Because of (1) variable and nonspecific clinical and radiologic findings, (2) the time lag and insensitivity of cultures, and (3) the dangers of invasive procedures, a concerted effort has been made to develop serologic tests that can be useful in the diagnosis of disseminated fungal infection. Promising methods, most still under investigation, include detection of markers for Candida in blood, including the enolase and mannan antigens,50 and metabolites ß-D glucan50 and D-arabinitol.51 None of these tests is currently sensitive and specific enough to establish a diagnosis of candidiasis. However, utilizing a combination of tests, as well as repeated sampling, may improve their reliability.50,51
Polymerase chain-reaction (PCR) detection of Candida DNA has been evaluated as a tool for diagnosing candidemia.52 In some studies, PCR testing has been shown to be highly sensitive for detecting the presence of disseminated candidiasis; in others, sensitivity has been low. In some studies, false-positive results remained a problem.52
Tests for determining the presence of circulating Aspergillus cell-wall antigens have been primarily directed at detecting galactomannan in blood, urine, BAL fluid, and CSF.53 Sensitivity is a major problem with all tests developed to date, and repeated tests are necessary, even when the more sensitive test methodologies are used.39 However, if a fungal antigen test is positive, it is a relatively good indicator of infection. It is not known how early in the course of infection galactomannan assays will become positive. In one study, positive findings on CT preceded detection of galactomannan by 7 days, time lags that could be critical in neutropenic HSCT patients.39 Other recent prospective studies suggest high positive and negative prediction values in neutropenic and HSCT patients, with positivity preceding development of clinical signs by one week or more.54 As galactomannan may be affected by the immune state of the host or by administration of prophylactic or preemptive antifungals, it may be that results of previous studies are variable because of the different antifungal agents used in populations studied.
PCR tests for Aspergillus are also in development. In one small study of 13 patients, PCR detected Aspergillus DNA in 8 patients a median of 4 days prior to radiologic diagnosis. In the remaining 5, PCR and radiologic studies pointed to the presence of aspergillosis at the same time.55 However, these exquisitely sensitive assays are associated with a significant incidence of false-positive tests. In fact, the incidence of false-positive results was almost as high as 25% with PCR assays of BAL fluid.56
Course Number: V035D
This CME Expires on July 1, 2005; no tests will be accepted after this date.
This course is accredited by
The University of Pittsburgh School of Medicine, Center for Continuing Education
and The International Immunocompromised Host Society