Acute Histoplasmosis Research Articles

Recurrent urban histoplasmosis, Indianapolis, Indiana, 1980-1981.

In January 1981, informal surveillance of acute histoplasmosis in Indianapolis, Indiana, revealed a marked increase in disease activity for the last quarter of 1980. Fifty-one patients with onset of acute histoplasmosis during this period were identified through review of hospital admissions, emergency room visits, and serologic records at Indianapolis hospitals and the Indiana State Board of Health. In a retrospective case-control study, the authors found a significant association between developing acute histoplasmosis during this period and working or attending classes in a 2 sq mi (5.2 sq km) area encompassing the Indiana University-Purdue University campus (p = 0.015, Fisher's exact test). A review of construction activities on or near the campus during the epidemic period suggested that the probable source of infection was excavation activity for a large new indoor swimming complex (natatorium). Skin tests and serosurveys of students on campus by a newly developed radioimmunoassay for histoplasmal immunoglobulin M antibodies supported the association of infection with exposure to this site (p less than 0.05).

Unusual Manifestations of Histoplasmosis in Childhood

Nine previously healthy children were seen with unique, and in several instances, unreported manifestations of acute histoplasmosis. Presenting manifestations included: obstructive airway disease; subacute parotitis; unilateral cervical lymphadenopathy; anterior mediastinal mass-simulating neoplasm; immune hemolytic anemia; a cutaneous lesion with regional lymphadenopathy; mediastinal mass and pericardial effusion; pulmonary infarction; and a symptom complex of cervical lymphadenopathy, CSF pleocytosis, arthritis, and interstitial nephritis. In eight children histoplasmosis was not initially considered, and the correct diagnosis was made only after complex, and sometimes invasive, diagnostic evaluation and considerable delay. All patients recovered fully without antifungal therapy. Reports of uncontrolled trials of new antifungal agents for treatment of histoplasmosis in immunocompetent hosts should be cautiously evaluated.

Serum Angiotensin Converting Enzyme Activity in Patients With Histoplasmosis

The association between increased serum angiotensin converting enzyme (ACE) activity and active sarcoidosis is well documented. During a recent outbreak of acute histoplasmosis, a disease that shares many of the clinical and roentgenographic features of sarcoidosis, we examined serum ACE activity. Twenty-one (25%) of 86 patients with histoplasmosis had increased serum ACE activity. There were neither roentgenographic nor other substantive clinical differences between the groups of patients with increased and normal ACE values. Therefore, an increase in serum ACE activity must not be assumed to be caused by sarcoidosis unless histoplasmosis had been excluded.

Primary acute histoplasmosis in guinea pigs exposed to aerosolized Histoplasma capsulatum.

Guinea pigs were examined as a possible in vivo model for human histoplasmosis. Guinea pigs were exposed to an aerosol of viable microconidia and mycelial fragments of Histoplasma capsulatum generated in a Henderson apparatus. Colonization and infection of the lungs occurred, with subsequent involvement of the regional lymph nodes and reticuloendothelial organs. Cultural recovery of the fungus from the nasopharynx and bronchoalveoli was initially high, but decreased with time. The mean number of colonies recovered from the lungs gradually increased, reaching a peak at 2 weeks, with involvement of the regional lymph nodes. Extrathoracic dissemination to the liver and spleen occurred in only a few animals. After 4 weeks, all tissues except the cervical and tracheobronchial lymph nodes were culturally negative; all specimens were culturally negative after 8 weeks. Disappearance of H. capsulatum from tissues appeared to correlate inversely with the development of hypersensitivity as measured by skin test reactivity. Histopathological studies supported cultural results and were similar to those described for primary human and canine histoplasmosis.

Acute pulmonary histoplasmosis presenting as adult respiratory distress syndrome: effect of therapy on clinical and laboratory features.

Three patients with acute pulmonary histoplasmosis presented with extensive, diffuse bilateral infiltrates on chest roentgenograms. Fungal elements were seen in the bronchial secretions of two patients; Histoplasma capsulatum was grown from the third patient and from soil from the patients' workplace. Two patients were severely hypoxemic and required short courses of amphotericin B therapy; in one of these two, progressive deterioration dictated corticosteroid therapy as well, with a dramatic clinical response. Radiologic resolution of disease occurred more quickly in the treated patients. Initial pulmonary function tests suggested mild restriction in each, with normal test results by the fourth month of follow-up. Our experience suggests that amphotericin B may shorten the course of acute histoplasmosis and that corticosteroid therapy may be efficacious in controlling the symptoms related to hyperresponsiveness in fulminant primary disease.

Acute Histoplasmosis: Description of an Outbreak in Northern Louisiana

An outbreak of acute histoplasmosis occurred in northern Louisiana in September 1977. All six men who cleared a field of bamboo cane known to be a blackbird roosting site were affected. All had clinical and roentgenographic findings of acute pulmonary histoplasmosis, and all recovered. Seroconversion or fourfold rise in antibody to Histoplasma capsulatum yeast--or mycelial-form antigens were demonstrated in five. Immunodiffusion testing showed that all six patients developed H capsulatum M bands, and two developed H bands specific for active infection. The H capsulatum was isolated from the soil in the cane field. This is the first report of an outbreak of histoplasmosis in Louisiana and the first known isolation of H capsulatum from Louisiana soil.

Acute histoplasmosis: Clinical, epidemiologic and serologic findings of an outbreak associated with exposure to a fallen tree

An outbreak of acute histoplasmosis occurred among 42 people who gathered for two days in May 1977 to cut and clear a fallen oak tree near Nashville (Williamson County), Tennessee. Thirty-two (76 per cent) of the participants had serologic evidence of infection; 20 (48 per cent) had acute pulmonary disease and of these, three required hospitalization. Frequent symptoms of acute pulmonary disease included fever, malaise, chest pain, headache, cough, myalgia, weight loss (≥ 5 pounds) and stomach cramps. Chest roentgenograms revealed abnormalities in 87 per cent of the ill participants. The disease developed in two dogs that were also present at the activities. Illness began an average of 14 days after exposure. Risk of illness was associated with sawing the tree, and loading wood and bark into a truck, as well as the length of the time spent near the tree. Tests for fungal antibodies in serum obtained from the participants and community controls, (those who lived in the county but did not have symptoms of respiratory illness) were used to establish criteria for serologic diagnosis. Immunodiffusion tests with initial serum samples were most useful for diagnosis; the presence of an M precipitin band was 75 per cent sensitive and was 97 per cent specific as judged by data from community controls. Similarly, the mycelial form antigen Histoplasma capsulatum complement fixation test at a titer ≥ 1:8 was 55 per cent sensitive and 97 per cent specific, and the yeast-form antigen complement fixation test at a titer of ⩾ 1:16 was 75 per cent sensitive and 77 per cent specific. When serum obtained four weeks after exposure (one to two weeks after onset of symptoms) was compared with serum obtained eight weeks after exposure, a fourfold increase in complement fixation antibodies was detected in 28 per cent of those infected.

Acute Cavitary Histoplasmosis

A case of acute cavitary histoplasmosis in the upper lobes is documented. The relationship of this entity to chronic cavitary histoplasmosis is discussed.

Histoplasmosis: an outbreak occurring among young men who visited one cave.

Sixteen cases of acute benign inhalational histoplasmosis were investigated after an outbreak of the disease in a group visiting a cave. The diagnosis was confirmed in 13 patients by chest X-ray examination, histoplasmin skin testing and serological examination. An attempt to isolate the organism Histoplasma capsulatum was unsuccessful. The epidemiology and relationship of the disease to bat ecology is discussed.

Acute Histoplasmosis in a Military Housing Area: Case Reports with Pulmonary Function Studies

Acute Histoplasmosis in a Military Housing Area: Case Reports with Pulmonary Function Studies

The Chanute Histoplasmosis Epidemic: New Variations of Urban Histoplasmosis

An epidemic of acute histoplasmosis occurred in a long-established residential neighborhood in central Illinois. Ten of the 28 individuals living in the five duplex buildings comprising the housing project had evidence of acute infection. The epidemic was unusual in that the infections apparently occurred as the result of adults tending their gardens and children playing under and about the tress of the area. No specific event, such as a construction project or the demolishing of an old building, was involved as a point source, as has usually been observed in past epidemics. The infections occurred sporadically over a summer and probably resulted from exposure to any one of several sites where the fungal organisms were shown to exist in the housing area.

Acute Histoplasmosis Presenting as the Adult Respiratory Distress Syndrome

Acute pulmonary histoplasmosis is generally a benign disease. Rarely it can cause fulminating life-threatening illness. The following presentation recounts a case of acute histoplasmosis with severe respiratory failure. The features of this patient's illness resemble those of the adult respiratory distress syndrome. The patient was managed with intubation, positive pressure ventilation with a volume-cycled respirator, positive end expiratory pressure, intermittent mandatory ventilation, corticosteroids, diuretics, and antifungal agents. Acute pulmonary histoplasmosis is generally a benign disease. Rarely it can cause fulminating life-threatening illness. The following presentation recounts a case of acute histoplasmosis with severe respiratory failure. The features of this patient's illness resemble those of the adult respiratory distress syndrome. The patient was managed with intubation, positive pressure ventilation with a volume-cycled respirator, positive end expiratory pressure, intermittent mandatory ventilation, corticosteroids, diuretics, and antifungal agents.

Acute reinfection pulmonary histoplasmosis. A report of six cases.

Acute reinfection pulmonary histoplasmosis. A report of six cases.

Histoplasmosis presenting as acute polyarthritis.

MIGRATORY polyarthritis was the predominant presenting manifestation of acute primary histoplasmosis in the following case. Case Report A 23-year-old student first noted pain, swelling and redness of the left ankle. Four days later the right ankle became similarly involved. After 3 days, bilateral ankle pain prevented him from attending classes. He recalled a mild cold about 1 week earlier and thereafter had experienced malaise and low-grade fever. On admission the temperature was 38.1°C, and the pulse 100. Both ankles showed diffuse swelling, marked tenderness, calor, and limited painful motion. The remainder of the examination was within normal limits. Fever (temperature . . .

Evaluation of a microtiter latex agglutination test for histoplasmosis.

Experiments were designed to evaluate a Microtiter latex agglutination (Micro-LA) test, as a serological aid in the diagnosis of histoplasmosis, and to compare this test with the conventional microtiter-complement fixation (CF) test for histoplasmosis. Sera tested were from cases of acute and chronic pulmonary and disseminated histoplasmosis, as well as from individuals not having histoplasmosis. Ninety-seven percent of the cases of acute pulmonary histoplasmosis had positive Micro-LA tests, whereas 91% had positive CF tests. Ninety-six percent of the patients having chronic pulmonary histoplasmosis showed positive Micro-LA tests and 91% had positive CF tests. In contrast, 64% of the cases of disseminated histoplasmosis had positive Micro-LA tests, whereas 82% had positive CF tests. None of these differences was statistically significant. Although there were no significant differences in complement fixing and agglutinating antibody cross-reactivity with Blastomyces antigens, more patients demonstrated CF titers than Micro-LA titers. Sera from patients with acute and chronic histoplasmosis showed higher Micro-LA titers than CF titers, whereas sera from cases of disseminated histoplasmosis showed higher CF titers. Histoplasmin skin testing has less of a boosting effect on agglutinating antibodies than on CF antibodies to histoplasmin. Anticomplementary sera can be used in the Micro-LA test. This test is simple to perform, and results can be obtained in 2 to 4 hr.

Evaluation of a Microtiter Latex Agglutination Test for Histoplasmosis

Experiments were designed to evaluate a Microtiter latex agglutination (Micro-LA) test, as a serological aid in the diagnosis of histoplasmosis, and to compare this test with the conventional microtiter-complement fixation (CF) test for histoplasmosis. Sera tested were from cases of acute and chronic pulmonary and disseminated histoplasmosis, as well as from individuals not having histoplasmosis. Ninety-seven percent of the cases of acute pulmonary histoplasmosis had positive Micro-LA tests, whereas 91% had positive CF tests. Ninety-six percent of the patients having chronic pulmonary histoplasmosis showed positive Micro-LA tests and 91% had positive CF tests. In contrast, 64% of the cases of disseminated histoplasmosis had positive Micro-LA tests, whereas 82% had positive CF tests. None of these differences was statistically significant. Although there were no significant differences in complement fixing and agglutinating antibody cross-reactivity with Blastomyces antigens, more patients demonstrated CF titers than Micro-LA titers. Sera from patients with acute and chronic histoplasmosis showed higher Micro-LA titers than CF titers, whereas sera from cases of disseminated histoplasmosis showed higher CF titers. Histoplasmin skin testing has less of a boosting effect on agglutinating antibodies than on CF antibodies to histoplasmin. Anticomplementary sera can be used in the Micro-LA test. This test is simple to perform, and results can be obtained in 2 to 4 hr.

Lung Function in Acute Pulmonary Histoplasmosis

Pulmonary function was investigated in four men one month after onset of acute histoplasmosis. Restrictive ventilatory impairment was found in one. Seven months later, his pulmonary function became normal. In the other three patients, a slight ventilation-perfusion unevenness was probably present.

Acute Granulomatous Hepatitis Due to Histoplasmosis

A 54-year-old man presenting with fever, hepatomegaly, and weight loss was found to have acute histoplasmosis, apparently involving only the liver. The diagnosis was established by culture of liver biopsy material and elevated complement fixation titers which declined in the convalescent phase of the patient's illness. Histological examination showed only granulomatous hepatitis. The patient recovered uneventfully without the use of systemic antifungal drugs. He did receive corticosteroids for a brief period. The patient now has been followed for 3 years and remains well. A recent liver biopsy showed only minimal periportal lymphocytic infiltration. A review of the literature fails to reveal a similar case. An analogy is drawn between this case and the acute self-limited pulmonary form of histoplasmosis. Culture of liver biopsy material showing granulomatous hepatitis is recommended in all cases where the etiology is not clear from other evidence.

Amphotericin B and Other Polyenic Antifungal Antibiotics

The polyenic antifungal antibiotics are a large group of related macrolides whose ring contains a rigid planar lipophilic portion and a flexible hydrophilic portion. These inhibit growth of fungi (but not of bacteria) and have significant value in treatment of intestinal or topical monilial infections. Amphotericin B is used systemically for the treatment of acute histoplasmosis and blastomycosis. After the initial demonstration of therapeutic utility, attention became focused on the in vitro biologic action of the polyenes. The critical step was identified as formation of a complex with the membrane sterol of sensitive organisms. The consequences of this binding are being examined using natural and artificial membranes. The surprising feature that has emerged is the wide variation in ultimate physiologic effects produced by the individual polyenes. Investigation of this problem should provide important information on membrane function as well as on the nature of the specific membrane complexes. Finally, and of great interest at the moment, physiologic and pharmacologic effects on sterol and steroid metabolism in animals have been observed. These changes are consistent with available information on the mechanism of the microbial action of the polyenes. The possible practical application of these discoveries is of great interest.

Immunology of the Mycoses

Summary The transformation of lymphocytes in vitro in the clinical types of histoplasmosis was studied by stimulation of peripheral blood lymphocytes with histoplasmin. Lymphocytes were obtained from five healthy histoplasmin-positive and five histoplasmin-negative donors as well as five patients who had acute histoplasmosis and five patients who had chronic histoplasmosis. The measurement of incorporation of radioactive thymidine into DNA was a more sensitive indicator of lymphocyte transformation than morphology. The uptake of thymidine, as expressed by a ratio of the radioactive counts from the antigne stimulated tubes and the unstimulated tubes (E′C), was greater for the healthy histoplasmin-positive donors (median E/C 66.7) than for the histoplasmin-negative donors (median E/C 4.9). Acute histoplasmosis patients (median E/C 51.1), as a group, reacted similarly to the healthy histoplasmin-positive donors. The chronic histoplasmosis patients (median E/C 22.6), on the other hand, reacted more like the histoplasmin-negative donors. The lymphocyte transformation, appeared to be depressed according to the severity of the clinical illness as well as by the presence of serum antibodies. Also, the transformation was depressed by heating serum at 56°C in a water bath for 30 min. No antibody against histoplasmin could be demonstrated in the culture fluid by means of the C-F test even when there was strong lymphocyte transformation.