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Immunomodulation by Histoplasma capsulatum products; polyclonal activation and mitogenic effects.

The presence of reactive spleen cells to sheep red blood cells (SRBC) in nonimmunized BALB/c mice injected with histoplasmin, the culture filtrate of Histoplasma capsulatum, was monitored for 21 days following inoculation. Polyclonal activation, as evidenced by a sharp increase in the number of anti-SRBC rosette-forming cells (RFC), as well as an enhanced response to heterologous non-cross-reactive erythrocytes from other species, was found in the spleens of these rodents on Days 11 to 13. Elimination of B-cell-derived RFC by the addition of complement indicated that the erythrocyte-binding cells consisted of both T- and B-lymphocytes. An immunosuppressive effect was detected if histoplasmin was injected 2 days before the antigen (SRBC), but could be reversed by injecting the filtrate 30 min prior to the antigen, as is found with polyclonal activators displaying immunosuppressive activity. Histoplasmin also had a mitogenic effect on lymphocyte obtained from the spleen, bone marrow, and thymus similar in magnitude to that produced by lipopolysaccharide (LPS) and concanaval in A. The biological significance of these findings is discussed.

Animals↗

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↗

Perforated granulomatous colitis caused by Histoplasma capsulatum.

A 57-year-old man who presented with an acute abdomen and clinically was thought to have perforated colonic diverticulitis, was found to have transmural granulomatous inflammation and perforation of colon that was caused by Histoplasma capsulatum. Although involvement of any part of the gastrointestinal tract may occur with disseminated histoplasmosis, the complication of intestinal perforation requiring emergency surgery (particularly in the colon) is extremely rare and warrants this case report with discussion of the various clinicopathologic features of gastrointestinal histoplasmosis and the occurrence of primary intestinal histoplasmosis.

Colon↗

Histoplasma capsulatum endocarditis.

Endocarditis is a rare manifestation of disseminated Histoplasma capsulatum infection. A 22-year-old man presented with a seven month history of fever, weight loss, and progressive aortic insufficiency. The diagnosis of H. capsulatum was suggested by a diagnostic rise in complement fixation titers and positive echocardiographic findings. The diagnosis was confirmed prior to surgery by positive bone marrow culture. Progressive congestive heart failure necessitated replacement of the aortic valve which subsequently grew H. capsulatum. In this case, a combination of amphotericin B therapy and valve replacement was curative.

Adult↗

Pericarditis caused by Histoplasma capsulatum.

Sixteen patients with pericarditis caused by Histoplasma capsulatum were studied. Fourteen were less than 30 years old, and no patient had an underlying illness or was receiving immunosuppressive therapy. All patients experienced a flu-like prodromal illness lasting from 2 weeks to 4 months. Pneumonitis or hilar adenopathy, or both, was found in 12; pleural effusion, uncommon in primary pulmonary histoplasmosis, was found in seven patients. Pericardial fluid, pleural fluid and bone marrow cultures yielded no growth. All patients demonstrated a fourfold or greater change in complement-fixing antibody titers. No patient had disseminated disease, and only one required treatment with ampholericin B. The illness ran a protracted course, and in six patients symptomatic pericarditis recurred. Ultimately all recovered. Ten patients were restudied 6 months to 12 years after recover. Only one patient had pericardial calcification, and none had constrictive pericarditis. This form of granulomatous pericarditis, unlike that caused by Mycobacterium tuberculosis, appears to carry a good prognosis.

Adolescent↗

Pneumocystis and Histoplasma infections in wild animals from the Amazon region of Brazil.

Routine examination of tissues from wild forest rodents from Amapá, north Brazil, revealed Pneumocystis carinii in lung smears from a newly captured Oryzomys capito (Cricetidae). Acute, fatal infections with this parasite are also recorded in a number of captive "coatimundis", Nasua narica (Carnivora: Procyonidae) and a sloth, Bradypus tridactylus (Edentata). Pneumocystis was also encountered in lung smears from a newly captured and apparently healthy sloth, Choloepus didactylus. The presence of infection in newly captured animals leads us to believe that the fatal, fulminating pneumocystosis seen in the captive Nasua and Bradypus was due to exacerbation of pre-existant infections acquired in their natural forest environment. Pneumocystis carinii is a well known cause of fatal, interstitial plasma-cell pneumonia in human infants and sometimes the weakened adult: the keeping of exotic pets such as the coatimundi is, therefore, not without some hazard in this respect. Histoplasma, another well known pathogen for man, was isolated from 4 rodents, Proechimys guyanensis (Echimyidae), all from virgin forest along the newly opened Trans Amazon Highway, Pará State, and from a single sloth, Choloepus didactylus, from near Belém, Pará. All these animals showed no symptoms of infection: isolation of the parasite was made by the inoculation of laboratory hamsters with saline suspensions of triturated liver and spleen.

Animals↗

Granulomatous mastitis caused by histoplasma and mimicking inflammatory breast carcinoma.

Two cases of a lobular, necrotizing granulomatous process causing a unilateral painful breast mass mimicking carcinoma are presented for comparison. While the morphologic appearance in each case was that of lobular granulomatous mastitis, the etiologic agent in one case appeared to be Histoplasma capsulatum, based on Grocott methenamine silver staining, and represents the second reported case of histoplasmosis involving only breast parenchyma. Awareness of the rare entity, granulomatous mastitis, is important for the pathologist because the definitive diagnosis is made microscopically. Thorough evaluation of the breast tissue is essential for its management and should eventually contribute to the clarification of its etiology.

Adult↗

Cutaneous Histoplasma capsulatum in a nonimmunocompromised patient with previously treated cutaneous Mycobacterium kansasii.

This report describes a black woman with a history of cutaneous Mycobacterium kansasii responsive to antituberculous drugs. A culture several years later of cutaneous lesions was also positive for Histoplasma capsulatum. Both cutaneous diseases are rare and most often occur in immunocompromised hosts. There is no known association between these two diseases. This patient may have an as-yet unidentified immunodeficiency that predisposes her to these rare infections. Her case emphasizes the importance of repeat biopsy for atypical skin lesions.

Dermatomycoses↗

The concurrent presence of systemic disease pathogens and cutaneous Kaposi's sarcoma in the same lesion: Histoplasma capsulatum and Kaposi's sarcoma coexisting in a single skin lesion in a patient with AIDS.

the concurrent presence of infectious organisms within cutaneous lesions of Kaposi's sarcoma (KS) in persons with the acquired immunodeficiency syndrome (AIDS) has been demonstrated. We report the first patient with AIDS in whom both KS and Histoplasma capsulatum were documented within the same cutaneous lesion. Pathogenic organisms of other fungal, mycobacterial, and viral diseases in KS lesions in other patients seropositive for human immunodeficiency virus are reviewed. Possible explanations for the coexistence of a focus of infection within a lesion of KS are discussed. It may be that in some patients the infection acts as a stimulus to induce vascular proliferation and subsequent development of sarcoma. There is also support for the idea of organism seeding in vascular tissues in the course of dissemination of infection. It is important to rule out the presence of coexistent infections or more than one pathologic process in skin lesions in patients with AIDS.

Acquired Immunodeficiency Syndrome↗

[Histoplasmosis, caused by Histoplasma capsulatum, and AIDS].

Histoplasma capsulatum histoplasmosis occurs frequently in endemic areas and with the AIDS outbreak, it appears as an opportunistic fungus involved in disseminated disease. We report the clinical, biological and treatment features of seven cases diagnosed in the CISIH of the Eastern part of Paris. Clinically, four patients were suffering from pulmonary symptoms, in three cases digestive disorders and in three cutaneous lesions. In all cases, the mycologic diagnosis was necessary. Amphotericin B and itraconazole were used as treatment for five patients (two died before the diagnosis was completed). Among these five subjects, four died (death was attributed to histoplasmosis in only one case). These observations emphasize the importance of this infection in HIV-infected patients coming from endemic areas.

AIDS-Related Opportunistic Infections↗

Lack of antibody induction following skin testing with histolyn-CYL: ELISA determinations with Histoplasma capsulatum yeast and mycelial phase antigens.

No significant increases in antibody levels (IgG, IgM) were detected when serum specimens obtained from individuals exhibiting a positive skin test to the Histoplasma capsulatum yeast phase reagent, Histolyn-CYL, were assayed by the indirect enzyme-linked immunosorbent assay (ELISA) using yeast and mycelial phase antigens.

Antibodies, Fungal↗

Prostatic abscess due to Histoplasma capsulatum in a patient with the acquired immunodeficiency syndrome.

Disseminated histoplasmosis is a systemic fungal infection that may occur in previously healthy or immunocompromised patients. The condition is being recognized with increasing frequency in persons infected with the human immunodeficiency virus. The most common organs involved include the lung, bone marrow, lymph nodes, liver, adrenals and central nervous system, with genitourinary involvement being exceedingly unusual. We describe a Histoplasma capsulatum prostatic abscess occurring after therapy for pulmonary histoplasmosis in a patient with the acquired immunodeficiency syndrome. The prostate may be a difficult focus from which to eradicate disseminated fungal infection in immunocompromised patients.

Abscess↗

Disseminated Histoplasma capsulatum infection presenting as genital ulcerations.

BACKGROUND: Histoplasma capsulatum infection in adults is most often subclinical but can result in disseminated disease with weight loss, fever, hepatosplenomegaly, and oropharyngeal ulcerations. Genital ulceration as the presenting sign of the disease has been reported rarely. CASE: A 63-year-old woman presented with multiple vaginal ulcerations due to chronic disseminated H capsulatum infection. Initial diagnosis was made by Papanicolaou and Giemsa-stained vulvar smears. Ketoconazole therapy resulted in clearing of the lesions in 5 weeks. CONCLUSION: Chronic disseminated histoplasmosis is an insidious and potentially fatal disease that can present rarely as genital mucocutaneous ulcerations in women. Prompt presumptive diagnosis can be accomplished by examination of smears obtained by ulcer abrasion, permitting institution of appropriate therapy.

Antifungal Agents↗

[Disseminated and central nervous system Histoplasma capsulatum infection mimicking neoplasm: difficulties in diagnosis, failure in management].

INTRODUCTION: Infection with Histoplasma capsulatum (Hc) is a rare importing disease in metropolitan France, the most often minor but sometimes letal in its spread form. EXEGESIS: A 58 years old French man, HIV seronegative, was admitted for an alteration of its general condition, disorder and buccal ulcerations. He had a prostate cancer history and came back in France after 17 years in Central Africa. The imaging showed numerous cerebral nodes, a bilateral adrenal tumor, and pulmonary calcifications. Histoplasmosis diagnosis has been done after neurosurgical cerebral biopsy which displayed characteristic Hc. The sick man died 4 months later with multivisceral failures, in spite of amphotericine B treatment followed by oral then intraveinous itraconazole. CONCLUSION: Even in an old tropical residence, ones can be able to conjure up a deep exotic fungal infection, and most specifically Hc histoplasmosis, in front of meaningful multivisceral lesions. Disseminated histoplasmosis (HD) with neurological location is misleading, mimicking tuberculosis or cancer. In order to obtain formal mycological evidence, ones have to make adapted biopsies. Antifungal agents must take into account medicinal interaction. Therefore, prognosis is bad, according to inoculum, immunodeficiency, age of disease and diagnosis delay.

Brain Neoplasms↗

CD40 ligand is not essential for induction of type 1 cytokine responses or protective immunity after primary or secondary infection with histoplasma capsulatum.

The induction of type 1 immune responses (interleukin [IL]-12, interferon [IFN]-gamma) has been shown to be important in mediating protection against many intracellular infections including Histoplasma capsulatum. Costimulatory molecules such as CD40 ligand (CD40L) have been shown to be a central regulator of type 1 responses in vivo. To study the role of CD40L in mediating protection against infection with H. capsulatum, CD40L-deficient (CD40L-/-) and CD40L+/+ mice were infected with H. capsulatum and assessed for various parameters. After a lethal challenge of H. capsulatum, CD40L-/- mice were not substantially different from CD40L+/+ mice in terms of mortality, fungal burden, or production of IFN-gamma, IL-12, nitric oxide, or tumor necrosis factor alpha. Moreover, CD40L-/- mice treated with anti-IFN-gamma or anti-IL-12 at the time of infection had accelerated mortality, providing further evidence that IL-12 and IFN-gamma are produced in vivo in the absence of CD40L. In addition, CD40L-/- mice infected with a sublethal dose of H. capsulatum survived infection, whereas all mice infected with the same dose and treated with anti-IFN-gamma had accelerated mortality, demonstrating that IFN-gamma but not CD40L was essential for primary immunity to H. capsulatum infection. Interestingly, depletion of either CD4+ or CD8+ T cells resulted in accelerated mortality in CD40L-/- mice, suggesting a critical role for these cells in response to infection. Finally, CD40L-/- mice initially infected with a sublethal dose of H. capsulatum were protected from secondary infection with a lethal dose of H. capsulatum, demonstrating that CD40L is not required for the maintenance of memory immunity.

Animals↗

Recurrent exposure to Histoplasma capsulatum in modern air-conditioned buildings.

BACKGROUND: Between 1989 and 1996, an epidemic of histoplasmosis occurred on a medical school campus. There had been numerous construction projects on the campus that involved previously wooded land and were adjacent to a large bird sanctuary. METHODS: We investigated the epidemic with active surveillance to detect cases, a histoplasmin skin-test survey, inspection of the air-filtration systems of the involved buildings, and cultures of soil samples. The investigation also included a simulation of entry into air-intakes of the buildings from spore sources by means of a wind-tunnel analysis of a model of the campus that used inert gas. After control procedures were instituted, sentinel population groups had follow-up with yearly serological tests. RESULTS: From 1989 through 1996, there were 29 cases of histoplasmosis that occurred among school employees. All cases with a defined onset began during periods of ongoing campus construction. Positivity rates for histoplasmin skin testing were higher among on-campus personnel (47%) than among off-campus employee control subjects (28%) (P<.001); the rates were highest in employees who worked on the upper floors of 2 research buildings. The air-handling units on the roofs of these buildings were not designed to exclude Histoplasma spores. The wind-tunnel experiment indicated that spores aerosolized in the bird sanctuary were not taken into campus buildings. CONCLUSIONS: The major sources of employee exposure to H. capsulatum spores were the construction sites. Low-level, recurrent exposures occurred over several years inside modern research buildings. This phenomenon, which has not been previously described, may play a role in the epidemiology of spore-transmitted diseases in urban settings.

Air Conditioning↗