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PubMed1984

Hematogenous histoplasmosis in the immunocompromised child.

Hematogenous (disseminated) histoplasmosis occurred in 31 of 4158 children with cancer or immune deficiency disorders. Approximately half of the 31 patients had pulmonary lesions, reacted to the histoplasmin skin test, and generated complement-fixing antibodies to Histoplasma capsulatum. In a comparative study delayed hypersensitivity to histoplasmin was demonstrated in 36 (5.7%) of 634 children at the time of diagnosis of cancer. Patients with cancer who were reactive to histoplasmin before treatment were at no greater, and possibly less, risk for hematogenous histoplasmosis than were nonreactors. All of the 27 patients who received treatment for greater than 1 day recovered; three had recurrences that responded to treatment.

Adolescent↗
PubMed2000

[Diagnostic usefulness of the intradermal test with histoplamin in non-endemic areas of histoplasmosis].

The histoplasmosis in Spain is an imported disease presenting in most of case diagnostic difficulties. In this paper, the intradermal skin test with Histoplasma capsulatum antigen as diagnostic method in immunocompetent patients with clinical and radiological signs compatible with histoplasmosis after being visited Central and South American endemic counties, in which this mycosis is endemic. Nine Spanish patients coming from different countries of Latin America with fever and acute respiratory symptoms compatible with histoplasmosis were studied. Other nine accompanying subjects and five controls were also evaluated. Patients underwent mycological cultures and and serological tests for H. capsulatum. Intradermal test with 1% histoplasmine were done in all patients. Serology and skin tests tests were also performed in accompanying people. Intradermal were done in healthy controls. Skin test with histoplasmine were positive in seven of the nine patients. Six of these showed precipitating antibodies against the same antigen. H. capsulatum was only isolated from bone marrow biopsy samples in one patient. The seven patients were given itraconazole by oral route and all symptoms improved after 2 and 4 weeks. In five accompanying subjects the skin test were also positive so that a subclinical histoplasmosis was diagnosed. In the remaining patients and healthy accompanying subjects histoplasmosis infection was excluded. In non endemic geographical areas of histoplasmosis intradermal skin test with histoplasmin when used in immunocompetent individuals is an easy and reliable method for the diagnosis of this mycosis as well as for epidemiological studies.

English Abstract↗
PubMed1987

[Delayed cutaneous response to different antigens in household contacts of leprosy patients and controls].

The delayed type hypersensitivity (DTH) response to PPD, candidin and histoplasmin, and Mitsuda reaction (MR) in household contacts (HC) of multibacillary (HCM) and paucibacillary (HCP) leprosy patients, and non exposed controls was studied. Intradermal tests with 0.1 ml. of each antigen were performed and read after 48 hours. Late nodular reaction to ML (MR) was evaluated at the 21st day post-challenge. As we had formerly demonstrated, MR was depressed in HCM. Interestingly, this reaction was also depressed in HCP to a lesser magnitude. HCM had a lower DTH response to histoplasmin in relation to PPD and candidin when persons were simultaneously challenged with the three antigens. According to these results we conclude that: a), HCM have a depression in late lepromin reaction; b), in HCP the depression in MR is of a lower magnitude. We hypothesize that in healthy contacts of bacilliferous patients an active mechanism of immunosuppression to mycobacterial antigens may be produced. Alterations in the skin response to histoplasmin is discussed.

Female↗
PubMed1981

Lymphocyte transformation in presumed ocular histoplasmosis.

Lymphocytes from individuals with inactive macular disciform lesions of presumed ocular histoplasmosis challenged with three histoplasmin antigens incorporated tritiated thymidine at a significantly higher rate than histoplasmin-stimulated lymphocytes of matched control and peripheral scar groups. This finding is consistent with the etiologic association of the disciform ocular syndrome and previous systemic infection with Histoplasma capsulatum. The disciform group had a higher mean response than the other two groups to pokeweed mitogen but not to phytohemagglutinin and had higher mean counts per minute to the specific antigens Toxoplasma gondii, Blastomyces dermatitidis, Cryptococcus neoformans, Mycobacterium tuberculosis, M battery, and M gaus, but not to Candida albicans. These data would suggest that individuals with the disciform lesion of presumed ocular histoplasmosis have a hyperreactive cellular immune response; this response may play an important role in the development of the disciform.

Adult↗
PubMed1991

Deficiency in the incorporation of labeled thymidine and inhibition in the biosynthesis of interleukin-2 in lymphocytes obtained from Histoplasma capsulatum infected mice.

The incorporation of (3H) thymidine and the biosynthesis of interleukin-2(IL-2) were investigated in Concanavalin A (ConA) and histoplasmin stimulated lymphocytes from spleen of infected Balb/c mice with the yeast phases of Histoplasma capsulatum. The ability to incorporate (3H) thymidine of Con A stimulated lymphocytes in culture from spleen of Histoplasma capsulatum infected mice, as well as the IL-2 content present in the supernatants of that cultures, were depressed along the first three weeks of the experiments, but starting week five, normal values were restored or even discretly increased. Incorporation of (3H) thymidine in histoplasmin stimulated lymphocytes remained inhibited along the seven weeks the experiment lasted. Results showed that inoculation of H. capsulatum yeast in mice provoked a temporary immunosuppression on cell mediated immunity, that can be explained by means of the inability of T cells to produce enough IL-2 necessary for the proliferation of T cells in culture.

Animals↗
PubMed1979

Histoplasmosis in South Carolina: support for the microfocus concept.

An outbreak of anthropurgic histoplasmosis occurred in rural South Carolina when a canebrake which served as a blackbird roost was cleared with a bulldozer. Seven days later the index patient became ill with histoplasmosis. Nine other patients contracted the disease, but only the index case was fatal. Serologic studies on the 10 patients demonstrated high titers in the histoplasmin latex agglutination test within two to three weeks after exposure. Serologic titers to the yeast-form Histoplasma capsulatum antigen in the complement fixation test appeared most frequently, but these antibodies were not diagnostic because complement-fixing antibodies to Blastomyces dermatitidis appeared at the same time. Soil studies demonstrated that viable particles of H. capsulatum persisted at declining levels over a nine-year period. A skin test survey showed that 27.3% of eighth grade students who resided within a 20 km radius of the contaminated site and who were lifelong residents of the same dwelling had a positive histoplasmin skin test.

Adolescent↗
PubMed1984

Significance of serum antibodies to Histoplasma capsulatum in endemic areas.

To evaluate the specificity of serologic tests for histoplasmosis in an endemic area, we studied sera from 104 consecutive healthy blood donors, testing for antibodies to either histoplasmin or Histoplasma yeast antigen, using complement fixation (CF), radioimmunoassay (RIA), and radial immunodiffusion (ID). Twenty-five subjects (24%) had CF antibody titers of 1:8 or 1:16 to one or both antigens; none had titers above 1:16. Nine subjects (9%) had RIA antibody titers of 1:8 or higher. No titers above 1:8 were found using the yeast antigen; five subjects had titers of greater than 1:16 to histoplasmin using RIA. No precipitin bands were found in any of these subjects. The results of four previous studies in endemic populations yielded similar or lower incidences of positive tests. CF antibody titers to either antigen, RIA antibody titers to yeast antigen of 1:32 or greater, or precipitin bands are rare in persons who live where histoplasmosis is endemic.

Adolescent↗
PubMed1976

Selective elimination of the delayed-type hypersensitivity response by extracorporeal thoracic duct filtration.

Calves were sensitized to tuberculin and histoplasmin. The delayed-type hypersensitivity skin response to these antigens was produced and the diameter of induration measured. Repeated skin tests prior to filtration demonstrated that the amount of induration produced by these skin tests was closely reproducible. Histoplasmin or tuberculin-coated columns were then introduced into a closed circuit extracorporeal thoracic duct circulation. A significant (P is less than 0.01) reduction or ablation of the delayed-type hypersensitivity response was obtained to the antigen used to coat the column. In contrast, no significant reduction occurred in the skin test response to the other antigen. Repeated skin tests to both antigens after the cessation of filtration showed a gradual rise toward prefiltration levels in the skin test to the filtered antigen. The results of these experiments indicate that a selective population of T lymphocytes can be removed from an in vivo system. The removal of these cells can selectively reduce a delayed-type hypersensitivity skin test response to a particular antigen. These results are consistent with the hypothesis that a type of in vivo selective immunosuppression can be produced by antigen-coated columns when they are placed in an extracorporeal thoracic duct lymph circulation system.

Absorption↗
PubMed2002

Cellular immune response in HIV-infected patients with histoplasmosis.

The relationship of immunity to Histoplasma capsulatum and CD4 count in HIV-1-infected patients is unknown. Samples of blood from people with HIV infection and from HIV-negative volunteers were assessed for immune responsiveness to the histoplasmin antigen using proliferation and interferon-gamma production as indicators of immunity. Results of histoplasmin skin tests, lymphoproliferative responses (LPR), and interferon-gamma production were positive in 9 of 20 (45%) HIV-negative controls, and in vitro measurements agreed highly with skin test reactivity. Among HIV-1-infected patients with recent histoplasmosis, skin test results were positive in none, LPR results were positive in 14%, and interferon-gamma production in 18%. Among HIV-1-infected patients with CD4 counts between 200 and 500 cells/mm(3), LPR was positive in 8% and interferon-gamma production in 33%, and among those with CD4 counts >500 cells/mm(3), LPR was positive in 31% and interferon-gamma production in 46%. In conclusion, immune responsiveness to H. capsulatum was depressed in HIV-1-infected persons with CD4 counts between 200 and 500 cells/mm(3), but approached normal in those with CD4 counts >500 cells/mm(3).

CD4 Lymphocyte Count↗
PubMed1967

Delayed hypersensitivity in man: a correlate in vitro and transfer by an RNA extract.

The migration of sensitized human monocytic-phagocytic cells from lymph-node tissue-culture suspensions was regularly and specifically inhibited by purified protein derivative or histoplasmin. Moreover, when nonsensitive cells were incubated with an RNA extract from lymph nodes of donors sensitive to purified protein derivative, histoplasmin, or both, the migration of these cells was specifically inhibited by these antigens. Ribonuclease inactivated the RNA extract.

Culture Techniques↗
PubMed1972

Evaluation of a microtiter latex agglutination test for histoplasmosis.

Experiments were designed to evaluate a Microtiter latex agglutination (Micro-LA) test, as a serological aid in the diagnosis of histoplasmosis, and to compare this test with the conventional microtiter-complement fixation (CF) test for histoplasmosis. Sera tested were from cases of acute and chronic pulmonary and disseminated histoplasmosis, as well as from individuals not having histoplasmosis. Ninety-seven percent of the cases of acute pulmonary histoplasmosis had positive Micro-LA tests, whereas 91% had positive CF tests. Ninety-six percent of the patients having chronic pulmonary histoplasmosis showed positive Micro-LA tests and 91% had positive CF tests. In contrast, 64% of the cases of disseminated histoplasmosis had positive Micro-LA tests, whereas 82% had positive CF tests. None of these differences was statistically significant. Although there were no significant differences in complement fixing and agglutinating antibody cross-reactivity with Blastomyces antigens, more patients demonstrated CF titers than Micro-LA titers. Sera from patients with acute and chronic histoplasmosis showed higher Micro-LA titers than CF titers, whereas sera from cases of disseminated histoplasmosis showed higher CF titers. Histoplasmin skin testing has less of a boosting effect on agglutinating antibodies than on CF antibodies to histoplasmin. Anticomplementary sera can be used in the Micro-LA test. This test is simple to perform, and results can be obtained in 2 to 4 hr.

Acute Disease↗
PubMed1979

Immunoregulatory responses in experimental disseminated histoplasmosis: depression of T-cell-dependent and T-effectory responses by activation of splenic suppressor cells.

The cellular immune responses of mice with disseminated histoplasmosis are markedly diminished in association with the generation of potent immunosuppressor activity by spleen cells. The zenith of suppressor activity was observed during most active infection, from 1 to 3 weeks after inoculation. During this time there was: (i) depression of the delayed-type hypersensitivity response to sheep erythrocytes and histoplasmin, (ii) impairment of concanavalin A- and histoplasmin-induced blastogenic transformations by splenocytes in vitro, (iii) depressed cytotoxic activity of spleen cells from infected mice, and (iv) marked suppression by splenocytes from infected mice of the primary antibody response to sheep erythrocytes by normal spleen cell cultures. With resolution of the infection by week 8, there was a shift of immunoregulatory function from dominant suppressor activity to expression of helper activity. At this time, delayed-type hypersensitivity responses to the above antigens were vigorous; furthermore, the cytotoxic activity and plaque-forming cell response of splenocytes from 8-week-infected mice were equal to or greater than normal control values. The shift in the immunoregulatory response from a suppressor to a helper mode indicated that the net amount of help or suppression measured at any given time during infection represented the algebraic sum of both helper and suppressor activities mediated by different populations or subpopulations of cells within the splenic microenvironment of infected mice.

Animals↗
PubMed1980

Immunoglobulin E in histoplasmosis.

Immunoglobulin M, G, A, and E serum levels were quantitated in 20 patients with active histoplasmosis (group I), 24 healthy subjects who were skin test positive to histoplasmin (group II), and 47 healthy persons who were skin test negative to histoplasmin (group III). The results established that patients with this disease have increased immunoglobulin G (P less than 0.05), immunoglobulin A (P less than 0.001), and immunoglobulin E (P less than 0.01) serum levels when compared with the 71 healthy subjects in groups II and III.

Acute Disease↗
PubMed1982

Blastogenic responses of lymphocytes from mice immunized by sublethal infection with yeast cells of Histoplasma capsulatum.

Blastogenic responses of spleen cells to histoplasmin and ribosomal antigens and to the mitogens concanavalin A. phytohemagglutinin, and lipopolysaccharide were studied in normal and immunized mice (10(5) live yeast cells of Histoplasma capsulatum given by the subcutaneous route). Cells (10(6) per well) were cultured with and without antigens and mitogens in microtiter plates with RPMI 1640-5% heat-inactivated normal mouse serum for 72 h at 37 degrees C. Cells were harvested after a 16- to 18-h pulse with 1 microCi of [3H]thymidine (6.7 Ci/mol), and thymidine incorporation was measured by scintillation counting. The initial blastogenic response to concanavalin A (54 X 10(3) cpm) was suppressed (P less than 0.001) from 4 to 14 days post-immunization and returned to control levels on day 21. The response to phytohemagglutinin was suppressed up to 21 days. Lipopolysaccharide responses, however, were affected to a lesser degree. Blastogenic responses to histoplasmin and H. capsulatum ribosomes were similar on day 0 in normal and immune lymphocytes, but by day 4 cells from immunized mice were more responsive (P less than 0.01). The maximum response to H. capsulatum antigens was detected on day 42 and was 9- to 16-fold higher than in controls. These results demonstrate in vitro responses of primed lymphocytes on exposure to H. capsulatum antigens and suppressed responses to mitogens during early stages of the immune response.

Animals↗
PubMed1990

Functional analysis of Histoplasma capsulatum-reactive T-cell hybridomas.

Activation of CD4+ T cells is a crucial step in the elimination of Histoplasma capsulatum yeast cells from tissues. However, only a limited amount of information exists concerning the immunobiology of H. capsulatum-reactive T cells that are CD4+. To facilitate the analysis of the functional activities of this T-cell subpopulation, we developed a panel of 10 murine T-cell hybridomas from splenocytes of immune C57BL/6 mice. All hybridomas reacted with monoclonal anti-CD4+ antibody and released interleukin-2 after stimulation with histoplasmin. Within 3 weeks, the reactivity of hybridomas to histoplasmin declined dramatically, yet the cells responded vigorously to yeast-phase preparations that were enriched for cytosol, cell wall, or cell membrane. Of 10 hybridomas studied, only one recognized heterologous fungal antigens. Responsiveness to yeast-phase antigens was restricted by I-Ab. We mapped determinants in cytosol and cell wall or cell membrane by the technique of one-dimensional T-cell immunoblotting. The patterns of responses of hybridomas to cytosol were nearly uniform. All hybridomas responded to two immunodominant regions in cytosol with masses ranging from less than or equal to 18 to 26 kilodaltons (kDa) and 35 to 39 kDa. All hybridomas tested responded to determinants in the cell wall or cell membrane preparation with masses of 35 to 39 kDa. These hybridomas provide a useful tool for defining yeast-phase antigens that trigger T-cell activation.

Animals↗
PubMed1976

Blocking effect of rheumatoid factor and cold agglutinins on complement fixation tests for histoplasmosis.

The blocking effect of rheumatoid factor (RF) and cold agglutinins (CA) on the detection of complement-fixing (CF) antibodies for Histoplasma capsulatum using a mycelial (histoplasmin) and a yeast antigen was studied. Sera from 213 patients serologically positive for histoplasmosis were screened for the presence of RF or CA. CF antibodies to H. capsulatum in sera containing RF or CA were studied before and after removal of these factors (RF and CA) by treatment with dithiothreitol. Results suggest that RF or CA may interfere with the CF reaction to the yeast antigen of H. capsulatum but not to the mycelial antigen (histoplasmin).

Agglutinins↗
PubMed1976

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.

Chronic Disease↗
PubMed1975

Distribution of Blastomyces dermatitidis in dogs with skin test and serologic results following airborne infection.

Reported is a short term (16 week) experiment to determine the distribution of B. dermatitidis in dogs when infected by the natural inhalation route by receiving about 250,000 viable particles during a 24h. exposure. Four dogs were positive to blastomycin and 1 to histoplasmin prior to exposure. Post exposure, all dogs developed positive skin tests to blastomycin by the 4th week with considerable cross reaction to histoplasmin. Serologic tests showed more poritive CF tests to Histoplasma than to Blastomyces so that the test appears of no practical value. Although 22 tissues were cultured on each dog, only 1 or 7 dogs was positive for B. dermatitidis by 2 weeks. At 4 weeks, 57% of the dogs were positive by culture and at 12, 15, and 16 weeks, all were positive. One dog developed eye lesions and became emaciated.

Air Microbiology↗