 1000/μL (usually < 500/μL), with predominantly mononuclear cells. CSF glucose is normal; protein is < 100 mg/dL. CSF bilirubin levels are higher than serum bilirubin levels.

The peripheral blood WBC count is normal or slightly elevated in most patients but may reach 50,000/μL in severely ill patients with jaundice. The presence of > 70% neutrophils helps differentiate leptospirosis from viral illnesses. Serum bilirubin is elevated out of proportion to elevations in serum aminotransferases. In jaundiced patients, bilirubin levels are usually < 20 mg/dL (< 342 μmol/L) but may reach 40 mg/dL (684 μmol/L) in severe infection.

Leptospirosis is confirmed if leptospires are isolated from clinical specimens or seen in fluids or tissues. Blood and CSF cultures are likely to be positive during the 1st wk of illness, when leptospires may be present and before antibody titers are detectable; urine cultures are likely to be positive during wk 1 to 3 of illness. The laboratory should be notified that leptospirosis is suspected because special media and prolonged incubation are required.

Leptospirosis is also confirmed by either of the following:

  • Leptospira agglutination antibody titer increases by ≥ 4-fold (microscopic agglutination test on paired samples obtained ≥ 2 wk apart).

  • When only a single specimen is available, titer is ≥ 1:800 in patients with typical symptoms and signs (or ≥ 1:400 or even ≥ 1:100 in regions where the prevalence of leptospirosis is low).

Molecular assays, such as PCR, can also confirm the diagnosis rapidly during the early phase of the illness. An IgM enzyme-linked immunosorbent assay (ELISA) detects infections within 3 to 5 days, but positive results should be confirmed by definitive testing (cultures, microscopic agglutination test, PCR).


  • Penicillin

  • Doxycycline

Antibiotic therapy is most effective when begun early in the infection.

In severe illness, one of the following is recommended:

  • Penicillin G 5 to 6 million units IV q 6 h

  • Ampicillin 500 to 1000 mg IV q 6 h

In less severe cases, one of the following may be given for 5 to 7 days:

  • Doxycycline 100 mg po q 12 h

  • Ampicillin 500 to 750 mg po q 6 h

  • Amoxicillin 500 mg po q 6 h

In severe cases, supportive care, including fluid and electrolyte therapy, is also important.

Patient isolation is not required, but urine must be handled and disposed of carefully.

Doxycycline 200 mg po given once/wk during a period of known geographic exposure prevents disease.

Key Points

  • Leptospirosis is a zoonosis that occurs in many domestic and wild animals (particularly dogs and rats); human infections are rare and are acquired by contact with infected urine or tissue or contaminated water or soil.

  • There are 2 phases of illness: septicemic and immune.

  • The septicemic phase starts abruptly with headache, severe muscular aches, fever to > 39° C, chills, cough, sore throat, and sometimes hemoptysis; this phase lasts 4 to 9 days.

  • The immune phase occurs between the 6th and 12th day of illness when antibodies appear in serum; fever and other symptoms recur, and some patients develop meningitis.

  • Weil syndrome is a severe form with jaundice and usually azotemia, anemia, diminished consciousness, and sometimes hemorrhagic manifestations.

  • Diagnose using blood cultures, CSF (in patients with meningeal findings), urine cultures, serologic tests, and PCR.

  • Treat severe illness with parenteral penicillin G or ampicillin and less severe cases with oral doxycycline, ampicillin, or amoxicillin.