Comparison of phenotypic and genotypic diagnosis of acute infections

I recently wrote about choosing the right methodology for the right disease based on the scientific article by Virginie Prendki et al. 2019.

Now a scientific article addressing this matter using our mariPOC platform and the world’s first rapid test for bocavirus has been published in a high ranking journal, Journal of Clinical Virology.

The paper concludes that bocavirus antigen detection has higher clinical specificity and positive predictive value (PPV) than bocavirus DNA qualitative PCRs and, as expected, somewhat lower sensitivity than bocavirus mRNA PCR detection. It is acknowledged that bocavirus antigen detection is beneficial and attractive in its rapidity and availability as a point-of-care test while mRNA PCR is suitable in lab environment.

The diagnosis of bocavirus infections has traditionally trusted on qualitative PCRs detecting viral DNA. The clinical value of this approach is low due to persistence of bocavirus DNA in the airways, leading to low clinical PPV. Measuring bocavirus mRNA is an ingenious approach to improve the clinical specificity of genotypic detection of bocavirus compared to DNA detection.

According to local guidelines in Turku, Finland, all children hospitalized with acute RTI are tested with the mariPOC antigen test. For the study, the PCR tests were performed retrospectively in the lab. Using the mRNA PCR as a reference, the qualitative DNA PCR specificity and PPV were as low as 87.2%, and 17.7%, respectively. Only about a fifth of the children with bocavirus DNA in the nasopharynx had an acute bocavirus infection. mariPOC bocavirus test had specificity and PPV of 100%. None of the low DNA-load samples harbored mRNA or antigen. An interesting piece of data, not included in the publication, was that about 50% of samples which were positive for bocavirus DNA but negative for mRNA and antigen, were positive for some other virus antigen tested by the multianalyte mariPOC test (mostly RSV and influenza A virus). This further supports the high clinical PPV of mariPOC testing and low value for qualitative PCR. The specificity is important in being able to trust the aetiology suggested by the lab test, for example in increasing the safety of not prescribing antibiotics.

In conclusion, the sensitivity of phenotypic testing is most often sufficient for testing of acute respiratory infections, while using “regular” PCR for “everything” leads to poor clinical accuracy with some pathogens. Another such well known example is adenovirus.