Early Diagnosis of Candidiasis in Premature Infants

Candida species are a leading cause of infectious mortality in newborns with the incidence
rates estimated at 4-18% in extremely low birth weight (ELBW) infants. 20-30% of these
infants are likely to die. Because candida can invade virtually all body tissues (eyes,
brain, heart, lung, liver, spleen, urinary tract, and joints), survivors of invasive Candida
infections are at risk of blindness, developmental delays, and the need for surgical and
other corrective procedures.

Time is of the essence in detecting and treating these infections, with infant mortality from
candidiasis largely attributed to duration of time for cultures to become positive for
Candida. Diagnosis of candidiasis is challenging - blood and urine tests are slow (taking up
to 72 hours to complete) and inaccurate in many cases, showing negative results despite
overwhelming disease in adults as well as children. These problems are likely made worse in
neonates, with smaller amounts of blood available for testing and infections that often
spread to tissues inaccessible for testing.

This observational study is evaluating the performance of new lab tests (beta-glucan assays,
Gas Chromatography Mass Spectrometry for D-arabinitol, and polymerase chain reaction tests)
compared to existing culture tests in detecting candida species fungal infections in
extremely low birth weight (ELBW) infants quickly and accurately.

In this study, 19 NICHD Neonatal Research Network sites enrolled 1,500 infants with birth
weights ≤1,000g by 72 hours of life; more than 100 of these infants later tested positive for
candidiasis. In the larger cohort, whenever cultures of blood or urine were obtained, or a
lumbar puncture was done, additional samples and clinical data were collected. These
additional samples are being tested using the new techniques under investigation. No
additional blood specimens were taken once participants had a positive blood culture for
candida. Note: Test procedure reagents are being provided the Duke University laboratory by
Cape Cod Incorporated and Rockeby; the Thrasher Research Fund is also providing support to
the Duke University laboratory.

Surviving study subjects completed a neurodevelopmental evaluation at 18-22 months corrected
age to evaluate potential early risk factors with long-term outcome.

Inclusion Criteria:

- Infants born ≤1,000g birth weight

- Infants >72 hours old and less than 120 days old

Exclusion Criteria:

- Prior positive blood culture for Candida

- Evidence of congenital candidiasis

- Parents/legal guardians refuse consent