Tests to diagnose invasive aspergillosis with 100 percent accuracy

The fungal infection invasive aspergillosis (IA) can be life threatening, especially in patients whose immune systems are weakened by chemotherapy or immunosuppressive drugs. Despite the critical need for early detection, IA remains difficult to diagnose. A study compared three diagnostic tests and found that the combination of nucleic acid sequence-based amplification (NASBA) and real-time quantitative PCR (qPCR) detects aspergillosis with 100% accuracy.

IA is caused by the fungus Aspergillus fumigatus, which is considered by many pathologists to be the world’s most harmful mold. ‘Traditional diagnostic methods, such as culture and histopathology of infected tissues, often fail to detect Aspergillus,’ comments lead investigator Yun Xia, PhD, of the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

In this retrospective study, scientists evaluated the diagnostic performance of two nucleic acid amplification assays (qPCR and NASBA) and one antigen detection method (galactomannan enzyme-linked immunosorbent assay [GM-ELISA]) using blood samples collected from 80 patients at high risk of IA. Of the 80 patients, 42.5% had proven or probable IA. The patients came from intensive care, haematology, neurology, nephrology, geriatrics, and other hospital departments.

The tests were evaluated singly and in combination. Individually, NASBA had the highest sensitivity (76.47%) whereas qPCR offered the highest specificity (89.13%). NASBA also was the test that best indicated that a patient did not have the infection (negative predictive value). NASBA and qPCR each had a high Youden index, a measure of the effectiveness of a diagnostic marker.

Combining the tests improved the outcomes. The combination of NASBA and qPCR led to 100% specificity and 100% positive predictive value (the probability that subjects truly have the infection).

‘Because each test has advantages and disadvantages, a combination of different tests may be able to provide better diagnostic value than is provided by a single test,’ says Dr. Xia. The combination of NASBA and qPCR should be useful in excluding IA in suspect cases, thus reducing both suffering and expense for immunocompromised patients. On the other hand, the combination of NASBA and qPCR could be more suitable for screening patients suspected of infection, because this assay had the highest sensitivity.’

The authors note that NASBA offers the advantages of rapid amplification (90 minutes) and simple operation with low instrument cost compared with qPCR and GM-ELISA. They caution that although GM-ELISA is widely and routinely used for aspergillosis diagnosis, this study indicates that it had low sensitivity (52.94%) with reasonable specificity (80.43%), making it ‘inferior to both NASBA and qPCR.’  EurekAlert