July 30, 2020

Kimberly Hanson, MD, ARUP section chief of clinical microbiology and an associate professor at the University of Utah School of Medicine, led a study of serum (1-3)- β-D-glucan tests that was published in the Cochrane Database of Systematic Reviews.

The performance of commercially available serum (1-3)-β-D-glucan (BDG) laboratory tests used to diagnose invasive fungal infections (IFIs) varies greatly depending on the clinical setting and test usage, according to a study on which ARUP Laboratories and the University of Utah (U of U) collaborated. The study was published in the Cochrane Database of Systematic Reviews, a prestigious and high-impact journal known for high-quality scientific examination.

The research has important implications for future research and clinical practice. First, additional high-quality studies are needed to lend true understanding to how BDG testing performs in different clinical situations. “This research helps us identify how future studies should be performed and which sorts of information they should include to allow us to draw meaningful conclusions about how BDG testing performs,” said Kimberly Hanson, MD, section chief of clinical microbiology at ARUP and an associate professor at the U of U School of Medicine.

Second, it is unclear whether BDG testing leads to earlier diagnosis and better outcomes for patients compared with prophylaxis or empiric therapy. “Clinicians can’t rely on this test alone to diagnose IFIs,” Hanson said. “Additional factors such as diagnostic imaging and other laboratory testing must be utilized for accurate diagnosis.”

IFIs are life-threatening, opportunistic infections that most commonly occur in immunocompromised or critically ill people. Current strategies for the prevention and management of IFIs include antifungal prophylaxis, preemptive therapy, empiric treatment, and treatment of established infection.

Although prophylactic and preemptive therapy are effective, these methods often result in treatment of uninfected individuals with unnecessary and costly medication, said Hanson, adding that early diagnosis and treatment are essential to optimize medical management and minimize morbidity and mortality for at-risk patients. Serum BDG testing is a rapid detection method that is commonly used in a clinical setting.

For this publication, Hanson and her coauthors Bob Schmidt, MD, Sandra White, and Brandon Walker investigated and compared the diagnostic accuracy of commercially available tests for serum BDG to detect selected IFIs among immunocompromised and critically ill people. 

Schmidt, director of ARUP’s Center for Effective Medical Testing and an associate professor at the U of U School of Medicine, described the process of writing and publishing a Cochrane review as “by far the most rigorous review process I have ever experienced.” This commitment to the production of high-quality, relevant, and up-to-date research makes Cochrane reviews one of the most trusted sources for medical information, Schmidt said. “We first submitted a protocol that was extensively reviewed by a panel of experts to ensure a high research standard.”

Upon approval of their protocol, authors White and Walker independently screened more than 8,600 published articles to determine whether to include them in this review. Of these, they selected 49 studies assessing the accuracy of five different BDG assays (Fungitell, Glucatell, Wako, Fungitec-G, and Dynamiker Fungus). The two authors then performed independent data extraction and quality assessment of all 49 studies. After this was completed by each individual author, any discrepancies were resolved by discussion or moderation with a third author. Next, the extracted data was analyzed using several statistical methods. 

Through analysis of data from all 49 published studies, the authors found that the use of commercial BDG assays for the diagnosis of IFIs shows wide variation in diagnostic accuracy.  Sensitivity and specificity values ranged from 27%-100% and 0%-100% respectively. This heterogeneity has many possible sources, including variable study design, use on different patient populations (e.g., immunodeficient vs. critically ill), differences in sampling frequency and number, and the fact that the tests target different organisms (e.g., all IFIs vs. Candida).

Because of the wide variation in sensitivity and specificity, coupled with divergent study methods and inconsistent result reporting, the authors did not perform a formal meta-analysis of the data. As such, the authors were able to summarize the published diagnostic accuracy of several BDG tests, but were unable to make a meaningful comparison between them. They were further unable to determine factors that may affect diagnostic accuracy of these tests. 

“This research was a tremendous effort performed by ARUP’s Center for Effective Medical Testing,” Hanson said. “This team is a valuable resource for ARUP to advance our academic mission and have access to experts capable of performing this sort of in-depth, systematic review and meta-analysis. They are an amazing, unique resource for ARUP and the U of U.”

Kirsten Meek, PhD, Medical Writer and Editor