Difference between clinical assessment and diagnosis
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We compared the clinical and laboratory features of human immunodeficiency virus (HIV)- and non-HIV-infected patients with penicilliosis marneffei. HIV-infected patients had a higher incidence of fungemia. A total of 85.7% of the HIV-negative patients had underlying diseases including hematologic malignancies or had received therapy with corticosteroids or cytotoxic agents. By aPenicillium marneffei-specific mannoprotein Mp1p enzyme-linked immunosorbent assay, serum antigen titers were found to be higher in HIV-positive patients, whereas serum antibody levels were found to be higher in HIV-negative patients.
Penicilliosis marneffei is a unique dimorphic fungal infection endemic in Southeast Asia. It is one of the commonest opportunistic infections among AIDS patients in areas of endemicity and is considered an indicator disease for AIDS (8,14). The clinical manifestations of penicilliosis in AIDS patients have been well described, whereas reports that have described penicilliosis in non-AIDS patients are limited. A comparison of the clinical features of the disease between AIDS and non-AIDS patients has not been reported so far.
The diagnosis of penicilliosis is traditionally confirmed by isolation of the fungus from clinical specimens. The problem of the prolonged incubation which may be required for culture has been addressed previously (18). A number of antigen and antibody detection assays have therefore been described in recent years. We previously reported on an indirect immunofluorescent assay for antibody detection in patients with penicilliosis (20). Subsequently, a novel gene, MP1, was cloned. MP1was found to encode an immunogenic mannoprotein, Mp1p (2). This allowed us to use this gene product for antigen and antibody detection in patients with suspected penicilliosis. In this article, we report on the microbiological diagnosis of penicilliosis by conventional culture and the serodiagnosis of penicilliosis in human immunodeficiency virus (HIV)- and non-HIV-infected patients and on the clinical features of HIV- and non-HIV-infected patients with penicilliosis.
Patients with culture-documented penicilliosis in Queen Mary Hospital, Hong Kong, from 1994 to 1999 were reviewed. Only patients for whom adequate clinical information and specimens for analysis were available were included in the study. Mortality was attributable to penicilliosis if death occurred within 14 days of diagnosis or if there were persistent positive fungal cultures at the time of death. There must have been no other concurrent diseases that might have contributed to the mortality. Serial serum samples were collected whenever possible and were stored at −70°C until use. Blood cultures were performed with the BACTEC 9240 system (Becton Dickinson, Sparks, Md.). The specimens were incubated for 14 days before being reported as negative. Positive fungal cultures were confirmed by Gram staining of a smear of the blood culture broth, followed by subculture onto Sabouraud dextrose agar (SDA) without cycloheximide with incubation at 25 and 37°C in room air. Penicillium marneffei was identified by the following criteria: (i) demonstration of thermal dimorphism by showing a conversion from the yeast form at 37°C to the mold form at 25°C, (ii) production of a diffusible red pigment from the mold form when it was cultured at 25°C on SDA, and (iii) the microscopic morphology of the mycelia including the presence of conidiophore-bearing biverticillate penicilli, with each penicillus being composed of four to five metulae with smooth-walled conidia (16). Clinical specimens other than blood were examined microscopically both by Gram staining and, after digestion with 20% KOH, for the presence of fungal elements. The specimens were then cultured on SDA at 25 and 37°C.