Abbott Pathogen Detection Platform Compares Well to PCR-based Gold Standards for Influenza A/B

A pan-pathogen molecular testing platform from Abbott has shown comparable sensitivity in detecting influenza A and B virus as two RT-PCR-based tests, according to a prospective analysis published online last week in the Journal of Virological Methods.

Researchers at Johns Hopkins School of Medicine examined 286 nasopharyngeal swabs collected from people who presented to an urban emergency room with flu-like symptoms during the 2012-2013 flu season.

The study compared the Respiratory Virus Surveillance (RVS) kit 2.5 on Abbott's reverse transcription PCR electro-spray ionization mass spectrometry, or RT-PCR/ESI-MS platform to two US Food and Drug Administration-cleared real-time PCR-based assays, Cepheid's Xpert Flu and Hologic's Prodesse ProFlu+.

The group had previously validated the Cepheid Xpert Flu platform using this data set, concluding that a fast test which does not require batch processing could be a boon to clinicians wishing to follow US Centers for Disease Control and Prevention antiviral prescribing guidelines.

While the Cepheid test has the advantage of being faster than traditional PCR, the Abbott RT-PCR/ESI-MS can provide genotype information and detect other pathogens.

"I like to think of it as a very nice intermediary platform between multiple type-specific assays where you have some a priori knowledge of the agent that you're looking for versus doing sequencing," Justin Hardick, first author on the study and research projects lab manager in Johns Hopkins' Division of Infectious Diseases, told GenomeWeb in an interview.

Hardick said the group previously compared the RT-PCR/ESI-MS technology to other gold standards, such as viral culture, and it usually performs favorably.

In the current study, the researchers calculated the sensitivity and specificity of the RVS kit relative to ProFlu+ alone as the gold standard, and to a combined Xpert Flu and ProFlu+ as the gold standard.

Using a combined gold standard is fairly common practice in these kinds of evaluations, Hardick said. "It helps whenever the two diagnostic tests that you're using as gold-standard methods don't agree. You would use a combined gold standard to focus only on the samples where both of those tests were in agreement," he said.

Using the combined gold standard led to a slight increase in sensitivity in influenza A detection — from 82 to 85 percent — while sensitivity for influenza B, and specificity of the assay for both viruses, remained maxed out between 99 and 100 percent.

One caveat Hardick noted was the small number of positives in the prospective sample set — 27 influenza A cases and 14 influenza B cases tested positive with both gold standard methods — although this was "in line with what you would expect to see in terms of the incidence of influenza in this part of the country for that particular season," he said.

Overall, the researchers concluded that the RVS kit on the Abbott platform "compared favorably" to the gold standards.

Importantly, the RT-PCR/ESI-MS method also provided basic genotype information about the viruses, revealing that all of the influenza A samples were H3N2, and 88 percent of the influenza B was Yamagata strain. The RVS kit was also able to identify additional respiratory viruses in 24 patients.

The RT-PCR/ESI-MS technology was developed by Ibis Biosciences, which was acquired by Abbott in 2009. Previously, an RT-PCR/ESI-MS system was marketed by the firm as Plex-ID, but the next generation of the Abbott platform, Iridica, recently launched and received CE marking late last year.

RT-PCR/ESI-MS amplifies targets that map to shared sequences of a huge range of pathogens. The system then uses mass spectroscopy to identify which pathogens are present. As such, it theoretically acts more like a general survey of which viruses, bacteria, or fungi might be present in a sample. Ibis Biosciences continues to maintain and expand the pathogen database, and Iridica is currently able to detect and differentiate 600 bacterial families, as well as 200 families of fungi and 13 families of virus, as previously reported by GenomeWeb.

The assay used in the JVM study, however, was a more targeted survey from Abbott. The RVS 2.5 kit is designed to detect Influenza A and B viruses, respiratory syncytial virus, coronaviruses, adenoviruses, metapneumovirus, and parainfluenza virus.

Many major diagnostics firms have entered the molecular influenza testing arena, as previously reported by GenomeWeb. Some of these assays boast advantages in time to result, or level of expertise required to perform the test. However, test choice may depend on research goals and project focus, Hardick said, noting that the RT-PCR/ESI-MS test is research use only and is not used in the clinic.

Abbott has not disclosed any plans to pursue US regulatory clearance for the platform, although it has released preliminary data from its Rapid Diagnosis of Infections in the Critically Ill, or RADICAL, study, which suggested the platform could reduce healthcare costs and length of hospital stays.