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PubMed2003

Cerebral histoplasmosis in the azole era: report of four cases and review.

We report four cases of cerebral histoplasmosis and discuss features of six additional cases reported in the medical literature in the past 10 years, when azoles have been available for therapy. Most patients with this disease are immunocompromised or have a history that suggests heavy exposure to Histoplasma capsulatum. Fever and other clinical findings of systemic toxicity caused by disseminated histoplasmosis may be absent; 5 of 10 patients did not manifest these findings. Although the mainstay of treatment for central nervous system histoplasmosis remains amphotericin B, 9 of the 10 patients received itraconazole or fluconazole either as initial therapy or after a course of treatment with amphotericin B.

Adult↗

PubMedDate not supplied

Itraconazole in the treatment of histoplasmosis associated with AIDS.

Twenty-seven patients suffering AIDS and disseminated histoplasmosis were included in this study, comprising twenty-three males and four females, from 18 to 46 years of age (mean = 32.9). The most frequent clinical manifestations were fever, weight loss, anaemia, skin lesions, pulmonary micronodules, hepatosplenomegaly and adenomegalies. All of them presented other infectious diseases or neoplasias frequently found in AIDS patients. The diagnosis of histoplasmosis was based upon the finding of Histoplasma capsulatum in microscopic examination or in cultures from the following specimens: skin scrapings, bone marrow aspiration, bronchoalveolar lavage, blood cultures, buccal biopsies and lymph node biopsy. Serologic reactions, searching for antibodies, were positive in 11 cases. Itraconazole by oral route, at a daily dose of 200 mg (24 cases) or 400 mg (3 cases), was administered for 6 months. Those patients who were clinically cured after receiving this scheme of treatment were treated with itraconazole 100 mg day-1 as a suppressive therapy. Twenty-three patients were considered responders, 1 as a non-responder and 3 non-assessable. The average survival time was 7.8 months and eleven cases are still alive. Itraconazole proved to be a useful medication in disseminated histoplasmosis associated with AIDS and it was very well tolerated.

Acquired Immunodeficiency Syndrome↗

PubMedDate not supplied

Retrospective serological study of histoplasmosis in Mexico.

Mycotic immunodiagnosis was performed in 325 patients with clinical evidence of systemic mycoses, over a 5-year period, from different hospitals of Mexico City. Results showed 168 individuals that presented one positive serological test to Histoplasma capsulatum antigens. From these, only 27 patients were serologically positive to two or more tests, such as tube precipitin, immunodiffusion, complement fixation, and ELISA, and developed signs and symptoms of a histoplasmosis clinically classified as primary pulmonary. Four of them presented an underlying disease including one positive HIV patient. Twenty-two came from endemic histoplasmosis zones of the country and most of them acquired the disease in caves or uninhabited houses. The diagnosis of histoplasmosis should be based on reliable laboratory data which could raise more significant information of its incidence in Mexico.

Adolescent↗

PubMedDate not supplied

African histoplasmosis: osteomyelitis of the radius.

Bone lesions in African histoplasmosis caused by Histoplasma capsulatum var, duboisii, without other signs of the infection, are often misdiagnosed as cancer. A case of isolated osteomyelitis due to this fungus in a 30-year-old woman is described. Diagnostic and therapeutic problems of isolated bone lesions in African histoplasmosis are discussed. A high diagnostic index of African histoplasmosis is advocated in isolated bone lesions in the endemic region of this disease.

Adult↗

PubMed2006

Disseminated histoplasmosis presenting as thrombotic microangiopathy.

BACKGROUND: Thrombotic microangiopathies (TMA) are systemic vasoocclusive disorders associated with significant morbidity and mortality. Rapid and reliable diagnosis of TMA is critical. The diagnosis is complicated by a lack of objective and sensitive laboratory testing as well as multiple concurrent diseases, including infectious processes. CASE STUDY: We report two cases of disseminated histoplasmosis associated with TMA manifestations in renal transplant recipients, including one patient with histologically documented renal microthrombi; both patients were referred for plasma exchange. After the diagnosis of histoplasmosis, the treatment plan was changed to antifungal medications, reduced immuno-suppression, and supportive care, with progressive resolution of TMA manifestations. CONCLUSION: TMA occurs in transplant populations in association with infections, medications, and other factors. Appropriate management includes recognition and treatment of possible etiological factors. Disseminated histoplasmosis should be considered in transplant patients presenting with TMA.

Adult↗

PubMed2001

Progressive gastrointestinal histoplasmosis leading to colonic obstruction two years after initial presentation.

A 37-yr-old man from Ecuador presented with abdominal pain, diarrhea, and weight loss. Endoscopy revealed duodenal histoplasmosis. The patient improved with antifungal therapy but was readmitted 2 yr later with diarrhea and fever. Colonoscopy revealed histoplasmosis lesions, including a constricting transverse colon lesion. The patient refused surgery and died of colonic perforation. We discuss the diagnosis and management of gastrointestinal histoplasmosis in this report.

Adult↗

PubMed2004

Pacinian corpuscle in the juxtaoral organ of Chievitz.

The juxtaoral organ of Chievitz (JOOC) is a normal permanent anatomical structure located within the soft tissue overlying the angle of the mandible in the buccotemporal space. Although the sensory organ nature of JOOC, repeatedly mentioned in German publications, has been neglected in the last decade by the American anatomists and pathologists, we incidentally found JOOC-type squamous epithelium accompanied by Pacinian corpuscles. This fortuitous finding appears to be the first report of the authentic Paciniform nerve endings within JOOC, supporting its mechanosensory function.

Adult↗

PubMed2004

Histoplasmosis in Australia: a report of a case with a review of the literature.

Histoplasmosis is a rare but serious fungal infection commonly presenting as mucosal ulceration of the oral cavity. It is increasingly recognized in Australia but the source of infection remains obscure and it is likely to be under-diagnosed. We report a case of chronic mucosal ulceration which failed to fully respond to periodontal therapy. Histology and culture of a gingival biopsy was consistent with histoplasmosis, and the patient responded favourably to treatment with oral itraconazole. Histoplasmosis may present to general dental practitioners as chronic mucosal ulceration and should be considered in the differential diagnosis of such lesions. Diagnosis is best made by culture and histology of biopsy specimens.

Antifungal Agents↗

PubMedDate not supplied

Itraconazole for the treatment of histoplasmosis in cats.

Eight cats with histoplasmosis were treated with itraconazole at 5 mg/kg per dose PO bid. There were multiple sites of infection, and 2 of the cats had hypercalcemia that was attributed to the histoplasmosis. All 8 cats were eventually cured, but 2 cats experienced recurrences of disease after completion of therapy, requiring 2 to 3 additional months of itraconazole. There were no clinically relevant adverse effects during treatment. Although a limited number of cats were treated, the study suggests that itraconazole is a well-tolerated and effective drug for the treatment of histoplasmosis in the cat.

Administration, Oral↗

PubMed1999

Comparison of a new triazole antifungal agent, Schering 56592, with itraconazole and amphotericin B for treatment of histoplasmosis in immunocompetent mice.

A murine model of intratracheally induced histoplasmosis was used to evaluate a new triazole antifungal agent, Schering (SCH) 56592, for treatment of histoplasmosis. MICs were determined for SCH 56592, amphotericin B, and itraconazole by testing yeast-phase isolates from 20 patients by a macrobroth dilution method. The MICs at which 90% of the isolates are inhibited were for 0.019 microgram/ml for SCH 56592, 0.5 microgram/ml for amphotericin B, and < or = 0.019 microgram/ml for itraconazole. Survival studies were done on groups of 10 B6C3F1 mice with a lethal inoculum of 10(5). All mice receiving 5, 1, or 0.25 mg of SCH 56592 per kg of body weight per day, 2.5 mg of amphotericin B per kg every other day (qod), or 75 mg of itraconazole per kg per day survived to day 29. Only 44% of mice receiving 5 mg of itraconazole/kg/day survived to day 29. Fungal burden studies done in similar groups of mice with a sublethal inoculum of 10(4) showed a reduction in CFUs and Histoplasma antigen levels in lung and spleen tissue in animals treated with 2 mg of amphotericin B/kg qod, 1 mg of SCH 56592/kg/day, and 75 mg of itraconazole/kg/day, but not in those treated with lower doses of the study drugs (0.2 mg of amphotericin B/kg qod, 0.1 mg of SCH 56592/kg/day, or 10 mg of itraconazole/kg/day). Serum drug concentrations were measured 3 and 24 h after the last dose in mice (groups of five to seven mice), each treated for 7 days with SCH 56592 (10 and 1 mg/kg/day) and itraconazole (75 and 10 mg/kg/day). Mean levels measured by bioassay were as follows: SCH 56592, 10 mg/kg/day (2.15 micrograms/ml at 3 h and 0.35 microgram/ml at 24 h); SCH 56592, 1 mg/kg/day (0.54 microgram/ml at 3 h and none detected at 24 h); itraconazole, 75 mg/kg/day (22.53 micrograms/ml at 3 h and none detected at 24 h); itraconazole, 10 mg/kg/day (1.33 micrograms/ml at 3 h and none detected at 24 h). Confirmatory results were obtained by high-pressure liquid chromatography assay. These studies show SCH 56592 to be a promising candidate for studies of treatment of histoplasmosis in humans.

Amphotericin B↗

PubMed2000

Comparison of a new triazole, posaconazole, with itraconazole and amphotericin B for treatment of histoplasmosis following pulmonary challenge in immunocompromised mice.

A murine model of intratracheally induced histoplasmosis in immunocompromised B6C3F(1) mice was used to evaluate a new triazole antifungal agent, posaconazole. This compound was previously shown to be comparable to amphotericin B and superior to itraconazole for the treatment of histoplasmosis in immunocompetent mice. The current study used mice that were depleted of T lymphocytes by intraperitoneal injection of anti-CD4 and anti-CD8 monoclonal antibodies beginning 2 days before infection and continuing at 5-day intervals until completion of the study. Groups of B6C3F(1) mice that were depleted of CD4 and CD8 T cells were infected with an inoculum of 10(4) Histoplasma capsulatum yeasts. All mice receiving posaconazole at 1 or 0.1 mg/kg of body weight/day, amphotericin B at 2 mg/kg every other day (qod), or itraconazole at 75 mg/kg/day survived to day 29. Only 60% of mice receiving itraconazole at 10 mg/kg/day and none receiving amphotericin B at 0.2 mg/kg qod survived to that date. Fungal burdens were determined at day 14 of infection, 1 day after discontinuation of therapy. Quantitative colony counts and Histoplasma antigen levels in lung and spleen tissues declined following treatment with amphotericin B at 2 mg/kg qod, posaconazole at 5 and 1 mg/kg/day, and itraconazole at 75 mg/kg/day but not in mice treated with amphotericin B at 0.2 mg/kg qod or itraconazole at 10 mg/kg/day. Posaconazole at 0.1 mg/kg/day reduced fungal colony counts and antigen levels in spleens but not in lungs. This study shows posaconazole activity for the treatment of histoplasmosis in immunosuppressed animals.

Amphotericin B↗

PubMed1999

Evaluation of a western blot test in an outbreak of acute pulmonary histoplasmosis.

A western blot (WB) test was evaluated for detection of antibodies against native glycosylated and chemically deglycosylated M and H antigens of Histoplasma capsulatum in serum obtained from patients during the acute phase of pulmonary histoplasmosis that occurred during an outbreak. Of 275 serum samples tested by immunodiffusion and complement fixation (CF) samples from 40 patients affected during this outbreak and from 37 negative controls were tested by WB test. A group of patients whose sera were negative for CF antibodies and precipitins early in the acute stage of histoplasmosis but who all seroconverted during convalescence 6 weeks later were tested with the WB test. Antibodies against untreated H and M antigens were detected at a 1:100 dilution by WB test in 45% of the 20 acute-phase serum samples and in all 20 of the convalescent-phase specimens. The WB test's sensitivity for acute-phase specimens increased to 90% (18 of 20 specimens) when H and M antigens were treated by periodate oxidation to inactivate susceptible carbohydrate epitopes. When native glycosylated antigens were used in the WB test, positive reactions were observed in negative control serum specimens (3 of 37 specimens; 8%) and in serum specimens obtained from asymptomatic persons screened as part of the outbreak investigation (13 of 20 specimens; 65%). These positive reactions were also attributed to glycosidic epitopes since the specificity of the WB test increased from 78 to 100% when periodate-treated H and M antigens were used. WB test with deglycosylated H and M antigens of histoplasmin provides a rapid, sensitive, and specific test to diagnose acute pulmonary histoplasmosis before precipitins can be detected.

Acute Disease↗

PubMed1991

Histoplasma variation and adaptive strategies for parasitism: new perspectives on histoplasmosis.

This review summarizes the biology of Histoplasma capsulatum in relation to a wide variety of corresponding pathologies in histoplasmosis. Features of these disease syndromes can be explained in part by natural variations within the fungal population and adaptations made by individual organisms to specific environments. H. capsulatum grows as mycelia and conidia in the soil; once inhaled, the organism undergoes a dramatic morphological and physiological conversion to a yeast form. The yeasts proliferate within the phagolysosomes of macrophages, using a variety of specific strategies for intracellular survival. Even avirulent strains or variants are able to avoid being killed by macrophages and instead establish inapparent or persistent infections. The ingested avirulent organisms assume enlarged shapes similar in appearance to those seen in histological sections of tissues from patients with histoplasmosis. Respiratory tract epithelial cells also appear to play a role in persistence: within them yeasts undergo phenotypic switching akin to the phase variation observed in other pathogens. This particular change involves the loss or modification of cell wall alpha-(1,3)-glucan, which is also correlated with the spontaneous appearance of avirulent variants. The repertoire of adaptive responses and natural variations within this species probably evolved from the need to adjust to a wide range of dynamic environments. In combination with the immune status of the host, these characteristics of H. capsulatum appear to influence the epidemiology, extent, and persistence of histoplasmosis.

Animals↗

PubMed2004

Blockade of endogenous leukotrienes exacerbates pulmonary histoplasmosis.

Leukotrienes are classical mediators of inflammatory response. New aspects of leukotriene function have recently been described. We examine here the previously unreported role that leukotrienes play in the regulation of cytokines in a murine model of histoplasmosis. We demonstrate that administration of MK 886, a leukotriene synthesis inhibitor, caused Histoplasma capsulatum-infected mice to die by the day 15 of infection, whereas the correlating death rate in untreated infected mice was 0%. Treating infected animals with MK 886 inhibited leukotriene synthesis but increased leukocyte recruitment to the lungs. Subsequent to this phenomenon, levels of tumor necrosis factor alpha, interleukin-1 (IL-1), IL-6, and KC chemoattractant cytokines and fungi in the lung parenchyma increased, as did inflammatory response. In contrast, IL-2, IL-5, IL-12, and gamma interferon cytokine levels actually decreased. Thus, murine response to pulmonary histoplasmosis may be leukotriene modulated. This finding may enable us to alter the course of the immune response and inflammation caused by histoplasmosis. The data from the present study suggest an important new strategy for immunologic or drug intervention in human patients.

Animals↗

PubMed1997

Molecular cloning and characterization of a recombinant Histoplasma capsulatum antigen for antibody-based diagnosis of human histoplasmosis.

Immunological cross-reactivity among fungi has hampered the development of specific serodiagnostic assays for histoplasmosis. We report the molecular cloning and characterization of a Histoplasma capsulatum cDNA (GH17) that encodes an antigen with immunodiagnostic potential. GH17 is an 810-bp cDNA which encodes a protein of 211 amino acid residues. The GH17 sequence has almost no significant homology with other sequences in GenBank. Southern blot analysis suggests that GH17 is confined to a single location in the genomic DNA of H. capsulatum. Immunoblots indicated that the protein product of GH17 (expressed as a 140-kDa beta-galactosidase fusion protein) was recognized by antibodies in 18 of 18 sera from histoplasmosis patients, but not by antibodies in sera from patients or animals infected with other fungi. GH17 was expressed in a prokaryotic expression vector, pPROEX-1, and recombinant protein was purified by preparative electrophoresis. Antibodies raised to this protein bound to a 60-kDa native antigen in immunoblots of H. capsulatum yeast antigen extract. These results suggest that GH17 encodes an H. capsulatum antigen that may be useful for the diagnosis of histoplasmosis in humans.

Amino Acid Sequence↗

PubMed2000

Histoplasmosis of the thyroid.

Fungal infection of the thyroid is rare. Most reported cases have involved Aspergillus, Coccidioides, and Candida species in the setting of disseminated disease. Infection of the thyroid with Histoplasma capsulatum is rarely reported as part of disseminated disease, even in geographic areas where histoplasmosis is endemic. We report a 52-year-old woman with a previous Hashimoto's disease and non-Hodgkin's lymphoma in which a diffuse enlarged thyroid gland with a large nodule was the only apparent locus of histoplasmosis. Fine-needle aspiration of the thyroid was an important diagnostic tool in establishing the diagnosis of histoplasmosis of the thyroid. The patient was initially treated with itraconazole (400 mg/day) for the fungal infection and six cycles of chemotherapy for the lymphoma. At a 6-month follow-up examination, the patient was doing well on suppressive therapy of itraconazole (200 mg/day), with no symptoms and with regression of the thyroid nodule and cervical adenopathy.

Antifungal Agents↗

PubMed1976

Cutaneous histoplasmosis.

Cutaneous lesions as a manifestation of histoplasmosis, primarily a disease of the respiratory system, are rare and most commonly appear secondary to progressive dissemination. A patient with documented progressive, disseminated histoplasmosis, having been treated previously with amphotericin B, presented on a second occasion with cutaneous lesions as the chief complaint. Biopsy and cultures of these lesions were positive for Histoplasma capsulatum. A review of the English literature revealed only 7 reported cases of secondary skin histoplasmosis in the past 20 years. All patients, including the current one, either had diseases associated with depressed immunity or were receiving steroid therapy.

Adult↗

PubMed1981

Radioimmunoassay: a sensitive screening test for histoplasmosis and blastomycosis.

Currently available serologic tests for histoplasmosis and blastomycosis have limited sensitivity. In order to develop a more sensitive screening test, the radioimmunoassay (RIA) technique was adapted to detect circulating antibodies to Histoplasma mycelial, Histoplasma yeast, and Blastomyces yeast antigens. Results were compared with those of complement fixation (CF) using serums from 4 groups of subjects. Group 1 (n = 104) consisted of consecutive healthy blood donors from an endemic area. Group 2 (n = 8) had active histoplasmosis and Group 3 (n = 12) had active blastomycosis. Group 4 (n = 30) had other chronic lung diseases. Among Group 1 subjects, elevated titers to at least 1 antigen were found in 13% using RIA and 21% using CF. Only 50% of patients with active mycoses (Groups 2 and 3) had elevated CF titers to a homologous antigen, whereas the RIA test was positive in 19 of 20 patients (95%). Elevated titers to 1 or more antigens was found in Groups 1 and 4, and frequent cross-reactions among the antigens occurred with both tests, indicating low specificities for both RIA and CF. The RIA is a sensitive and rapid screening test for histoplasmosis and blastomycosis, and a negative RIA using the 3 antigens tested makes the diagnosis of active infection very unlikely in immunologically competent patients.

Adolescent↗