Development of a novel antigen detection test for histoplasmosis

Abstract

Histoplasmosis is an important systemic fungal infection, particularly among immunocompromised individuals living or travelling in areas of endemicity, who, without antifungal therapy, may develop a progressive disseminated fatal infection. For such patients, the detection of antibody responses by immunodiffusion or complement fixation test is of limited use. In contrast, the detection of Histoplasma capsulatum circulating antigens may provide a more practical approach to the rapid diagnosis of the disease. Accordingly, an inhibition enzyme-linked immunosorbent assay (ELISA) for the detection of a 69-to 70-kDa H. capsulatumspecific determinant and incorporating a species-specific murine monoclonal antibody was developed. With sera from patients with different forms of the disease (n ‫؍‬ 35), the overall sensitivity of the test was found to be 71.4%, while the specificity was found to be 98% with normal human sera from areas of endemicity (n ‫؍‬ 44) and 85.4% with sera from patients with other chronic fungal or bacterial infections (n ‫؍‬ 48). This novel, highly specific ELISA provides a significant addition to the existing diagnostic tests for the detection of histoplasmosis.

Multicenter Validation of Commercial Antigenuria Reagents To Diagnose Progressive Disseminated Histoplasmosis in People Living with HIV/AIDS in Two Latin American Countries

“…Cross-reactions were observed in three samples from patients with paracoccidioidomycosis (PCM). Prior studies of H. capsulatum antigenuria tests have reported cross-reactivities of 28% and 88% with urine from patients with PCM (10,29,30). It is important to note that PCM is diagnosed much less frequently than histoplasmosis in PLHIV, and there are several other immunological tests that help in the diagnosis of PCM (2,17).…”

Management of bilateral uveitis in aToxoplasma gondii‐seropositive cat with histopathologic evidence of fungal panuveitis

“…An antigen test also was negative. The H.‐capsulatum antigen detection test is most sensitive in human patients with disseminated or acute pulmonary histoplasmosis 30 and false negatives are common in experimental subjects with a low fungal burden 31 . Although this case did not appear to have disseminated fungal disease or a large fungal load, the diagnosis of ocular histoplasmosis could not be excluded on the basis of this negative result.…”

Immunotherapy against Systemic Fungal Infections Based on Monoclonal Antibodies

“…Mice challenged with opsonized yeast survived a lethal H. capsulatum inoculum [164]. However, as demonstrated by the IgG2b mAb to Hsp60 [168], not all mAbs to H. capsulatum surface antigens are protective, which was similarly demonstrated with a non-protective IgG1 mAb to 70-kDa cell surface antigen [165]; however, because the IgG1 to the 70-kDA is highly specific for H. capsulatum, it is a candidate for use in serological diagnosis [169,170].…”