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PubMed2001

Multicenter case-control study of risk factors for histoplasmosis in human immunodeficiency virus-infected persons.

We conducted a multicenter case-control study to identify risk factors for histoplasmosis among persons with acquired immunodeficiency syndrome (AIDS) and to evaluate predictors of a poor outcome (defined as death or admission to the intensive care unit). Patients with histoplasmosis were each matched by age, sex, and CD4 lymphocyte count to 3 controls. From 1996 through 1999, 92 case patients and 252 controls were enrolled. Of the case patients, 81 (89%) were men, 50 (55%) were black, 78 (85%) had a CD4 lymphocyte count of <100 cells/microL, 80 (87%) were hospitalized, and 11 (12%) died. Multivariable analysis found that receipt of antiretroviral therapy and of triazole drugs were independently associated with a decreased risk of histoplasmosis. Chronic medical conditions and a history of infections with herpes simplex virus were associated with poor outcome. Triazoles should be considered for chemoprophylaxis for persons with AIDS, especially those who take part in high-risk activities that involve frequent exposure to soil, who have CD4 lymphocyte counts of <100 cells/microL, and who live in areas where histoplasmosis is endemic.

AIDS-Related Opportunistic Infections↗

PubMed2002

Antifungal therapy for central nervous system histoplasmosis, using a newly developed intracranial model of infection.

The outcome of central nervous system (CNS) histoplasmosis is often unfavorable. Although fluconazole plays an integral role in treatment of fungal meningitis, its role in the treatment of histoplasmosis is hampered by reduced activity and potential development of resistance. A murine model of CNS histoplasmosis was used to evaluate the hypothesis that a combination of amphotericin B and fluconazole therapy would be superior to amphotericin B monotherapy. Groups of B6C3F(1) mice were infected by injection of Histoplasma capsulatum into the subarachnoid space. The addition of fluconazole hindered the antifungal effect of amphotericin B, as determined by measurement of fungal burden, suggesting antagonism in the brain. Fluconazole was less effective as a single agent than was amphotericin B, despite the greater penetration of fluconazole into brain tissues. The hypothesis that amphotericin B-fluconazole combination therapy would be superior to amphotericin B monotherapy for treatment of CNS histoplasmosis was not supported by this study.

Amphotericin B↗

PubMed1987

Transient fungemia in acute pulmonary histoplasmosis: detection by new blood-culturing techniques.

Transient fungemia has been thought to occur with acute pulmonary histoplasmosis in humans, but this has never been confirmed. We report two cases of acute pulmonary histoplasmosis in which transient fungemia was detected by the lysis-centrifugation blood-culturing technique. Both patients had self-limited acute pulmonary histoplasmosis, and neither was treated with antifungal therapy. Follow-up evaluation at three years and at 17 months disclosed no evidence of active pulmonary or disseminated disease. Transient Histoplasma capsulatum var. capsulatum fungemia may occur with acute pulmonary histoplasmosis. Fungemia may be prevented or arrested by an intact immune system or by other factors not yet known.

Acute Disease↗

PubMedDate not supplied

The spectrum of histoplasmosis in a general hospital: a review of 55 cases diagnosed at Barnes Hospital between 1966 and 1977.

Between 1966 and 1977, 55 patients at Barnes Hospital were proven to have manifestations of histoplasmosis. Five patients had acute pulmonary histoplasmosis, four of whom demonstrated unusually severe disease. Disseminated histoplasmosis was documented in 19 cases. Four of these patients demonstrated dissemination during a severe and protracted but self-limited illness. The other 15 patients had progressive disease. Most of these patients were immune compromised and presented with fever of unknown origin. Therapy most benefited those who completed a course of greater than or equal to 1.5 gm of amphotericin B. Chronic pulmonary histoplasmosis was documented in 14 individuals. Large (> 1.5 cm), solitary pulmonary coin lesions, excised from 14 patients, were found to consist of exuberant granulomas containing yeast. Organisms were recovered from pleural effusions of two patients and demonstrated histologically in the tissue of one individual who presented with fibrosing mediastinitis.

Adolescent↗

PubMed2004

Laryngeal histoplasmosis.

Histoplasma capsulatum is an endemic fungus found in moist, fertile soil; in North America, it is most prevalent in the river valleys of the central United States. Most primary infections in the immunocompetent host are asymptomatic or are thought to be a flu-like illness. Disseminated histoplasmosis most commonly occurs in immunosuppressed patients. Histoplasmosis infection involving the larynx is an extremely rare manifestation. Here, we describe the case of an immunocompetent man with symptomatic, acute pulmonary histoplasmosis with laryngeal involvement who presented with a chief complaint of hoarseness. We also review the literature of immunocompetent patients with laryngeal histoplasmosis.

Adult↗

PubMed1975

Koch's stulates and experimental ocular histoplasmosis.

The present study shows clearly that focal choroiditis is produced in rabbits by infecting the animals with a mycelial form of H. capsulatum. Identification of this organism as the pathogenic agent was made by histopathological and mycological observations. This fungus was recovered from infected ocular lesions in those eyes enucleated within four weeks following the appearance of uveitus-a time period consistent with the clinical and pathological appearance of multiple granulomas in the choroid. The absence of organisms in the contralateral eyes of these same animals at eight weeks suggests perhaps that recovery was associated with the emergence of immunity by two months following the appearance of uveitus. This is supported in part by our previous study, which supplied evidence that animals were protected from further uveitis on subsequent reinfections (after they had recovered from their initial infection) by a mycelial or yeast form of the fungus. Similar protection was also seen in animals that had prior exposures to heat-killed organisms. Moreover, onset of the ocular changes occurred usually two weeks after infection. This evidence strongly suggests that the experimental choroiditis may be immunologically induced. H. capsulatum recovered from infected eyes (Groups I and II) produced identical ocular lesions clinically and histopathologically when injected into normal animals (Groups IA and IIA). Fulfillment of Koch's postulates in experimental ocular histoplasmosis was achieved within only one month following the appearance of uveitis. This may be of fundamental importance in that efforts to demonstrate a causal relationship between the ocular picture and benign systemic histoplasmosis have been unsuccessful in man. Because of the striking similarity between the experimental choroiditis in rabbits and the changes observed in presumed ocular histoplasmosis in man, studies in primates are necessary. Since the ocular anatomy is similar in monkeys and in man, there remains the necessity to reproduce the hemorrhagic disciform lesion of the macula, which represents the gravest aspect of presumed ocular histoplasmosis.

Animals↗

PubMed1975

Diagnosis and management of minimal recurrences of macular histoplasmosis.

Disease in the macula from ocular histoplasmosis has been ascribed to (1) traction of a scar, (2) fresh areas of choroiditis, and (3) reactivation of a scar. Traction of a scar is probably a rare cause. The rationale for early use of corticosteroids in attacks of ocular histoplasmosis is based on the hypothesis that the underlying disease is an inflammation. The concept of a choroiditis could fit with what is assumed to happen in the case of second and third hypotheses, those of fresh choroiditis and reactivation of a scar. The goal of therapy is to stop the inflammation before it is clinically recognizable by the ophthalmologist, so that little or no damage to vision results. Whether corticosteroids might work by suppression of an immunological response or simply by curtailing the severity of the choroiditis, or both, is not known. We do know from clinical experience that corticosteroids do not appear to be deleterious to the ocular histoplasmosis. When they were first tried, we were wary about using them in a "fungal" disease. As experience grew, we learned that our mistakes were usually not from using too great a quantity of corticosteroids for too long a time but the opposite; from using too small amounts of corticosteroids for too short a time. Clinically, most attacks of macular histoplasmosis occur at the sites of previous scars, with little or no sign of any choroiditis. At present, there are six poorly defined hypotheses of how this may occur: (1) symbiosis, (2) secondary infection, (3) vascular decompensation [2], (4) immunological reaction [3], (5) altered structure [1], and (6) failure of precapillary arteriole [5]. Corticosteroids might be helpful in any of these instances. I believe that the attack that usually takes the form of an enlargement of the atrophic histo spot is caused by an immunological response in this area that develops into a mild spreading choroiditis. It is possible that with a reduction of the patient's resistance, live H. capsulatum or an antigenic component of it escapes from one of the viscera to lodge in the sensitized area of the atrophic choroid where a choroiditis previously existed. At this site, a fresh, mild choroiditis is activated. This choroiditis then persists for a variable period before either becoming quiescent or progressing into the neovascular stage, with the growth of a net through Bruch's membrane and the pigment epithelium and under the sensory retina. The rationale for the early and intensive use of corticosteroids is to try to abort the attack of choroiditis before it reaches the stage of becoming recognizable by the ophthalmologist.

Adrenal Cortex Hormones↗

PubMed1994

The Histoplasma capsulatum antigen assay in disseminated histoplasmosis in children.

Progressive disseminated histoplasmosis is often fatal without treatment and requires rapid and accurate laboratory diagnosis. Radioimmunoassay for Histoplasma capsulatum var. capsulatum antigen has been established as a sensitive and accurate diagnostic technique for disseminated histoplasmosis in adults; this study examines the radioimmunoassay in children. The clinical and laboratory records of 26 patients 18 years old or younger in whom H. capsulatum antigen was detected in urine by radioimmunoassay and at least one other positive corroborative standard test were evaluated. Twenty-two (85%) had disseminated disease, and 4 (15%) had self-limited pulmonary disease. Positive corroborative tests included serologic tests in 17 of 22 (77%) patients tested, tissue stains in 5 of 9 (56%) and fungal cultures in 16 of 24 (67%). Patients with disseminated histoplasmosis had a greater degree of antigenuria than those with self-limited infection. In 20 patients with progressive disease treated with amphotericin B, antigen levels declined, and the decrease in antigenuria correlated with clinical improvement. The radioimmunoassay for H. capsulatum antigen in urine is an important test in the diagnosis of disseminated histoplasmosis and is useful for assessing the efficacy of treatment. The presence of urinary antigen is strong evidence for progressive disease that requires treatment.

Adolescent↗

PubMed1996

Disseminated histoplasmosis in children: the role of itraconazole therapy.

OBJECTIVES: To describe the clinical characteristics and laboratory diagnosis of seven children with disseminated histoplasmosis and evaluate the effectiveness of itraconazole therapy in this severe form of the mycosis as well as to determine the long term results of such treatment. METHODS: The diagnosis of histoplasmosis was based on the direct observation of Histoplasma capsulatum var. capsulatum and/or on the isolation of the fungus from pathologic materials; the results of the serologic tests were taken into consideration. Chest roentgenograms also contributed to the diagnosis. PATIENTS: The patients were seven rural children, five girls and two boys, ages 1 to 14 years (mean, 4.6), with a confirmed diagnosis of disseminated histoplasmosis and who had no underlying disease other than malnourishment. RESULTS: The seven children experienced a subacute febrile syndrome for 4 months accompanied by anorexia, weight loss and signs of reticuloendothelial involvement such as lymph node hypertrophy, hepatomegaly and/or splenomegaly. The lung revealed roentgenographic alterations consisting mainly of nodular infiltrates. All patients received itraconazole orally in a mean dosage of 7.2 mg/kg/day, for variable periods (3 to 12 months), depending on the individual response and the toxic effects of the medication. One of the patients who was improving after 1 month of treatment was taken from the hospital by his guardian against medical advice and died shortly afterward. The remaining six patients responded to the treatment with marked clinical improvement and showed negative cultures and decreases in anti-H. capsulatum antibody titers after 3 months of treatment. Only one patient, the youngest and most severely affected child, exhibited hepatotoxicity, which subsided when itraconazole was discontinued. Extended follow-up studies revealed no relapses. CONCLUSION: The results of this study indicate that itraconazole is effective for treatment of disseminated childhood histoplasmosis. More studies should be performed to determine the most appropriate dosage and the optimal duration of itraconazole treatment in children.

Adolescent↗

PubMed1999

Disseminated histoplasmosis in infants.

BACKGROUND: Disseminated histoplasmosis usually occurs in immunocompromised patients who reside in Histoplasma capsulatum-endemic regions. It has also been described in immunocompetent infants after exposure to a large inoculum of the pathogen resulting in case fatality rates of 40 to 50%. METHODS: From 1983 through 1996 all infants with documented disseminated histoplasmosis were treated with amphotericin B followed by daily ketoconazole for 3 months. Immunologic workups were performed at the time of diagnosis and at 4 to 6 weeks of therapy. Surviving patients were followed for at least 1 year. Time to resolution of signs and symptoms was recorded, as were complications. RESULTS: We managed 40 patients with disseminated histoplasmosis. The age in months at diagnosis was 15.3+/-10.2 (mean +/- SD), and 24 were male. All patients were from endemic regions and they presented with fever, spleen and/or liver enlargement and hematologic abnormalities. Diagnosis was made by histology and culture of bone marrow, spleen, lymph node, bronchoalveolar or liver samples. Twenty patients presented with T cell deficiency that resolved at 4 to 6 weeks of therapy in all of the retested patients, and 10 of 12 tested patients had hyperglobulinemia that resolved. Thirty-five (88%) patients were cured by treatment; 4 died and 1 relapsed. CONCLUSIONS: Disseminated histoplasmosis should be considered in infants from endemic areas who present with fever, hepatosplenomegaly and hematologic abnormalities. These patients develop transient hyperglobulinemia and T cell deficiency that resolve with treatment. Treatment with amphotericin B followed by an oral azole for 3 months is effective in most patients.

Amphotericin B↗

PubMed1992

Disseminated histoplasmosis in patients with AIDS.

Disseminated histoplasmosis (DH) is recognized as an opportunistic infection in patients with the human immunodeficiency virus (HIV), especially in regions where histoplasmosis is endemic. At the Kansas University Medical Center 148 patients were hospitalized with the diagnosis of AIDS from December 1983 to March 1991; 23 of these patients (16%) had disseminated histoplasmosis. The charts of these 23 patients were reviewed. Clinical signs and symptoms included fever (91%), cough (65%), and weight loss (48%). Splenomegaly, hepatomegaly, or lymphadenopathy was present in 52% of all patients. Anemia (39%), leukopenia (65%), and thrombocytopenia (52%) were common, and 22% had pancytopenia. Diagnosis was made by peripheral smear examinations (organisms visualized on 7 of 22 smears [32%]), blood cultures (positive for H capsulatum in 16 of 20 patients, [80%]), bone marrow cultures (positive in 14 of 15 patients, [93%]), and bone marrow aspirate and biopsy examinations (organisms seen on 18 of 21 stains, [86%]). The combination of these four tests revealed the diagnosis of DH in 23 of 23 patients (100%). Induction and maintenance amphotericin B therapy was given to all but 2 patients, and currently 8 of the 23 are alive. DH is a common opportunistic infection in AIDS patients from regions endemic for histoplasmosis. When DH is suspected, a peripheral smear examination, blood cultures, bone marrow cultures and bone marrow aspirate and biopsy should be done to make the diagnosis, since suppression of the disease is possible with appropriate therapy.

AIDS-Related Opportunistic Infections↗

PubMed1995

Disseminated histoplasmosis in a patient from a nonendemic area who has acquired immunodeficiency syndrome.

Disseminated histoplasmosis is a serious opportunistic infection in patients with the acquired immunodeficiency syndrome (AIDS), often seen as the first manifestation of the syndrome. However, cases are reported almost exclusively from patients who live in or have traveled to endemic areas. We describe a case of disseminated histoplasmosis in a black woman with a 50-lb weight loss and marked weakness that occurred over a 6-month period. This case is one of the few in which disseminated histoplasmosis occurred as the first manifestation of AIDS in a patient in a nonendemic area. We believe it to be the first case reported in Michigan in which the patient has no history of prior residence in an endemic area. Disseminated histoplasmosis should be suspected in patients with AIDS and unexplained febrile illness, even in nonendemic areas.

AIDS-Related Opportunistic Infections↗

PubMed1997

Itraconazole maintenance treatment for histoplasmosis in AIDS: a prospective, multicenter trial.

PURPOSE: To study the efficacy and safety of maintenance treatment with itraconazole for disseminated histoplasmosis in patients with AIDS. PATIENTS AND METHODS: This was a prospective, multicenter, open-label study conducted at university-based hospitals participating in the AIDS Clinical Trial Group (ACTG). Forty-six AIDS patients with mild to moderate disseminated histoplasmosis who had successfully completed 12 weeks of induction treatment with itraconazole were treated with itraconazole, 200 mg once daily (42 patients) or 400 mg once daily (4 patients). Patients were followed at monthly intervals with clinical and laboratory assessment for relapse or toxicity. Primary outcome measures were relapse of histoplasmosis and survival. Secondary outcome measures included drug-limiting toxicity and changes in serum and urine Histoplasma polysaccharide antigen (HPA) levels. RESULTS: Two patients relapsed during a median follow-up period of 87 weeks. The 1-year relapse-free rate was estimated to be 95.3% (95% CI, 85.3%-99.7%). One relapse may have been related to poor adherence to treatment and the second to concurrent administration of rifampin. From the start of maintenance treatment, the estimated 1-year survival rate was 73.0% (95% CI, 67.5%-77.9%). Five patients discontinued treatment because of suspected drug toxicity, three of whom had possible or probable hepatotoxicity. Median serum and urine HPA levels declined significantly during treatment. The only patient in whom antigen levels rose >2 U developed clinical relapse 1 week later; antigen levels were unavailable in the other relapsing patient. CONCLUSIONS: Itraconazole, 200 mg daily, is effective in preventing relapse of disseminated histoplasmosis in patients with AIDS. It is generally well tolerated, but clinicians should be alert for drug interactions and possible hepatotoxicity.

AIDS-Related Opportunistic Infections↗

PubMed2004

A large histoplasmosis outbreak among high school students in Indiana, 2001.

BACKGROUND: A histoplasmosis outbreak occurred in an Indiana high school in November-December 2001. METHODS: To describe the risk factors for this outbreak, we conducted a cohort study of all available students and staff (N = 682) and an environmental investigation. RESULTS: Of the 523 (77%) persons who displayed serologic evidence of recent Histoplasma capsulatum infection, 355 (68%) developed symptoms consistent with acute pulmonary histoplasmosis. Rototilling of soil in a school courtyard known to be a bird roosting site had been performed during school hours on November 12, 2001, 14 days before both the peak of the onset of illness and a rise in student absenteeism. Being a student (odds ratio, 3.3; 95% confidence interval, 2.2-5.0) and being a student in a classroom near the courtyard during the rototilling (odds ratio, 3.1; 95% confidence interval, 1.8-5.2) were independently associated with infection and symptomatic illness. H. capsulatum was isolated from environmental samples, including soil from the courtyard and dust collected from a filter of a heating, ventilating and air-conditioning system. CONCLUSIONS: Soil-disrupting activities within a school courtyard caused the largest outbreak to date of histoplasmosis among adolescents. Improved efforts are needed to educate the community in endemic areas about histoplasmosis to prevent the occurrence of such outbreaks in the future. In addition, increased awareness among health care providers of this disease would facilitate appropriate diagnosis and treatment.

Adolescent↗

PubMed2006

Disseminated histoplasmosis presenting as a unilateral cranial nerve VIII mass: a case report.

OBJECTIVE: To report a unique presentation of disseminated histoplasmosis. STUDY DESIGN: Case report. SETTING: University hospital, tertiary referral center. PATIENT: Our patient presented with vertigo, tinnitus, and unilateral hearing loss, and was initially found to have a 5-mm enhancing left internal auditory canal mass, as revealed by a magnetic resonance imaging (MRI) scan. Subsequently, the patient developed multiple focal neurologic deficits. INTERVENTIONS: Magnetic resonance imaging and treatment with intravenously administered amphotericin B, with subsequent oral administration of itraconazole. MAIN OUTCOME MEASURES: Clinical presentation and imaging findings of Histoplasmosis involving the cranial nerve VIII. RESULTS: A subsequent MRI scan revealed enlargement of the initial lesion and multiple parenchymal lesions. Further workup revealed a pulmonary lesion; the diagnosis of disseminated histoplasmosis was made on the basis of bronchoalveolar lavage culture. CONCLUSION: Infectious processes, including disseminated histoplasmosis, should be considered in the differential of internal auditory canal masses, especially in the setting of rapid progression of symptoms.

Bronchoalveolar Lavage Fluid↗

PubMed2006

Histoplasmosis among human immunodeficiency virus-infected people in Europe: report of 4 cases and review of the literature.

We reviewed the clinical, microbiologic, and outcome characteristics of 72 patients with human immunodeficiency virus (HIV)-associated histoplasmosis (4 newly described) reported in Europe over 20 years (1984-2004). Seven cases (9.7%) were acquired in Europe (autochthonous), whereas the majority involved a history of travel or arrival from endemic areas. The diagnosis of progressive disseminated histoplasmosis (PDH) was made during life in 63 patients (87.5%) and was the acquired immunodeficiency syndrome (AIDS)-presenting illness in 44 (61.1%). Disease was widespread in 66 patients (91.7%) and localized in 6 (8.3%), with the skin being the most frequent site of localized infection. Overall skin involvement was reported in 47.2% of the patients regardless of whether histoplasmosis was acquired in Africa or South America. Reticulonodular or diffuse interstial infiltrates occurred in 52.8%. The diagnosis was made during life by histopathology plus culture in 44 patients (69.8%), histopathology alone in 18 (28.5%), and culture alone in 1 (1.5%). During the induction phase amphotericin B and itraconazole (74.6%) were the single most frequently used drugs. Both drugs were also used either in combination (10.2%) or in sequential therapy (11.8%). Cumulative mortality rate during the induction phase of treatment was 15.2%. Overall, 37 patients died (57.8%); death occurred early in the course in 18 (28.1%). Seven of 40 patients (17.5%) who responded to therapy subsequently relapsed. Autopsy data in 13 patients confirmed the widespread disseminated nature of histoplasmosis (85%) among AIDS patients with a median of 4.5 organs involved. The results of the present report highlight the need to consider the diagnosis of PDH among patients with AIDS in Europe presenting with a febrile illness who have traveled to or who originated from an endemic area.

Adult↗

PubMed2006

Increased incidence of disseminated histoplasmosis following highly active antiretroviral therapy initiation.

To determine whether the initiation of highly active antiretroviral therapy (HAART) had any influence on the incidence of disseminated histoplasmosis, a retrospective cohort study was performed on 1551 patients followed for up to 12 years. After controlling for CD4 counts, age, and sex, patients taking HAART for 2 months or less were more likely to develop disseminated histoplasmosis than untreated patients (respectively, hazard ratio, 3.7 [95% confidence interval, 1.57-8.7]; P = 0.003). In contrast, after 6 months of HAART, treated patients were less likely to develop disseminated histoplasmosis than untreated patients (hazard ratio, 0.6 [95% confidence interval, 0.37-0.98], P = 0.04). This increased incidence suggests that the initiation of HAART and the subsequent immune reconstitution may reveal undiagnosed latent disseminated histoplasmosis.

Antiretroviral Therapy, Highly Active↗

PubMed2004

Isolated gastrointestinal histoplasmosis: case report and review of the literature.

The usual manifestation of histoplasmosis is in the form of respiratory illness. We report the case of a 67-year-old man who presented with chronic diarrhea and did not respond to the conventional treatment, including that for Clostridium difficile. He was found to have isolated colonic histoplasmosis infection, which was treated with itraconazole. There was no evidence of any disseminated disease. His only immunocompromised state was end-stage renal disease, for which he was on chronic hemodialysis. Although it is well documented as a part of disseminated histoplasmosis, our extensive review of the literature did not reveal any reported case of isolated colonic histoplasmosis in a patient on hemodialysis.

Aged↗