Pediatric Leptospirosis Workup

  • Author: Patrick W Hickey, MD, FAAP; Chief Editor: Russell W Steele, MD   more...
 
Updated: Jul 27, 2010
 

Laboratory Studies

  • In leptospirosis, because of long culture times and low recovery rates, low sensitivity of acute serology alone, and the time required to obtain paired acute and/or convalescent serologic results, these tests should not be the basis on which treatment is initiated. In a patient with compatible symptoms and a plausible exposure history, empiric therapy should be started.
  • Leptospires may be identified directly from infected tissues by using dark-field microscopy or direct fluorescent-antibody assay. Cultures of blood, cerebrospinal fluid (CSF), urine, and affected organs (eg, kidney) may yield positive results. Coordinate sample collection in consultation with the local microbiology laboratory because processing requires specialized techniques.
    • Leptospires may be cultured on selective media (eg, Fletcher, Stuart, Ellinghausen), combined with neomycin or 5-fluorouracil.
    • To improve the sensitivity, multiple inoculates are incubated for as many as 4 months before dark-field microscopy results are confirmed.
    • During the first 7-10 days of symptoms, blood and CSF may produce positive cultures. After that, the urine, which may contain leptospires for weeks to months, should be cultured. Urine cultures should be plated in 2 hours or less to ensure viability of the leptospire.
    • Consultation with the local microbiology laboratory is essential.
  • Serologic identification of leptospires may be more useful clinically if performed rapidly; however, the traditional gold standard, the microscopic agglutination testing (MAT) is available only at reference laboratories, such as the Centers for Disease Control and Prevention (CDC).
    • In the United States, 3 additional serologic tests available are available: the Indirect hemaglutination assay (Focus Technologies, Cyprus, CA), the leptospirosis immunoglobulin (IgM) Dip-S-Tick test (PanBio Integrated Diagnostics; Baltimore MD), and the Leptospira immunoglobulin G (IgG) enzyme-linked immunosorbent assay (PanBio Integrated Diagnostics; Baltimore MD).
    • An indirect fluorescent antibody test, the microcapsule agglutination test, the dried latex agglutination test, and several dipstick tests are available internationally.
  • MAT uses a battery of antigens taken from common (frequently locally endemic) leptospire serovars. Positive results are defined as a 4-fold rise in titer between acute and convalescent specimens.
    • A single titer exceeding 1:200 or serial titers exceeding 1:100 suggest leptospirosis; however, neither is diagnostic.
    • Reported sensitivity and specificity of the MAT are as high as 92% and 95%, respectively. Positive predictive values of 95% and negative predictive values of 100% also have been documented.
    • False-negative MAT findings may result from testing a single specimen obtained before the immune phase of disease. Test accuracy is also affected by appropriate selection of antigens for the battery, necessitating discussion with the laboratory about which serovars are suspected or predominate in the region where the case originated. MAT false-positive results may occur with cases of Legionella,Lyme disease, and syphilis.
    • MAT is further limited by its time-consuming nature and the need for a reference laboratory (eg, CDC in Atlanta, GA; World Health Organization [WHO]/Food and Agriculture Organization [FAO] Collaborating Centers in Amsterdam, the Netherlands, and in Brisbane, Australia).
  • Indirect hemaglutination assay is a rapid and easily performed method of diagnosis that is based on genus-specific antibodies.
    • Serum from patients is mixed with either antigen-coated or uncoated control cells in a microtiter tray. The tray is incubated for 1 hour, and results are read on a scale ranging from 0 to ++++.
    • Initial testing has demonstrated a sensitivity of 92-100% (with matched acute and convalescent sera) and a specificity of 94-95%. Obtaining samples as early as day 6.8 (study mean) lowered sensitivity to 81%; follow-up testing on day 8 (study mean) increased sensitivity to 100%. These levels of accuracy contrast with results obtained by researchers at the Hawaii Department of Health and the CDC who found only 15% sensitivity before the 14th day of illness. Convalescent testing after day 14 improved sensitivity to 68%. A possible explanation for this variation is differences in regional strains.
  • The dipstick test IgM dot-enzyme-linked immunosorbent assay kit is simple enough for basic laboratories to perform and can yield results in approximately 1 hour using serum, plasma, heparinized whole blood, or finger-stick capillary blood samples.
    • As many as 4 dots appear during positive reactions. A finding of 2 or more well-defined dots is considered positive. An observation of one or no dots is considered negative.
    • The test uses L biflexa serovar Patoc 1 strain antigens to bind antibodies.
    • The test has excellent sensitivity (95.5%) and specificity (98.8%) when paired acute and convalescent sera are evaluated. Single acute-phase sera sensitivity is 52%.
    • The CDC recommends referring positive results for confirmatory testing.
  • Additional diagnostic tests for leptospirosis, particularly the polymerase chain reaction (PCR), are undergoing testing and presently have no widespread clinical use.
  • Detailed discussion of the diagnostic techniques and culture methods is available in Human Leptospirosis: Guidance for Diagnosis, Surveillance and Control.[2]
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Contributor Information and Disclosures
Author

Patrick W Hickey, MD, FAAP  Assistant Professor of Pediatrics and Preventive Medicine, Uniformed Services University of the Health Sciences; Consulting Staff, Department of Pediatrics, Division of Pediatric Infectious Disease, Walter Reed Army Medical Center

Patrick W Hickey, MD, FAAP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Society of Tropical Medicine and Hygiene, and Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Gary J Noel, MD  Department of Pediatrics, Clinical Associate Professor, Weill Medical College of Cornell University

Gary J Noel, MD is a member of the following medical societies: Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Pharmacy Editor, eMedicine

Disclosure: Nothing to disclose.

Joseph Domachowske, MD  Professor of Pediatrics, Microbiology and Immunology, Department of Pediatrics, Division of Infectious Diseases, State University of New York Upstate Medical University

Joseph Domachowske, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Society for Microbiology, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Robert W Tolan Jr, MD  Chief, Division of Allergy, Immunology and Infectious Diseases, The Children's Hospital at Saint Peter's University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine

Robert W Tolan Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Phi Beta Kappa, and Physicians for Social Responsibility

Disclosure: GlaxoSmithKline Honoraria Speaking and teaching; MedImmune Honoraria Speaking and teaching; Merck Honoraria Speaking and teaching; Sanofi Pasteur Honoraria Speaking and teaching; Baxter Healthcare Honoraria Speaking and teaching; Novartis Honoraria Speaking and teaching

Chief Editor

Russell W Steele, MD  Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine

Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, and Southern Medical Association

Disclosure: Nothing to disclose.

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