Aspergillus fumigatus and Aspergillus flaws are the most common cause of invasive mould infections worldwide and carry a high mortality. Corticosteroid therapy and Cushing's disease are associated with an increase in invasive aspergillosis. Corticosteroids impair immune function in mammals and, specifically, the conidicidal activity of human macrophages, which was thought to be sufficient explanation for this increased risk. However, w e have found a 3 0 4 0 % increase in growth rate of A. fumigatus and A. flaws exposed to pharmacological doses of hydrocortisone (a human glucocorticoid), suggesting an alternative or additional mechanism for the association. No significant effect was observed with other human steroids such as testosterone, oestradiol or progesterone, though a smaller (21 %) but significant growth rate increase was obtained with the fungal sterol ergosterol. The presence of a ligandheceptor system is therefore possible in pathogenic Aspergillus spp. Although corticosterone-binding proteins have been identified in some yeast species, a demonstrable physiological effect has been lacking. Interruption of the putative ligand/receptor interaction could have a major effect on the growth and pathogenicity of A. fumigatus, providing opportunities for the development of alternative therapeutic strategies to those currently available.

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The efficacy and safety of recombinant human interferon gamma (rIFN-gamma) in the reduction of opportunistic disease in patients with advanced HIV-1 infection are assessed. A 12-month double-blind, placebo-controlled, multicenter, Phase III trial of rIFN-gamma in HIV-positive patients with CD4 < 100 x 10(9)/liter on stable antiretroviral therapy. Eighty-four patients were allocated treatment on a 1:1 basis to rIFN-gamma or placebo. Patients received rIFN-gamma 0.05 mg/m(2) or 0.9% saline subcutaneously three times weekly for 48 weeks (optional extension to 18 months). The primary end point was the incidence of opportunist infections (CDC categories B/C). Secondary end points included mortality, immunological, and virological parameters. Patients on placebo had a mean of 3.45 opportunist infections (OIs) in the first 48 weeks. Patients treated with rIFN-gamma had a mean of 1.71 OIs (p = 0.04). However, the model showed overdispersion and the inclusion of a dispersion factor raised the p value to 0.13. rIFN-gamma appeared to have a particular effect on the incidence of Candida, herpes simplex, and cytomegalovirus infections. Three-year survival in the rIFN-gamma arm was 28% compared to 18% in the placebo group (not significant). rIFN-gamma-associated side-effects of headache, fatigue, rigors, influenza-like symptoms, depression, myalgia, and granulocytopenia were reversible. There was no evidence for HIV activation. Although not significant, the trend towards decreased opportunistic infections and increased survival warrants consideration of further trials of rIFN-gamma. The study gives additional information on the safety profile of this cytokine.

Seventeen cases of infections due to Cunninghamella species have been reported worldwide in humans, and there have been only three survivors. We report a case of paranasal sinusitis due to Cunninghamella bertholletiae in an elderly patient who had diabetes mellitus and myelodysplasia. After receiving 7 weeks of therapy with deoxycholate amphotericin B (44 mg/kg or a total of 3 g) and rifampin, the patient was cured and did not have to undergo radical surgery.