D-ARABINITOL AS A DIAGNOSTIC MARKER FOR CANDIDIASIS

D-arabinitol is a major metabolite of the medically important
Candida species, and animals and humans with invasive candidiasis
have higher serum and urinary arabinitol/creatinine ratios than
uninfected controls. This is a proposal to study D-arabinitol
further as a diagnostic marker for candidiasis. Two methods will
be developed to measure D-arabinitol stereoselectively in body
fluids and tissue homogenates. One approach will be to measure
D,L-arabinitol by gas chromatography (GC) in portions of each
specimen that are treated with and without the Klebsiella
pneumoniae NAD: oxidoreductase D-arabinitol dehydrogenase
(ADH); insofar as ADH degrades D-arabinitol completely and
stereoselectively, the difference can be considered the D-
enantiomer. A second approach will be to resolve D- from L-
arabinitol by multidimensional GC with a conventional and chiral
capillary column in series; the enantiomers will then be quantified
individually. These stereoselective analytical methods will then
be used to study the effects on D-arabinitol appearance of the
diet, microbial colonization of the gastrointestinal tract, host
metabolism, corticosteroids and sarcoidosis in animals and/or
humans without invasive candidiasis. The diagnostic sensitivity
and specificity of elevated D-arabinitol/creatinine ratios will be
studied prospectively in high risk patients and using stored
specimens previously collected from infected animals and humans.
D-arabinitol measurements will also be compared to tests for
anti-Candida antibodies and for Candida antigens. Lastly,
whether the effects of antifungal therapy can be assessed
quantitatively be serial D-arabinitol measurements will be studied
in rats with experimental candidiasis.