Diagnosis of fungal infections: current status

Diagnosing infections remains a problem in the management of fungal diseases, particularly in the immunocompromised host. Signs and symptoms are non-specific, colonization is difficult to distinguish from invasive disease, blood cultures are commonly negative and patients are often unable to undergo invasive diagnostic procedures. This situation has led to the strategy of initiating empirical therapy in the high-risk patient. A variety of tests has been applied to several body fluids. At the simplest level, the clinician must be familiar with the appearance of various fungi in tissue. Non-culture methods include antibody- and antigen-based assays, metabolite detection and molecular identification. The latter includes PCR identification of fungal DNA from body fluid samples using conserved or specific genome sequences. Detection of glucan in blood has been achieved using crab amoebocyte lysate. With aspergillosis, predictive clinical correlates have been defined, respiratory tract cultures are highly predictive of invasive disease in the appropriate setting and certain CT scan findings enable early diagnosis. Bronchoalveolar lavage is also very useful. Galactomannan antigen testing of blood is routine in some European centres, with EIA methodology supplanting agglutination because of apparently greater sensitivity. PCR has been made specific by genus-specific probes, with 100% sensitivity and reasonable specificity. In candidosis, the number of sites of colonization correlates with invasion. Tests for mannan antibodies and antigenaemia are currently of interest. Metabolite assays appeared promising but have not been pursued commercially. In cryptococcosis, pronase treatment of serum has reduced false positives and false negatives, and improved reproducibility of titres. Birdseed agar improves culture specificity. In coccidioidomycosis, serology is the exemplar for all mycology. Gene probes have accelerated diagnosis by culture. In histoplasmosis, the antigenuria test's high sensitivity and specificity has dispelled the chronic confusion in interpreting antibody test results.