Pathology of the mycoses in patients with the acquired immunodeficiency syndrome (AIDS).
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Biomedical subjects
Publications and source records attributed to F W Chandler.
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Fusarium moniliforme was demonstrated to be the etiologic agent in an Italian case of eumycotic mycetoma. The fungus produced white granules, which measured 80 X 133 by 212 X 478 microns. Their edges were entire or lobed and were surrounded by an eosinophilic homogeneous material. The hyphae comprising the granules were not embedded in cement. The etiologic agent, first considered to be an Acremonium species, was restudied and identified as F. moniliforme on the basis that it not only produced chains of microconidia but also curved, multi-septate macroconidia typical of the genus Fusarium.
The effects of subchronic inhalation exposure to isobutyl nitrite (IBN) on body weight, selected organ weights, hematology, and gross pathology and histopathology of BALB/c mice were evaluated. Mice of both sexes were exposed at 0, 20, 50, or 300 ppm IBN for 6.5 h/d, 5 d/wk for up to 18 wk. Most changes in measured indices occurred in mice exposed at 300 ppm IBN and included decreased thymus weight (females); decreased liver weight (males); decreased white blood cell counts (males); mild focal hyperplasia and vacuolization of the epithelium lining bronchi and bronchioles of the lungs (males and females). Organ weight and hematologic changes, however, were not accompanied by any observed histologic changes. In addition, elevated methemoglobin concentrations were detected in mice of both sexes exposed at 50 and 300 ppm IBN. Body weights were not adversely affected by exposure. These data suggest that mild tissue injury, restricted to the lung, and methemoglobinemia are the major toxic effects observed following exposures of mice to IBN at concentrations up to 300 ppm for 18 wk. No treatment-related effects were noted in mice exposed at 20 or 50 ppm IBN, except for slight elevations in methemoglobin concentrations in mice exposed at 50 ppm.
The authors describe spheric to ovoid chlamydoconidia and mucoraceous hyphae in tissues from four patients, two with cutaneous and two with pulmonary zygomycosis. The diagnosis in each case was confirmed by immunofluorescence staining and the presence of characteristic hyphae in tissue. It is important that these conidia be recognized, because they can easily be mistaken for other fungi, nematode ova, or other microorganisms in tissue sections, thereby resulting in the potential for misdiagnosis.
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Staphylococcus aureus from patients with toxic shock syndrome (TSS) produce TSS toxin 1. We transferred, by a bacteriophage, the ability to produce TSS toxin 1 from a TSS toxin 1-positive to a TSS toxin 1-negative strain of S. aureus. This recombinant strain produced TSS toxin 1 as confirmed by isoelectric focusing, immunodiffusion, radioimmunoassay, and autoradiography. The recombinant produced TSS-like illness in rabbits, and was significantly (P less than 0.001) more lethal than the recipient strain. Both strains produced fever and diarrhea, but, in addition, rabbits challenged with the recombinant also developed lowered blood pressure (P = 0.002), conjunctival hyperemia, erythroderma, and respiratory distress. Histopathological findings in rabbits challenged with the recombinant strain were remarkably similar to those described for humans with TSS, e.g., erythrophagocytosis, liver "triaditis," and vasodilatation. This study demonstrates that this protein may contribute to the pathogenesis of the TSS.
A case of zygomycosis caused by Apophysomyces elegans in a diabetic, obese female is described. The fungus gained entry into the body through injury to the skin, penetrating the keratin, epidermis, and dermis. Hyphal angioinvasion was observed. Fungal elements invaded the subcutaneous fat, skeletal muscle fibers, nerves, and large blood vessels, resulting in the spread of the infection. The rapidity with which A. elegans invaded the blood vessels left no choice except amputation of the leg to stop the spread of the infection. This zygomycetous fungus closely resembles Absidia corymbifera. It is distinguished by its prominent campanulate apophyses. In its gross colony characteristics and failure to sporulate on routinely used media it resembles Saksenaea vasiformis.
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The cyst forms of Pneumocystis carinii in specimens stained with methenamine silver contain single or paired discrete foci of enhanced staining that measure 1-2 micron in maximum size. The nature of these foci and their location within the cysts have been disputed. We demonstrate by electron microscopy of silver-stained sections that the darkly stained foci correspond to a focal thickening of the cyst wall and are unrelated to sporozoites and other intracystic organelles. The morphology of these structures by light microscopy is characteristic, and their recognition is helpful in identifying P. carinii cysts and in differentiating them from yeast-form fungi and argyrophilic tissue elements in histologic sections and cytology specimens.
Lymph nodes of patients symptomatically infected with the acquired immunodeficiency syndrome (AIDS) virus show a spectrum of morphologic changes ranging from marked lymphoid hyperplasia to marked lymphocytic depletion. These changes can be grouped into three distinct patterns. The type I pattern features follicular and paracortical hyperplasia, and is associated with chronic lymphadenopathy. The type II pattern, which shows diffuse lymphoid hyperplasia but loss of germinal centers, signifies evolution of chronic lymphadenopathy to AIDS. The type III pattern shows marked lymphocytic depletion and represents the end-stage lymph node seen in fatal AIDS. These histologic patterns are closely correlated with the clinical and immunologic status of patients infected with the AIDS virus.
Frozen sections of lymph nodes from 20 homosexual men with chronic generalized lymphadenopathy and of lymph nodes showing follicular hyperplasia from 14 patients without known risk factors of the acquired immunodeficiency syndrome were studied with monoclonal antibodies to T-cell subsets and to the HLA-DR antigen. In T-cell areas of the lymph nodes, excluding tertiary paracortical nodules, the mean T-helper-to-T-suppressor ratio (Th/Ts) +/- 1 SEM was significantly lower in the homosexual group (1.07 +/- 0.06) when compared with the control group (2.49 +/- 0.23), P less than .0001. In seven homosexual men, cell suspensions from the same lymph nodes were analyzed using a fluorescence-activated cell sorter. Results obtained by this method and by immunohistochemistry were comparable except in a homosexual man whose lymph node contained large tertiary paracortical nodules. Although the Th/Ts ratios of the blood and lymph nodes of the same patients were both low, there was not good correlation between the two sets of values (r = .2). Furthermore, there was not good correlation between blood lymphocyte count and lymph node Th/Ts ratios (r = .45). The lymph node Th/Ts ratios of the homosexual patients show less variations compared with the control group. The patient who subsequently developed multiple opportunistic infections had the lowest value. Whether the lymph node Th/Ts ratio has prognostic significance in patients with the lymphadenopathy syndrome warrants further investigation.
Listeriosis was diagnosed in 7 bushy-tailed jirds (Sekeetamys calurus). Death in all cases was acute, and there were no clinical signs. Necropsy revealed necrotizing lesions in the liver, intestines, spleen, and hepatic and mesenteric lymph nodes. On histologic examination large numbers of gram-positive coccobacilli were seen in the lesions. Pneumonitis was seen in 6 jirds, and small numbers of bacteria were seen in the lungs in all cases except one. Diagnosis was based on bacterial culture of the liver in 2 jirds and on immunofluorescence of bacteria when tissue specimens from 2 other jirds were stained with fluorescein-labelled antiglobulins specific for Listeria monocytogenes.
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A 3-year-old Collie bitch was euthanatized two weeks after the onset of blindness and deafness. The hearing deficit had been localized by clinical signs, brain stem auditory evoked responses, and impedance audiometry. Protothecosis was diagnosed by cytologic and histologic examinations. The organism was identified as Prototheca zopfii . Organisms and granulomatous lesions were found in kidney, heart, liver, skeletal muscle, thyroid gland, colon, bronchial lymph node, brain, and cochlea.
A patient with the acquired immune deficiency syndrome and Legionella pneumophila infection of the maxillary sinus is described. The organism was identified by direct immunofluorescence staining of sinus tissue. Because the Legionella species are intracellular pathogens, it is not surprising that this patient with a cellular immune defect was infected. However, no other site of Legionella infection was found. This appears to be the first reported case of upper respiratory tract infection by a Legionella species.
The complete pathogenesis of toxic shock syndrome (TSS) has yet to be elucidated. Unmasking the complex interactions among bacterial products, host factors, and possibly tampon components requires a suitable in vivo model. For this purpose, subcutaneous chambers implanted in rabbits were inoculated with Staphylococcus aureus isolated from patients with TSS. Infected rabbits developed illness characterised by multisystem involvement that included periportal inflammation of the liver, erythrophagocytosis in the spleen and lymph nodes as well as extreme vascular dilatation and epithelial lesions similar to those described in patients with TSS. Concentrations of serum creatinine (P less than 0.03) and triglycerides (P less than 0.04) were significantly raised in rabbits infected with TSS strains compared with rabbits infected with non-TSS strains of S. aureus. Both TSS and non-TSS strains of S. aureus produced fever and diarrhoea, but TSS strains were significantly (P less than 0.05) more lethal and more likely to produce respiratory distress and lowered blood pressure. This model may help to prove or disprove proposed mechanisms for the development of TSS.
Concentrations of arabinitol, mannose, and mannan in serum have independently been reported to be elevated in patients with invasive candidiasis. These three marker substances were compared in a rabbit model. Twelve rabbits, immunosuppressed with cortisone, were infected intravenously with Candida albicans 3181A. Six uninfected control animals also received cortisone, and four rabbits were neither infected nor immunosuppressed. Blood samples, drawn from 2 days before to 14 days after infection, were assayed for serum mannan by sandwich enzyme immunoassay, antibodies to mannan by indirect enzyme immunoassay, arabinitol and mannose by gas-liquid chromatography, and serum creatinine. Serum mannan, negative before infection, peaked in all infected animals 4 days after infection (mean, 18 ng/ml) and decreased thereafter. Significant increases (2 standard deviations greater than mean in normals) in arabinitol, the arabinitol/creatinine ratio, and mannose were found in 12, 8, and 12 of the infected rabbits, respectively, but also in all 6 uninfected animals receiving cortisone. Only serum mannan was specific in this immunosuppressed rabbit model.
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