According to a rule by the Food and Drug Administration (FDA), RIDTs for influenza A and B are required to have a sensitivity of at least 80% and a specificity of at least 95% compared to an FDA-cleared nucleic acid based-test or other currently appropriate and FDA accepted comparator methods other than a correctly performed viral culture method [28]. A recent systematic review and meta-analysis, which was searched to May 2017, compared accuracy of traditional RIDTs, rapid NAATs, and DIAs in patients with suspected influenza [5]. For diagnosis of influenza A and B, the pooled sensitivities of DIAs including the Quidel Sofia rapid influenza FIA were 80.0% and 76.8%, respectively [5].
In the present study, when compared to RT-PCR, the pooled sensitivity of the Quidel Sofia rapid influenza FIA to identify influenza A and B were 78% and 72%, respectively, which indicate that our findings did not quite reach the target level of sensitivity required by the FDA. Therefore, some patients with negative results on the Quidel Sofia rapid influenza FIA may still be confirmed to have an influenza infection by alternative and more sensitive diagnostic methods.
Influenza type could have an effect on the accuracy of RIDTs. A previous meta-analysis revealed that overall RIDTs had increased sensitivity for detection of influenza A compared with influenza B (64.6% vs. 52.2%; p = 0.05) [29]. Influenza A virus causes more severe disease, higher influenza-associated hospitalization, and death compared to influenza B virus [29]. More severe virulence of influenza A may cause higher viral burden, which can lead to relatively high sensitivity [19]. In the present study, although the pooled sensitivity of the Quidel Sofia rapid influenza FIA to identify influenza A tended to be higher than that for influenza B, there was no statistical difference.
The Quidel Sofia rapid influenza FIA has the advantages of providing a simple, fast, and easy method for viral testing. The pooled specificity of this tool in our study was approximately 98%, above the target level for both influenza A and B. From these findings, we believe that clinicians would be able to diagnose influenza with assurance on the basis of a positive result from the Quidel Sofia rapid influenza FIA.
Large heterogeneities are commonly reported in systematic reviews of studies on diagnostic test accuracy, and substantial between-study heterogeneity among the enrolled studies was also observed in the present study [30]. Age is a probable source of heterogeneity for between-studies in the pooled estimates. In the present study, the pooled sensitivities of the Quidel Sofia rapid influenza FIA were significantly higher by approximately 12 percentage points for influenza A and 46 percentage points for influenza B in children compared to adults. The duration of influenza virus shedding is commonly measured from symptom onset to shedding cessation time, and children have been reported to have a tendency to shed the virus for a longer duration compared to adults [31]. Longer duration of influenza virus shedding in children might be associated with a higher sensitivity of this test compared to adults. However, because the number of studies that distinguish children from adults is very small, our findings should be interpreted with caution.
The sensitivity observed in one study was significantly lower than that observed in most studies [24]. In this study, an older patient population (median age 57 years) and a study protocol that did not specify the need for particular symptoms and duration of illness may have contributed to the reduced sensitivity [24]. These factors may have been affected by low virus shedding [24]. In our sensitivity analysis conducted after excluding this study [24], the pooled sensitivity of the Quidel Sofia rapid influenza FIA across studies on influenza A was slightly increased.
To the best of our knowledge, this is the first meta-analysis to investigate the Quidel Sofia rapid influenza FIA for detection of influenza. However, potential limitations of the present study should be considered when interpreting our results. First, because this present study was based on a relatively small number of trials, our results should be carefully interpreted with limited statistical power. Second, we could not make an assessment for publication bias since no reliable methods exist to investigate this issue in diagnostic test accuracy studies [32]. Third, although we used RT-PCR as the control reference for influenza diagnosis, two included studies used both RT-PCR and virus culture as reference standards. This use of dual reference standards may elicit the introduced bias due to diagnostic differences between references standards. However, for the pooled sensitivities and specificities across studies on the Quidel Sofia rapid influenza FIA to identify influenza A and B, there were no significant differences between RT-PCR and virus culture and only RT-PCR as control references. Finally, as a sample for viral diagnosis, nasopharyngeal aspirates would present with higher quality than nasopharyngeal swabs. Although we tried to investigate the diagnostic accuracy of the Quidel Sofia rapid influenza FIA according to the type of sample, we were not able to perform this analysis because of data limitations.