Skip to main content
Top
Published in: BMC Infectious Diseases 1/2014

Open Access 01-12-2014 | Research article

Performance of seven serological assays for diagnosing tularemia

Authors: Valérie Chaignat, Marina Djordjevic-Spasic, Anke Ruettger, Peter Otto, Diana Klimpel, Wolfgang Müller, Konrad Sachse, George Araj, Roland Diller, Herbert Tomaso

Published in: BMC Infectious Diseases | Issue 1/2014

Login to get access

Abstract

Background

Tularemia is a rare zoonotic disease caused by the Gram-negative bacterium Francisella tularensis. Serology is frequently the preferred diagnostic approach, because the pathogen is highly infectious and difficult to cultivate. The aim of this retrospective study was to determine the diagnostic accuracy of tularemia specific tests.

Methods

The Serazym®Anti-Francisella tularensis ELISA, Serion ELISA classic Francisella tularensis IgG/IgM, an in-house ELISA, the VIRapid® Tularemia immunochromatographic test, an in-house antigen microarray, and a Western Blot (WB) assay were evaluated. The diagnosis tularemia was established using a standard micro-agglutination assay. In total, 135 sera from a series of 110 consecutive tularemia patients were tested.

Results

The diagnostic sensitivity and diagnostic specificity of the tests were VIRapid (97.0% and 84.0%), Serion IgG (96.3% and 96.8%), Serion IgM (94.8% and 96.8%), Serazym (97.0% and 91.5%), in-house ELISA (95.6% and 76.6%), WB (93.3% and 83.0%), microarray (91.1% and 97.9%).

Conclusions

The diagnostic value of the commercial assays was proven, because the diagnostic accuracy was >90%. The diagnostic sensitivity of the in-house ELISA and the WB were acceptable, but the diagnostic accuracy was <90%. Interestingly, the antigen microarray test was very specific and had a very good positive predictive value.
Appendix
Available only for authorised users
Literature
2.
go back to reference Sjostedt A: Tularemia: history, epidemiology, pathogen physiology, and clinical manifestations. Ann N Y Acad Sci. 2007, 1105: 1-29. 10.1196/annals.1409.009.CrossRefPubMed Sjostedt A: Tularemia: history, epidemiology, pathogen physiology, and clinical manifestations. Ann N Y Acad Sci. 2007, 1105: 1-29. 10.1196/annals.1409.009.CrossRefPubMed
3.
go back to reference Rotz LD, Khan AS, Lillibridge SR, Ostroff SM, Hughes JM: Public health assessment of potential biological terrorism agents. Emerg Infect Dis. 2002, 8 (2): 225-230. 10.3201/eid0802.010164.CrossRefPubMedPubMedCentral Rotz LD, Khan AS, Lillibridge SR, Ostroff SM, Hughes JM: Public health assessment of potential biological terrorism agents. Emerg Infect Dis. 2002, 8 (2): 225-230. 10.3201/eid0802.010164.CrossRefPubMedPubMedCentral
4.
go back to reference Dennis DT, Inglesby TV, Henderson DA, Bartlett JG, Ascher MS, Eitzen E, Fine AD, Friedlander AM, Hauer J, Layton M, Lillibridge SR, McDade JE, Osterholm MT, O’Toole T, Parker G, Perl TM, Russell PK, Tonat K, Working Group on Civilian Biodefense: Tularemia as a biological weapon: medical and public health management. JAMA. 2001, 285 (21): 2763-2773. 10.1001/jama.285.21.2763.CrossRefPubMed Dennis DT, Inglesby TV, Henderson DA, Bartlett JG, Ascher MS, Eitzen E, Fine AD, Friedlander AM, Hauer J, Layton M, Lillibridge SR, McDade JE, Osterholm MT, O’Toole T, Parker G, Perl TM, Russell PK, Tonat K, Working Group on Civilian Biodefense: Tularemia as a biological weapon: medical and public health management. JAMA. 2001, 285 (21): 2763-2773. 10.1001/jama.285.21.2763.CrossRefPubMed
5.
go back to reference Splettstoesser W, Guglielmo-Viret V, Seibold E, Thullier P: Evaluation of an immunochromatographic test for rapid and reliable serodiagnosis of human tularemia and detection of Francisella tularensis-specific antibodies in sera from different mammalian species. J Clin Microbiol. 2010, 48 (5): 1629-1634. 10.1128/JCM.01475-09.CrossRefPubMedPubMedCentral Splettstoesser W, Guglielmo-Viret V, Seibold E, Thullier P: Evaluation of an immunochromatographic test for rapid and reliable serodiagnosis of human tularemia and detection of Francisella tularensis-specific antibodies in sera from different mammalian species. J Clin Microbiol. 2010, 48 (5): 1629-1634. 10.1128/JCM.01475-09.CrossRefPubMedPubMedCentral
6.
go back to reference Splettstoesser WD, Tomaso H, Al Dahouk S, Neubauer H, Schuff-Werner P: Diagnostic procedures in tularaemia with special focus on molecular and immunological techniques. J Vet Med B Infect Dis Vet Public Health. 2005, 52 (6): 249-261. 10.1111/j.1439-0450.2005.00863.x.CrossRefPubMed Splettstoesser WD, Tomaso H, Al Dahouk S, Neubauer H, Schuff-Werner P: Diagnostic procedures in tularaemia with special focus on molecular and immunological techniques. J Vet Med B Infect Dis Vet Public Health. 2005, 52 (6): 249-261. 10.1111/j.1439-0450.2005.00863.x.CrossRefPubMed
7.
go back to reference Grunow R, Splettstoesser W, McDonald S, Otterbein C, O’Brien T, Morgan C, Aldrich J, Hofer E, Finke EJ, Meyer H: Detection of Francisella tularensis in biological specimens using a capture enzyme-linked immunosorbent assay, an immunochromatographic handheld assay, and a PCR. Clin Diagn Lab Immunol. 2000, 7 (1): 86-90.PubMedPubMedCentral Grunow R, Splettstoesser W, McDonald S, Otterbein C, O’Brien T, Morgan C, Aldrich J, Hofer E, Finke EJ, Meyer H: Detection of Francisella tularensis in biological specimens using a capture enzyme-linked immunosorbent assay, an immunochromatographic handheld assay, and a PCR. Clin Diagn Lab Immunol. 2000, 7 (1): 86-90.PubMedPubMedCentral
8.
go back to reference Johansson A, Berglund L, Eriksson U, Goransson I, Wollin R, Forsman M, Tarnvik A, Sjostedt A: Comparative analysis of PCR versus culture for diagnosis of ulceroglandular tularemia. J Clin Microbiol. 2000, 38 (1): 22-26.PubMedPubMedCentral Johansson A, Berglund L, Eriksson U, Goransson I, Wollin R, Forsman M, Tarnvik A, Sjostedt A: Comparative analysis of PCR versus culture for diagnosis of ulceroglandular tularemia. J Clin Microbiol. 2000, 38 (1): 22-26.PubMedPubMedCentral
9.
go back to reference WHO: World health organization guidelines on Tularaemia. Epidemic and Pandemic Alert and Response. 2007, Geneva: World Health Organization WHO: World health organization guidelines on Tularaemia. Epidemic and Pandemic Alert and Response. 2007, Geneva: World Health Organization
10.
go back to reference Schmitt P, Splettstoesser W, Porsch-Ozcürümez M, Finke EJ, Grunow R: A novel screening ELISA and a confirmatory Western blot useful for diagnosis and epidemiological studies of tularemia. Epidemiol Infect. 2005, 133 (4): 759-766. 10.1017/S0950268805003742.CrossRefPubMedPubMedCentral Schmitt P, Splettstoesser W, Porsch-Ozcürümez M, Finke EJ, Grunow R: A novel screening ELISA and a confirmatory Western blot useful for diagnosis and epidemiological studies of tularemia. Epidemiol Infect. 2005, 133 (4): 759-766. 10.1017/S0950268805003742.CrossRefPubMedPubMedCentral
11.
go back to reference Porsch-Ozcürümez M, Kischel N, Priebe H, Splettstoesser W, Finke EJ, Grunow R: Comparison of enzyme-linked immunosorbent assay, Western blotting, microagglutination, indirect immunofluorescence assay, and flow cytometry for serological diagnosis of tularemia. Clin Diagn Lab Immunol. 2004, 11 (6): 1008-1015.PubMedPubMedCentral Porsch-Ozcürümez M, Kischel N, Priebe H, Splettstoesser W, Finke EJ, Grunow R: Comparison of enzyme-linked immunosorbent assay, Western blotting, microagglutination, indirect immunofluorescence assay, and flow cytometry for serological diagnosis of tularemia. Clin Diagn Lab Immunol. 2004, 11 (6): 1008-1015.PubMedPubMedCentral
12.
go back to reference Rusnak JM, Kortepeter MG, Hawley RJ, Anderson AO, Boudreau E, Eitzen E: Risk of occupationally acquired illnesses from biological threat agents in unvaccinated laboratory workers. Biosecur Bioterror. 2004, 2 (4): 281-293. 10.1089/bsp.2004.2.281.CrossRefPubMed Rusnak JM, Kortepeter MG, Hawley RJ, Anderson AO, Boudreau E, Eitzen E: Risk of occupationally acquired illnesses from biological threat agents in unvaccinated laboratory workers. Biosecur Bioterror. 2004, 2 (4): 281-293. 10.1089/bsp.2004.2.281.CrossRefPubMed
13.
go back to reference Ericsson M, Sandstrom G, Sjostedt A, Tarnvik A: Persistence of cell-mediated immunity and decline of humoral immunity to the intracellular bacterium Francisella tularensis 25 years after natural infection. J Infect Dis. 1994, 170 (1): 110-114. 10.1093/infdis/170.1.110.CrossRefPubMed Ericsson M, Sandstrom G, Sjostedt A, Tarnvik A: Persistence of cell-mediated immunity and decline of humoral immunity to the intracellular bacterium Francisella tularensis 25 years after natural infection. J Infect Dis. 1994, 170 (1): 110-114. 10.1093/infdis/170.1.110.CrossRefPubMed
14.
go back to reference Bockemühl J, Roth J: Brucella titers in subclinical infections due to Yersinia enterocolitica serotype O:9 in a pig-breeding farm (author’s transl). Zentralbl Bakteriol Orig A. 1978, 240 (1): 86-93.PubMed Bockemühl J, Roth J: Brucella titers in subclinical infections due to Yersinia enterocolitica serotype O:9 in a pig-breeding farm (author’s transl). Zentralbl Bakteriol Orig A. 1978, 240 (1): 86-93.PubMed
15.
go back to reference Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig LM, Moher D, Rennie D, de Vet HC, Lijmer JG: Standards for reporting of diagnostic accuracy group: the STARD statement for reporting studies of diagnostic accuracy: explanation and elaboration: the standards for reporting of diagnostic accuracy group. Croat Med J. 2003, 44 (5): 639-50.PubMed Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig LM, Moher D, Rennie D, de Vet HC, Lijmer JG: Standards for reporting of diagnostic accuracy group: the STARD statement for reporting studies of diagnostic accuracy: explanation and elaboration: the standards for reporting of diagnostic accuracy group. Croat Med J. 2003, 44 (5): 639-50.PubMed
16.
go back to reference Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig LM, Lijmer JG, Moher D, Rennie D, de Vet HC: Standards for reporting of diagnostic accuracy group: towards complete and accurate reporting of studies of diagnostic accuracy: the STARD initiative: the standards for reporting of diagnostic accuracy group. Croat Med J. 2003, 44 (5): 635-8.PubMed Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig LM, Lijmer JG, Moher D, Rennie D, de Vet HC: Standards for reporting of diagnostic accuracy group: towards complete and accurate reporting of studies of diagnostic accuracy: the STARD initiative: the standards for reporting of diagnostic accuracy group. Croat Med J. 2003, 44 (5): 635-8.PubMed
17.
go back to reference Anjum MF, Tucker JD, Sprigings KA, Woodward MJ, Ehricht R: Use of miniaturized protein arrays for Escherichia coli O serotyping. Clin Vaccine Immunol. 2006, 13 (5): 561-567. 10.1128/CVI.13.5.561-567.2006.CrossRefPubMedPubMedCentral Anjum MF, Tucker JD, Sprigings KA, Woodward MJ, Ehricht R: Use of miniaturized protein arrays for Escherichia coli O serotyping. Clin Vaccine Immunol. 2006, 13 (5): 561-567. 10.1128/CVI.13.5.561-567.2006.CrossRefPubMedPubMedCentral
18.
go back to reference Tärnvik A, Priebe HS, Grunow R: Tularaemia in Europe: an epidemiological overview. Scand J Infect Dis. 2004, 36 (5): 350-5. 10.1080/00365540410020442.CrossRefPubMed Tärnvik A, Priebe HS, Grunow R: Tularaemia in Europe: an epidemiological overview. Scand J Infect Dis. 2004, 36 (5): 350-5. 10.1080/00365540410020442.CrossRefPubMed
19.
go back to reference Eliasson H, Back E: Tularaemia in an emergent area in Sweden: an analysis of 234 cases in five years. Scand J Infect Dis. 2007, 39 (10): 880-889. 10.1080/00365540701402970.CrossRefPubMed Eliasson H, Back E: Tularaemia in an emergent area in Sweden: an analysis of 234 cases in five years. Scand J Infect Dis. 2007, 39 (10): 880-889. 10.1080/00365540701402970.CrossRefPubMed
20.
go back to reference Evans ME, Gregory DW, Schaffner W, McGee ZA: Tularemia: a 30-year experience with 88 cases. Medicine (Baltimore). 1985, 64 (4): 251-269.CrossRef Evans ME, Gregory DW, Schaffner W, McGee ZA: Tularemia: a 30-year experience with 88 cases. Medicine (Baltimore). 1985, 64 (4): 251-269.CrossRef
21.
go back to reference Meric M, Willke A, Finke EJ, Grunow R, Sayan M, Erdogan S, Gedikoglu S: Evaluation of clinical, laboratory, and therapeutic features of 145 tularemia cases: the role of quinolones in oropharyngeal tularemia. APMIS. 2008, 116 (1): 66-73. 10.1111/j.1600-0463.2008.00901.x.CrossRefPubMed Meric M, Willke A, Finke EJ, Grunow R, Sayan M, Erdogan S, Gedikoglu S: Evaluation of clinical, laboratory, and therapeutic features of 145 tularemia cases: the role of quinolones in oropharyngeal tularemia. APMIS. 2008, 116 (1): 66-73. 10.1111/j.1600-0463.2008.00901.x.CrossRefPubMed
22.
go back to reference Sharma N, Hotta A, Yamamoto Y, Fujita O, Uda A, Morikawa S, Yamada A, Tanabayashi K: Detection of Francisella tularensis-specific antibodies in patients with tularemia by a novel competitive enzyme-linked immunosorbent assay. Clin Vaccine Immunol. 2013, 20 (1): 9-16. 10.1128/CVI.00516-12.CrossRefPubMedPubMedCentral Sharma N, Hotta A, Yamamoto Y, Fujita O, Uda A, Morikawa S, Yamada A, Tanabayashi K: Detection of Francisella tularensis-specific antibodies in patients with tularemia by a novel competitive enzyme-linked immunosorbent assay. Clin Vaccine Immunol. 2013, 20 (1): 9-16. 10.1128/CVI.00516-12.CrossRefPubMedPubMedCentral
23.
go back to reference Cubero Ribas A, Menegotto F, González Cabrero S, Gutiérrez P, Bratos Pérez MA, Delgado JM, Orduña A: Evaluación de un nuevo test inmunocromatográfico (Virapid®Tularemia) para el diagnóstico serológico de tularemia humana. 2011, Malaga, Spain. Cubero Ribas A, Menegotto F, González Cabrero S, Gutiérrez P, Bratos Pérez MA, Delgado JM, Orduña A: Evaluación de un nuevo test inmunocromatográfico (Virapid®Tularemia) para el diagnóstico serológico de tularemia humana. 2011, Malaga, Spain.
24.
go back to reference Kiliç S, Celebi B, Yeşilyurt M: Evaluation of a commercial immunochromatographic assay for the serologic diagnosis of tularemia. Diagn Microbiol Infect Dis. 2012, 74 (1): 1-5. 10.1016/j.diagmicrobio.2012.05.030.CrossRefPubMed Kiliç S, Celebi B, Yeşilyurt M: Evaluation of a commercial immunochromatographic assay for the serologic diagnosis of tularemia. Diagn Microbiol Infect Dis. 2012, 74 (1): 1-5. 10.1016/j.diagmicrobio.2012.05.030.CrossRefPubMed
25.
go back to reference Tomaso H, Mooseder G, Dahouk SA, Bartling C, Scholz HC, Strauss R, Treu TM, Neubauer H: Seroprevalence of anti-Yersinia antibodies in healthy Austrians. Eur J Epidemiol. 2006, 21 (1): 77-81. 10.1007/s10654-005-5047-z.CrossRefPubMed Tomaso H, Mooseder G, Dahouk SA, Bartling C, Scholz HC, Strauss R, Treu TM, Neubauer H: Seroprevalence of anti-Yersinia antibodies in healthy Austrians. Eur J Epidemiol. 2006, 21 (1): 77-81. 10.1007/s10654-005-5047-z.CrossRefPubMed
Metadata
Title
Performance of seven serological assays for diagnosing tularemia
Authors
Valérie Chaignat
Marina Djordjevic-Spasic
Anke Ruettger
Peter Otto
Diana Klimpel
Wolfgang Müller
Konrad Sachse
George Araj
Roland Diller
Herbert Tomaso
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2014
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/1471-2334-14-234

Other articles of this Issue 1/2014

BMC Infectious Diseases 1/2014 Go to the issue