Microscopy and latex antigen negative cryptococcal meningitis.

A HIV-positive patient presented with cryptococcal meningitis that was not detected by cerebrospinal fluid (CSF) latex antigen and direct microscopy. The diagnosis was confirmed by culture of the CSF and subsequent urine culture, both of which yielded an apparently acapsular strain of Cryptococcus neoformans. After 19 months the patient relapsed and capsulated yeasts were observed on this occasion on direct microscopy of the CSF. The latex antigen test was strongly positive. Culture again yielded an apparently acapsular isolate. Retrospective culture of all isolates obtained from this patient in sterile CSF resulted in the formation of capsules. This was confirmed by the requirement of normal non heat inactivated serum for neutrophil-cryptococcus attachment to occur in vitro. Although antigen and direct microscopy are frequently relied upon to diagnose cryptococcal meningitis, a negative result does not exclude the condition.

The prevalence of dermatophyte infection in well-controlled diabetics and the response to Trichophyton antigen.

The prevalence of dermatophyte infection was assessed in 100 patients with well-controlled insulin-dependent diabetes, and in a control group of 100 non-diabetics matched for age, sex, occupation and sporting activity. Immediate and delayed responses to intradermal testing with Trichophyton antigen were recorded in both groups. The overall infection rate (skin and nails) was 19% in diabetics and 17% in controls. There was a higher infection rate in the skin of diabetics (17%) than in controls (8%), but this was not significant. Nail infection was seen in 12% of diabetics and in 11% of controls. Intradermal testing with Trichophyton antigen gave a higher proportion of both immediate and delayed positive results in diabetics. However, more control patients showed only an immediate positive response or only a delayed one. There was no evidence of an increased infection rate in those with immediate positive responses or of diminished infection rates in those with delayed positive responses, and no correlation with oral Candida infection. These findings applied equally to diabetics and controls.

Invasive aspergillosis in two patients with acute lymphoblastic leukaemia in complete remission.

Invasive aspergillosis is a disease of the immunosuppressed patient. We describe two patients with acute lymphoblastic leukaemia who attained complete remission, with partial or complete bone marrow recovery, but who went on to develop fatal invasive aspergillosis contemporaneous with recovery of neutrophil counts. Quantitative recovery of peripheral blood neutrophil counts does not guarantee control of Aspergillus infection, perhaps due to functional neutrophil deficiencies post-chemotherapy, and specific defensive strategies adopted by the organism itself.

Chronic necrotising pulmonary aspergillosis treated with itraconazole.

A patient with longstanding ankylosing spondylitis developed chronic necrotising pulmonary aspergillosis, which was successfully treated with itraconazole.

Immunoblot fingerprinting Aspergillus fumigatus.

A new technique for typing Aspergillus fumigatus is presented. This is based on immunoblot fingerprinting each isolate against a rabbit hyperimmune antiserum raised against A. fumigatus NCTC 2109. All isolates were typable and reproducibility for the 16 antigenic bands which formed the basis of the system was excellent. Discrimination was better than silver staining and revealed 11 types among the 21 isolates from eight patients with an aspergilloma. Each aspergilloma could be due to either a single or multiple types.

Morphological studies on clinical isolates of Aspergillus fumigatus.

Morphological variation was examined in 19 strains of Aspergillus fumigatus Fres. isolated from the sputum of five patients with aspergilloma. For each patient a series of variant strains was obtained which exhibited gross differences in growth rate, colour and texture of the colony. On microscopical examination, some of the strains were found to produce markedly abnormal fruiting heads which were uncharacteristic for the species. Scanning electron microscopy revealed that the variant produced conidia of anomalous size, shape and surface-sculpturing. The significance of the isolation of morphological variants of A. fumigatus in sputum and their selection in vivo are discussed.

Inhibition of phagocyte migration and spreading by spore diffusates of Aspergillus fumigatus.

Previous studies have shown that spores of Aspergillus fumigatus inhibit phagocytosis and killing by macrophages and polymorphonuclear leucocytes. In order to identify the mechanisms of this interference with host defences, we have examined the effects of A. fumigatus spore diffusates on phagocytic cell function. For comparison, we have used spore diffusates of the non-pathogenic fungus Penicillium ochrochloron. The diffusates of A. fumigatus reduced the number of human polymorphonuclear leukocytes migrating towards a known chemoattractant by approximately 50% (p less than 0.001). In addition spore diffusates of A. fumigatus significantly decreased (p less than 0.001) the capacity of primed mouse peritoneal exudate cells to spread on glass. Spore diffusates of P. ochrochloron showed no comparable inhibitory effects. These studies have shown that spore diffusates of A. fumigatus inhibit the movement of the phagocytic cell membrane and are thus able to interfere with a primary function of phagocytic cells.

Resistance of spores of Aspergillus fumigatus to ingestion by phagocytic cells.

Phagocytic cells are believed to have an important role in the eradication of fungal spores from the lung. The ability of human and mouse cells to phagocytose the opportunistic fungus Aspergillus fumigatus has been examined, spores of the non-pathogenic fungus Penicillium ochrochloron being used for comparison. Most spores became associated with cells. Those of A fumigatus appeared to remain bound to the surface of the phagocyte rather than being ingested; in contrast, P ochrochloron spores appeared to be phagocytosed more readily, although they also were seen, in small numbers, o n the cell surface. In view of the subjective nature of these observations, the effects of spore diffusates on phagocytosis were examined. Diffusates from spores of A fumigatus were shown to inhibit phagocytosis of antibody coated radiolabelled sheep red blood cells by primed mouse phagocytic cells. Diffusates of spores of P ochrochloron had no such effect. These results suggest that when spores of A fumigatus become bound to the surface of phagocytes they are able to release a substance that inhibits their ingestion while having little or no effect on surface binding.

Suppression of host defences by Aspergillus fumigatus.

An important feature of the microbicidal action of phagocytic cells is their ability to produce reactive oxygen intermediates. In an attempt to identify the mechanisms by which the fungus Aspergillus fumigatus resists normal host defences the effect of spores and spore diffusates of A fumigatus on the production of superoxide anion and hydrogen peroxide by primed rodent phagocytic cells has been measured. For comparison we have used the non-pathogenic fungus Penicillium ochrochloron. Production of these reactive oxygen intermediates in response to A fumigatus was significantly lower than that in response to P ochrochloron. A similar reduction was achieved by diffusate prepared from freshly washed spores. The inhibitory component was of low molecular weight (less than 14,000) and its effect was dose dependent. These results suggest that spores of A fumigatus fail to trigger and also inhibit the production of reactive oxygen intermediates by phagocytic cells.

Pseudallescheriasis in northern Britain.

Five cases of Pseudallescheria boydii infection are reported from the northern part of the United Kingdom. None of the patients had travelled abroad. Three cases of otitis in which P. boydii was associated with bacterial infections were diagnosed within a 6-month period. A lady who had diabetes mellitus presented with a pulmonary fungus ball in a pre-existent cavity caused by a previous bacterial infection. After minor trauma at the site of an old skin graft, a farmer's wife developed an ulcer on the dorsum of the right ankle. Precipitating antibodies were demonstrated except in two of the cases of ear infection. The management of the individual cases is discussed.

Ketoconazole and fungal sinusitis.

A case of a young man with chronic sinusitis. After many years and multiple surgical procedures, fungal hyphae were noted. The patient made a complete recovery with oral ketoconazole.

Penicillium allergic alveolitis: faulty installation of central heating.

A married couple presented with an illness typical of allergic alveolitis. A careful search of their home revealed a leak in the central heating system with a heavy fungal growth on wet flooring and linoleum. Two species of Penicillium, P chrysogenum and P cyclopium, were isolated from floorboards, linoleum, and settle plates. Antibodies against both these fungi were demonstrated in the serum of both patients by an enzyme linked immunosorbent assay (ELISA). Allergic alveolitis caused by P chrysogenum and P cyclopium has not been described previously.