Monitoring gp43 Antigenemia in Paracoccidioidomycosis Patients during Therapy

Abstract

Paracoccidioidomycosis (PCM) is a systemic fungal disease that is particularly important among individuals living and working in rural areas of endemicity in Latin America. Detection of anti-Paracoccidioides brasiliensis antibodies is of limited value due to false-negative results. Detection of P. brasiliensis-gp43 circulating antigen is a practical approach for a specific diagnosis of the disease. In a previous study we described an inhibition enzyme-linked immunosorbent assay able to detect the 43-kDa P. brasiliensis antigen in sera of 100% of patients with the acute form of PCM and in 95.31 and 100% of patients with the chronic multifocal and unifocal forms of PCM. To investigate its potential application for the follow-up of PCM patients during treatment, antigen levels were monitored at regular intervals for up 8 to 12 months in serum samples from 23 patients. The results showed that treatment with itraconazole resulted in decreasing levels of circulating gp43 that were correlated with the reduction of anti-gp43 antibodies. It was also observed that by the end of 12 months of treatment gp43 levels were <5 g/ml in all patients.

Serology of paracoccidioidomycosis

“…Recently, we have studied the behavior of gp43 antigenemia during the treatment of PCM patients with Itraconazole (ITZ) until the apparent cure at the end of therapy (i.e., after 8-12 months) [55]. PCM is a chronic fungal infection that chiefly involves the reticulo-endothelial system (RES), as well as the lungs.…”

Fatal Fungemia due to Paracoccidioides lutzii

“…On the other hand, PCM serology has evolved over the years 28 and been reported to be an essential tool for rapid diagnosis 29,30 and patient follow-up. 6,31 Unfortunately, from a seroepidemiological point of view, the diagnosis of PCM caused by divergent phylogenetic species is difficult based on antigenic preparations of the reference strain B-339 (PS3), 7,8 and none of the serological tests developed to date are able to clearly diagnosis PCM caused by the five cryptic species, which favors delayed diagnosis and false negative results. Our negative results for the double immunodiffusion test using the antigenic preparation of the B-339 strain are in agreement with previous studies, 7,8 which reinforces the idea of antigenic variability in the genus Paracoccidioides.…”

“…Our negative results for the double immunodiffusion test using the antigenic preparation of the B-339 strain are in agreement with previous studies, 7,8 which reinforces the idea of antigenic variability in the genus Paracoccidioides. The negative serology should not be interpreted only as the absence of antibodies caused by immunosuppression 32 or drug therapy 31 ; thus, we emphasize the need for specific antigenic preparation from autochthonous strains, in addition to the use of the standard preparation of B-339, to improve the sensitivity and specificity of the serological test. We hypothesized that several cases of PCM caused by different phylogenetic species in the genus Paracoccidioides may have been underestimated in Latin America when only preparations derived from the standard strain B-339 were used.…”

Attempts at a peptide vaccine against paracoccidioidomycosis, adjuvant to chemotherapy

“…Recently, it has been reported that anti-gp70 mAbs were protective against experimental PCM [48]. Both gp43 and gp70 are markers for monitoring the regression of PCM through their decreased antigenemia and specific antibody response in patients submitted to chemotherapy [49,50].…”