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by Larry M. Bush, MD, Maria T. Perez, MD

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.

Leptospirosis, a zoonosis occurring in many domestic and wild animals, may cause inapparent illness or serious, even fatal disease. There is a carrier state in which animals shed leptospires in their urine for years. Human infections are acquired by direct contact with infected urine or tissue or indirectly by contact with contaminated water or soil. Outbreaks frequently follow exposure to contaminated flood water. 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 water). Dogs and rats are other common probable sources.

Cases of leptospirosis must be reported to the Centers for Disease Prevention and Control (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. The disease 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

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 see Lumbar puncture (spinal tap); 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.

Diagnosis is confirmed if leptospires are isolated from clinical specimens or seen in fluids or tissues, if Leptospira agglutination antibody titer increases by ≥ 4-fold (microscopic agglutination test), or if titer is ≥ 1:800 in patients with typical symptoms and signs.


  • Penicillin

  • Doxycycline

Antibiotic therapy is most effective when begun early in the infection. In severe illness, penicillin G 5 to 6 million units IV q 6 h or ampicillin 500 to 1000 mg IV q 6 h is recommended. In less severe cases, doxycycline 100 mg po q 12 h, ampicillin 500 to 750 mg po q 6 h, or amoxicillin 500 mg po q 6 h may be given for 5 to 7 days. 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 and serologic testing.

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

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