Efficacy of cell-free antigens in evaluating cell immunity and inducing protection in a murine model of histoplasmosis.

Histoplasma capsulatum is a dimorphic pathogenic fungus that causes a wide spectrum of disease when mycelial fragments are inhaled. Resistance to H. capsulatum is dependent on cellular immunity mediated by T cells and macrophages. Here we standardized the production of extracts containing cell-free antigens (CFAgs) and observed their efficacy in evaluating cellular immunity during murine histoplasmosis. CFAgs induced a more potent delayed-type hypersensitivity (DTH) response in H. capsulatum-infected mice than did histoplasmin-a classical antigen. This DTH response to CFAgs is able to determine the immune status of infected mice and to predict their death. Moreover, CFAgs stimulated spleen cells from immune mice to produce higher amounts of gamma interferon (IFN-gamma) in vitro. Finally, immunization with CFAgs protected against a lethal inoculum of H. capsulatum. These results demonstrate that CFAgs may be useful for the evaluation of cellular immune response and as a potential source for the development of a vaccine against histoplasmosis.

[Mycoses frequency in three communities in the North mountain of the State of Puebla]. / Frecuencia de micosis en tres comunidades de la sierra norte de Puebla.

In order to know mycosis frequency in the North of the State of Puebla, Mexico, in habitants from the communities of Ayotoxco, Mazatepec and Zacatipan were studied. Previous medical study biological samples were submitted to direct examination, smear and culture. Histoplasmin and sporotrichin skin test were applied to 57 individual from Zacatipan. From 110 patients 146 mycological studies were performed. Eighty six cases (59%) of mycosis were detected: 43 finger or toenails onychomycosis, 25 tinea pedis, seven tinea capitis, four cases of tinea manum and, finally, five cases of seborrhoeic dermatitis and two of pitiriasis versicolor. We isolated: 18 streins of dermatophytes, mainly Trichophyton rubrum and T. mentagrophytes (11 and 5 strains respectively); 12 cultures of non-dermatophytes filamentous fungi; six cases of mycelia sterile; six yeast strains, most of them Candida spp but none C. albicans. From 57 patients to whom skin tests were applied, five of them (8.8%) were positive to both antigens; ten positive (17.6%) only to histoplasmin and eight (14%) to sporotrichin. This study showed that rural population from Puebla present a high frequency of superficial mycosis (61% of mycological studies). Considering the percentage of positive skin test we suppose that there are many not diagnosed sporotrichosis and histoplasmosis cases.

Epidemiologic surveys of histoplasmin and paracoccidioidin sensitivity in Brazil

Esta publicacao visa a tornar acessiveis os resultados obtidos em inqueritos epidemiologicos sobre histoplasmose e paracoccidioidomicose, realizados no Brasil, atraves das reacoes intradermicas de histoplasmina e paracoccidioidina. Ela justifica-se porque os resultados aqui relacionados, em grande parte, nao foram publicados em revistas cientificas. Os resultados que conseguimos colecionar sao apresentados nas tabelas: 1-sobre histoplasmose e 2-sobre paracoccidioidomicose. Ao todo sao relacionados 88 inqueritos sobre histoplasmose e 58 sobre paracoccidioidomicose. No final da publicacao sao feitos comentarios sobre os itens a serem obedecidos em inqueritos desta natureza

Experimental pulmonary histoplasmosis and emphysema.

Chronic pulmonary histoplasmosis often occurs in the setting of emphysema. However, it is unknown whether emphysema directly predisposes to the development of the necrotizing lesions of chronic pulmonary histoplasmosis. We evaluated this possibility using a murine model of pulmonary histoplasmosis. Using intratracheal inoculation of elastase, we induced pulmonary emphysema in Balb/c mice. When mice with emphysema were challenged intranasally with H. capsulatum (HC) yeast cells, the course of their disease was not significantly different from that of normal mice. Mice were also exposed to HC antigens by sublethal intranasal challenge with viable or heat-killed HC, or immunized with histoplasmin. Prior sublethal challenge with viable HC did not cause prolonged illness or increased mortality in the setting of emphysema. In contrast, such mice were protected against a severe rechallenge. Additional studies showed that intranasal administration of heat-killed HC or subcutaneous immunization with histoplasmal antigens had neither protective nor deleterious effects on the course of histoplasmosis. Therefore, in this murine model, we could not substantiate an interaction of underlying emphysema with acute primary or rechallenge pulmonary histoplasmosis.

Estudio epidemiologico de reactores a la histoplasmina y tuberculina en indigenas del Alto Caura, Estado Bolivar 1984-1985 / Epidemiological study of histoplasmin and tuberculine reactors in indigen from Alto Caura. Estado Bolivar 1984-1985

Se realizó un estudio epidemiológico sobre la histoplasmosis y tuberculosis entre indígenas del Alto Caura en el Estado Bolívar. La muestra poblacional estudiada correspondió a distintos grupos étnicos que presentaron elementos condicionantes del medio y diversas patologías, correspondiendo a las comunidades indígenas de Santa Maria de Erebato (Makiritares), Kanaracuni (Makiritares) y Guaña (Yanomami). La muestra estudiada fue de 201 personas (21,9%) de la población total, predominando el sexo femenino 122 (60,7%) sobre el masculino 79 (39,3%). Se aplicaron 201 dosis de histoplasmina y 170 de tuberculina, la lectura de las pruebas cutáneas fue posible en 194 histoplasmino-reacciones, obteniéndose 50 reactores positivos (25,8%) para la histoplasmina y 63 (38,4%) para la tuberculina. El mayor porcentaje de positividad para ambas pruebas cutáneas se observó en Santa Maria de Erebato, no evidenciándose reactores positivos a la histoplasmina en Guaña, a la vez que el sexo femenino presentó mayor porcentaje de positividad a la histoplasmina en grupo etário de 45-64 años en 36 casos (72,0%), también a la tuberculina con 40 reactores (63,5%) en grupo etário de 25-44 años. En estas comunidades, la tuberculosis y la histoplasmosis son endémicas, hay mayor riesgo de contraer tuberculosis que histoplasmosis, el mayor índice de tuberculino-reactores se encontró en personas cuyas edades oscilaban entre los 25 y 44 años y el de histoplamino-reactores de encontró en personas de 45 a 64 años

The value of the skin test and complement fixation test in the diagnosis of chronic pulmonary histoplasmosis.

Histoplasmin skin test results in patients with chronic pulmonary histoplasmosis from Missouri and Texas were compared to results in a previous study of U.S. Navy recruits. When consideration was given to geographic areas from which persons from each group were admitted to the study, it was found that the recruits were as likely to have a positive skin test as were those with the disease. In a similar manner, the Texas histoplasmosis patients were compared to groups of patients from that state with chronic obstructive pulmonary disease and with pulmonary tuberculosis. Again, no significant differences were found. It was concluded that the histoplasmin skin test is not of value in the diagnosis of chronic pulmonary histoplasmosis. Histoplasmosis complement fixation test data from the chronic pulmonary histoplasmosis group were compared to data from the chronic obstructive pulmonary disease and pulmonary tuberculosis groups. The usefulness of the complement fixation test in chronic pulmonary histoplasmosis is limited, as with any test, by false-positive and false-negative reactions. A decision theory method was used to define the limits of usefulness.

Effect of immunosuppressants on dogs exposed two and one-half years previously to Blastomyces dermatitidis.

Observation of 33 dogs exposed to Blastomyces dermatitidis over a 2 1/2 year period is reported. During the first 1 1/2 years six dogs died and 23 (77%) developed skin lesions. Clinical evidence of disease in all the animals then subsided and remained so through another year of observation. Nine animals were sacrificed after 120 weeks and several tissues were cultured from each one. The remaining 18 were given immunosuppressants--azathioprine, prednisone, and cyclophosphamide--for eight weeks prior to autopsy. About one-half of the dogs were found to be infected with Histoplasma capsulatum and all were negative for B. dermatitidis by culture. The dogs were thought to have been inadvertently exposed to H. capsulatum during the first eight weeks of observation from a nearby soil plot before being moved to a more remote shelter. Skin testing with histoplasmin and blastomycin and complement-fixation (CF) tests, performed at various intervals after exposure to B. dermatitidis, appeared to reflect the course of disease with the number of reactors to the H. capsulatum antigens remaining relatively high while the number of reactors to B. dermatitidis antigens fell with the passage of time. The blastomycin skin test results in these dogs, however, persisted far longer than positive Blastomyces CF results. These data suggest that most dogs exposed to B. dermatitidis exhibit clinical symptoms of disease after about 12 weeks, persisting for about one year. The majority of animals recover spontaneously and completely. With H. capsulatum, however, the infection can be subclinical for at least a two-year period.

Delayed-type hypersensitivity responses to a cell wall fraction of the mycelial phase of Coccidioides immitis.

A skin test-active fraction was isolated from the mycelial-phase cell walls of Coccidioides immitis. This alkali-soluble, water-soluble antigen (C-ASWS) elicited positive reactions in 22 of 24 (92%) of the Coccidioides-sensitized guinea pigs whereas only 14 (54%) of the same guinea pigs reacted to commercial coccidioidin (BioCox). None of the 21 Histoplasma-sensitized guinea pigs cross-reacted with the C-ASWS antigen. Footpad tests in mice actively infected with Coccidioides further established the efficacy of the C-ASWS antigen in eliciting a delayed-type hypersensitivity response. One-microgram doses of C-ASWS produced reactions comparable to 100-mug doses of nondialyzable coccidioidin (Smith's lot 64 D4). The C-ASWS fractions isolated from three different C. immitis strains showed similar reactivity in terms of the number of positive reactions produced in Coccidioides-sensitized guinea pigs. However, the induration responses (diameter in millimeters) elicited by the C-ASWS fraction of one strain were significantly less than those elicited by the C-ASWS fractions of the other two C. immitis strains.