Diagnosis of Neuroparacoccidioidomycosis by Detection of Circulating Antigen and Antibody in Cerebrospinal Fluid

ABSTRACT Neuroparacoccidioidomycosis (neuroPCM) is the central nervous system infection by the fungus Paracoccidioides brasiliensis. Its diagnosis is a difficult task that depends on neuroimaging techniques such as computed tomography and magnetic resonance imaging. However, the detection of circulating P. brasiliensis antigens in body fluids by inhibition enzyme-linked immunosorbent assay (inh-ELISA) has provided encouraging results. In this study, 14 cerebrospinal fluid (CSF) and 11 serum samples of patients with neuroPCM were analyzed by inh-ELISA for detection of circulating glycoprotein antigens of 43 kDa (gp43) and 70 kDa (gp70). Circulating gp43 and gp70 antigens were detected in all CSF samples from patients with neuroPCM at mean concentrations of 19.3 and 6.8 μg/ml, respectively. In addition, both gp43 and gp70 antigens were detected in 10 of 11 serum samples analyzed at mean concentrations of 4.6 and 4.0 μg/ml, respectively. By immunodiffusion test, CSF samples were determined to be negative in 13 of 14 samples. The detection of anti-gp43 and anti-gp70 antibodies by conventional ELISA showed positive results for all CSF samples, with titers ranging from 1:50 to 1:51,200. Therefore, the high sensitivity of the inh-ELISA technique in detecting gp43 and gp70 antigens in the CSF of neuroPCM patients strongly indicates that this assay can be considered as a powerful diagnostic tool. In addition, the finding of anti-gp43 and anti-gp70 antibodies in CSF samples by conventional ELISA also seems to be a promising diagnostic method for this special modality of PCM.

[1]  F. Queiroz-Telles,et al.  Detection of Paracoccidioides brasiliensis gp70 Circulating Antigen and Follow-Up of Patients Undergoing Antimycotic Therapy , 2004, Journal of Clinical Microbiology.

[2]  F. Queiroz-Telles,et al.  Monitoring gp43 Antigenemia in Paracoccidioidomycosis Patients during Therapy , 2004, Journal of Clinical Microbiology.

[3]  H. Teive,et al.  Central nervous system paracoccidioidomycosis: clinical features and laboratorial findings. , 2004, The Journal of infection.

[4]  Z. P. Camargo,et al.  Simplified method for producing Paracoccidioides brasiliensis exoantigens for use in immunodiffusion tests. , 2003, Medical mycology.

[5]  S. R. de Almeida,et al.  Characterization of gp70 and Anti-gp70 Monoclonal Antibodies in Paracoccidioides brasiliensis Pathogenesis , 2003, Infection and Immunity.

[6]  R. Mamoni,et al.  Negative Immunodiffusion Test Results Obtained with Sera of Paracoccidioidomycosis Patients May Be Related to Low-Avidity Immunoglobulin G2 Antibodies Directed against Carbohydrate Epitopes , 2003, Clinical Diagnostic Laboratory Immunology.

[7]  F. Queiroz-Telles,et al.  Detection of Circulating gp43 Antigen in Serum, Cerebrospinal Fluid, and Bronchoalveolar Lavage Fluid of Patients with Paracoccidioidomycosis , 2003, Journal of Clinical Microbiology.

[8]  F. Queiroz-Telles,et al.  Anti-gp43 antibodies in the cerebrospinal fluid of patients with central nervous system involvement by paracoccidioidomycosis. , 2002, American journal of clinical pathology.

[9]  L. Rizzo,et al.  Ocular and central nervous system paracoccidioidomycosis in a pregnant woman with acquired immunodeficiency syndrome. , 2002, American journal of ophthalmology.

[10]  W. Fagundes-Pereyra Central nervous system paracoccidioidomycosis: analysis of 13 cases with immunofluorescence research of gp43 antigen , 2001 .

[11]  S. Nouér,et al.  Endemic regions of paracoccidioidomycosis in Brazil: a clinical and epidemiologic study of 584 cases in the southeast region. , 1999, The American journal of tropical medicine and hygiene.

[12]  R. Hay,et al.  Antigenemia in Patients with Paracoccidioidomycosis: Detection of the 87-Kilodalton Determinant during and after Antifungal Therapy , 1998, Journal of Clinical Microbiology.

[13]  R. Hay,et al.  Use of monoclonal antibodies in diagnosis of paracoccidioidomycosis: new strategies for detection of circulating antigens , 1997, Journal of clinical microbiology.

[14]  G. D. Del Negro,et al.  IgG, IgM and IgA antibody response for the diagnosis and follow-up of paracoccidioidomycosis: comparison of counterimmunoelectrophoresis and complement fixation. , 1997, Journal of Medical and Veterinary Mycology.

[15]  E Brummer,et al.  Paracoccidioidomycosis: an update , 1993, Clinical Microbiology Reviews.

[16]  L. Travassos,et al.  Production of Paracoccidioides brasiliensis exoantigens for immunodiffusion tests , 1988, Journal of clinical microbiology.

[17]  M. R. Montenegro,et al.  Paracoccidioidomycosis: a recently proposed classification of its clinical forms. , 1987, Revista da Sociedade Brasileira de Medicina Tropical.

[18]  M. Franco,et al.  Host-parasite relationships in paracoccidioidomycosis. , 1987, Journal of medical and veterinary mycology : bi-monthly publication of the International Society for Human and Animal Mycology.

[19]  L. Travassos,et al.  Exocellular components of Paracoccidioides brasiliensis: identification of a specific antigen , 1986, Infection and immunity.

[20]  C. Lacaz,et al.  Immunoenzymatic absorption test for serodiagnosis of paracoccidioidomycosis , 1984, Journal of clinical microbiology.

[21]  M. M. Bradford A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. , 1976, Analytical biochemistry.