Case Based Pediatrics For Medical Students and Residents
Department of Pediatrics, University of Hawaii John A. Burns School of Medicine
Chapter VI.28. Leptospirosis
Selina S.P. Chen, MD, MPH
October 2002

Return to Table of Contents

A 14 year old male, previously healthy, presents to the emergency department with a one week history of fever, malaise, abdominal discomfort, calf pain and a mild sore throat. He denies any cough, hemoptysis, dyspnea, chills, night sweats, anorexia, nausea, vomiting, or dysuria. His urine output is good. There is no history of trauma, blood transfusions, or recent travel.

He lives with his parents. His father is a fisherman and his mother is a housewife. He is in the 9th grade with a 3.1 GPA. He is the captain of the school swim team. He also swims in streams and canals. He denies substance abuse and sexual activity.

Exam: VS T 38.4C, P 110, RR 18, BP 130/80 mm Hg. Height and weight are at the 50th percentile. He is alert in no acute distress. He is noted to have a moderate conjunctival suffusion (redness of the conjunctiva), with scleral icterus. His pharynx is injected, but his tonsils are not enlarged. His neck is supple with 1 cm anterior lymphadenopathy. Heart is regular with no murmur. His lungs are clear. His abdomen has normoactive bowel sounds with tender hepatomegaly; but no rebound or guarding. His extremity muscle strength is 4/5. His lower extremity muscles are tender to palpation. Homans sign is negative. No nodules are palpable.

Labs: WBC 9,000 with 80% polymorphonuclear leukocytes, hemoglobin 14 g/dL, platelet count 60,000. Coagulation times are normal. BUN 70 mg/dL, creatinine 3 mg/dL, total bilirubin 10 mg/dL, direct bilirubin 8 mg/dL, AST 80 UI/L, ALT 70 U/L. CPK 1,800 UI/L. UA shows ketones >160mg/dL, >100 red blood cells per high-powered field. No pyuria, organisms or casts are seen on UA. Chest and abdominal radiographs are normal.

He is admitted to the hospital and started on IV penicillin empirically for possible leptospirosis. Culture and serology studies are pending.

Leptospirosis (from Greek leptos, meaning "fine," and speira, meaning "a coil") is a zoonosis, which was first discovered as a disease of sewer workers by Landouzy in 1883. However, Adolf Weil of Heidelberg reported the clinical entity of fever, jaundice, hemorrhage, and renal failure in 1886. The causative organism was independently isolated in 1915 by German and Japanese investigators. The cause of many diseases was then discovered to be due to leptospira species. These diseases include pretibial fever, swineherd's disease, canefield fever in Australia, seven-day fever in Japan, swamp or mud fever in Europe, and Fort Bragg fever in the United States. The same Japanese investigators shortly discovered the role of rats as carriers. Rats are the most common reservoirs; however, many mammals have since been identified as reservoirs, especially cattle and feral pigs in Hawaii. Spread of leptospirosis can occur by contact with urine, blood or tissues from infected persons. The organisms enter the body through breaks in the skin or through mucous membranes. Infection is commonly acquired by bathing in contaminated water or by drinking contaminated water.

Leptospirosis presents with great clinical variability from a mild flu-like illness to an acute life-threatening condition, known as Weil's syndrome. Two major clinically recognizable syndromes are observed: anicteric leptospirosis (90%) and the more severe and potentially lethal form, icteric leptospirosis or Weil's syndrome (10%). The incubation period lasts 1-2 weeks.

Each syndrome has two distinct phases: the septic phase and the immune phase. The septic phase lasts 4-7 days, consisting of a flu-like syndrome. Leptospira can be found in the bloodstream and cerebral fluid. The immune phase lasts 4-30 days, consisting of aseptic meningitis, uveitis, iritis, rash, hepatic, and renal involvement. Leptospira can then be found in the urine and aqueous humor.

In anicteric leptospirosis, the septic phase is characterized by fever, headache, abdominal pain, anorexia, nausea, vomiting, and myalgia. The most common physical finding is conjunctival suffusion (reddening of the eye surface) without purulent discharge. Other signs include maculopapular skin rashes, pharyngeal injection, lymphadenopathy, hepatomegaly, and splenomegaly. The immune phase is characterized by less prominent fever, more intense headache, aseptic meningitis, conjunctival suffusion, uveitis, hepatosplenomegaly, rash, and pulmonary involvement.

Icteric leptospirosis, previously known as Weil's syndrome, is a more serious and potentially fatal syndrome. The septic and immune phases are not as distinct. The septic phase resembles anicteric leptospirosis. The immune phase is characterized with hepatorenal and vascular dysfunction. Jaundice and azotemia may develop.

Most cases of leptospirosis are self-limited, but complications include uveitis, renal failure, hemorrhage, DIC, acute respiratory distress syndrome, myocarditis, and rhabdomyolysis. Liver failure is generally reversible. In the absence of jaundice, the disease is rarely fatal. Oliguria is the only independent factor which adds to mortality risk. Other risk factors include dyspnea, alveolar infiltrates on chest radiography, repolarization abnormalities on electrocardiogram, and leukocytosis. Deaths have been attributed to myocarditis, irreversible septic shock, acute respiratory failure, and multiple organ failure.

Routine laboratory findings in leptospirosis are often non-diagnostic. CBC often reveals normal leukocyte counts (usually <10,000, but may range between 3,000 to 26,000), with neutrophilia in two-thirds of patients, and an elevated erythrocyte sedimentation rate. Anemia occurs with later presentations. Thrombocytopenia is seen most commonly in patients with azotemia. Urinalysis may show microscopic hematuria, proteinuria, pyuria, and granular casts. Aseptic meningitis is the hallmark presentation of the immune stage of anicteric leptospirosis. CSF examination shows a pleocytosis (<500) with an early neutrophilic or lymphocytic and late mononuclear cell predominance, normal glucose, and mildly elevated protein (50-110 mg/dL).

Jaundice is only observed in patients with Weil's syndrome. These patients can develop hepatic and renal dysfunction and hemorrhage. Serum bilirubin is usually <20 mg/dL, but can reach up to 60-80 mg/dL, predominantly as conjugated bilirubin. Liver function test can be elevated twofold to threefold. Hypoprothrombinemia occurs in a minority of patients. Myositis with elevated creatinine phosphokinase occurs in half of the patients.

Chest radiographs may reveal small nodular densities that can progress to infiltrates or consolidation. Pathologically, infiltrates are caused by hemorrhagic pneumonitis.

The diagnosis of leptospirosis is confirmed by isolation of the organism from any clinical specimen or seroconversion or fourfold increase in antibody titers. Leptospira can be cultured with special media from blood or CSF in the first 10 days and urine cultures are positive during the second week of illness and remain positive for up to 30 days after the resolution of symptoms. Growth in culture requires special semisolid, protein-supplemental media and takes at least one week (up to three months). Therefore, the diagnosis is made more frequently by serologic testing. A number of serologic tests are employed including micro-agglutination test (MAT), macroscopic agglutination test, indirect hemagglutination, and ELISA. Although MAT is considered the gold standard, it is not readily available in many institutions. ELISA is typically first performed and if suggestive, MAT can then be sent to the CDC in Atlanta. Newer studies utilizing polymerase chain reaction (PCR) are being investigated.

Differential diagnoses include dengue fever, hemorrhagic yellow fever, malaria, influenza, Louse-borne epidemic relapsing fever, tick-borne endemic relapsing fever, arthropod-borne and rodent-borne pathogens. Although dropped from the list of national notifiable diseases since 1994, leptospirosis remains a reportable illness in Hawaii.

Penicillin or tetracycline-based antibiotics, preferably doxycycline, are the antibiotics of choice even when treatment is delayed. In less ill patients, an oral dose of doxycycline for one week shortens the course of early leptospirosis. Intravenous penicillin used in severely ill patients reduces the duration of fever and renal dysfunction. In the most severe forms, patients must be admitted to an ICU for supportive therapy and close observation. Close monitoring and management of electrolytes, dehydration, hypotension, and hemorrhage are the mainstay of therapy. Although renal failure often resolves spontaneously, some patients may require temporary hemodialysis. Administration of vitamin K can help correct hypoprothrombinemia.

Doxycycline can prevent infection; however, exposure is difficult to predict. Prevention is best accomplished by effective rat control and avoidance of known contaminated water sources or infected urine.


1. The most specific physical finding of leptospirosis include:
. . . . . a. fever
. . . . . b. conjunctival suffusion
. . . . . c. renal failure
. . . . . d. myalgia

2. More characteristic findings in the immune phase of anicteric leptospirosis include:
. . . . . a. fever
. . . . . b. jaundice
. . . . . c. renal failure
. . . . . d. aseptic meningitis

3. Good prognostic factors for the patient in our case include all of the following, except:
. . . . . a. good urine output
. . . . . b. normal leukocytes
. . . . . c. normal coagulation tests
. . . . . d. no infiltrates on chest radiography

4. Leptospira are easily (ie., routinely) cultured from:
. . . . . a. blood
. . . . . b. plasma
. . . . . c. urine
. . . . . d. CSF
. . . . . e. none of the above

5. Therapy of leptospirosis may include all of the following except:
. . . . . a. alkalinization of urine
. . . . . b. supportive therapy
. . . . . c. doxycycline
. . . . . d. penicillin

6. Which clinical factor best distinguishes the life threatening form of leptospirosis from the more common self-limited form of leptospirosis?
. . . . . a. azotemia
. . . . . b. pneumonia
. . . . . c. meningitis
. . . . . d. dehydration
. . . . . e. jaundice <


1. Farr RW. Leptospirosis. Clin Infect Dis 1995;21:1-8.

2. Chaparro S, et al. Chapter 65- Borrelia and Leptospira Species. In: Wilson WR et al (eds). Current Diagnosis and Treatment in Infectious Diseases. 2001, New York: McGraw-Hill, pp. 686-689.

3. Faine S, et al. Leptospira and Leptospirosis. 1999, Melbourne, Australia: MediSci.

4. Shieh WJ, et al. Chapter 49- Leptospirosis. In: Guerrant RL et al (eds). Tropical Infectious Diseases: Principles, Pathogens, and Practice. 2001, Charlottesville: Churchill Livingstone, pp. 547-555.

5. Amaya-Villar R, et al. Fulminant leptospirosis in a previously healthy man. Intensive Care Med 2001;27:616.

6. Dupont H, et al. Leptospirosis: Prognostic Factors Associated with Mortality. Clin Infect Dis 1997;25:720-724.

Answers to questions




4.e. None of the above. Leptospira are difficult to culture. Culture requires special laboratory techniques not available at most clinical labs. Thus, the diagnosis is usually confirmed by serology.


6.e. Jaundice indicates icteric leptospirosis, which is a more serious condition which has a higher mortality rate. Azotemia is an additional marker of severity.

Return to Table of Contents

University of Hawaii Department of Pediatrics Home Page