Saturday, 21 December 2013

More confirmation that rapid influenza diagnostic tests (RIDTs) should be used in context

The Texas Department of State Health Services have a useful couple of paragraphs from an Influenza Health Alert that puts into context reliance on the convenient and rapid, but ultimately intensive rapid influenza tests.


Rapid Lab Tests: Rapid Influenza Diagnostic Tests (RIDTs) can be useful to identify influenza virus infection, but false negative test results are common during influenza season. Clinicians should be aware that a negative RIDT result does NOT exclude a diagnosis of influenza in a patient with suspected influenza. When there is clinical suspicion of influenza and antiviral treatment is indicated, antiviral treatment should be started as soon as possible, even if the result of the RIDT is negative, without waiting for results of additional influenza testing.


Mike Coston also has an excellent article touching on some of the many other viruses that can cause influenza-like illness and on rapid testing, over on his blog, Avian Flu Diary. I highly recommend it.

Cost is always an important factor when hospitals and attached diagnostic laboratories consider how to address infections. Rapid turnaround time is another major cost because, for those small number of viruses with this option available, an antiviral drug can be administered and there seem to be benefits from doing this as early as possible for severe influenza. In some cases of course, a vaccine is available to block severe disease from occurring when you get infected (they don't stop infection, but a response to a vaccine is much safer than a bad response to an actual virus infection, as we've seen in the recent media for H1N1 in Texas. 

During flu season, influenza virus is an obvious cause for a spike in hospital admissions for acute respiratory symptoms - but if confirmation of that pathogen relies on a testing platform that can miss a third of infected individuals (only 17/45 PCR positives were detected by am RIDT in Ref#2) then antivirals may not be used in time. In a more recent comparison of RIDTs using PCR results as the standard, viral load in the upper airway (less virus gave fewer positives - duh), age (the young and elderly were less often positive), presentation time (sampling >2-days after onset of illness reduced the proportion of positivity), virus type (less sensitive for subtype B infections than A) and whether there was pneumonia or not (the former were less often positive perhaps reflecting less viral replication in the upper airway than in the lower airway?) were factors in how well the antibody-based RIDTs performed. Sensitivity ranged from 50% to 94%. These 2 studies used samples from the upper airways (swabs or nasopharyngeal aspirates respectively, as suggested by the BD™ Directigen EX Flu A+B assay, Alere™ Influenza A & B Test and the QuickVue® 117 Influenza A+B test)

In these instances, PCR-based methods (used as the "gold standard" in those published evaluations) shine but they take longer to generate a result and require more expertise to conduct than a rapid test. The slightly longer time is not just because they take hours to conduct instead of the minutes of a rapid test (remembering that viral lab diagnoses used to take days not hours) but because lab testing is only part of a process which also involves paperwork and passing verified and signed off results and information to all concerned clicnial parties and patients. That can take more time-and sometimes be a bottleneck for result release. Its hard for a patient's family and friends to wait, but the results will be that much more reliable when they come.

A feature of influenza season is the concurrently reduced levels of activity of other viruses. Influenza tends to "push out" a lot of other viruses during it's peak season - probably reflecting influenza's ability to dominate the immune response in an infected individual, and by extrapolation, reduces the number of susceptible individuals at the community level, remembering that the majority of influenza cases are acute upper respiratory tract illnesses.

So it looks more like the Montgomery County deaths may have been due to the high levels of influenza A(H1N1)pdm09 virus generally circulating in them there parts. A KHOU news outlet report, also circulated on ProMED, suggest that 4 Montgomery county deaths were due to H1N1, as well as other sine the regions. However, the Montgomery County Public Health District reports only 2 H1N1-confirmed deaths, so things are still a little confusing there. And as for whet other viruses may also be in these patients...so far, who knows?


A brief guide to some terms used in these sorts of discussions (also from Ref #2 below)

Sensitivity
No. of true positives / no of true positives and false negatives

Specificity
No. of true negatives / no of true negatives and false positives

Positive predictive value
No. of true positives / no of true positives plus no. of false positives

Negative predictive value
No. of true negatives/ no of true negatives


References and further reading...
  1. FluTrackers story. http://www.flutrackers.com/forum/showthread.php?p=517368#post517368
  2. Accuracy of rapid influenza diagnostic test and immunofluorescence assay compared to real time RT-PCR in children with influenza A(H1N1)pdm09 infection. http://www.ncbi.nlm.nih.gov/pubmed/23175329
  3. Clinical and Virologic Factors Associated with Reduced Sensitivity of Rapid Influenza Diagnostic Tests in Hospitalized Elderly and Young Children. http://www.ncbi.nlm.nih.gov/pubmed/24285739