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PubMed1987

Repeatedly relapsing disseminated histoplasmosis: clinical observations during long-term follow-up.

We report three patients (followed up for 13, 9, and 12 years) who had multiple episodes of disseminated histoplasmosis. Clinically, all three patients had high yields of positive cultures and all developed corticoadrenal insufficiency; all survived the recurrent relapses. One patient had unilateral progressive panophthalmitis, with ocular cultures positive for Histoplasma capsulatum. These relapses occurred despite conventional treatment with large doses of amphotericin B. Prolonged remissions were associated with using small doses of this drug. One patient had a long-term remission while taking ketoconazole daily for more than four years. These patients did not have conditions associated with immunosuppression. Lymphocyte proliferation to mitogens and, in one patient, to histoplasmin, was markedly reduced at the time of relapse and when tested preceding a relapse. All three patients showed a reversal to normal lymphocyte proliferation at the time of the longest last remission.

Female↗

PubMed1990

Development of long-term specific cellular immunity after acute Blastomyces dermatitidis infection: assessments following a large point-source outbreak in Wisconsin.

Ninety-five persons exposed to a point-source of Blastomyces dermatitidis in Wisconsin in 1984 were evaluated 3 months after exposure for the development of specific cellular immunity, and the 48 infected persons were again evaluated 7 and 21 months after exposure. The immune response was assessed by an assay of [3H]thymidine uptake by lymphocytes proliferating in response to stimulation with Blastomyces alkali- and water-soluble antigen (B-ASWS) or blastomycin and by skin testing with blastomycin. At 3 months, 36 (84%) of 43 patients demonstrated a proliferative response to B-ASWS (mean value of experimental [E]-control [C] counts, 16,852 +/- 2664, and of E/C, 42.2 +/- 5.3). None of the patients demonstrated a proliferative response to blastomycin, and only 19 (41%) of 45 patients tested had a positive blastomycin skin test. By 21 months, 47 (98%) of the 48 patients demonstrated a proliferative response to B-ASWS on at least one testing date. Of those initially positive, 82% had a persistently positive proliferative response at 21 months; mean E-C and E/C values were comparable to those seen at 3 months. None of the 47 uninfected persons demonstrated a proliferative response to B-ASWS: 7 with positive histoplasmin skin tests had a mean E-C value of 1094 +/- 432, and the 40 others, a mean value of 1139 +/- 212. A proliferative response to B-ASWS in exposed individuals is a reliable marker of specific cellular immunity in blastomycosis and the response persists in most patients for up to at least 2 years.

Acute Disease↗

PubMed1979

Pulmonary histoplasmosis associated with exploration of a bat cave.

Approximately 14 days after exploring a limestone cave in northcentral Florida in February 1973, an 18-year-old female developed a respiratory illness with pronounced shortness of breath and cyanosis. The following day, an 18-year-old male presented to the hospital with similar complaints. The association of illness with their recent caving experience prompted further epidemiologic investigation. Twenty-nine members of a church-sponsored youth group explored the implicated cave. Twenty-three of them later became ill with complaints of cough, afternoon fever and sweats, chest discomfort, and dyspnea on exertion. Histoplasmin skin tests were positive in 18 of 24 individuals tested. Serum for complement fixation (CF) was positive in 12 of 26. Testing of area residents revealed a low incidence of skin test and CF positivity (7% and 0%, respectively). That spelunkers are at risk of acquiring pulmonary histoplasmosis has been noted previously; in Florida this has been related to the exploration of caves infested with bats. This is the largest reported outbreak of acute pulmonary histoplasmosis that has been associated with spelunking and further points out that only those individuals who enter the cave are at risk of acquiring the disease, and not those who reside in the surrounding area.

Adolescent↗

PubMed1978

Recurrent disseminated histoplasmosis.

A patient who has had three distinct recurrences of disseminated histoplasmosis over 22 years is presented. Measurements of cellular and humoral immune response to histoplasmin antigens were compared with previously reported data. Although initially sulfisoxazole therapy led to regression of disease, over the past 13 years she has required three courses of amphotericin B, each time with resolution of signs and symptoms. Despite minimal evidence of a cellular or humoral immune response to this organism, the patient has done well. Although disseminated histoplasmosis is often a fatal disease, this woman has tolerated the infection well.

Adult↗

PubMed1994

Histoplasmosis during childhood.

To define the clinical presentation of histoplasmosis among hospitalized children, we reviewed the charts of patients treated for histoplasmosis at Vanderbilt University Children's Hospital during the years 1968 through 1988. Thirty-five patients with histoplasmosis diagnosed by culture, pathologic examination, or serologic testing were identified, including 29 patients (83%) with pulmonary/mediastinal infection, 5 (14%) with disseminated disease, and 1 (3%) with primary cutaneous histoplasmosis. The most common symptoms included fever, present in 26 patients (74%), and cough, present in 20 (57%). Of 26 patients with fever, 18 (69%) had fever of > 2 weeks' duration and 7 (27%) had temperatures > or = 40.5 degrees C (> or = 105 degrees F). Abnormal physical findings were few, but 19 patients (54%) had wheezing. Chest radiographs were obtained in all cases except one; 31 (91%) showed abnormalities, including adenopathy in 25 cases (74%) and infiltrates in 19 (56%). Histoplasmin skin tests were positive for 22 (96%) of the 23 patients tested. No cases of classic disseminated histoplasmosis of infancy were identified. Histoplasmosis should be considered in the differential diagnosis when children living in endemic areas are evaluated for persistent fever, cough, and/or wheezing, particularly if adenopathy is seen on the chest radiograph.

Adult↗

PubMedDate not supplied

Biological and sociocultural approaches of histoplasmosis in the State of Guerrero, Mexico.

Histoplasmosis is a deep mycosis with a high prevalence in America. Its aetiological agent, Histoplasma capsulatum, is found in Mexico, mainly in confined spaces, where it grows on bat guano or bird droppings. A research project has been developed in the State of Guerrero, Mexico, where many contaminated caves and mines are visited by individuals and epidemic outbreaks have been recorded. Data concerning human skin test response to histoplasmin antigen, host genetic predisposition to Histoplasma infection, sociocultural, socioeconomical and ethnobiological aspects of the disease in Guerrero are summarized in this paper.

Culture↗

PubMed1980

Oral histoplasmosis treated with miconazole.

A case of localised histoplasmosis of the gingivae, with no osseous involvement is described in a 50-year-old man. The diagnosis was based on histology, growth on culture and a positive histoplasmin latex test. Therapy was commenced with intravenous amphotericin but was changed to intravenous miconazole because of serious immediate side effects and the development of marked renal impairment and moderate suppression of erythropoiesis. Rebiopsy of the gingival margin showed therapy to be effective. No source of the infection could be traced.

Amphotericin B↗

PubMed1983

Persistent cutaneous cellular immune responsiveness in a nursing home population.

Mantoux-type skin tests were applied to 29 elderly residents of an intermediate care floor of a nursing home. Eight antigens were used with each resident, and the size of the reactions was measured at 6, 24, 48, and 72 hours. All but one resident had at least one response greater than or equal to 3 mm at 48 or 72 hours, and most had more than one response of that size. At 48 compared with 72 hours, there was one more responder and the mean size of the reactions to each antigen was greatest. However, there were two responders at 72 hours who did not react at 48 hours, and the total number of reactions in the group was greater at the later reading. Only one resident did not produce any response at either 48 or 74 hours. The minimum number of antigens needed to identify all responsive subjects was five (PPD-Avian, coccidioidin, histoplasmin, streptokinase-streptodornase, and trychophytin). The purified protein derivative of tuberculin skin test was repeated on subjects who had an initial response less than 10 mm, and one increase of more than 6 mm was observed in a resident who was initially unresponsive to that antigen.

Aged↗

PubMedDate not supplied

Comparative evaluation of the Premier enzyme immunoassay, micro-immunodiffusion and complement fixation tests for the detection of Histoplasma capsulatum var. capsulatum antibodies.

A total of 178 sera, including 68 from proven cases of histoplasmosis (65 positive for the presence of Histoplasma capsulatum var. capsulatum antibodies and three positive for antigen), 93 from patients with suspected histoplasmosis but with no laboratory evidence of H. capsulatum var. capsulatum infection, 14 from humans with heterologous fungal and non-fungal infections and three from normal individuals, were tested for IgG H. capsulatum antibodies and M or M and H precipitins by enzyme immunoassay (EIA) (Meridian Diagnostics, Cincinnati, OH, USA) and microimmunodiffusion (MID) respectively. Sixty-three of the 68 histoplasmosis case sera demonstrated IgG antibody, and 65 of 68 demonstrated the presence of specific precipitins in the MID test. Nine positive case sera, when tested with the Laboratory Branch complement fixation (LBCF) test, reacted positively to whole yeast and histoplasmin antigens (titres 1:8 to 1:512). Three histoplasmosis case sera repeatedly tested negative for IgG, specific precipitins and complement-fixing antibodies, whereas they were positive for Histoplasma antigen. Eighteen of 95 sera from patients without evidence of histoplasmosis demonstrated IgG antibody in the EIA only. Among these positive sera, three out of three cases of aspergillosis and three out of five cases of blastomycosis were confirmed. Sera from HIV-infected and healthy individuals did not show IgG or M and/or H antibodies to H. capsulatum. Ninety-three sera were negative by both EIA and MID. The EIA for IgG was less sensitive (97%) than MID (100%). The specificity of EIA and MID was 84% and 100% respectively.

Antibodies, Fungal↗

PubMed1963

Tuberculin hypersensitivity: studies with radioactive antigen and mononuclear cells.

The type and fate of mononuclear cells of guinea pigs hypersensitive to tuberculin were studied by means of purified protein derivative labeled with I(125) and mononuclear cells labeled with tritiated thymidine. Purified protein derivative labeled with I(125) was taken up in vitro by lymphocytes and neutrophils from animals that were either sensitive or nonsensitive to tuberculin, but it was bound more frequently by the cells of sensitive animals. Passive transfer of tuberculin hypersensitivity by means of lymphocytes labeled with tritiated thymidine indicated that significant numbers of radioactive cells migrated to the site where the skin was tested with purified protein derivative only when the test was made immediately after transfusion. Although skin reactions from tests made with purified protein derivative 24 hours after transfusion were comparable to those from tests made immediately, the number of labeled cells at the sites of the later tests was not consistently larger than it was in controls (Histoplasmin reactions). Thus transfused tuberculin-sensitive cells are neither always attracted to the sites of the test with purified protein derivative nor are they required in large numbers at the site for a positive reaction to develop.

Animals↗

PubMed1967

Soluble antigens for immunofluorescence detection of Histoplasma capsulatum antibodies.

Soluble antigens from Histoplasma capsulatum in the mycelial and yeast phase were purified by gel filtration, fixed onto paper discs, and employed in an indirect immunofluorescence procedure to detect antibody in sera from individuals infected with H. capsulatum. The elution patterns of crude histoplasmin passed through Sephadex G-200 revealed two minor peaks of protein showing immunofluorescence, complement fixing, and precipitating-antigen activity. A large peak containing the pigment and other low molecular weight materials showed no serological activity. A polysaccharide antigen obtained from fragmented, deproteinized yeast-phase cells was reactive in the fluorescent-antibody test but showed no antigen activity in complement fixation or precipitin tests. Although certain sera from culturally proven cases of blastomycosis, coccidioidomycosis, and cryptococcosis reacted with the purified Histoplasma antigens, preliminary evaluation indicated that the immunofluorescence technique may be of value as a screening procedure for the serodiagnosis of histoplasmosis.

Antibodies↗

PubMed1970

Comparison of macrocomplement and microcomplement fixation techniques used in fungus serology.

A comparative evaluation was performed on the micro- and macrocomplement fixation (CF) tests that are used as standard procedures in the serodiagnosis of blastomycosis, coccidioidomycosis, and histoplasmosis. Tests with 937 sera from suspected and culturally proven cases of these diseases against yeast-form antigens of Blastomyces dermatitidis and Histoplasma capsulatum and against the soluble antigens, coccidioidin and histoplasmin, revealed that the microtiters were within +/- 1 dilution of the macrotiters in 83 to 93% of the sera. Tests on randomly coded quality control sera revealed the microform of the CF test to be highly reproducible. Our studies indicate that the results obtained by the two tests have similar diagnostic and prognostic interpretations. Because of the sensitivity, reproducibility, economy, and ease of performance, the microtest is highly recommended for use in fungus serology.

Blastomyces↗

PubMed1973

Specific immunodiffusion test for blastomycosis.

A specific immunodiffusion test for blastomycosis has been developed. The test permitted the detection of approximately 80% of 113 proven cases of blastomycosis. Two diagnostically important precipitins designated A and B were frequently recognized in patients with blastomycosis. Routine use of reference sera containing the A and B precipitins in immunodiffusion tests would permit the specific diagnosis of blastomycosis without the need for parallel tests with coccidioidin and histoplasmin.

Antigens, Fungal↗

PubMed1977

Antigenic, chemical, and structural properties of cell walls of Histoplasma capsulatum yeast-form chemotypes 1 and 2 after serial enzymatic hydrolysis.

Cell walls of Histoplasma capsulatum yeast-form chemotypes 1 (chem 1) and 2 (chem 2) treated sequentially with several polysaccharolytic enzymes and Pronase yielded soluble, nondialyzable polysaccharides at each step, which were analyzed for monosaccharides, protein composition, and serological activity. Polysaccharide recovered after digestion of chem 1 walls with beta(1-->3)-glucanase contained glucose > mannose > glucosamine > galactose. This fraction (chem 1 betaG(1)) was analyzed by polyacrylamide gel electrophoresis and contained a component having an apparent molecular weight of 120,000. The chem 1 betaG(1) fraction was reactive in immunodiffusion (ID), producing an immune precipitate not identical to the H and M factors of histoplasmin. In a side-by-side ID comparison with extracts of chem 2, the chem 1 betaG(1) antigen contained an additional determinant not found in chem 2 extracts when tested with goat antiserum to H. capsulatum. Therefore, the chem 1 antigen gave preliminary ID evidence of antigenic group specificity. A chemical difference observed was the absence of glucosamine from chem 2 polysaccharide. In complement fixation (CF) tests, 9 of 17 sera from human histoplasmosis patients reacted with chem 1 betaG(1), but some cross-reactivity with sera of patients with other systemic mycoses occurred. The immunoelectrophoretic patterns of chem 1 wall-derived polysaccharides showed a marked shift in mobility after Pronase digestion, implying the presence of covalent peptides. The ultrastructural appearance and serological activity of intact walls and enzyme-resistant mural cores were also studied. The surface of the mural cores of both chemotypes was perforated and frayed. In shadow-cast preparations both fibrillar and globular areas persisted in the mural cores. The CF end point serum dilutions showed an increase after alpha- and beta-glucanase extractions of chem 2 walls and fourfold reduction after Pronase digestion. The mural cores of both chemotypes were still reactive in CF tests and retained some ability to bind fluorescent antibody. The chem 1 mural core reacted with specific fluorescein-labeled H. capsulatum antiglobulins produced by adsorption with Blastomyces dermatitidis, thus indicating at least partial retention of H. capsulatum-specific factors. The presence of galactose, mannose, and glucose was detected in the mural cores as well as enriched levels of amino sugar, despite exposure to chitinase.

Antigens, Fungal↗

PubMed1983

Pharmacological modulation of suppressor cell activity in mice with disseminated histoplasmosis.

Indomethacin and cyclophosphamide (CY) were used in an attempt to modify the suppressive effects of spleen cell populations from mice with disseminated histoplasmosis at 1 week of infection. In vitro addition of indomethacin did not alter the depressed plaque-forming cell response to sheep erythrocytes of normal spleen cells cocultured with unfractionated or nylon wool-fractionated spleen cells from infected mice. Likewise, indomethacin given intraperitoneally did not enhance the subnormal in vivo plaque-forming cell response of spleen cells from infected mice. Conversely, 20 mg of CY per kg given intraperitoneally 2 days before or 6 h after the inoculation with Histoplasma capsulatum partially reversed the suppression effected by splenic T cells (nylon wool passed) in vitro, whereas 50 mg of CY per kg given intraperitoneally 6 h after the injection of H. capsulatum ablated suppressor T cell activity in vitro; neither dosage of CY altered the suppression mediated by unseparated or nylon wool-adherent spleen cells. Furthermore, the administration of 50 mg of CY per kg failed to improve the depressed footpad responses of mice infected for 1 week to sheep erythrocytes in sheep erythrocyte-sensitized mice or to histoplasmin. These findings indicate that in experimental disseminated histoplasmosis, suppression effected by splenic T cells can be alleviated by CY; however, there is a persistent immunosuppressor mechanism(s) that cannot be counteracted by either indomethacin or CY.

Animals↗

PubMed1986

Modulation of cellular immune responses in mice with disseminated histoplasmosis by recombinant interleukin-2.

Depression of the cellular immune responses in mice with disseminated histoplasmosis is associated with deficient production of interleukin-2 (IL-2) by splenocytes. Therefore, we examined whether a highly purified preparation of IL-2, recombinant human IL-2 (rIL-2), could modify the cellular immune responses in infected mice and whether this lymphokine could alter the severity of histoplasmosis in animals. Exogenous rIL-2, at concentrations of up to 1,000 U/ml, failed to augment the proliferative responses to concanavalin A by unfractionated splenocytes or splenic T cells from mice infected for 1 week. In addition, rIL-2 did not modulate the plaque-forming cell response to sheep erythrocytes by splenocytes from these same mice. However, at week 3, rIL-2 in concentrations ranging from 10 to 1,000 U/ml considerably augmented the proliferative response to concanavalin A and plaque-forming cell response to sheep erythrocytes by splenocytes from infected mice. Kinetics studies demonstrated that rIL-2 exerted maximal immunoregulatory activity when added on day 0 or 1 to cultures of splenocytes. In vivo administration of rIL-2, 200 to 20,000 U/day, for 10 days to normal and 3-week-infected mice did not alter the proliferative activity of splenocytes to concanavalin A; 200,000 U of rIL-2 per day actually depressed the proliferative responses of splenocytes from normal and infected mice. In vivo, rIL-2 did not modify delayed-type hypersensitivity responses to sheep erythrocytes or to histoplasmin by normal and infected mice. Moreover, treatment with rIL-2 in vivo did not reduce the number of Histoplasma CFU in spleens of mice. Thus, despite the immunoenhancing effect of rIL-2 in vitro, this lymphokine failed to exert similar effects in vivo.

Animals↗

PubMed1986

Development and characterization of Histoplasma capsulatum-reactive murine T-cell lines and clones.

Experimental studies have suggested that antigen-specific T lymphocytes are important mediators of resistance to infection with the pathogenic fungus Histoplasma capsulation. To gain a better understanding of the role of T lymphocytes, we developed murine T-cell lines and clones that recognized Histoplasma antigens. These T cells were of the helper/inducer phenotype (Thy-1.2+ Lyt-1+ L3T4+ Lyt-2-) and exerted multiple immunological functions. T-cell lines and 12 clones proliferated vigorously in response to histoplasmin; the T-cell lines and 6 clones also were reactive with heterologous fungal antigens prepared from either Blastomyces dermatitidis or Coccidioides immitis. Recognition of antigen by T cells was H-2 restricted; in the absence of antigen, four clones demonstrated alloreactivity. All T-cell clones conferred local delayed-type hypersensitivity responses when injected with antigen into footpads of mice. Ten of 12 T-cell clones released interleukin-2 after stimulation with antigen, and all clones tested secreted interferon. Moreover, culture supernatants from antigen-stimulated clones armed peritoneal macrophages to inhibit intracellular growth of H. capsulatum yeast cells. All clones assayed exerted nonspecific help. Thus, development of T-cell clones should facilitate analysis of the regulatory properties of Histoplasma-specific T cells.

Animals↗

PubMed1989

Development and characterization of a monoclonal antibody against the tube precipitin antigen of Coccidioides immitis.

Primary infection with Coccidioides immitis is commonly accompanied by the production of an immunoglobulin M precipitin antibody which is detected by the tube precipitin (TP) assay or by the immunodiffusion assay for TP antibody (IDTP assay). In the present investigation, spleen cells from spherulin-immunized BALB/c mice were fused with SP2/O Ag14 myeloma cells, and the resulting hybridomas were screened for antibody to the IDTP antigen by using an enzyme-linked immunosorbent assay. Positive hybridomas were cloned by limiting dilution and injected into pristane-primed mice for ascites production. Characterization of antibody reactivity was accomplished with the IDTP assay, two-dimensional immunoelectrophoresis, and immunoblotting. An immunoglobulin G1 monoclonal antibody which reacts with the IDTP antigen of C. immitis is described. The epitope that is recognized by the monoclonal antibody is also present, but to a lesser extent, on a second coccidioidal antigen which has been designated antigen 2. The monoclonal antibody was not reactive in immunoblots of histoplasmin or blastomycin, indicating that the epitope recognized by this antibody may be specific for C. immitis.

Animals↗