Central nervous system paracoccidioidomycosis: analysis of 13 cases with immunofluorescence research of gp43 antigen

CENTRAL NERVOUS SYSTEM PARACOCCIDIOIDOMYCOSIS: ANALYSIS OF 13 CASES WITH IMMUNOFLUORESCENCE RESEARCH OF GP43 ANTIGEN. (ABSTRACT)^*.DISSERTATION. BELO HORIZONTE, 2001.

WALTER J. FAGUNDES-PEREYRA^**

Paracoccidioidomycosis (PCM) is a systemic granulomatous disease caused by Paracoccidioides brasiliensis, prevalent in Latin America, particularly in Brazil. Central nervous system (CNS) involvement occur in about 10% of cases, although such cases are uncommon in the literature.

Thirteen cases of neuroparacoccidioidomycosis were studied emphasizing clinical manifestations, neuroradiology and immunology. The 43,000 dalton glycoprotein (gp43) is the main exocellular antigen of P. brasiliensis, which is probably related with fungus virulence. The gp43 elicits an efficient antibody response which does not protect again progressive PCM; its secretion and circulation as a free antigen or as immunocomplexs may inhibit "natural killer" cells activity, induce T suppressor cells and promote binding to laminin which may have a role in fungal dissemination; may also carry aggregated molecules with proteolytic activity.

The gp43 antigen was investigated by indirect immunofluorescence in specimen of brain biopsy containing paracoccidioides granuloma. We studied in vitro the response of peripheral blood mononuclear cells from patients with PCM presenting with CNS involvement to antigenic fractions from P. brasiliensis yeast cell lysate (PbAg). The fraction 0 (F0) were obtained using anion-exchange chromatography on a FPLC system. IgG antibodies anti-P. brasiliensis (anti-PbAg and anti-F0) were evaluated in serum, plasma and cerebrospinal fluid (CSF). They were mesasured by ELISA and detected by Western Blot.

After literature review, 129 cases of neuroparacoccidioidomycosis were found, including our 13 patients. The most frequent symptoms were motor deficits (53.8%), cognitive disturbance (53.8%), weight loss (46.1%), headaches (46.1%) and seizures (46.1%). Computerized tomography (CT) scans were obtained in all cases and magnetic resonance imaging (MRi) was used in one case. Serology for HIV was done in ten patients (76.9%), and all the tests were negatives. Granulomatous forms were present in all patients. Four (30.8%) of them had also meningeal involvement (mixed form). The diagnosis was confirmed by the demonstration of P. brasiliensis in all the cases, twelve (92.3%) by histophathological examination and one (7.7%) in the CSF.

Indirect immunofluorescence revealed the presence of gp43 antigen in all studied cases. ELISA and Western Blot disclosed IgG antibodies anti-P. brasiliensis (anti-PbAg and anti-F0) in sera and plasma. However, it was not observed in the CSF.

Amphotericin B was used in twelve patients (92.3%), one of them by intraventricular infusion. In eight patients (61.5%), trimethopim and sulfamethoxazole were used, and, in two (15.4%), sulfadiazine and pirimetamine. Fluconazole, ketoconazole and itraconazole were each one used in a different patient as well. Six patients died (46.1%) and seven (53.9%) had satisfatory outcome. The follow-up period ranged from 2 to 74 (M=30,9) months.

In conclusion, the CNS involvement in paracoccidioidomycosis is more frequent and more serious than thought before. The clinical manifestations, CT scans and MRi findings are not specific of paracoccidioidomycosis. Indirect immunofluorescence, ELISA and Western Blot can be used in the detection of P. brasiliensis antigens and antibodies with satisfatory sensibility. Further studies are still needed aiming at the increase of knowledge about this disease, which has high mortality rates.

KEY WORDS: paracoccidiodomycosis, central nervous system, gp43 protein.

*

Paracoccidioidomicose no sistema nervoso central – análise de 13 casos com pesquisa do antígeno gp 43 por imunofluorescência (Resumo). Dissertação de Mestrado, Santa Casa de Belo Horizonte (Área: Medicina). Orientador: Alfredo M. Góes. Co-orientadores: Atos Alves de Sousa e Francisco das Chagas Lima e Silva.

Publication Dates

• Publication in this collection
  28 Nov 2001
• Date of issue
  Dec 2001