Merck Manual

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Larry M. Bush

, MD, FACP, Charles E. Schmidt College of Medicine, Florida Atlantic University;

Maria T. Vazquez-Pertejo

, MD, FACP, Wellington Regional Medical Center

Reviewed/Revised Nov 2022

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 second phase sometimes includes hepatic, pulmonary, renal, and meningeal involvement. Diagnosis is by culture and serologic testing. Treatment is with antibiotics such as doxycycline or penicillin.

Spirochetes are distinguished by the helical shape of the bacteria. Pathogenic spirochetes include Treponema, Leptospira, and Borrelia. Both Treponema and Leptospira are too thin to be seen using brightfield microscopy but are clearly seen using darkfield or phase microscopy. Borrelia are thicker and can also be stained and seen using brightfield microscopy.

Leptospirosis, a zoonosis occurring in many domestic and wild animals, may cause inapparent illness or serious, even fatal disease in humans. 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, goats, and pigs. These animals can shed leptospires in their urine for years. Dogs, cattle, pigs, mice, 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. Aerosol inhalation of droplet nuclei is a less common mode of entry. 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 fresh water). Outbreaks have been reported outside the US after heavy rainfall or freshwater flooding. Leptospira can survive for several weeks to months in freshwater sources (eg, lakes, ponds). However, they can survive for only a few hours in salt water.

Cases of leptospirosis in the US must be reported to the Centers for Disease Control and Prevention (CDC). The 100 to 200 reported annual US cases (highest incidence is in Puerto Rico followed by Hawaii) 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 of Leptospirosis

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

Leptospirosis is characteristically biphasic, although a few patients have only a fulminant monophasic illness.

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 third or fourth 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 second, or immune, phase occurs between the 6th day 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. Lung involvement may be severe with pulmonary hemorrhage. This phase typically lasts from 4 to 30 days.

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, hemoptysis, petechiae, purpura, and ecchymoses, then develop and rarely progress to subarachnoid, adrenal, or gastrointestinal hemorrhage. Thrombocytopenia may occur. Signs of hepatocellular and renal dysfunction appear from the third to sixth 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 case fatality rate is 5 to 10% (up to 40% in severe cases); it is higher in patients > age 60.

Diagnosis of Leptospirosis

  • Blood cultures

  • Serologic testing

  • Sometimes polymerase chain reaction (PCR)

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

Meningeal findings mandate lumbar puncture Lumbar Puncture (Spinal Tap) Lumbar puncture is used to do the following: Evaluate intracranial pressure and cerebrospinal fluid (CSF) composition (see table ) Therapeutically reduce intracranial pressure (eg, idiopathic... read more ; the cerebrospinal fluid (CSF) cell count is between 10 and 1000/mcL (0.01 to 1 × 109/L), and usually < 500/mcL (< 0.5 × 109/L), with predominantly mononuclear cells. CSF glucose is normal; protein is < 100 mg/dL (1 g/L).

The peripheral blood white blood cell count is normal or slightly elevated in most patients but may reach 50,000/mcL (50 × 109/L) 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 micromol/L) but may reach 40 mg/dL (684 micromol/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 first week of illness, when leptospires may be present and before antibody titers are detectable; urine cultures are likely to be positive during week 1 to week 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 weeks apart).

  • When only a single specimen is available, titer is ≥ 1:800 in patients with typical symptoms and signs (or ≥ 1:200 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 (early in the course of the infection when antibiotic therapy is most effective), but positive results should be confirmed by definitive testing (eg, cultures, microscopic agglutination test, PCR).

Treatment of Leptospirosis

  • Penicillin

  • Doxycycline

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

In severe illness, one of the following is recommended:

  • Penicillin G 1.5 million units IV every 6 hours for 7 days

  • Ampicillin 500 to 1000 mg IV every 6 hours for 7 days

  • Ceftriaxone 1 g IV every 24 hours for 7 days

In severe cases, supportive care, including fluid and electrolyte therapy and sometimes renal replacement therapy and/or blood transfusion, is also important.

In less severe cases, one of the following may be given:

  • Doxycycline 100 mg orally every 12 hours for 5 to 7 days

  • Ampicillin 500 to 750 mg orally every 6 hours for 5 to 7 days

  • Amoxicillin 500 mg orally every 6 hours for 5 to 7 days

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

Prevention of Leptospirosis

To prevent disease, doxycycline 200 mg orally once a week is given 1 to 2 days before and continuing through the period of known geographic exposure.

Key Points

  • Leptospirosis is a zoonosis that occurs in many domestic and wild animals (particularly dogs and rats); human infections are rare in the US 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, conjunctival suffusion, and sometimes hemoptysis; this phase lasts 4 to 9 days.

  • The immune phase occurs between the 6th day 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, cerebrospinal fluid (in patients with meningeal findings), urine cultures, serologic tests, and polymerase chain reaction testing.

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

Drugs Mentioned In This Article

Drug Name Select Trade
Ceftrisol Plus, Rocephin
Acticlate, Adoxa, Adoxa Pak, Avidoxy, Doryx, Doxal, Doxy 100, LYMEPAK, Mondoxyne NL, Monodox, Morgidox 1x, Morgidox 2x , Okebo, Oracea, Oraxyl, Periostat, TARGADOX, Vibramycin, Vibra-Tabs
Amoxil, Dispermox, Moxatag, Moxilin , Sumox, Trimox
NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
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