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A 50-year-old woman with a history of kidney transplant presented with 2 days of abdominal pain after 6 months of recurrent streptococcal pharyngitis, fevers, weight loss and a new rash on her chest and back. Her examination was notable for a unilateral tonsillar exudate and 2-3 mm pink papules with a fine scale over her chest and back. CT of the abdomen and chest demonstrated several large lymph nodes, and laboratory investigation revealed new cytopenias and elevated transaminases. Urine antigen testing for Histoplasma capsulatum was negative, but a fungal complement fixation panel was reactive for Histoplasma antibodies. Skin biopsy revealed intracellular organisms consistent with H. capsulatum She underwent treatment with liposomal amphotericin B but due to nephrotoxicity, drug interactions and worsening transaminitis, therapy was changed to itraconazole. The diagnosis and management of disseminated histoplasmosis presents multiple challenges, which are of particular importance in patients with a history of renal transplantation., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Histoplasmosis is a rare disease in nonendemic areas. We report a case of a 23-year-old male patient who presented with fever of unknown origin, cytopenias, organomegaly, and allograft dysfunction 4 months after renal transplant with father as donor. Bone marrow examination showed intracellular budding yeast cells, which was confirmed as histoplasmosis by culture of bone marrow biopsy sample. The patient was treated with intravenous liposomal amphotericin and responded well.

Objectives: Serum and urine antigen (SAg, UAg) detection are common tests for Histoplasma capsulatum. UAg detection is more widely used and reportedly has a higher sensitivity. We investigated whether SAg detection contributes meaningfully to the initial evaluation of patients with suspected histoplasmosis., Methods: We reviewed 20,285 UAg and 1,426 SAg tests ordered from 1997 to 2016 and analyzed paired UAg and SAg tests completed on the same patient within 1 week. We determined the positivity rate for each test., Results: Of 601 paired specimens, 542 were concurrent negatives and 48 were concurrent positives (98% agreement). Medical records were available for eight of 11 pairs with discrepant results. UAg was falsely positive in six instances, truly positive once, and falsely negative once., Conclusions: These findings support using a single antigen detection test, rather than both UAg and SAg, as an initial screen for suspected histoplasmosis. This aligns with the current practice of most physicians.

Histoplasmosis is a fungal infection caused by a dimorphic fungus, Histoplasma capsulatum. We report a first case of disseminated histoplasmosis in a 34-year-old woman, infected with human immunodeficiency virus (HIV), originating from Ivory Coast and living in Tunisia for 4 years. She was complaining from fever, chronic diarrhoea and pancytopenia. The Histoplasma capsulatum var. capsulatum was identified by direct microscopic examination of the bone marrow. She was treated by Amphotericin B, relayed by itraconazole. Even though a regression of symptoms and normalization of blood cell count (BCC), the patient died in a respiratory distress related to CMV hypoxemic pneumonia., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

We report a case of ileo-colonic Histoplasmosis without apparent respiratory involvement in a patient who had previously undergone an orthotopic liver transplant (OLT) for primary biliary cholangitis 15 years earlier. The recipient lived in the United Kingdom, a non-endemic region for Histoplasmosis. However, she had previously lived in rural southern Africa prior to her OLT. The patient presented with iron deficiency anaemia, diarrhoea, abdominal pain and progressive weight loss. She reported no previous foreign travel, however, it later became known that following her OLT she had been on holiday to rural southern Africa. On investigation, a mild granulomatous colitis primarily affecting the right colon was identified, that initially improved with mesalazine. Her symptoms worsened after 18 mo with progressive ulceration of her distal small bowel and right colon. Mycobacterial, Yersinia, cytomegalovirus and human immunodeficiency virus infections were excluded and the patient was treated with prednisolone for a working diagnosis of Crohn's disease. Despite some early symptom improvement following steroids, there was subsequent deterioration with the patient developing gram-negative sepsis and multi-organ failure, leading to her death. Post-mortem examination revealed that her ileo-colonic inflammation was caused by Histoplasmosis., Competing Interests: Conflict-of-interest statement: No conflict of interests are declared by any authors.

Background: The prevalence of the Histoplasma capsulatum var. capsulatum (Hcc) histoplasmosis may be underestimated West Africa, both because the diagnosis is not mentioned in the early stages of the disease and due to limited biological resources available., Case Report: We report a case of disseminated histoplasmosis due to Hcc in a Senegalese HIV patient. The diagnosis was suspected following the demonstration of small encapsulated yeasts within neutrophils on a thin blood smear. It was further confirmed using a specific real-time PCR applied on a DNA specimen extracted from the thin blood smear., Conclusion: To the best of our knowledge, this is the first case of Hcc infection diagnosed in Senegal. Blood smear may be a valuable screening tool in the case of bloodstream dissemination and can be used for further molecular approaches to confirm the diagnosis.

Background: Treatment monitoring is subjective and disease relapse is common in cats with histoplasmosis. The Histoplasma antigen enzyme immunoassay (EIA) is a noninvasive test used for determining disease remission and detecting disease relapse in humans with histoplasmosis. The utility of the antigen EIA for these purposes in cats remains unknown., Hypothesis/objectives: Those Histoplasma antigen concentrations in urine and serum would decline with antifungal treatment and that antigen elimination would be an indicator of clinical remission in cats with histoplasmosis treated with antifungal treatment., Animals: Fifteen client-owned cats with histoplasmosis., Methods: Masked observational study. Cats were monitored monthly during antifungal treatment. Time of clinical remission and serum and urine antigen elimination were determined for each cat., Results: Twelve of 15 cats achieved clinical remission. At the time of diagnosis, antigen was detectable in urine in 14/15 (93%) cats and in serum in 11/15 (73%) cats. Both serum (P < .0005) and urine (P < .0001) antigen concentrations significantly decreased over time with effective treatment. Antigen elimination was sensitive [urine, 90.0% (95% CI 72.3-97.4%); serum, 90.4% (68.2-98.3%)] but less specific [urine, 64.6% (51.7-75.8%); serum, 52.1% (37.4-66.5%)] for disease remission. Urine antigen was positive in both cats and serum antigen was positive in 1 cat at the time of disease relapse., Conclusions and Clinical Importance: Measurement of Histoplasma antigen in urine and serum might be useful tests for determining disease remission and relapse in cats with histoplasmosis. Further research is needed to investigate the importance of low-level antigenemia and antigenuria., (Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Histoplasmosis is worldwide systemic mycoses caused by the dimorphic fungus Histoplasma capsulatum. The isolation and identification of H. capsulatum in culture is the reference test for histoplasmosis diagnosis confirmation. However, in the absence of it, serology has been used as a presumptive diagnosis through antibody and antigen detection. The purpose of the present study was to validate an immunoassay method (western blot) for antibodies detection in the diagnosis of histoplasmosis., Methods: To validate the western blot (WB) a study was conducted using 118 serum samples from patients with histoplasmosis and 118 serum controls collected from January 2000 to December 2013 in residents of the Rio de Janeiro State, Brazil. Diagnostic validation parameters were calculated based on the categorization of results obtained in a 2 × 2 table and subjected to statistical analysis. In addition, the viability of deglycosylated histoplasmin antigen (ptHMIN) onto nitrocellulose membranes previously sensitized was evaluated during the same period., Results: The WB test showed sensitivity of 94.9 %, specificity of 94.1 %, positive predictive value of 94.1 %, negative predictive value of 94.9 %, accuracy of 94.5 %, and almost perfect precision. Besides, the strips have proved to be viable for using at least 5 years after ptHMIN antigen sensitization., Conclusion: Western blot test using ptHMIN provides sensitive, specific, and faster results. Therefore, could be considered a useful tool in the diagnosis of histoplasmosis being used by public health system, even in situations where laboratory facilities are relatively limited.

Histoplasmosis, one of the most important mycoses, needs to be diagnosed rapidly and accurately. The main method used to diagnose histoplasmosis is serological detection of antibodies to the Histoplasma capsulatum H and M antigens. Several other protein antigens have been reported in H. capsulatum; however, they have not been used for diagnosis. In this study, we explored novel antigens that were detected during H. capsulatum infection. We obtained a protein mixture from H. capsulatum yeast cells after vigorous mixing in a 0.1% Triton X-100 solution. From the resultant pool, we detected nine spots that reacted with sera from patients with histoplasmosis and identified eight seroactive proteins with mass spectrometry. The seroactive proteins were purified, and their antigenicities were tested with an enzyme-linked immunosorbent assay (ELISA). ELISA revealed that the titer of the patients' sera to N-acetylated α-linked acidic dipeptidase was significantly higher than those of healthy volunteers (P < 0.01). These data indicate that N-acetylated α-linked acidic dipeptidase of H. capsulatum is recognized as a major antigen during histoplasmosis., (Copyright © 2015 Elsevier Inc. All rights reserved.)

We determined the value of culture and serological tests used to diagnose histoplasmosis. The medical records of 391 histoplasmosis patients were analyzed. Diagnosis of the mycosis was assessed by culture, complement fixation, and immunodiffusion tests; 310 patients (79.5%) were male, and 184 patients (47.1%) were infected with human immunodeficiency virus (HIV). Positivity value for cultures was 35.7% (74/207), reactivity of serological tests was 95.2% (160/168), and a combination of both methodologies was 16.9% (35/207) for non-HIV patients. Positivity value for cultures was 75.0% (138/184), reactivity of serological tests was 92.4% (85/92), and a combination of both methodologies was 26.0% (48/184) for HIV/acquired immunodeficiency syndrome (AIDS) patients; 48.1% (102/212) of extrapulmonary samples from HIV/AIDS patients yielded positive cultures compared with 23.1% (49/212) in non-HIV patients. Lymphocyte counts made for 33.1% (61/184) of HIV/AIDS patients showed a trend to low CD4+ numbers and higher proportion of positive cultures. These results indicate that culture is the most reliable fungal diagnostic method for HIV/AIDS patients, and contrary to what is generally believed, serological assays are useful for diagnosing histoplasmosis in these patients.

The aim of the study was to detect the rDNA sequences and their regions in Histoplasma capsulatum, which could be considered species-specific and used as a molecular method for this diagnosis by the technique of nested polymerase chain reaction (nested PCR), employing specific sequences (primers) for H. capsulatum: 18S rDNA region (HC18), 100 kDa (HC100) and the sequence 5.8 S-ITS rDNA (HC5.8). The PCR sequences HC18, HC100 and HC5.8 resulted in a specificity of 100%. The molecular assays may increase the specificity, sensitivity and speed in the diagnosis of Histoplasmosis.

Disseminated histoplasmosis is an emerging infection in patients with cellular immune deficiency in non-endemic countries, caused by the migration from endemic regions and the development of travels. Diagnosis can be challenging in this context because rapid diagnostic tools such as Histoplasma antigen detection or appropriate molecular tools are generally unavailable, serology is often negative in immunosuppressed patients, and isolation of the fungus from cultures often takes several weeks. Here, we report the contribution of galactomannan serum detection for the management of an HIV-infected patient with disseminated histoplasmosis.

Ocular histoplasmosis syndrome (OHS) is a significant cause of vision loss in young and middle-aged adults. We report here a case of an immunocompetent 37-year-old man who presented fever, malaise, headache, and anterior cervical lymphadenopathy for one week, after which he started to experience a sudden loss in visual acuity of his right eye. Fluorescent angiography and an optical coherent tomography demonstrated the presence of a type II choroidal neo-vascular membrane in the right eye, suggesting a diagnosis of OHS. A peripheral blood sample was tested by nested PCR to detect Histoplasma capsulatum using a set of primers known to amplify a DNA sequence coding for a specific 100-kDa protein of this fungus (Hc100-PCR). The blood sample was Hc100-PCR-positive and sequence analysis showed an identity of 97% with the reference sequence. The patient received intravitreal bevacizumab injection and itraconazol therapy, leading to an improvement in media vision acuity. In this case, the molecular test provided evidence linking the ocular lesions with an earlier infection by H. capsulatum and demonstrated that the Hc100-nested PCR assay is a valuable tool in the diagnosis of histoplasmosis.

We report the identification of Histoplasma capsulatum var. capsulatum from whole blood in a renal transplant patient with disseminated histoplasmosis using colorimetric microtiter-plate PCR. This modality demonstrated utility in reaching a definitive diagnosis in a timely manner. Blood fungal cultures in this case remained negative, suggesting that molecular assays may facilitate the laboratory diagnosis of disseminated histoplasmosis.

Histoplasmosis is a common endemic mycosis in the Americas, often causing severe disease in patients with AIDS. Antigen detection has become an important method for rapid diagnosis of histoplasmosis in the United States but not in Central or South America. Isolates from patients in the United States are predominantly found to be class 2 isolates when typed using the nuclear gene YPS3, while isolates from Latin America are predominantly typed as class 5 or class 6. Whether infection with these Latin American genotypes produces positive results in the Histoplasma antigen assay has not been reported. In this study, we have compared the sensitivity of antigen detection for AIDS patients from Panama who had progressive disseminated histoplasmosis to that for those in the United States. Antigenuria was detected in the MVista Histoplasma antigen enzyme immunoassay (EIA) in 95.2% of Panamanian cases versus 100% of U.S. cases. Antigenemia was detected in 94.7% of the Panamanian cases versus 92% of the U.S. cases. Two clinical isolates from Panama were typed using YPS3 and were found to be restriction fragment length polymorphism class 6. We conclude that the MVista Histoplasma antigen EIA is a sensitive method for diagnosis of histoplasmosis in Panama.

False-positive Histoplasma antigenemia was reported in solid organ allograft recipients who had received rabbit anti-thymocyte globulin (RATG, RATG) caused by human anti-rabbit antibodies (HARA). A second-generation Histoplasma antigen detection assay was developed to overcome false positivity caused by HARA. With the second-generation assay, false-positive results were eliminated in 18 of 19 cases without reduction in the sensitivity in patients with histoplasmosis. In fact, sensitivity for detection of antigenuria in patients with acquired immunodeficiency syndrome and disseminated histoplasmosis was higher in the second-generation assay. Physicians should be aware of the potential for false-positive results in sandwich immunoassays in specimens from patients who have received RATG.

A new real-time PCR-based assay was used for detecting DNA of Histoplasma capsulatum in serum samples collected from four HIV-infected patients with proven histoplasmosis. The assay targeted the ITS1 region of rDNA and its in vitro sensitivity, specificity and reproducibility were evaluated. The technique detected DNA of H. capsulatum in all of the HIV-infected patients with proven histoplasmosis (4/4, 100%). The PCR result was positive for seven of the ten (70%) samples studied. The assay's specificity was determined to be 100%, since the method was negative for 25 other serum samples (10 from patients with proven aspergillosis and 15 from healthy controls). The PCR assay is a new and promising diagnostic alternative and further investigation is warranted.

Histoplasma capsulatum is a thermally dimorphic ascomycete that is a significant cause of respiratory and systemic disease in mammals including humans, especially immunocompromised individuals such as AIDS patients. As an environmental mold found in the soil, it is a successful member of a competitive polymicrobial ecosystem. Its host-adapted yeast form is a facultative intracellular pathogen of mammalian macrophages. H. capsulatum faces a variety of environmental changes during the course of infection and must survive under harsh conditions or modulate its microenvironment to achieve success as a pathogen. Histoplasmosis may be considered the fungal homolog of the bacterial infection tuberculosis, since both H. capsulatum and Mycobacterium tuberculosis exploit the macrophage as a host cell and can cause acute or persistent pulmonary and disseminated infection and reactivation disease. The identification and functional analysis of biologically or pathogenically important H. capsulatum genes have been greatly facilitated by the development of molecular genetic experimental capabilities in this organism. This review focuses on responsiveness of this fungus to its environment, including differential expression of genes and adaptive phenotypic traits.

Histoplasmosis is an important systemic fungal infection, particularly among immunocompromised individuals, who may develop a progressive disseminated form which is often fatal if it is untreated. In such patients, the detection of antibody responses for both diagnosis and follow-up may be of limited use, whereas the detection of Histoplasma capsulatum var. capsulatum antigens may provide a more practical approach. We have recently described an inhibition enzyme-linked immunosorbent assay (ELISA) for the detection in patients' sera of a 69- to 70-kDa H. capsulatum var. capsulatum-specific antigen which appears to be useful in diagnosis. To investigate its potential for the follow-up of histoplasmosis patients during treatment, antigen titers in the sera of 16 patients presenting with different clinical forms of histoplasmosis were monitored at regular intervals for up to 80 weeks. Sera from four of five patients with the acute form of the disease showed rapid falls in antigenemia, becoming antigen negative by week 14 (range, weeks 10 to 16). Sera from four patients with disseminated histoplasmosis showed falls in antigen levels; three of them became antigen negative by week 32; the fourth patient became negative by week 48. In contrast, antigen titers in four of six AIDS patients with the disseminated form of the disease remained positive throughout follow-up. Sera from only one patient who presented with the chronic form of the disease were analyzed, and this individual's serum became antigen negative by week 9. The inhibition ELISA is shown to be of particular use in the monitoring of non-AIDS patients with the acute and disseminated forms of the disease and may complement existing means of follow-up.

The reliability of MYCO/F Lytic medium in the BACTEC 9240 blood culture system was evaluated by comparing its performance to that of the Isolator system for the recovery of fungi and to that of the ESP II system for the recovery of mycobacteria. Of 717 specimens of blood cultured for fungi, 24 were positive; 12 samples were positive with both systems, 7 samples were positive with the Isolator system only, and 5 samples were positive with MYCO/F Lytic medium only. Fourteen samples grew Histoplasma capsulatum; both systems detected H. capsulatum in seven samples but the Isolator system alone detected H. capsulatum in seven samples. The mean times to the detection of H. capsulatum were 8 days (range, 4 to 13 days) for MYCO/F Lytic medium and 9 days (range, 6 to 18 days) for the Isolator system; the mean times to identification were 20 days (range, 15 to 24 days) for isolates recovered with MYCO/F Lytic medium and 11 days (range, 6 to 18 days) for those recovered with the Isolator system (P < 0.05). Cryptococcus neoformans was isolated from 10 fungal cultures; five isolates grew in both systems, and five isolates grew in MYCO/F Lytic medium only. The mean times to detection of C. neoformans were 4 days (range, 2 to 6 days) for MYCO/F Lytic medium and 7 days (range, 5 to 7 days) for the Isolator system (P < 0.05); the mean times to identification were 15 days (range, 7 to 27 days) for isolates recovered with MYCO/F Lytic medium and 8 days (range, 7 to 11 days) for those recovered with the Isolator system. Of the 687 samples of blood cultured for mycobacteria, 64 blood samples from 42 patients grew mycobacteria (58 grew Mycobacterium avium complex, 4 grew Mycobacterium kansasii, and 2 grew Mycobacterium tuberculosis); 42 isolates were recovered with both systems, 18 were isolated with MYCO/F medium only, and 4 were isolated with the ESP II system only alone (P < 0.05). The mean time to detection of mycobacteria with MYCO/F Lytic medium was 14 days, whereas it was 17 days with the ESP II system (P < 0.05). In summary, the combination of MYCO/F Lytic medium and the BACTEC 9240 instrument is an excellent blood culture system for the growth and detection of mycobacteria. A valid assessment of MYCO/F Lytic medium with regard to fungal isolation, however, was not possible due to the small number of isolates recovered.

A yeast-phase-specific gene, yps-3, has been identified in the virulent Histoplasma capsulatum strain, G217B. Although DNA sequencing of the genomic yps-3 gene from G217B failed to detect homologies with known proteins, the 5' end of a yps-3 cDNA contained a consensus signal sequence. A 519-bp fragment of the cDNA containing the translational stop codon was linker modified and inserted into the bacterial expression vector, pATH 1. Escherichia coli extracts containing the pATH 1 vector alone expressed a major 34-kDa TrpE polypeptide following induction with indoleacrylic acid, while the pATH 1/yps-3 construct produced a predominant 54-kDa TrpE/yps-3 fusion protein. Polyclonal rabbit sera directed against G217B reacted exclusively with the 54-kDa fusion protein in Western blots (immunoblots); serum samples from three patients with acute pulmonary or disseminated histoplasmosis were also positive. To localize the yps-3 protein within G217B, a monoclonal antibody (MAb 7.1) which recognized the yps-3 portion of the fusion protein was generated. A 17.4-kDa protein was detected with MAb 7.1 in Western blots prepared from cell wall fractions of G217B; cytoplasmic fractions were unreactive. No yps-3 antigen was detected in either fraction of the Downs strain, which fails to express the yps-3 gene. MAb 7.1 also detected a 17.4-kDa antigen in ethanol-precipitated culture supernatants derived from G217B. These findings localize the yps-3 gene product to the cell wall and culture supernatants, where the protein may influence the phase transition or the maintenance of the yeast state.

A prospective study was carried out in two groups of individuals: a group 1 (n = 40) included workers from a poultry farm, with potential occupational risk of exposure to Histoplasma capsulatum, etiologic agent of histoplasmosis, and a group 2 (n = 16), persons without occupational risk of exposure to the agent. Histoplasmin skin test was performed in both groups, and three sera were obtained from each individual: 1) before skin test was done, 2) 30 days after, and 3) 180 days after it. In both groups the histoplasmin skin test, even when the test was positive, was not a sufficient antigenic booster to provoke an increase in the H. capsulatum antibody levels capable to be detected by the serologic tests used (ELISA and Double Immunodiffusion). These results contribute to improve the interpretation of ELISA test values in the diagnosis of histoplasmosis.

We sought to determine whether measurement of Histoplasma capsulatum var. capsulatum antigen concentration in tissues and blood provided a marker for antifungal effect of itraconazole in a nonlethal murine model of histoplasmosis. Treatment with itraconazole (Sporanox), in cyclodextrin, was evaluated in a pulmonary model of histoplasmosis. Mice infected with 4.0 x 10(7) yeast-phase organisms by endotracheal inoculation were treated with itraconazole, 1.5 mg twice daily by gavage, for 10 consecutive days, beginning on day 4 of infection. All mice were sacrificed on day 15 of infection. Blood, spleen, and lung tissues were removed for culture and quantification of antigen. Numbers of organisms were significantly lower in spleens from the treated group: 20.8 +/- 41.8 vs. 65.8 +/- 39.1 in the control group, P = 0.017. Numbers of organisms in lung were 9.6 +/- 27.3 colony forming units in treated versus 24.2 +/- 36.3 in control animals, P = 0.267. Antigen concentrations in spleen tissue and serum were lower in treated versus control mice: spleen, 1.8 +/- .6 units in treated versus 11.0 +/- 2.3 in controls, P < 0.001; serum, 0.8 +/- 0.2 units in treated versus 2.2 +/- 1.0 units in controls, P < 0.001. Lung antigen concentrations were similar in the two groups, 19.2 +/- 1.4 units in treated compared to 17.9 +/- 3.0 units in control mice, P = 0.142. The cyclodextrin formulation of itraconazole (Sporanox) demonstrated antifungal activity in experimental histoplasmosis. Antigen detection was a useful marker for antifungal effect.

An indirect micro-ELISA system is presented for diagnosing histoplasmosis. The diagnostic criteria are defined by using sera from 12 patients who are histoplasmosis carriers. For this group, the optical density values were superior to 1,000; use was made of 43 sera from blood bank donors and 9 sera from children without a history of exposure. The optical density values in these cases were inferior to 0,200. The significant difference found led to the diagnostic criterion for confirming 3 histoplasmosis carriers who showed clinical manifestations but had been negative to double immunodiffusion. Thus, the usefulness of the proposed micro-ELISA system for early diagnosis was proved.

We report the recovery of Histoplasma capsulatum from blood specimens cultured for Mycobacterium sp. in BACTEC 13A radiometric medium. H. capsulatum was recovered from six of eight blood specimens submitted for mycobacterial cultures from five human immunodeficiency virus-positive individuals. Initial positive metabolic signals occurred at a mean of 11 days, but no organisms were detected with acid-fast stains. The bottles remained positive, and after an additional incubation (mean, 8 days), yeast cells morphologically compatible with H. capsulatum were detected when aliquots were stained with acridine orange. Therefore, when radiometric mycobacterial blood cultures with persistent positive metabolic signals and negative acid-fast stains are encountered, acridine orange staining and subculturing for a variety of microorganisms, including fungi, e.g., H. capsulatum, should be considered.

Factors modulating host resistance to Histoplasma capsulatum are only partially understood. The role of iron-binding proteins in infectious diseases has been an area of recent in-depth investigation. The present study reaffirmed the necessity of iron for growth of H. capsulatum. Transferrin saturation was found to be of importance in withholding iron, and antigen-specific antibody had no added effect. Serums of patients with various clinical classes of histoplasmosis were found to exhibit abnormalities in iron metabolic parameters. However, based on transferrin saturation data, iron withholding by transferrin does not appear to be a significant host defense mechanism in vivo. Further studies presented herein suggest a protective effect of phagocytosis and sequestration by the macrophage-phagocyte system.

A method is described by which a soluble antigen was prepared from the yeast phase of Histoplasma capsulatum. This soluble preparation had a specificity greater than that of whole-cell yeast-phase antigens. In complement fixation tests with sera from human cases of histoplasmosis, blastomycosis, and coccidioidomycosis, the soluble antigen reacted in 12.1% of 141 tests with heterologous sera, whereas conventional whole-cell yeast antigens reacted in 47.3% of 91 tests with heterologous sera. The reactivities of the two types of antigens with homologous sera were essentially the same.