Leptospirosis Workup

Laboratory studies are used for two purposes—to confirm the diagnosis and to determine the extent of organ involvement and severity of complications. Laboratory confirmation of leptospirosis can be accomplished in 2 different ways.

Isolation of the leptospires from human tissue or body fluids is the criterion standard. Urine is the most reliable body fluid to study because the urine contains leptospires from the onset of clinical symptoms until the third week of infection. Other body fluids (eg, blood, cerebrospinal fluid [CSF]) contain the organism, but the window of opportunity to isolate them is shorter.

Tissues (ie, liver, muscle, kidney, skin, eyes) are also sources of identification of the leptospires but are obviously more complicated to acquire. Isolation of leptospires can be difficult and time consuming, involving reference laboratories and often taking several months to complete.

More often, paired acute and convalescent serum specimens are used to confirm the diagnosis. Again, this is a delayed means of confirmation because the acute sera are collected 1-2 weeks after onset of symptoms, and the convalescent sera are collected 2 weeks afterward. Antileptospire antibodies in these samples are detected using the microscopic agglutination test (MAT). The Centers for Disease Control and Prevention (CDC) laboratory in Atlanta, Georgia, performs the MAT using 23 leptospire antigens. A 4-fold rise in MAT titer between acute and convalescent sera with any of these antigens confirms the diagnosis of leptospirosis.

See the image below.

Faster laboratory methods may strongly suggest the diagnosis of leptospirosis, but they may be no more readily available than the CDC laboratory in Atlanta. A single MAT titer of 1:800 on any sera or identification of spirochetes on dark-field microscopy, when accompanied by the appropriate clinical scenario, is strongly suggestive.

In suspected leptospirosis, further laboratory studies should be routinely performed to determine the extent and severity of organ involvement after the acute phase of illness. A CBC count is necessary.

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Significant anemia due to pulmonary and gastrointestinal hemorrhage can occur. The platelet count may be diminished as a component of DIC.

Levels of blood urea nitrogen and serum creatinine may be profoundly elevated in the anuric or oliguric phase. Tubulointerstitial nephritis is the main cause of acute renal injury in Weil disease. In addition, renal magnesium and potassium wasting is common in persons with leptospirosis.^[11]

Serum bilirubin levels elevate as part of the obstructive disease due to capillaritis in the liver. Levels of hepatocellular transaminases are elevated less often and less significantly (usually < 200 U/L). Jaundice and bilirubinemia disproportional to hepatocellular damage is common in leptospirosis; alkaline phosphatase levels may be elevated 10-fold.

Coagulation times may be elevated in patients with hepatic dysfunction and/or DIC.

Serum creatine kinase levels (MM fraction) are often elevated in patients with muscular involvement.

Analysis of the CSF is useful only in excluding other causes of bacterial meningitis. Leptospires is routinely isolated from the CSF, but this finding does not change management of the disease.

Imaging studies are also useful in determining the extent and severity of organ involvement.

The most common abnormality on chest radiography is bilateral diffuse airspace disease. Chest radiography may also reveal cardiomegaly and pulmonary edema due to myocarditis. In patients with alveolar hemorrhage due to pulmonary capillaritis, the lung parenchyma may contain multiple patchy infiltrates.

Biliary tract ultrasonography can reveal an acalculous cholecystitis.

Shortly after inoculation and during the incubation period, leptospires are actively replicating in the liver. The leptospires then disseminate throughout the body and infect multiple tissues.

Silver staining and immunofluorescence are used to identify leptospires in the liver, spleen, kidney, CNS, muscles, and heart. During this acute phase, histology reveals these organisms without much inflammatory infiltrate. In addition to the finding of leptospires during histologic examination, the pathologic effects of leptospiral toxins are also apparent. See the image below.

Leptospirosis may be seen as an infective systemic vasculitis.^[12] Leptospiral toxins break down endothelial cell membranes of capillaries. This toxin-mediated process allows for extravasation of blood and leptospires from blood vessels into the supported parenchyma. Secondarily, because the capillaries are no longer functional, ischemia and cell death can occur. Later in infection, mononuclear cells predominate in the areas of this focal cell necrosis.

Leptospires can be identified in immunologically privileged sites, such as renal tubules, CNS, and the anterior chamber of the eyes, for weeks to months after the initial infection. In nonhuman animals, the intended hosts of infection, the leptospires establish residence in these immunologically privileged sites. Provided that the animal survives the initial infection, a chronic carrier state is then established, and histology reveals leptospires at these sites for years after initial infection.