Blog
About

  • Record: found
  • Abstract: found
  • Article: found
Is Open Access

Accuracy of a Dual Path Platform (DPP) Assay for the Rapid Point-of-Care Diagnosis of Human Leptospirosis

Read this article at

Bookmark
      There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

      Abstract

      BackgroundDiagnosis of leptospirosis by the gold standard serologic assay, the microscopic agglutination test (MAT), requires paired sera and is not widely available. We developed a rapid assay using immunodominant Leptospira immunoglobulin-like (Lig) proteins in a Dual Path Platform (DPP). This study aimed to evaluate the assay's diagnostic performance in the setting of urban transmission.MethodologyWe determined test sensitivity using 446 acute and convalescent sera from MAT-confirmed case-patients with severe or mild leptospirosis in Brazil. We assessed test specificity using 677 sera from the following groups: healthy residents of a Brazilian slum with endemic transmission, febrile outpatients from the same slum, healthy blood donors, and patients with dengue, hepatitis A, and syphilis. Three operators independently interpreted visual results without knowing specimen status.ResultsThe overall sensitivity for paired sera was 100% and 73% for severe and mild disease, respectively. In the acute phase, the assay achieved a sensitivity of 85% and 64% for severe and mild leptospirosis, respectively. Within seven days of illness onset, the assay achieved a sensitivity of 77% for severe disease and 60% for mild leptospirosis. Sensitivity of the DPP assay was similar to that for IgM-ELISA and increased with both duration of symptoms (chi-square regression P = 0.002) and agglutinating titer (Spearman ρ = 0.24, P<0.001). Specificity was ≥93% for dengue, hepatitis A, syphilis, febrile outpatients, and blood donors, while it was 86% for healthy slum residents. Inter-operator agreement ranged from very good to excellent (kappa: 0.82–0.94) and test-to-test reproducibility was also high (kappa: 0.89).ConclusionsThe DPP assay performed acceptably well for diagnosis of severe acute clinical leptospirosis and can be easily implemented in hospitals and health posts where leptospirosis is a major public health problem. However, test accuracy may need improvement for mild disease and early stage leptospirosis, particularly in regions with high transmission.

      Author Summary

      Leptospirosis is an important cause of acute fever in the tropics and the mortality rate may exceed 15% in patients with severe disease manifestations. The gold standard serological test for diagnosing leptospirosis, the microagglutination test or MAT, requires significant laboratory resources and results are not timely. Improved diagnostics are therefore critically needed to identify patients and outbreaks earlier and to thereby prevent unnecessary deaths. The need for a rapid diagnostic test is particularly acute in resource-poor settings where leptospirosis is a major public health problem and sophisticated laboratories are unavailable. In this study, we measured the diagnostic accuracy of the novel Dual Path Platform (DPP) for leptospirosis using serum from patients with mild and severe disease. The DPP assay detected up to 85% of severe leptospirosis and 64% of mild leptospirosis patients using the initial clinical specimen collected at hospital presentation and its diagnostic performance was comparable to a commonly used IgM-ELISA. Furthermore, the DPP assay produces a result in 20 minutes and can be more easily implemented in field settings than existing diagnostic technologies. The commercially available DPP kit offers the simple, accurate, and quick diagnosis of leptospirosis and, consequently, more timely clinical and public health decision-making.

      Related collections

      Most cited references 43

      • Record: found
      • Abstract: found
      • Article: not found

      Leptospirosis.

      Leptospirosis is a worldwide zoonotic infection with a much greater incidence in tropical regions and has now been identified as one of the emerging infectious diseases. The epidemiology of leptospirosis has been modified by changes in animal husbandry, climate, and human behavior. Resurgent interest in leptospirosis has resulted from large outbreaks that have received significant publicity. The development of simpler, rapid assays for diagnosis has been based largely on the recognition that early initiation of antibiotic therapy is important in acute disease but also on the need for assays which can be used more widely. In this review, the complex taxonomy of leptospires, previously based on serology and recently modified by a genotypic classification, is discussed, and the clinical and epidemiological value of molecular diagnosis and typing is also evaluated.
        Bookmark
        • Record: found
        • Abstract: found
        • Article: not found

        Urban epidemic of severe leptospirosis in Brazil. Salvador Leptospirosis Study Group.

        Leptospirosis has, traditionally, been considered a sporadic rural disease. We describe a large urban outbreak of leptospirosis. Active surveillance for leptospirosis was established in an infectious-disease referral hospital in Salvador, Brazil, between March 10 and Nov 2, 1996. Patients meeting case criteria for severe manifestations of leptospirosis were recruited into the study. The diagnosis was confirmed in the laboratory with the microagglutination test and identification of leptospires in blood or urine. Risk factors for death were examined by multivariate analyses. Surveillance identified 326 cases of which 193 (59%) were laboratory-confirmed (133) or probable (60) cases. Leptospira interrogans serovar copenhageni was isolated from 87% of the cases with positive blood cultures. Most of the cases were adult (mean age 35.9 years [SD 15.9]), and 80% were male. Complications included jaundice (91%), oliguria (35%), and severe anaemia (26%). 50 cases died (case-fatality rate 15%) despite aggressive supportive care including dialysis (in 23%). Altered mental status was the strongest independent predictor of death (odds ratio 9.12 [95% CI 4.28-20.3]), age over 37 years, renal insufficiency, and respiratory insufficiency were also significant predictors of death. Before admission to hospital, 42% were misdiagnosed as having dengue fever in the outpatient clinic; an outbreak of dengue fever was taking place concurrently. An epidemic of leptospirosis has become a major urban health problem, associated with high mortality. Diagnostic confusion with dengue fever, another emerging infectious disease with a similar geographic distribution, prevents timely intervention that could minimise mortality.
          Bookmark
          • Record: found
          • Abstract: found
          • Article: not found

          Towards complete and accurate reporting of studies of diagnostic accuracy: The STARD Initiative.

          To comprehend the results of diagnostic accuracy studies, readers must understand the design, conduct, analysis, and results of such studies. That goal can be achieved only through complete transparency from authors. To improve the accuracy and completeness of reporting of studies of diagnostic accuracy in order to allow readers to assess the potential for bias in the study and to evaluate its generalizability. The Standards for Reporting of Diagnostic Accuracy (STARD) steering committee searched the literature to identify publications on the appropriate conduct and reporting of diagnostic studies and extracted potential items into an extensive list. Researchers, editors, methodologists and statisticians, and members of professional organizations shortened this list during a 2-day consensus meeting with the goal of developing a checklist and a generic flow diagram for studies of diagnostic accuracy. The search for published guidelines on diagnostic research yielded 33 previously published checklists, from which we extracted a list of 75 potential items. The consensus meeting shortened the list to 25 items, using evidence on bias whenever available. A prototypical flow diagram provides information about the method of patient recruitment, the order of test execution, and the numbers of patients undergoing the test under evaluation, the reference standard, or both. Evaluation of research depends on complete and accurate reporting. If medical journals adopt the checklist and the flow diagram, the quality of reporting of studies of diagnostic accuracy should improve to the advantage of the clinicians, researchers, reviewers, journals, and the public.
            Bookmark

            Author and article information

            Affiliations
            [1 ]Duke University School of Medicine, Durham, North Carolina, United States of America
            [2 ]Centro de Pesquisa de Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil
            [3 ]Instituto de Saúde Coletiva, Universidade Federal da Bahia, Salvador, Brazil
            [4 ]Bio-Manguinhos, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
            [5 ]Departamento de Medicina Clínica, Universidade de Pernambuco, Recife, Brazil
            [6 ]Chembio Diagnostic Systems, Medford, New York, United States of America
            [7 ]Yale University Schools of Public Health and Medicine, New Haven, Connecticut, United States of America
            University of Washington, United States of America
            Author notes

            The authors have read the journal's policy and have the following conflicts: AIK and MGR are holders of the U.S. patent 8,124,110 for the proteins with repetitive bacterial-Ig-like (Big) domains present in Leptospira species used as antigens in the DPP assay. JE holds U.S. patent 7,879,597 for the dual path immunoassay device (DPP) evaluated in this study. JE, KPL, and RG are employees of Chembio Diagnostic Systems, Inc., which developed the DPP assay for leptospirosis and has transferred the DPP technology to the Brazilian Ministry of Health.

            Conceived and designed the experiments: SAN GSR CLA DT KPL MAM AIK. Performed the experiments: SAN CLA DT AOD AHOG. Analyzed the data: SAN GSR KPL AIK. Contributed reagents/materials/analysis tools: DBMF RG JE KPL MGR MAM AIK. Wrote the paper: SAN GSR KPL. Reviewed and approved the final version of the manuscript: SAN GSR CLA DT AOD AHOG DBMF RG JE KPL MGR MAM AIK.

            Contributors
            Role: Editor
            Journal
            PLoS Negl Trop Dis
            PLoS Negl Trop Dis
            plos
            plosntds
            PLoS Neglected Tropical Diseases
            Public Library of Science (San Francisco, USA )
            1935-2727
            1935-2735
            November 2012
            1 November 2012
            : 6
            : 11
            23133686
            3486890
            PNTD-D-12-00720
            10.1371/journal.pntd.0001878
            (Editor)

            This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

            Counts
            Pages: 8
            Funding
            This work was supported by the following grants: (1) National Institutes of Health R44 AI072856; (2) NIH U01 AI088752; (3) NIH R01 AI052473; (4) NIH D43 TW00919; (5) NIAID SBIR R44 A1072856; and (6) NIH Office of the Director, Fogarty International Center, Office of AIDS Research, National Cancer Center, National Eye Institute, National Heart, Blood, and Lung Institute, National Institute of Dental & Craniofacial Research, National Institute On Drug Abuse, National Institute of Mental Health, National Institute of Allergy and Infectious Diseases Health, and NIH Office of Women's Health and Research through the International Clinical Research Scholars and Fellows Program at Vanderbilt University (R24 TW007988) and the American Relief and Recovery Act. Additional support was provided by the National Council for Scientific and Technological Development, Brazilian Ministry of Science and Technology (CNPq/MCT); the Department of Science and Technology, Secretariat of Science Technology and Strategic Inputs, Brazilian Ministry of Health (DECIT/MS) (554788/2006-3); and the Oswaldo Cruz Foundation, Brazilian Ministry of Health (Bio-Manguinhos and Gonçalo Moniz Research Center Letters of Agreement 01/1999, 01/2000, 04/2002, 02/2003, 08/2005, 03/2006, 03/2007, 03/2008, 03/2009, 03/2010, 03/2011, and 03/2012). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
            Categories
            Research Article
            Biology
            Immunology
            Immunologic Techniques
            Immunoassays
            Medicine
            Clinical Immunology
            Immunologic Techniques
            Immunoassays
            Diagnostic Medicine
            Test Evaluation
            Epidemiology
            Clinical Epidemiology
            Global Health
            Infectious Diseases
            Bacterial Diseases
            Leptospirosis
            Neglected Tropical Diseases
            Leptospirosis

            Infectious disease & Microbiology

            Comments

            Comment on this article