How Accurate Are Rapid Influenza Diagnostic Tests?

Caroline Chartrand; Madhukar Pai

Disclosures

Expert Rev Anti Infect Ther. 2012;10(6):615-617. 

Abstract and Introduction

Introduction

Influenza is a common disease that occurs in yearly epidemics throughout the world. Although the majority of infected individuals will exhibit a self-limited acute febrile illness or remain asymptomatic, influenza can lead to significant morbidity and mortality. Each year, 3–5 million individuals develop severe disease and 250,000–500,000 die as a result of influenza.[101]

Identifying influenza early as the cause of an acute febrile respiratory illness is important for patient management. Antiviral treatments for influenza have been shown to reduce the duration of symptoms, hospitalizations and mortality,[1,2] and as such are recommended in hospitalized patients, those with severe illness and those at high risk of complications because of age or associated conditions.[3,4] However, antiviral therapy must be started early in the course of illness to produce maximum benefit, ideally within 48 h of symptom onset.[1,4] This leaves clinicians with a very narrow window of opportunity to influence the outcome of the disease. Knowledge of a patient's influenza status at the time of the clinical encounter also has the potential to reduce additional testing and antibiotic prescription,[5–7] which are prescribed in up to one-third of patients with a sole diagnosis of influenza.[8] However, the clinical diagnosis of influenza, based on fever and cough or sore throat, has been shown to have only moderate sensitivity (64%) and specificity (67%).[9]

Conventional laboratory diagnostic tests for influenza are considered gold standards, but are seldom able to give clinicians a timely result. Viral culture has a turnaround time of at least 48 h (for shell vial culture), and even RT-PCR, which has a turnaround time of 4–6 h, is usually run in batches, which may delay the results. These tests also require sophisticated laboratory infrastructure that is unlikely to exist outside of hospitals, while most patients with influenza are likely to be seen in community or outpatient settings. This has led to the development of an array of rapid influenza diagnostic tests (RIDTs). These immunochromatographic assays are simple to use, give a simple yes/no result in 15–20 min and are, in some cases, licensed to be used at the point-of-care, such as a physician's office or an emergency department. However, their reported accuracy has varied widely, with sensitivity ranging from 10 to 80%.[3,4]

So, how accurate are RIDTs and what value do they have for clinical practice? To address this question, we recently published a meta-analysis to summarize available evidence on the diagnostic accuracy of RIDTs.[10] The analysis included 119 articles evaluating 26 different commercial RIDTs, which were compared with a reference standard of either RT-PCR or viral culture. Overall, RIDTs had a modest sensitivity of 62.3% (95% CI: 57.9–66.6) and a high specificity of 98.2% (95% CI: 97.5–98.7%), corresponding to a positive likelihood ratio of 34.5 (95% CI: 23.8–45.2) and a negative likelihood ratio of 0.38 (95% CI: 0.34–0.43). For the clinician, this means that although false-negatives are frequent (occurring in nearly four out of ten negative RIDTs), a positive test is unlikely to be a false-positive result. A diagnosis of influenza can thus confidently be made in the presence of a positive RIDT. However, a negative RIDT result is unreliable and should be confirmed by traditional diagnostic tests if the result is likely to affect patient management.

In our meta-analysis, the sensitivity of RIDTs was highly variable, while specificity was consistently high (Figure 1). This was partly explained by a 13% higher sensitivity in children than in adults (66.6% [95% CI: 61.6–71.7] vs 53.9% [95% CI: 47.9–59.8]) and a higher sensitivity for detecting influenza A versus influenza B (64.6% [95% CI: 59.0–70.1] vs 52.2% [95% CI: 45.0–59.3]). Despite reports to the contrary,[11] we found no important difference in accuracy for detecting the influenza A H1N1 2009 pandemic strains compared with other seasonal strains. Also, no significant difference in accuracy was found between the different commercial brands of RIDTs, among the different respiratory specimens and between tests performed in the laboratory or at the point-of-care. Knowing in which situation RIDTs are likely to be more accurate may help clinicians tailor their use for maximum effectiveness.

Figure 1.

Accuracy of rapid influenza diagnostic tests: data from a meta-analysis of 159 diagnostic accuracy studies (from 119 articles). Hierarchical summary receiver-operating characteristic curve plot. Individual studies are shown as open circles whose size is proportionate to the size of the study. The summary point is shown as a closed circle, representing the pooled accuracy estimates (sensitivity and specificity). The hierarchical summary receiver-operating characteristic curve is shown as a dashed line. Reproduced with permission from [10].

Despite their modest sensitivity, because of their rapid turnaround time, RIDTs could occupy a place at the point-of-care that more accurate tests, such as RT-PCR, are currently unable to fill. They are first-line tests that provide clinicians with an immediate answer that can be confirmed at a later date by more time-consuming definitive testing, if needed. Decisions regarding antiviral therapy, antibiotics and additional testing are taken within minutes of the clinical encounter, long before results from RT-PCR or viral culture become available. These decisions are currently based on clinical judgment, which has a greatly inferior accuracy compared with RIDTs. Although RIDTs are far from perfect, they can supplement the clinician judgment and help rule in influenza, in patients with influenza-like illness. Although a negative RIDT cannot rule out influenza, the clinician is left with exactly the same options as before, to send a sample (probably taken simultaneously with the one for the RIDTs) for RT-PCR or viral culture or to rely solely on clinical judgment.

It appears that it is when they are used at the point-of-care, outside of a laboratory setting, that RIDTs find their most useful application in the diagnosis algorithm for influenza. Although many of these tests are licensed for use outside of a laboratory setting, their usage requires staff training and adherence to specific protocols (for example, many of these tests have to be read after a specific amount of time), causing interruption in the clinical work flow and increasing demands on already busy clinic and emergency department personnel, which are potential obstacles to their widespread implementation. However, other rapid tests with similar demands, such as the rapid strep test, have found a place in many physicians' offices. Efforts must therefore be made to overcome barriers to point-of-care use of RIDTs, in order to ensure their optimal use.

The vast array of RIDTs and the continued development of new ones indicate that these tests are probably here to stay. If appropriately used during influenza epidemics or outbreaks at the point-of-care, RIDTs could help set up appropriate infection-control measures, start early antiviral therapy in high-risk patients and enable clinicians to make informed decisions regarding diagnostic investigations and empirical antibiotic usage. Clinical trials are needed to confirm whether RIDTs indeed have clinical impact and can be cost-effective to healthcare systems.

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