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Please check out our Clinical Diagnostics section, PCR Diagnostic Test Kit section, and Fungal Diagnostic Kits section to find manufacturers that sell these products
Among the human pathogenic fungi are both yeasts and molds. The most common human pathogenic fungi are the yeast-like Candida species (spp.), and the most common invasive molds are the Aspergillus spp. Pathogenic fungi can be found in virtually every environment, and hospitals are no exception. Perhaps they are best known as causes of vaginitis (Candida spp., primarily C. albicans) and pulmonary hypersensitivity (Aspergillus spp.). Healthy hosts suffer from these localized conditions, but because of intact physical barriers and active immune surveillance, do not develop disseminated infections. For susceptible patients, however, disseminated candidiasis and aspergillosis are common concerns. These multisystem infections remain difficult to diagnose and frequently end in death, with mortality rates up to 50% for disseminated candidiasis. As opportunistic pathogens, these fungi show an affinity for the critically ill, occurring in the settings of immunosuppression, including chemotherapy, transplantation, and HIV/AIDS; hyperalimentation, burns, and ulcers. With advances in critical care, oncology, and transplant medicine, more and more patients enter the ranks of those susceptible to disseminated disease.
Early Diagnosis of Disseminated Candidiasis and Disseminated Aspergillosis is Essential
With the introduction of medications such as voriconazole, posaconazole, liposomal amphotericin, and the echinocandins, treatment can be effective if initiated early. Therefore, there is renewed emphasis on the need for early diagnosis of disseminated candidiasis and aspergillosis. Unless a specific nidus of infection is suspected (for example, a pulmonary Aspergillus lesion), a mainstay of diagnosis is blood culture, which, even with the introduction of automated blood culture methods, has suboptimal speed and sensitivity. Aspergillosis, which is usually acquired by the airborne route, can be identified microscopically from bronchoscopy samples, but sensitivity is still only 45% to 60%. Traditionally, clinicians have been forced to start empiric antifungal therapy in response to any unexplained fever or shock in susceptible patients. It is not uncommon for a disseminated Aspergillus infection to be discovered only at autopsy. Three assays that may offer solutions to these problems have been approved for use in the diagnosis of disseminated fungal infections.
- The FDA-cleared and CE-marked Fungitell® Assay, manufactured by Associates of Cape Cod Incorporated (East Falmouth, MA), is a reliable assay that detects (1→3)-ß-D-glucan in serum in as little as one hour. (1→3)-ß-D-glucan is a component of the fungal cell wall, and is found in a number of medically important fungi such as Candida spp., Aspergillus spp., Fusarium spp., Coccidioides immitis, Histoplasma capsulatum, Acremonium, and Saccharomyces cerevisiae. The assay is based on a modification of the Limulus (horseshoe crab) amebocyte lysate (LAL) coagulation cascade, which glucan readily activates. The Fungitell reagent is prepared from lysed amebocytes (crab blood cells), which are treated to remove the factor C (lipopolysaccharide-dependent) pathway and restrict the assay to the factor G (glucan-dependent) pathway, which results in high specificity for (1→3)-ß-D-glucan. The pathway activates a clotting enzyme that cleaves p-nitroaniline from a chromogenic peptide substrate. This in turn allows photometric readout at a wavelength of 405 nm. The entire assay is carried out in a microwell plate, and there are no wash steps. All the added reagents remain in the well. A positive test is a (1→3)-ß-D-glucan level ≥80 pg/mL.
- Bio-Rad Laboratories, Inc. (Hercules, CA) offers the Platelia™Aspergillus Ag Kit. It is an FDA-cleared enzyme immunoassay for the detection of the Aspergillus galactomannan antigen in serum and bronchoalveolar lavage fluid. It uses the rat monoclonal antibody EBA-2 to detect circulating galactomannan antigen in serum samples. The galactomannan antigen is released in the circulation of immunosuppressed patients during active invasive aspergillosis. The results are expressed in index values. The assay is in a 96-well microplate with breakable strips, and results are available in 3 hr.
- Myconostica (Cambridge, U.K.) offers the MycAssay™ Aspergillus, a CE-marked Real-Time PCR assay for the detection of Aspergillus DNA in the lower respiratory tract and from serum samples. When MycAssay Aspergillus is used in conjunction with the company’s fungal DNA extraction system, MycXtra®, results are available within 3 hr of receipt of the sample. The assay is validated for use on the SmartCycler®, AB7500 (1.4), LightCycler® 2.0, and Stratagene Mx3000 series from Cepheid (Sunnyvale, CA). The limit of detection of this assay is <50 target copies. The assay features an internal amplification control for every reaction to highlight false-negative results, and uses closed-tube reactions and single-use reagents to lower the risk of contamination. The company reports that compared with culture, the assay has sensitivity, specificity, positive, and negative predictive values of 94%, 77%, 91%, and 83%, respectively. Compared with clinical diagnoses, the assay has sensitivity, specificity, positive, and negative predictive values of 94%, 91%, 97%, and 83%, respectively.
Please check out our Clinical Diagnostics section, PCR Diagnostic Test Kit section, and Fungal Diagnostic Kits section to find manufacturers that sell these products