MMWR: Evaluating RIDTs

 

 

# 6688

 

RIDTs, or Rapid Influenza Detection Tests, 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 n the past (see No Doesn’t Always Mean No).

 

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, on their Rapid Diagnostic Testing for Influenza webpage, cautions:

 

     Reliability and Interpretation of Rapid Test Results

• 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 diagnostic tests are approximately 50-70% when compared with viral culture or reverse transcription polymerase chain reaction (RT-PCR), and specificities of rapid diagnostic tests for influenza are approximately 90-95%.
  • 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 seasons.
  • 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.

 

Which means that while a positive result carries a pretty high confidence level, a negative result is considered less reliable.

 

Today’s MMWR carries an evaluation of 11 commercial  Rapid Influenza Diagnostic Tests that were available during the 2011-2012 season. They 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.

 

It’s a lengthy report, and you’ll probably want to follow the link to read more about the methods, and results. A few excerpts follow, after which I’ll have a little more.

 

 

Evaluation of 11 Commercially Available Rapid Influenza Diagnostic Tests — United States, 2011–2012

Weekly

November 2, 2012 / 61(43);873-876

Accurate diagnosis of influenza is critical for clinical management, infection control, and public health actions to minimize the burden of disease. Commercially available rapid influenza diagnostic tests (RIDTs) that detect the influenza virus nucleoprotein (NP) antigen are widely used in clinical practice for diagnosing influenza because they are simple to use and provide results within 15 minutes; however, there has not been a recent comprehensive analytical evaluation of available RIDTs using a standard method with a panel of representative seasonal influenza viruses.

 

This report describes an evaluation of 11 Food and Drug Administration (FDA)–cleared RIDTs using 23 recently circulating influenza viruses under identical conditions in a laboratory setting to assess analytical performance.

 

Most RIDTs detected viral antigens in samples with the highest influenza virus concentrations, but detection varied by virus type and subtype at lower concentrations.

 

Clinicians should be aware of the variability of RIDTs when interpreting negative results and should collect test samples using methods that can maximize the concentration of virus antigen in the sample, such as collecting adequate specimens using appropriate methods in the first 24–72 hours after illness onset. The study design described in this report can be used to evaluate the performance of RIDTs available in the United States now and in the future.

(Continue . . . )

 

 

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:

 

Guidance for Clinicians on the Use of Rapid Influenza Diagnostic Tests

 

You’ll find several decision tree charts on this page, including the following two which are used to interpret RIDT results during periods when influenza viruses are circulating in the community.

 

In part 1, the RIDT returns a positive result.

In Part 2, the RIDT returns a Negative result.

 

 

While these test kits can provide help with diagnostic and treatment decisions for individual patients in clinical settings, they are probably more valuable when used to identify influenza outbreaks in institutions, like hospitals, schools, or nursing homes.

 

Even if each individual result can’t be fully trusted, a few positive results out of a confined population displaying influenza-like symptoms can help guide decisions regarding prevention and control.

Of course, better rapid tests are obviously 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.

A Side By Side Comparison Of Rapid Influenza Tests

 

 

# 4686

 

 

Of primary interest to clinicians, I suppose, but we’ve a new study showing the wide divergence of sensitivity of RIDTs (Rapid Influenza Detection Tests) sometimes called IRDTs to various strains of influenza A and B – including avian strains.

 

These tests are generally used in doctor’s offices, clinics, and ERs to quickly (less than 30 minutes) test for the influenza virus.  

 

Their accuracy has come under increasing fire over the past couple of years, however.

A few blogs on the subject include:

 

A Tale of Two Headlines

PLoS Currents: Improving Diagnostic Efficiency Of H1N1

No Doesn’t Always Mean No

 

According to the CDC:

The rapid tests vary in terms of sensitivity and specificity when compared with viral culture or RT-PCR. Product insert information and research publications indicate that:

• Sensitivities are approximately 50-70%
• Specificities are approximately 90-95%

 

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 various RIDTs are designed to show if someone tests positive for the Influenza A or B virus, but not the strain of flu.

 

Today from the Journal of Microbiology, we look at a side-by-side comparison of 20 different IRDTs available in Japan.  

 

Sensitivity of influenza rapid diagnostic tests to H5N1 and 2009 pandemic H1N1 viruses

Yuko Sakai-Tagawa, Makoto Ozawa, Daisuke Tamura, Quynh Mai Le, Chairul A. Nidom, Norio Sugaya, and Yoshihiro Kawaoka

J. Clin. Microbiol. published ahead of print on 16 June 2010, doi:10.1128/JCM.00439-10

 

Abstract

Simple and rapid diagnosis of influenza is useful to treatment decision-making in the clinical setting. Although many influenza rapid diagnostic tests (IRDTs) are available for the detection of seasonal influenza virus infections, their sensitivity for other viruses, such as H5N1 viruses and the recently emerged swine-origin pandemic (H1N1) 2009 virus, remains largely unknown.

Here, we examined the sensitivity of 20 IRDTs to various influenza virus strains, including H5N1 and 2009 pandemic H1N1 viruses. Our results indicate that the detection sensitivity to swine-origin H1N1 viruses varies widely among IRDTs, with some tests lacking sufficient sensitivity to detect the early stages of infection when the virus load is low.

 

 

Viruses tested include seasonal H1N1, seasonal H3N2, seasonal Type B, 16 different (human and avian) H5N1 viruses, H5N2, H5N3, H9N2, H7N7, and 3 clades of pandemic H1N1.

 

You’ll find that that these tests all are not created equally, and that it is important to match the test to the virus you are testing for.   As stated in the report:

 

Our findings emphasize the importance of selecting the right IRDT for rapid diagnosis of non-seasonal
influenza viruses, since the sensitivity of the IRDTs we tested varied by as much as 100-fold.

 

 

Obviously, we are in need of better, more accurate, rapid influenza tests – particularly when it comes to picking up novel or avian strains of the virus.

 

This is a detailed report and well worth reading, particularly if you are involved in the selection of RIDTs for your practice.

A Tale of Two Headlines

 

 

# 4355

 

 

Yesterday, in the wake of the release of a study in the journal Pediatrics on the efficacy of RIDTs (Rapid Influenza Diagnostic Tests), there were a number of news reports that seemed to depict the results in vastly different ways.

 

We’ll look at the headline and lede of two of them.

 

Health Day News saw it this way:

 

Rapid Flu Test Most Accurate for Young Kids

HealthDay News

A widely available rapid influenza diagnostic test is good, but not perfect, in determining whether a child has the flu, a new study shows.

(Continue. . . . )

 

While Medpage Today reported:

 

Rapid Tests Fail at Ruling Out H1N1 in Kids

By Todd Neale, Staff Writer, MedPage Today
Published: February 15, 2010

Rapid influenza tests have poor sensitivity for detecting pandemic H1N1 flu in children, two studies showed.

(Continue . . . )

 

Confused?  

 

One report says the test is `good but not perfect’, while the other states that it has `poor sensitivity’.  

 

In truth, both headlines are correct . . .  despite giving disparate  impressions.     

 

I’ll try to explain why.

 

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 various RIDTs are designed to show if someone tests positive for the Influenza A or B virus, but not the strain of flu.

 

According to the CDC:

 

The rapid tests vary in terms of sensitivity and specificity when compared with viral culture or RT-PCR. Product insert information and research publications indicate that:

• Sensitivities are approximately 50-70%
• Specificities are approximately 90-95%

 

The study in question today is entitled:

 

Performance of a Rapid Influenza Test in Children During the H1N1 2009 Influenza A Outbreak

Andrea T. Cruz, MD, MPH^a,b, Gail J. Demmler-Harrison, MD^b,c,d, A. Chantal Caviness, MD, MPH, PhD^a, Gregory J. Buffone, PhD^c, Paula A. Revell, PhD^c,

 

 

Here researchers evaluated the performance of RIDTs used at two different hospitals (that were capable of confirmatory rRT-PCR & Viral Culture Testing) over last summer.  They were then able to determine the accuracy of one of 10 FDA approved RIDTs (BinaxNOW) .

 

A couple of excerpts from the abstract.  Then some discussion.

 

Results  . . . With rRT-PCR as the reference, overall test sensitivity was 45% (95% confidence interval [CI]: 43.3%–46.3%) and specificity was 98.6% (95% CI: 98.1%–99%).  . . . .  RIDT sensitivity was significantly higher in young infants and children younger than 2 years than in older children.

Conclusions The RIDT had relatively poor sensitivity but excellent specificity in this consecutive series of respiratory specimens obtained from pediatric patients.

 

 

In other words, if the test said someone had influenza, it was right almost all of the time (Note: This was during a time of high influenza activity). 

 

But the test failed to detect influenza in roughly half the patients that were infected.

 

So the first headline Rapid Flu Test Most Accurate for Young Kids is true, since the report states that `sensitivity was significantly higher in young infants and children younger than 2 years.’

 

As is the second headline - Rapid Tests Fail at Ruling Out H1N1 in Kids – since overall, `The RIDT had relatively poor sensitivity.’

Contrary to popular belief, a 45% sensitivity level doesn’t mean that the test will be right less than half the time.  That depends on the actual incidence of influenza in the community when the test is taken.

 

As we’ve discussed before, influenza makes up but a fraction of all of the ILI’s (Influenza-like-Illnesses) that circulate in a community.   During the summer, that percentage drops into the low single digits, while at the height of flu season, it can approach 50%. 

 

The other ILI culprits include Coronaviruses, metapneumovirus, parainfluenzavirus, respiratory syncytial virus (RSV), any of the myriad Rhinoviruses (Common cold), and some adenoviruses.

 

None of these are influenzas, and so none would be expected to test positive with the RIDT.  

 

The following comes, again, from the CDC.

 

Accuracy Depends Upon Prevalence

The positive and negative predictive values vary considerably depending upon the prevalence of influenza in the community.

• False-positive (and true-negative) influenza test results are more likely to occur when disease prevalence is low, which is generally at the beginning and end of the influenza season.
• False-negative (and true-positive) influenza test results are more likely to occur when disease prevalence is high, which is typically at the height of the influenza season.

Clinical Considerations of Testing When Influenza Prevalence is Low

When disease prevalence is relatively low, the positive predictive value (PPV) is low and false-positive test results are more likely. By contrast, when disease prevalence is low, the negative predictive value (NPV) is high, and negative results are more likely to be true.

 

 

The interpretation of positive results should take into account the clinical characteristics of the case. If an important clinical decision is affected by the test result, the rapid test result should be confirmed by another test, such as viral culture or polymerase chain reaction (PCR).

Clinical Considerations of Testing When Influenza Prevalence Is High

When disease prevalence is relatively high, the NPV is low and false-negative test results are more likely. When disease prevalence is high, the PPV is high and positive results are more likely to be true.

 

 

So, to recap.  

 

If there’s a lot of flu around, and you test positive, there’s a pretty good chance you really have the flu.   

 

If you test negative . . .  well, doctors are urged not to base a diagnosis solely on a negative test.   Somewhere around 30% are probably false negatives.

 

 

 

And If there’s not much flu going around? 

 

Even if you test positive, there’s a pretty good chance you don’t have the flu.  

 

But a negative test (while not exclusionary) is substantially more likely to be true.

 

Obviously, given the ambiguity of all of this, a more accurate RIDT is something that doctors would be eager to get their hands on.