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Journal of Clinical Microbiology, May 2007, p. 1528-1534, Vol. 45, No. 5
0095-1137/07/$08.00+0     doi:10.1128/JCM.02344-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Leptospira Immunoglobulin-Like Proteins as a Serodiagnostic Marker for Acute Leptospirosis{triangledown}

Julio Croda,1 João G. R. Ramos,1 James Matsunaga,2,3 Adriano Queiroz,1 Akira Homma,4 Lee W. Riley,5 David A. Haake,2,3 Mitermayer G. Reis,1 and Albert I. Ko1,6*

Gonçalo Moniz Research Center, Oswaldo Cruz Foundation, Brazilian Ministry of Health, Salvador, Brazil,1 Division of Infectious Diseases, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California,2 Department of Medicine, UCLA School of Medicine, Los Angeles, California,3 Biomanguinhos, Oswaldo Cruz Foundation, Brazilian Ministry of Health, Rio de Janeiro, Brazil,4 School of Public Health, University of California, Berkeley, California,5 Division of International Medicine and Infectious Disease, Weill Medical College of Cornell University, Ithaca, New York6

Received 19 November 2006/ Returned for modification 25 February 2007/ Accepted 6 March 2007

There is an urgent need for improved diagnosis of leptospirosis, an emerging infectious disease which imparts a large disease burden in developing countries. We evaluated the use of Leptospira immunoglobulin (Ig)-like (Lig) proteins as a serodiagnostic marker for leptospirosis. Lig proteins have bacterial immunoglobulin-like (Big) tandem repeat domains, a moiety found in virulence factors in other pathogens. Sera from patients identified during urban outbreaks in Brazil reacted strongly with immunoblots of a recombinant fragment comprised of the second to sixth Big domains of LigB from L. interrogans serovar Copenhageni, the principal agent for transmission in this setting. Furthermore, the sera recognized an analogous LigB fragment derived from L. kirschneri serovar Grippotyphosa, a pathogenic serovar which is not endemic to the study area. The immunoblot assay detected anti-LigB IgM antibodies in sera from 92% (95% confidence interval, 85 to 96%) of patients during acute-phase leptospirosis. The assay had a sensitivity of 81% for sera from patients with less than 7 days of illness. Anti-LigB antibodies were found in sera from 57% of the patients who did not have detectable anti-whole-Leptospira responses as detected by IgM enzyme-linked immunosorbent assay and microagglutination test. The specificities of the assay were 93 to 100% and 90 to 97% among sera from healthy individuals and patients with diseases that have clinical presentations that overlap with those of leptospirosis, respectively. These findings indicate that the antibody response to this putative virulence determinant is a sensitive and specific marker for acute infection. The use of this marker may aid the prompt and timely diagnosis required to reduce the high mortality associated with severe forms of the disease.


* Corresponding author. Mailing address: Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz/MS, Rua Waldemar Falcão, 121, Salvador, Bahia 40295-001, Brazil. Phone: 55 71 3176-2302. Fax: 55 71 3176-2281. E-mail: aik2001{at}med.cornell.edu

{triangledown} Published ahead of print on 14 March 2007.


Journal of Clinical Microbiology, May 2007, p. 1528-1534, Vol. 45, No. 5
0095-1137/07/$08.00+0     doi:10.1128/JCM.02344-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




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