Spherulin and Coccidioidin: Cross-Reactions in Dermal Sensitivity to Histoplasmin and Paracoccidioidin

Abstract

Until recently coccidioidin has been the only antigenic preparation available for detecting delayed dermal sensitivity induced by an experience with Coccidioides immitis. It is prepared from autolysates of the mycelial phase (saprophytic) of the fungus. A more sensitive reagent, spherulin, was developed in 1969 from the spherule phase (parasitic) of the organism. Use of spherulin showed that coccidioidin failed to detect approximately 30% of individuals specifically sensitive to C. immitis. However the potential of spherulin to detect cross-sensitivity induced by Histoplasma capsulatum was unknown. This information was considered to be germane because of the capacity of coccidioidin to detect a histoplasmal experience. Accordingly, both reagents as well as paracoccidioidin were compared simultaneously in 365 Colombian soldiers from areas endemic for histoplasmosis but not for coccidioidomycosis. At standard strength both preparations detected nonspecific responses in 0.8% to 3% of the histoplasmin negative and positive subgroups, respectively. At 10-times standard strength both preparations cross-detected histoplasmin sensitivity comparably; 5.1% to 7.1% of histoplasmin-pos'itive subjects reacted with the coccidioidal antigens. No pattern of cross-reactivity was observed between paracoccidioidin sensitivity and sensitivity to the coccidioidal antigens. coccidioidin; histoplasmin; paracoccidioidin; spherulin

Persistent Cutaneous Cellular Immune Responsiveness in a Nursing Home Population

“…The explanation for this is not readily apparent. Coccidioidin skin tests are said to be largely specific for infection by that organism; some cross‐reactivity occurs because of infections by Blastomyces dermatiditis and Histoplasma capsulatum 11, 13, 14, 16–20 . While disease due to Blastomyces dermatiditis and Histoplasma capsulatum is more common in North Carolina than that due to Coccidioides immitis , 12, 13, 15, 17, 21–28 the prevalence in this study of positive skin tests was lower for the former organisms than for coccidioidin itself.…”

Antigenic analysis of coccidioidin and spherulin determined by two-dimensional immunoelectrophoresis

“…At the highest antibody concentration (Ig diluted 1:2, Fig. la), several precipitates were weak and barely discernible (Ags 12,13,14,22,24). These were not detectable at lower antibody concentrations.…”

“…Spherulin, which has become available more recently than coccidioidin, has not resolved this problem. Levine et al (20,22) reported spherulin more sensitive but no more specific than coccidioidin as reagents for intradermal tests. Huppert et al (15) found both reagents equally sensitive in serological tests, but spherulin was significantly less specific than coccidioidin.…”

“…The more recent development of cultural methods for reproducible in vitro growth of the parasitic cycle (7)(8)(9)19) made possible the production of spherulin: i.e., soluble antigens derived from endosporulating spherules. Comparison of these two preparations revealed that spherulin was equally specific but more sensitive than coccidioidin as a skin-testing reagent (20,22), but spherulin was considerably less specific than coccidioidin in serological tests (15). Since both coccidioidin and spherulin are crude preparations and undoubtedly contain multiple antigens, analysis of the antigen composition of each might reveal not only differences between the two, but also antigens common among other pathogenic fungi.…”

Coccidioidomycosis: Changing Perceptions and Creating Opportunities for Its Control

“…David became interested in the cellular immune responses to Coccidioides and began working with Hillie in the field trials of a new skin-testing antigen, spherulin. 27,[36][37][38][39] As part of his other interests, Dr. Levine also tested antifungal drugs for pharmaceutical firms because his lab was well versed in the murine model of coccidioidal infection. One of the drugs tested by Dr. Levine was miconazole, sent to him by Janssen Pharmaceutical Company.…”