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PubMed1994

Histoplasmosis in Missouri: historical review and current clinical concepts.

Histoplasmosis is particularly common in Missouri, and many important clinical observations about the disease were made in this state in the 1950s and 1960s. When the AIDS epidemic spread to Missouri in the mid-1980s, histoplasmosis became recognized as a common and important opportunistic infection among Missourians with AIDS. Clinicians must maintain a high level of suspicion for histoplasmosis in any HIV-infected patient who presents with unexplained fever, particularly if the patient has evidence of hepatosplenomegaly, generalized lymphadenopathy, pancytopenia, abnormal liver function tests, or bilateral pulmonary infiltrates. The diagnosis of histoplasmosis can be established rapidly by observation of organisms on peripheral blood smear or bone marrow biopsy specimens or by Histoplasma Polysaccharide Antigen testing. The diagnosis can be confirmed by blood cultures in most cases. Histoplasmosis in AIDS is invariably fatal if not treated. Treatment consists of two phases: initial induction therapy and subsequent lifelong maintenance therapy. Amphotericin B and itraconazole are extremely effective for induction and maintenance therapy; fluconazole appears to be effective maintenance therapy. Strategies for the prevention of histoplasmosis in high risk patients are being evaluated currently.

Histoplasmosis↗
PubMed2000

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

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

English Abstract↗
PubMed1965

RELATIONSHIP OF HISTOPLASMIN AGAR-GEL BANDS AND COMPLEMENT-FIXATION TITERS IN HISTOPLASMOSIS.

Wiggins, Geraldine L. (Communicable Disease Center, Atlanta, Ga.), and Joseph H. Schubert. Relationship of histoplasmin agar-gel bands and complement-fixation titers in histoplasmosis. J. Bacteriol. 89:589-596. 1965.-Culture filtrates of various strains of Histoplasma capsulatum were studied with sera from patients with histoplasmosis, by use of the agar-gel and complement-fixation tests. It was found that the filtrates represented three types: those containing H and M components, those with H only, and those with neither H nor M. The same strain of H. capsulatum often produced culture filtrates of more than one type. Complement fixation showed that only the filtrates having both the H and M components were sufficiently sensitive as diagnostic antigens to detect the antibodies in histoplasmosis. H and M fractions prepared by ion-exchange chromatography were found to produce more than one band; therefore, it was concluded that the available fractions were not pure. The formation and identification of bands were affected by the concentration of the antigen and the arrangement of the wells containing the antigen and serum. The optimal concentration of the antigen varied, depending on the position of these reagents. The method found most practical for the identification of bands in unknown sera consisted of selecting the optimal concentration of the components with a box titration, by use of antigen having both the H and M components, placing known positive sera in wells adjacent to the unknown sera, and studying the sera for lines of identity. The M band was usually closest to the antigen well, and the H was nearest the serum well. These bands could be reversed by dilution, adjusting the H antibodies so that they equalled or exceeded the M antibodies. One human serum in which the bands were reversed showed the H bands at a higher serum dilution than that obtained with the M band. Patients with culturally proven histoplasmosis had the M band in their serum regardless of the stage of disease or length of duration; only 4 of 10 patients in the active stage of histoplasmosis also had the H band. The low prevalence of the H band would eliminate it as a diagnostic tool for detecting the active stage of the disease. Other bands obtained with histoplasmin antigen in the sera from proven cases were of no assistance in determining the clinical status of the patient.

Agar↗
PubMed1965

CORRELATION OF FLUORESCENT ANTIBODY, HISTOPATHOLOGY, AND CULTURE ON TISSUES FROM 372 ANIMALS EXAMINED FOR HISTOPLASMOSIS AND BLASTOMYCOSIS.

Porter, Billie M. (Communicable Disease Center, Kansas City, Kan.), Barbara K. Comfort, Robert W. Menges, Robert T. Habermann, and Coy D. Smith. Correlation of fluorescent antibody, histopathology, and culture on tissues from 372 animals examined for histoplasmosis and blastomycosis. J. Bacteriol. 89:748-751. 1965.-In a survey in the midwestern United States, tissues from 372 animals including 16 species were examined for Histoplasma capsulatum and Blastomyces dermatitidis. All of the specimens were cultured and studied by use of the fluorescent-antibody (FA) technique, and histopathological studies of tissue sections were done. Among the 372 animals, 300 were negative by all three methods of examination, 34 had blastomycosis, and 21 had histoplasmosis. The remaining 17 were positive for histoplasmosis with the FA technique but were negative by histopathology and culture. An animal was considered to have histoplasmosis or blastomycosis only when the specific fungus was isolated or demonstrated in tissue sections or exudates from cutaneous lesions. Of the 34 blastomycosis cases, 25 (74%) were positive by FA, 32 (94%) by histopathology, and 11 (32%) by culture. Of the 21 histoplasmosis cases, 15 (71%) were positive by FA, 16 (76%) by histopathology, and 14 (67%) by culture. It appeared that FA, histopathology, or culture alone was insufficient for a diagnosis. All three techniques should be employed for the most satisfactory diagnostic results.

Animals↗
PubMed2003

A large outbreak of histoplasmosis among American travelers associated with a hotel in Acapulco, Mexico, spring 2001.

During spring 2001, college students from Pennsylvania reported an acute febrile respiratory illness after returning from spring break vacation in Acapulco, Mexico. Acute pulmonary histoplasmosis was presumptively diagnosed and the cluster of illness was reported to the Centers of Disease Control and Prevention. A large investigation then ensued, which included finding student-travelers for interviews and requesting sera for histoplasmosis testing. We defined a clinical case by fever and at least one of the following: cough, shortness of breath, chest pain, or headache, in an Acapulco traveler during March-May 2001. A laboratory-confirmed case had positive serology. An initial study determined that the likely site of histoplasmosis exposure was Hotel H; we therefore performed a large cohort study among travelers who stayed at Hotel H. Of 757 contacted, 262 (36%) met the clinical case definition. Of 273 serum specimens tested, 148 (54%) were positive. Frequent use of Hotel H's stairwells, where construction was ongoing, was associated with increased risk of illness (relative risk = 10.5, 95% confidence interval = 3.7-30.5; P < 0.001). This is the first histoplasmosis outbreak associated with a hotel undergoing construction. Hotels in endemic areas should consider construction precaution measures to prevent histoplasmosis among their guests.

Adolescent↗
PubMed1978

Isolated nodular cutaneous histoplasmosis. The initial manifestation of recurrent disseminated disease.

Cutaneous manifestations of histoplasmosis may be divided into primary and secondary lesions. Primary cutaneous histoplasmosis is rare; to our knowledge, there are only three reported cases in the literature. Secondary cutaneous histoplasmosis develops during the course of disseminated disease. An isolated nodule of the hand was the initially appearing sign of recurrent disseminated disease in our patient. Because of the extreme rarity of primary cutaneous histoplasmosis, cutaneous lesions that are proven to be due to histoplasmosis should alert the physician to the presence of disseminated disease.

Adult↗
PubMed2006

Disseminated histoplasmosis in a liver transplant recipient.

A 61-yr-old liver transplant recipient presented with abdominal cramping and nonbloody diarrhea resulting in orthostasis. Multiple ulcerations throughout the colon were seen during endoscopy, and biopsies from the ulcer edges revealed histoplasmosis. Treatment with a course of itraconazole improved the diarrhea. The patient later presented with pericarditis and symptomatic pleural effusions, the latter of which was confirmed to be a result of disseminated histoplasmosis. Treatment with amphotericin B led to resolution. Histoplasmosis should be considered in liver transplant patients with diarrhea and large ulcers in the colon. The presence of disseminated histoplasmosis should be ruled out once colonic histoplasmosis has been diagnosed.

Amphotericin B↗
PubMed1988

Gastrointestinal histoplasmosis.

Three cases are reported of gastrointestinal histoplasmosis in patients who came from the Caribbean or South America and had lymphoma, acquired immunodeficiency syndrome, and prior local radiation therapy. The patients had small-bowel obstruction with ileal involvement, mucosal erythema, and friability on colonoscopy with colonic involvement and an exophytic rectal mass with rectal involvement. Review of the 77 reported cases of gastrointestinal histoplasmosis shows that this is a clinical subset of disseminated histoplasmosis. With gastrointestinal involvement, pulmonary symptoms are uncommon and gastrointestinal symptoms predominate. Fever is less common than in other forms of dissemination. The most common lesions are a mass or ulcers, which often mimic inflammatory bowel disease or carcinoma. Terminal ileal involvement predominates in one third. The complement fixation test was positive in about three quarters of cases tested, but the skin test is not diagnostically useful. In one quarter of patients there is other evidence of immunosuppression. In the immunosuppressed, gastrointestinal histoplasmosis must be considered, even in a patient from a nonendemic area, who presents with lesions appearing like carcinoma or inflammatory bowel disease. When feasible, endoscopic examination and biopsy with stains and culture for histoplasmosis is recommended for diagnosis. Medical management is recommended, with surgery reserved for acute emergencies or when mandatory for diagnosis.

Adult↗
PubMed1994

Oral histoplasmosis in a patient infected with HIV. A case report.

Histoplasmosis is a frequent complication of HIV infection and is usually the result of reactivation. In the immunocompromised host, histoplasmosis may cause a chronic pulmonary infection or disseminated disease. In the setting of disseminated disease, oral lesions are present in 30% to 50% of patients and may occur in almost every part of the oral mucosa. The most common sites are the tongue, palate, and buccal mucosa. In some cases, oral lesions appear to be the primary or only manifestation of disease. We have been able to find only five case reports in the literature of histoplasmosis in HIV infection with oral lesions. In two of the cases, histoplasmosis was apparently localized to the oral cavity, whereas two cases also had evidence of disseminated disease, the fifth was undetermined. We report one such case of apparently localized oral histoplasmosis in a patient with HIV infection.

AIDS-Related Opportunistic Infections↗
PubMed1989

Histoplasma capsulatum polysaccharide antigen detection in diagnosis and management of disseminated histoplasmosis in patients with acquired immunodeficiency syndrome.

PURPOSE: Disseminated histoplasmosis is a serious and often rapidly progressive, opportunistic infection in patients with acquired immunodeficiency syndrome (AIDS), supporting the importance of rapid diagnostic tests. We investigated Histoplasma capsulatum polysaccharide antigen (HPA) detection, a promising new method for rapid diagnosis of histoplasmosis. PATIENTS AND METHODS: Sixty-one cases of disseminated histoplasmosis in patients with AIDS form the basis of this report. Control cases were patients with AIDS who had other opportunistic infections and whose cultures were negative for H. capsulatum. A slightly modified radioimmunoassay procedure was used to measure the levels of HPA in urine and blood specimens. RESULTS: High levels of HPA were detected in the urine of 59 of 61 (96.7%) and the blood of 37 of 47 (78.7%) patients with AIDS complicated by disseminated histoplasmosis. Treatment with amphotericin B reduced levels of HPA in the urine in 19 of 21 (90.5%) and the serum of all 10 patients tested. HPA levels increased in the urine in all eight and in the serum in all five patients with culture-proven relapse. CONCLUSION: In conclusion, HPA detection offers a rapid method for diagnosing disseminated histoplasmosis. Additional experience is required to establish the role of this test in monitoring the effects of treatment and in identifying relapse in patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed2000

[Histoplasmosis due to Histoplasma capsulatum capsulatum and HIV infection].

PURPOSE: Histoplasmosis due to Histoplasma capsulatum is a granulomatous fungic infection which appears opportunistic and disseminated in immunocompromised patients, especially among HIV patients in whom it can lead to death. Histoplasmosis is endemic in numerous areas worldwide, but in Europe most of the cases reported are imported. We describe the clinical features and the available diagnosis methods issued from our experience in French Guyana. METHODS: Contamination occurs by inhalation of spores contained in dust. Most endemic areas are located on the American continent, including the French West Indies, where the incidence of histoplasmosis among HIV patients in French Guyana varies from 1.2 to 2.2% per year. In non-immunocompromised patients, histoplasmosis is asymptomatic most of the time. In HIV patients, the disseminated form is common and may occur many years after exposure to the fungus. RESULTS: Non-specific symptoms, similar to those of either tuberculosis or other opportunistic infections, may reveal disseminated histoplasmosis in patients with AIDS. Early treatment (amphotericin B or itraconazole) is effective; however, it should be followed by a lifelong antifungic treatment (itraconazole) to prevent relapse. CONCLUSION: The infection should be suspected in any febrile HIV-infected patient with CD4 blood cell count < 200/mm3, if he/she ever travelled in an endemic zone. Direct examination of smear relating to clinical symptoms help guide diagnosis, while culture will confirm it after at least 4 weeks. Efficient serologic techniques for HIV-infected patients are not available in Europe.

AIDS-Related Opportunistic Infections↗
PubMed1982

[Ocular histoplasmosis].

Reports of ocular histoplasma mycosis demonstrated serologically and in tissue are rare in Europe. This is principally due to the fact that histoplasmosis is not endemic in Europe (in contrast to the USA). A second reason is that it is hard to find laboratories which have experience in the differential diagnosis of histoplasmosis and forms of uveitis. In cases of uveitis it would be desirable to include histoplasmosis in the differential diagnosis and to use more staining methods (silver nitrate methenamine, fluorescein serology) and immunologic tests (intracutaneous test with histoplasmin, complement fixation test, countercurrent immuno-electrophoresis) for histoplasmosis. Report on a case of ocular histoplasmosis, positive in the skin test and in immunodiffusion, contracted 19 years previously in Mississippi, USA.

Adult↗
PubMed1986

An outbreak and review of cave-associated histoplasmosis capsulati.

Three male college students from Florida developed acute onsets of fever, chills, shortness of breath, and cough within one day of each other, and all were eventually hospitalized for four to 29 days. All chest x-ray films showed diffuse reticulonodularities in both lung fields. Laboratory studies confirmed the diagnosis of histoplasmosis. The three students had been 'spelunking' (cave exploring) 6 to 7 days before their onset of symptoms. One of four soil samples collected in the caves was positive for Histoplasma capsulatum by the indirect mouse inoculation procedure. Of three investigators who entered the implicated caves, two developed acute febrile illness within 15-21 days. One investigator was hospitalized for 18 days with a confirmed diagnosis of histoplasmosis. Investigation identified an additional case (the person had entered the caves 6 months before this episode), but was not reported to health authorities. Spelunkers should be aware of the potential risk of histoplasmosis and how to avoid infection. Physicians should be cognizant of cave-associated histoplasmosis, inquire about spelunking in persons who develop febrile respiratory illnesses with diffuse nodularities on chest x-ray films, and report such cases to their health department. A review of 42 reported outbreaks of cave-associated histoplasmosis and the approach to environmental control of infected caves are included.

Adult↗
PubMed1983

Thrombocytopenia associated with histoplasmosis and an elevated platelet associated IgG.

A patient with primary pulmonary histoplasmosis, symptomatic thrombocytopenia, and an associated elevation of platelet associated IgG during the acute phase of the illness is described. Whereas thrombocytopenia has been reported previously in patients with disseminated histoplasmosis, it appears that thrombocytopenia in a patient with nondisseminated histoplasmosis has not been described. Although certain clinical findings suggested idiopathic thrombocytopenic purpura, corticosteroids were not administered, and lymph node biopsy documented the presence of Histoplasma capsulatum. Similarly, elevated platelet associated IgG levels apparently have not been reported previously in thrombocytopenic patients with histoplasmosis. Possible mechanisms for thrombocytopenia associated with histoplasmosis are discussed.

Adult↗
PubMed1996

Histoplasmosis and blastomycosis.

Histoplasmosis and blastomycosis are caused by dimorphic fungi, can be epidemic or endemic, and can produce a spectrum of illness, from subclinical infection to progressive disseminated disease. Diagnosis of both is best made by visualization of yeast in tissue or by culture. Itraconazole is the drug of choice for treatment of both histoplasmosis and blastomycosis, except in cases of life-threatening infection, for which amphotericin B is indicated. A heavy inoculum of Histoplasma capsulatum may cause acute pulmonary infection in an otherwise healthy host, resulting in fever, hypoxia, and pulmonary infiltrates. Opportunistic histoplasmosis develops as chronic pulmonary histoplasmosis in those with a structural defect in the lung (emphysema) or as disseminated histoplasmosis in patients with cellular immune deficiency (due to immunosuppressants or AIDS). Blastomyces dermatitidis causes both pulmonary and extrapulmonary disease. Lung involvement may mimic bacterial pneumonia, while chronic presentations mimic lung cancer or tuberculosis. Skin is the most common extrapulmonary site of disease, followed by bone, prostate, and central nervous system.

AIDS-Related Opportunistic Infections↗
PubMed2000

Incremental cost-effectiveness of laser therapy for choroidal neovascularization associated with histoplasmosis.

PURPOSE: Laser photocoagulation has been shown in a large clinical trial to be efficacious in reducing the degree of vision loss occurring secondary to choroidal neovascularization (CNV) associated with ocular histoplasmosis. Nevertheless, data are lacking concerning the impact of the therapy on quality of life and its value to stakeholders in health care. Recently, information concerning the utility value of visual states has become available. Accordingly, the authors undertook to ascertain the cost-effectiveness of laser photocoagulation for the treatment of extrafoveal CNV occurring in eyes with ocular histoplasmosis. METHODS: Design--A computer simulation, econometric model is presented to evaluate the incremental cost-effectiveness of laser photocoagulation therapy, as compared with the natural course of the disease, for the treatment of patients with extrafoveal CNV associated with ocular histoplasmosis. The model applies long-term visual data from previous clinical trials, utility analysis (which reflects patient perceptions of quality of life), decision analysis with Markov modeling, and present value analysis with discounting to account for the time value of money. Outcome measure--Cost per quality-adjusted life-year gained from treatment. RESULTS: Laser photocoagulation therapy for extrafoveal CNV associated with ocular histoplasmosis costs $4167 1999 US dollars (at a 3% discount rate) for each quality-adjusted life-year gained from treatment. Sensitivity analysis shows that changing the discount rate substantially alters the cost-effectiveness, with a value of $1339 at a 0% discount rate and $56,250 at a 10% discount rate. CONCLUSIONS: Compared with therapeutic modalities for other disease entities, laser therapy for the treatment of extrafoveal CNV associated with ocular histoplasmosis appears to be a cost-effective treatment from the patient preference-based point of view.

Adult↗
PubMed2001

Presumed ocular histoplasmosis syndrome: update on epidemiology, pathogenesis, and photodynamic, antiangiogenic, and surgical therapies.

Presumed ocular histoplasmosis involves the classic triad of discrete atrophic choroidal scars in the macula or midperiphery known as histo spots, peripapillary atrophy, and choroidal neovascularization, which leads to severe loss of central vision. The histo spots from which the choroidal neovascularization develop do not show active inflammation but do represent focal defects in Bruch membrane that could facilitate development of choroidal neovascularization. The macular photocoagulation studies unequivocally show the benefit of photocoagulation compared with observation in reducing the risk of vision loss in patients with presumed ocular histoplasmosis, well defined extrafoveal or juxtafoveal choroidal neovascularization, and choroidal neovascularization in the peripapillary area. However, laser treatment itself causes an absolute scotoma correlating with the site of the laser photocoagulation scar, and subfoveal choroidal neovascularization is not amenable to laser photocoagulation because this would cause a blinding central scotoma. Consequently, other treatments have been sought. The Verteporfin in Ocular Histoplasmosis study evaluated photodynamic therapy for subfoveal choroidal neovascularization caused by presumed ocular histoplasmosis and demonstrated stabilization of the choroidal neovascularization and visual acuity benefit. In addition to photodynamic therapy, antiangiogenic compounds are being developed for choroidal neovascularization caused by age-related macular degeneration, and these agents will likely be of benefit in presumed ocular histoplasmosis associated choroidal neovascularization. Finally, submacular surgery for the removal of subfoveal choroidal neovascularization has promising results. The results of these research efforts will produce more effective therapeutic approaches in the future.

Angiogenesis Inhibitors↗
PubMed2006

American histoplasmosis in developing countries with a special focus on patients with HIV: diagnosis, treatment, and prognosis.

PURPOSE OF REVIEW: Histoplasmosis due to Histoplasma capsulatum var capsulatum is a frequent systemic fungal infection in the Americas. Diagnostic and therapeutic options differ between North and South America. Disseminated histoplasmosis is an AIDS-defining infection. Prognostic factors of potentially severe presentations must be evaluated in order to facilitate the initial therapeutic choice. RECENT FINDINGS: Patients with HIV with disseminated infections presenting with severe pulmonary and renal impairment have a poor prognosis. Cutaneous presentations are more frequent in HIV patients in South America than in North America. A murine model has shown that South American isolates have a greater virulence that North American isolates. These differences are due in part to diagnostic delays in resource-poor countries. SUMMARY: Direct examination of May-Grünwald-Giemsa-stained smears or tissues in suspected histoplasmosis is a simple means of confirming the diagnosis in resource-poor settings. Studies of prognostic factors should further refine indication criteria to guide first-line treatment choice between amphotericin B and itraconazole. The association of tuberculosis and histoplasmosis is frequent in HIV patients and presents diagnostic and therapeutic challenges that may be difficult to resolve in resource-poor settings. It is important that affordable generic drugs for treating histoplasmosis be made widely available in resource-poor countries.

HIV Infections↗