Tests

1st tests to order

CBC and differential

Test
Result
Test

Leukocytosis and thrombocytopenia in the absence of disseminated intravascular coagulation in the acute/initial phase. May show anemia secondary to hemorrhage in the immune phase.

Result

high WBC count; low platelet count; anemia

urinalysis

Test
Result
Test

Should be ordered in all patients in the acute/initial phase.

Result

mild proteinuria; pyuria; hematuria; hyaline or granular casts

microscopic agglutination test (MAT)

Test
Result
Test

MAT paired acute and convalescent sera taken 2 weeks apart.

Result

fourfold increase between acute and convalescent sera is diagnostic

enzyme-linked immunosorbent assay (ELISA)

Test
Result
Test

ELISA is used commonly for early diagnosis (IgM).[61] A positive result should be confirmed with another test, ideally MAT or PCR if available.[56]

Result

positive during immune phase

polymerase chain reaction (PCR)

Test
Result
Test

Can provide a more timely diagnosis during the acute phase, if available. Can be amplified from serum, urine, aqueous humor, and other tissues; however, the best specimen is serum. The transience of leptospires in body fluids means that a negative PCR test does not exclude leptospirosis.[56]

There is substantial variability between studies assessing the accuracy of PCR and real-time PCR, and it is uncertain whether PCR or real-time PCR is better in detecting leptospirosis. There is preliminary evidence that PCR is more sensitive on blood samples collected early in the disease course.[57] [ Cochrane Clinical Answers logo ]

Result

positive for Leptospira DNA

darkfield examination

Test
Result
Test

Direct visualization of spirochete in blood or urine specimens. Likely to be positive during acute/initial phase. Darkfield examination has poor sensitivity and specificity.[Figure caption and citation for the preceding image starts]: Microscopic agglutination test with live antigen using darkfield microscopy techniqueImage provided by the CDC and the Public Health Image Library [Citation ends].com.bmj.content.model.Caption@9f478a2

Result

presence of spirochetes

blood culture

Test
Result
Test

Leptospires can be isolated from blood during the first week to 10 days (acute/initial phase). Culture is insensitive and slow and is therefore not recommended as the sole diagnostic method.[50]

Result

positive after 1 week to 4 months

cerebrospinal fluid (CSF) culture

Test
Result
Test

Leptospires can be isolated from CSF during the first week to 10 days (acute/initial phase). Culture is insensitive and slow and is therefore not recommended as the sole diagnostic method.[50]

Result

positive after 1 week to 4 months

ECG

Test
Result
Test

Should be performed in all patients owing to associated arrhythmias secondary to myocarditis. Cardiac monitoring is also recommended during treatment.

Result

atrial fibrillation; atrial flutter; tachycardia; premature ventricular contractions or ventricular tachycardia

chest x-ray

Test
Result
Test

Pulmonary involvement present during immune phase in leptospirosis.[2][67] Cases in which chest radiographs detect air-space nodules have been associated with severe leptospirosis.[67]

Result

small nodular densities and patchy alveolar infiltrates; air-space nodules

LFTs

Test
Result
Test

Should be ordered in all patients in the immune phase.

Result

elevated aminotransferases and/or alkaline phosphatase

conjugated bilirubin

Test
Result
Test

Should be ordered in all patients in the immune phase.

Result

elevated direct bilirubin; markedly elevated conjugated bilirubin levels (≤80 mg/dL)

metabolic profile

Test
Result
Test

Should be ordered in all patients in the immune phase.

Result

elevated BUN and creatinine; hypokalemia

serum pancreatic enzymes

Test
Result
Test

A small proportion of patients develop acute pancreatitis as a complication, which can be fatal.[8]

Result

amylase and lipase may be elevated

CSF analysis

Test
Result
Test

Should be ordered in all patients in the immune phase. Indicates aseptic meningitis.

Result

cell counts below 500/mm³ with lymphocytic pleocytosis; elevated protein; normal glucose

Tests to consider

urine culture

Test
Result
Test

May be ordered in the immune phase.

Result

positive after 1 week to 4 months if collected during second week of disease

renal biopsy

Test
Result
Test

Diagnostic for acute interstitial nephritis, immune-complex glomerulonephritis. Usually performed during the immune phase and recommended in patients with renal involvement in order to document the type of kidney injury.

Result

findings include tubulointerstitial inflammatory cell infiltrate of lymphocytes; plasma cells; macrophages; and polymorphonuclear infiltrates with focal areas of tubular necrosis

lung biopsy

Test
Result
Test

Findings associated with severe hemorrhagic pneumonitis in immune phase.[68][69][70]

Result

pulmonary congestion; focal areas of hemorrhage indicative of severe hemorrhagic pneumonitis

staining methods

Test
Result
Test

Includes silver staining, immunoperoxidase staining, and immunofluorescent staining. These staining methods are not widely used.[Figure caption and citation for the preceding image starts]: Silver stain on liver biopsy showing leptospiresImage provided by the CDC and the Public Health Image Library [Citation ends].com.bmj.content.model.Caption@4b62d98

Result

identifies presence of spirochete in tissue

latex agglutination

Test
Result
Test

Shown to be sensitive and specific.[62]

Result

positive

western blot

Test
Result
Test

Shown to be sensitive and specific.[62]

Result

positive

quantitative PCR

Test
Result
Test

Has been evaluated as an aid to provide an accurate and fast diagnosis in patients presenting with clinical manifestations suggestive of leptospirosis in endemic areas.[63]

Some studies have found that leptospiremia levels measured by quantitative PCR are associated with disease severity when obtained early in infection; this may be a valuable method to predict clinical course.[44]

Result

positive

Emerging tests

lateral flow assays

Test
Result
Test

While not yet widely employed, lateral flow assays are a promising diagnostic modality, although there is considerable variability in published data regarding their sensitivity (55% to 93%) and specificity (57% to 99%).[64] Several factors may account for this variability (including variations in reference tests and the stage of infection when the testing was performed, with a lower sensitivity described in the first week of infection).[64]

Result

positive

cytokines

Test
Result
Test

Current evidence suggests that interleukin (IL)-1b, IL-2, IL-4, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-alpha levels are higher in severe cases of leptospirosis in comparison with mild cases.[65] The day of infection appears to be an important determinant of cytokine level; further studies are needed before cytokine levels can be used to monitor infection.[65][66]

Result

higher levels may indicate severe infection

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