Indication - Influenza
Influenza A and B antigen
Instrument-based point-of-care immunoassay
First added in 2019
Changed in 2020
Aid to diagnosis
To aid in the diagnosis of seasonal influenza infection ; (Not recommended for surveillance testing)
Nasal swab, Nasopharyngeal swab, Nasopharyngeal aspirate or wash
WHO prequalified or recommended products
WHO supporting documents
Use of influenza rapid diagnostic tests (2010) https://apps.who.int/iris/handle/10665/44304/ Manual for the laboratory diagnosis and virological surveillance of influenza (2011) https://apps.who.int/iris/handle/10665/44518; Global Epidemiological Surveillance Standards for Influenza (2014) https://www.who.int/influenza/resources/documents/WHO_Epidemiological_Influenza_Surveillance_Standards_2014.pdf; https://www.who.int/health-topics/influenza-seasonal#tab=tab_1
ICD11 code: 1E32
Summary of evidence evaluation
There is strong evidence from systematic reviews (5) that older rapid tests for influenza are highly specific but vary in sensitivity, with a mean value of only 60%. Thus, these RDTs can only be used to confirm influenza and not to rule it out. The newer digital immunoassays (antigen detection tests) with an automated reader are more sensitive (77–80% overall), especially for children (83–88%), but require the use of an instrument and are more expensive than older RDTs.
Summary of SAGE IVD deliberations
Clinical diagnosis of influenza is difficult because its manifestations are often nonspecific. Rapid, point-of-care diagnosis can help to ensure prompt initiation of antiviral therapy, fewer ancillary diagnostic tests, fewer hospitalizations and less unnecessary use of antibiotics. While traditional rapid ICTs have been used for several decades, their sensitivity remains suboptimal. The newer digital immunoassays are substantially more sensitive, with comparable specificity. These assays can be performed at primary care level by trained health workers and are likely to improve patient outcomes and surveillance. The cost–effectiveness of these tests in LMICs has not been demonstrated, and sample collection requires training.
SAGE IVD recommendation
The SAGE IVD recommended conditional inclusion on the EDL of the rapid immunoassay for influenza, only for patient management and pending issuance of updated WHO guidelines within 1 year. The Group noted that the older rapid ICTs are not sensitive enough and are likely to be phased out, while newer digital immunoassays are sensitive and rapid and could be used for diagnosis at points of care. The simpler lateral flow tests are useful for detection if no other tests are available but should not be used for surveillance and should meet international performance standards. The Group recommended that rapid immunoassays for influenza be a priority for WHO prequalification and that WHO urgently update its influenza guidelines.
Details of submission from 2020
Disease condition and its impact on patients: Seasonal influenza causes disease all year, globally. Illness ranges in severity: most people recover within 1 week without requiring medical attention, but influenza can lead to hospitalization and death. Does this test meet a medical need? The RDT provides a result within 10–15 min, therefore allowing physicians and nurses to diagnose influenza and decide on treatment at a single patient visit. How the test is used: Immunoassays for influenza are typically used at or close to points of care as a single test in patients with suspected influenza.
Public health relevance
Prevalence: Worldwide, seasonal influenza is estimated to result in 3–5 million cases of severe illness and about 290 000–650 000 deaths from respiratory conditions. The US Centers for Disease Control and Prevention estimated that influenza has caused 9.3–49.0 million cases of illness, 140 000–960 000 hospitalizations and 12 000–79 000 deaths annually in the USA since 2010. WHO states that the estimated national influenza burden determines influenza prevention and control programmes; however, reliable data are not available for LMICs. Socioeconomic impact: The WHO project on the burden of influenza, in partnership with the Pandemic Influenza Preparedness framework, is improving understanding of the burden of influenza (1).
WHO or other clinical guidelines relevant to the test
WHO recommendations on the use of rapid testing for influenza diagnosis (2, 3). The latest guideline is from 2010 and should be updated. Laboratory confirmation of influenza virus from throat, nasal and nasopharyngeal secretions or tracheal aspirates or washings is commonly done by direct antigen detection, virus isolation or detection of influenza-specific RNA by RT-PCR.
Evidence for clinical usefulness and impact
WHO Recommendations on the use of rapid testing for influenza diagnosis (2) indicate that a rapid diagnostic test performed within 48 h of the onset of symptoms can have important implications for case management, including the use of antiviral agents. Other benefits may include the isolation and cohorting of confirmed cases to prevent nosocomial outbreaks and a reduction in inappropriate use of antibiotics. Use of rapid tests that provide timely evidence of influenza virus infection should be considered; however, test performance depends on the prevalence of influenza in the community. A low prevalence outside the normal influenza season can lead to an increase in false-positive results.
Evidence for economic impact and/or cost–effectiveness
In 2010, computer simulations were used to evaluate the economic value of seven strategies for testing and managing seasonal and pandemic influenza: clinical judgement alone, PCR, an RDT at points of care, a combination of a point-of-care test and clinical judgement, clinical judgement with confirmation by PCR, treating everyone with antivirals and treating no one with antivirals (4). For healthy adults < 65 years presenting with influenza-like illness in a seasonal influenza scenario, strategies were cost–effective only from a societal perspective. Clinical judgement, followed by PCR and point-of-care testing, was found to be cost–effective in situations of a high influenza probability. Doubling the hospitalization risk and mortality (representing either individuals at higher risk or more virulent strains) made clinical judgement to decide on prescription of antiviral agents cost–effective, as did PCR testing, point-of-care testing and point-of-care testing in conjunction with clinical judgement. For healthy adults ≥ 65 years, PCR was the most cost–effective option, the closest competitor being clinical judgement, with an accuracy ≥ 50%. Point-of-care testing plus clinical judgement were cost–effective for higher probabilities of influenza. Treating all patients with influenza-like illness with antiviral agents was cost–effective only for older adults. This study showed the importance of accuracy, with PCR or highly sensitive clinical judgement.
Ethical issues, equity and human rights issues
Consent is required to obtain a sample. RDTs for influenza are readily accessible for use in outpatient settings. The typical price in the US of US$ 9–15 per test may limit access in LMICs. However, pricing of the same products in LMIC’s may not be the same as in the US and was not available at the time of submission.
1. Special issue: influenza disease burden. Influenza Other Resp Viruses. 2018;12(1):1–192 (https:// onlinelibrary.wiley.com/toc/17502659/12/1, accessed April 2019). 2. WHO recommendations on the use of rapid testing for influenza diagnosis. Geneva: World Health Organization; 2005 (https://www.who.int/influenza/resources/documents/RapidTestInfluenza_ WebVersion.pdf, accessed April 2019). 3. Use of influenza rapid diagnostic tests. Geneva: World Health Organization; 2010 (https://apps. who.int/iris/bitstream/handle/10665/44304/9789241599283_eng.pdf;sequence=1, accessed April 2019). 4. Lee BY, McGlone SM, Bailey RR, Wiringa AE, Zimmer SM, Smith KJ, et al. To test or to treat? An analysis of influenza testing and antiviral treatment strategies using economic computer modelling. PLoS One. 2010;5(6):e11284. 5. Bruning AHL, Leeflang MMG, Vos JMBW, Spijker R, de Jong MD, Wolthers KC, et al. Rapid tests for influenza, respiratory syncytial virus, and other respiratory viruses: a systematic review and meta-analysis. Clin Infect Dis. 2017;65(6):1026–32. 6. Merckx J, Wali R, Schiller I, Caya C, Gore GC, Chartrand C, et al. Diagnostic accuracy of novel and traditional rapid tests for influenza infection compared with reverse transcriptase polymerase chain reaction: a systematic review and meta-analysis. Ann Intern Med. 2017;167(6): 394–409.