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PubMed1981

Transfer factor therapy for histoplasmosis in a patient with Hodgkin's disease.

A patient with recurrent chronic histoplasmosis was diagnosed also as having Hodgkin's disease. Studies of cell-mediated immunity (CMI) demonstrated no reaction to histoplasmin by skin test, lymphocyte transformation (LT), or leukocyte inhibition factor (LIF) assay. Clinical and immunologic studies were performed during treatment with 19 doses of dialyzable transfer factor (TF) prepared from a normal donor with strong CMI against histoplasmin. Transfer of CMI to the patient was demonstrated by all three tests. All tests reverted to nonreactive during the period of observation. Repeated doses of dialyzable TF were followed by reconversion of skin tests. The LIF assay was most reactive. Reactivation of histoplasmosis occurred during antimetabolic therapy for Hodgkin's disease; however, the lesions cleared rapidly when TF was added to amphotericin B. Amphotericin B was administered at a dosage of 25 mg three times each week during the entire study.

Adult↗
PubMed1995

Selection of skin test antigens to evaluate PPD anergy.

BACKGROUND: A purified protein derivative (PPD) tuberculin skin test may be nonreactive because of cutaneous anergy, technical problems with the test, or absence of tuberculosis infection. This study investigated the sensitivity and specificity of five test agents in measuring cutaneous anergy when the PPD test is nonreactive. Agents evaluated include antigens for Candida, mumps, histoplasmin, tetanus, and Trichophyton. METHODS: Delayed-type hypersensitivity skin test records were analyzed in 1113 patients admitted to the University of Texas Health Center at Tyler from December 1988 through June 1993. These patients were admitted with initial diagnoses of diseases other than active tuberculosis or human immunodeficiency virus infection. RESULTS: Patients with a negative PPD test reacted most often to the control skin test Candida (63.5%), followed by mumps (52.2%), histoplasmosis (37.2%), tetanus (35.7%), and Trichophyton (6.1%). Analysis of these data indicates that the use of more than three of the four most commonly reactive control tests (Candida, mumps, and histoplasmin or tetanus) yielded minimal additional precision in the determination of skin test anergy compared with using all five control skin tests. This finding remained constant whether the PPD was considered negative at < 5 mm, < 10 mm, or < 15 mm of induration. CONCLUSIONS: In controlling for false-negative PPD tests, the use of three skin test antigens, Candida, mumps, and tetanus, should provide reliable control for delayed-type hypersensitivity anergy.

Animals↗
PubMed1964

HISTOPLASMOSIS IN MONTREAL DURING THE FALL OF 1963, WITH OBSERVATIONS ON ERYTHEMA MULTIFORME.

Although Montreal is in an endemic area, significant clinical histoplasmosis with systemic manifestations has been, until recently, infrequently diagnosed. However, since the autumn of 1963, 31 cases of clinically significant histoplasmosis have been seen by the authors. These were divided into two groups: (1) patients in whom the diagnosis was established on the basis of histological and/or cultural demonstration of the fungus; (2) patients in whom the diagnosis was based on a positive histoplasmin skin test, a complement fixation antibody titre of 1:32 or greater and compatible clinical and radiological findings. An additional group of 11 patients who presented with erythema multiforme was investigated and a heretofore unrecognized relationship between histoplasmosis and erythema multiforme was established.

Adolescent↗
PubMed1987

Experimental histoplasmosis in the beige mouse.

Mice carrying the beige mutation (bg/bg) on a C57Bl/6 background were challenged with Histoplasma capsulatum. bg/bg mice had higher mortality and higher lung tissue fungal counts in their lungs than either bg/+ or C57Bl/6 mice challenged with equal inocula. Immunologic studies showed that bg/bg mice developed normal delayed-type hypersensitivity (DTH) reactions to histoplasmin, but had deficient NK cell cytotoxic activity against YAC-1 target cells. Studies of macrophage killing of H. capsulatum in vitro showed that T lymphocytes of either bg/+ or bg/bg mice were able to activate fungal killing by bg/+ but not by bg/bg macrophages. These studies, while not excluding a role for the NK cell, suggest that macrophage dysfunction may be critical in the greater susceptibility of the bg/bg mouse and, by extension, that macrophage function is of major importance in host defense against H. capsulatum.

Animals↗
PubMed1990

Modifications of the immune response induced by Histoplasma capsulatum products.

To understand the host-parasite relationship in histoplasmosis, mice were inoculated with histoplasmin (HP), the filtrate of aged cultures of Histoplasma capsulatum, and the immune response of these mice towards sheep red blood cells (SRBC) and to trinitrophenyl hapten was studied. The filtrate abrogated completely the primary antibody response to both antigens as measured by the number of spleen hemolytic plaque forming cells when HP was administered at doses greater than 200 micrograms two days before the antigen. Suppression was elicited by HP when it was injected either intravenously, intraperitoneally, or subcutaneously. Inoculation with HP and antigen on the same day did not result in suppression. The secondary antibody response was not modified at any dose. Variation of the response with time was determined by counting the number of rosette forming cells (RFC) to SRBC every two days for a total of 21 days. Antibody-mediated RFC ('B' rosettes) were depressed throughout the experiment, while the number of non 'B', presumably T, RFC did not vary from control values. In animals inoculated with HP alone, high number of RFC were detected on day 11 after HP inoculation, suggesting that HP may have polyclonal activation effects. These results support the possibility that H. capsulatum evades the immune defenses by induction of a suppressive phenomenon in which the afferent limb of the immune response is not involved. This effect appeared to be induced directly by a product of the fungus, instead of by factors generated during the immune response to this microorganism.

Animals↗
PubMed1986

Immunocytochemical staining of Histoplasma capsulatum at the electron microscopic level.

Rabbits were immunized with histoplasmin emulsified in Freund's complete adjuvant. Antibody raised in these rabbits was exposed to Histoplasma capsulatum yeast cells, either in tissue culture medium, or after in vitro or in vivo phagocytosis by mouse macrophages. The sites of antibody binding were identified using an immunoperoxidase technique. At least two sites of antibody binding were identified, one to the fungal cell wall and the other to the outer cell membrane. Within 6 h after phagocytosis by macrophages, fungal cell walls appeared roughened, with what appeared to be cell wall antigen released into the phagolysosome, appearing associated with the phagolysosome membrane, and possibly adjacent macrophage cytoplasm. Similar staining of fungal antigen was noted in alveolar macrophages which had ingested Histoplasma capsulatum after a respiratory challenge. This method may be useful in detailing the host/pathogen interactions which occur in human pulmonary histoplasmosis.

Animals↗
PubMed1981

Susceptibility of immunodeficient mice to challenge infection with Histoplasma capsulatum.

Groups of mice were neonatally thymectomized and treated with antithymocyte serum (ATS) prior to challenge infection with viable yeast phase (YP) Histoplasma capsulatum G-17M. Moderate leucocytosis and moderate lymphopenia were seen in immunodeficient animals after infection. Surviving immunodeficient mice exhibited low levels of migration inhibition activity, while peritoneal exudate cells and spleen cells harvested from surviving infected and untreated normal mice showed significant migration inhibition in the presence of histoplasmin antigen. The LD50 values for YP cells of H. capsulatum were 1.1 x 10(6) for normal untreated mice, 6.0 x 10(5) for thymectomized mice, and 6.3 x 10(5) for ATS-treated mice. Thymectomized mice that also received ATS treatment exhibited an LD50 of 1.7 x 10(5) and were 6.5 times more susceptible to infection then normal mice. Mice which were either thymectomized or treated with ATS were 1.7 times as susceptible as normal mice to infection with H. capsulatum. The criterion of susceptibility is a decrease in the LD50 value.

Animals↗
PubMed1978

The status of histoplasmosis in Brazil.

Thirty four cases of the progressive form of histoplasmosis, five epidemics of the mycosis, many histoplasmin skin test surveys and few clinical or histological evidences of the benign form of the disease were reported in Brazil. The occurrence of the infection in animals and the isolation of H. capsulatum from soil have also been reported.

Adolescent↗
PubMed1994

Histoplasmosis capsulati in Italy: autochthonous or imported?

Reports of a few apparently autochthonous cases of human histoplasmosis and results of epidemiological research suggested the autochthonous presence of the disease in Italy. Identifying two new histologically documented cases of Italian patients, who had never been abroad, and, the positive results of a histoplasmin reactivity survey carried out in the Province of Cremona, Italy confirmed this possibility.

Adolescent↗
PubMed2005

Histoplasmosis infection in Spanish travelers to Latin America.

The aim of the study presented here was to assess the incidence of histoplasma infection in a cohort of 342 individuals in Spain who had traveled to Latin America for the first time. The histoplasmin skin test was positive in 20% of the travelers, and Central America posed a higher risk for infection than South America (p=0.013). Sleeping outdoors (p=0.031) and the duration of travel (p=0.016) were also identified as significant risk factors. Serological testing demonstrated poor overall sensitivity for detecting infection in the travelers, but for the symptomatic acute cases the results were improved. Histoplasmosis must be considered in patients presenting with fever (odds ratio=3.51 [1.52-8.12]) or cough (odds ratio=4.24 [1.32-13.58]) after visiting Latin America. The results of this study have public health implications and indicate the risks of acquiring histoplasmosis should be included in pre-travel counseling.

Adult↗
PubMed1987

Paracoccidioidin sensitization in Guyana--a preliminary skin test survey in hospitalized patients and laboratory workers.

Thirty-one percent of a group of 49 hospitalized patients or laboratory workers in Guyana showed positive intradermal paracoccidioidin tests in the presence of negative histoplasmin reactions. In 2 patients (4%), the intradermal reactions to paracoccidioidin were greater than 10 mm in diameter. The prevalence of positive reactors in a selected population suggests that paracoccidioidomycosis may be endemic in Guyana although no clinical case has been reported from the country. A further survey in a larger, unselected population would lead to a clearer understanding of the problem.

Adolescent↗
PubMed2005

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.

Animals↗
PubMed1985

Lack of antibody induction by Histolyn-CYL, a new skin-testing reagent for histoplasmosis.

Histolyn-CYL, a yeast phase skin-test reagent, was administered to 85 histoplasmin-sensitive subjects living in the United States and South America. In a multicenter study, sera were obtained at the time the skin tests were read and again 3 weeks later. In no instance did the skin test induce significant complement-fixing antibody changes or antibodies detected by immuno-diffusion.

Adult↗
PubMed1976

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.

Animals↗
PubMed1985

An outbreak of histoplasmosis in a prison.

An investigation of three suspected cases of pulmonary histoplasmosis among 600 employees at a New York prison in a nonendemic area resulted in identification of 12 additional previously unrecognized cases. The 15 cases presented with diagnostic findings between February 1978 and October 1981; 10 were in prison employees, three in inmates and two in community persons. Unlike other outbreaks, cases presented over several years with chronic pulmonary lesions in the absence of an episode marked by acute respiratory illnesses. Of the 13 prison-associated cases, seven had undergone diagnostic thoracotomies for chest x-ray abnormalities. A skin test survey of a random sample of employees showed 53% to have positive histoplasmin skin tests compared with 11% in a community control population (chi 2 = 23.4, p less than 0.001). Over 63% of employees on the job for two or more years reacted positively compared with only 13% of those employed less than two years. Testing of some inmates showed 84% with residence of two years or more to be positive, compared with 20% for those with less than two years. A review of potential exposure sources revealed three sites where bird dropping accumulations had been cleared in 1978-1979. Four specimens from two of these areas were positive for Histoplasma capsulatum. The affected sites were treated with a 3% formalin solution and there have been no subsequent cases.

Adult↗
PubMed1975

Prognostic criteria in macular histoplasmic choroiditis.

1. Fifty percent of 22 patients "desensitized" to histoplasmin developed subsequent activity, as compared to 44% of 23 patients without "desensitization." 2. Prednisone-induced remission of subclinical activity in patients monitoring their own central fields appears to be the most rewarding therapy for these desperate patients.

Argon↗
PubMed1972

Factors influencing the production of H and M antigens by Histoplasma capsulatum: development and evaluation of a shake culture.

Studies were undertaken to improve the production of histoplasmin for use in complement-fixation tests and in the determination of H and M antibodies. A shake culture method performed at 25 C was developed with a yeast-phase inoculum. Eight strains of Histoplasma were tested in three synthetic media to evaluate the effects of strain and medium on H and M antigen production. Intrastrain variation was negligible, and antigen production was reproducible. All of the strains produced H antigen; six strains produced both H and M antigens, and two produced only H antigen. The time of H and M antigen appearance varied with the medium; M antigen appearance was dependent upon the strain and medium used. Titers of M antigen appeared to be greater in stagnant culture.

Antibodies↗
PubMed1974

Characterization of the precipitin bands detected in the immunodiffusion test for paracoccidioidomycosis.

In order to characterize the precipitin bands detected in the immunodiffusion test for paracoccidioidomycosis, a study was undertaken in 54 patients with the disease. On the basis of the pattern of known control sera, the three commonly observed lines of precipitate were designated as 1, 2, and 3 according to their location in the immunodiffusion plate. At time of diagnosis, 28 of the patients exhibited all three bands, 16 gave two bands, and 10 showed only one precipitin line. Over 50 of the sera with three bands had high complement fixation titers (above 1:512), whereas those with one band exhibited lower titers. A similar picture was obtained with the quantitative agar-gel techniques, where titers of 1:64 and above were more commonly observed in sera with three precipitin lines. Follow-up studies carried out in 18 patients revealed that band 3 disappeared first, followed by band 2, and, finally, by band 1. At the end of 2 to 3 years, 85.7% of the patients had lost band 3, 75% band 2, and only 27.7% band 1. Cross-reactions with histoplasmin were found in eight patients who gave the M precipitin line with this antigen. It was found that the latter band and our paracoccidioidin band 3 fused, producing lines of identity. Bands 1 and 2 were specific. The implications of these findings are discussed.

Blastomycosis↗