Wednesday, 10 September 2014

100% accuracy for diagnosis of Invasive Aspergillosis

A recent report on the diagnosis of invasive aspergillosis concludes that the use of a combination of two quite new PCR-based tests gives investigators the ability to detect aspergillosis with 100% accuracy. That is a pretty optimistic claim given that the best PCR-based molecular tests to date have sensitivity rates of 79% (i.e. the proportion of patients identified by the test who are known to have invasive aspergillosis) and specificity of 94% (i.e. the proportion of patients who are known not to have invasive aspergillosis that are correctly identified by the test) in blood samples - see recent diagnostics review.

The authors of the paper state that they have used two nucleic acid amplification techniques - one amplifies single standed RNA (NASBA) thus presumably largely works by amplifying expressed genes or other sequences, the other amplifies DNA sequences (qPCR) thus presumably identifies whole or fragmented fungal cells. Each will use sequences that are specific to Aspergillus.

The paper claims that use of a combination of these two tests (which separately have sensitivities of 77% and 68% respectively, specificity of 80% and 89% respectively) gives perfect specificity of 100% , meaning all those identified as not having aspergillosis were correct diagnoses.

The combination of tests also gives 100% positive predictor value (PPV) which is a measure of its accuracy i.e. the number of known positives compared with the number of positives indicated by the tests. Given that this figure refers to the proportion of a population that are identified correctly it suggests that the expected number of positives were identified. However the authors do not highlight the figure for the sensitivity of the combined tests other than mention that it was 'the most sensitive' of the combinations tested.

These figures are striking and offer much encouragement for those in need of a reliable diagnostic test for invasive aspergillosis. In this study the sample population was quite small (80 patients) and analysis was done retrospectively, which is an approach with several weaknesses.

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