With flu season soon to be upon us, the CDC has released extensive updated guidance for clinicians on when to use, and how to interpret the results of, RIDTs (Rapid Influenza Diagnostic Tests) – and just as importantly - when additional laboratory testing might be warranted.
The full guidance documents are available at:
- UPDATE: Rapid Diagnostic Testing for Influenza: Information for Health Care Professionals Friday, October 02, 2015
- UPDATE: Guidance for Clinicians on the Use of Rapid Influenza Diagnostic Tests Friday, October 02, 2015
- UPDATE: Rapid Diagnostic Testing for Influenza: Information for Clinical Laboratory Directors Friday, October 02, 2015
- UPDATE: Influenza Signs and Symptoms and the Role of Laboratory Diagnostics Friday, October 02, 2015
The above guidance documents are lengthy, technical, and of greatest interest to medical professionals, but an overview can give us a pretty good idea of their importance.
RIDTs are popular in-office test kits that are designed to detect Influenza A and Influenza B infections in 15 minutes or so. They are quick, convenient and reasonably inexpensive - but their accuracy has come under scrutiny in the past (see MMWR: Evaluating RIDTs).
In this 2012 study, 11 commercially available Rapid Influenza Diagnostic Tests that were were tested against 23 flu viruses (16 A & 6 B strains) that have circulated in the United States since 2006. Each virus was tested at five different dilution strengths, in order to gauge relative sensitivity of these tests.
All but one managed to correctly return a positive result at the highest tested viral concentration, but at lower titers the results were highly variable.
The two main measures of the accuracy of a diagnostic test are sensitivity and specificity.
- Sensitivity is defined as the ability of a test to correctly identify individuals who have a given disease or condition.
- Specificity is defined as the ability of a test to exclude someone from having a disease or illness.
The CDC has this to say about the accuracy of these tests:
Proper interpretation of test results is very important for accurate clinical management of patients with suspected influenza. The reliability of rapid diagnostic tests depends largely on the conditions under which they are used. Understanding some basic considerations can minimize being misled by false-positive or false-negative results.
- Sensitivities of rapid influenza diagnostic tests are approximately 50-70%, and specificities of rapid diagnostic tests for influenza are approximately 90-95%, when compared with viral culture or reverse transcription polymerase chain reaction (RT-PCR)
- False-positive (and true-negative) results are more likely to occur when disease prevalence in the community is low, which is generally at the beginning and end of the influenza season.
- False-negative (and true-positive) results are more likely to occur when disease prevalence is high in the community, which is typically at the height of the influenza season.
In simple terms, if you’ve got classic flu symptoms, but your RIDT comes back negative – and it’s the height of the flu season – there’s still a pretty good chance you have the flu. Note: some of these false negatives may be due to the stage of infection which influences viral load or sample collection methods.
At this point, you may be wondering how doctors are supposed to interpret results from a test that may, or may not, correctly show when a patient has the flu.
It gets pretty complicated, but the CDC provides guidance on not only how to interpret the results, but also under what circumstances they recommend using these diagnostic kits at:
You’ll find several decision tree charts on this page, including the following one which advises whether Rapid Influenza Testing is appropriate during periods when influenza viruses are circulating in the community.
Given only a 50%-70% sensitivity with seasonal A & B flu strains, you might be wondering how well these test kits perform when encountering a non-seasonal (aka novel, swine, or avian) strain or subtype of the flu.
The results – at least on the swine variant viruses – have been mixed.
In the Influenza and Other Respiratory Viruses journal a 2102 paper called Analytical detection of influenza A(H3N2)v and other A variant viruses from the USA by rapid influenza diagnostic tests found:
All RIDTs evaluated in this study detected the seasonal influenza A(H3N2) virus, although detection limits varied among assays. All but one examined RIDT identified the influenza A(H1N1)pdm09 virus. However, only four of seven RIDTs detected all influenza A(H3N2)v, A(H1N2)v, and A(H1N1)v viruses. Reduced sensitivity of RIDTs to variant influenza viruses may be due to amino acid differences between the NP proteins of seasonal viruses and the NP proteins from viruses circulating in pigs.
This year we’ve seen 5 swine variant human infections identified, although given the sparse surveillance and testing, it is very likely this under represents the true number of cases in the United States.
This winter we’ve potentially a new wrinkle, in that HPAI H5 is expected to return via migratory birds, perhaps in greater volume than we saw last year.
While human infection has not been reported with the strains circulating in North America, that could conceivably change over time (or other subtypes could be imported, such as we’ve seen over the past two years with H7N9 and H5N1 in Canada).
The CDC advises clinicians to consider additional laboratory testing (viral culture or RT-PCR) when:
- A patient tests negative by RIDT when community influenza activity is high and laboratory confirmation of influenza is desired.
- A patient tests positive by RIDT and the community prevalence of influenza is low, and a false positive result is a consideration.
- A patient has had recent close exposure to pigs or poultry or other animals and novel influenza A virus infection is possible (e.g., influenza A viruses circulate widely among swine and birds, including poultry, and also can infect other animals such as horses and dogs)
Obviously, better rapid tests are needed. Not just for common seasonal strains, but ideally for all flu strains.
But until they become available, doctors must carefully weigh RIDT results along with the patient’s clinical signs and symptoms - and level of flu in the community - in order to come up with the best diagnosis.