Blog
About

34
views
0
recommends
+1 Recommend
1 collections
    12
    shares
      • 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

          Background

          Diagnosis 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.

          Methodology

          We 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.

          Results

          The 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).

          Conclusions

          The 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

                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
                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.

                Article
                PNTD-D-12-00720
                10.1371/journal.pntd.0001878
                3486890
                23133686

                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.

                Page count
                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