Indication - Influenza
Influenza A and B nucleic acid test (NAT)
First added in 2019
Changed in 2020
To diagnose seasonal influenza
Nasal swab, Nasopharyngeal swab, Nasopharyngeal aspirate or wash
WHO prequalified or recommended products
WHO supporting documents
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 https://www.who.int/influenza/resources/documents/WHO_Epidemiological_Influenza_Surveillance_Standards_2014.pdf
ICD11 code: 1E32
Summary of evidence evaluation
There is strong evidence for the high accuracy of nucleic acid amplification tests (NAATs). In a meta-analysis of 13 studies of NAATs, the estimated sensitivity for detecting influenza A was 91.6% (84.9 ; 95.9), and that for detecting influenza B was 95.4% (87.3% ; 98.7%). The pooled specificity was about 99% (3).
Summary of SAGE IVD deliberations
Clinical diagnosis of influenza is difficult because the manifestations are often nonspecific. PCR for influenza is the most sensitive rapid test and is widely held to be the reference standard for detection of influenza-specific RNA, with high sensitivity and high specificity. PCR is also necessary for surveillance in national hospitals and reference laboratories. Their uptake in LMICs is, however, limited by economic factors and lack of infrastructure and training.
SAGE IVD recommendation
The SAGE IVD recommended inclusion on the EDL of the PCR test for influenza, noting that it is the most sensitive rapid influenza test for both clinical management and surveillance. They further recommended that point-of-care tests could be used in the primary care settings as well as in district hospitals and in secondary and tertiary care facilities.
Details of submission from 2020
Disease condition and 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 the test meet a medical need? Molecular tests for Influenza are rapid, automated IVD tests for qualitative detection of influenza A and B in nasal or nasopharyngeal swabs or washes eluted in viral transport medium. A molecular amplification technique, e.g. PCR or isothermal amplification, is used to target and detect conserved regions of the influenza virus in the nucleic acid hybridization reaction. A test result is obtained within 10–15 min, allowing physicians and nurses to diagnose influenza and decide on treatment at a single patient visit. The performance is far more reliable than that of RDTs, but the tests are more expensive. Although the best results are obtained from a nasopharyngeal swab, which is uncomfortable to obtain from patients, molecular tests also perform well with nasal swabs, which are much easier to obtain, especially from small children. How the test is used: PCR-based influenza tests are typically used at or close to points of care as a single test in patients with suspected seasonal influenza. Some manufacturers provide multiplex PCR tests for both influenza A and B and respiratory syncytial virus A and B in the same reaction.
Public health relevance
Prevalence: Worldwide, influenza epidemics are 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
The WHO guideline is from 2010 and should be updated. Laboratory confirmation of influenza virus from throat, nasal and nasopharyngeal secretions or tracheal aspirate 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
Several studies have shown that molecular tests are more accurate than RDTs; however, no recent studies were found that showed that molecular assays that give results within 15–20 min improve clinical outcomes or antimicrobial stewardship.
Evidence for economic impact and/or cost–effectiveness
Only one study was found of the cost–effectiveness of rapid molecular testing for influenza (2). A decision analytical model was used to simulate the outcomes of a hypothetical cohort of elderly patients presenting with influenza-like illness at outpatient clinics in Hong Kong (China) during the peak influenza season, with rapid PCR and with clinical judgement alone. The outcome measures included direct medical cost, hospitalization rate, mortality rate, QALY loss and incremental cost per QALY saved. PCR was cost–effective in 60.6% and 99.4% of 10 000 Monte Carlo simulations of willingness to pay threshold one and three times the gross domestic product per capita, respectively. Whereas RDTs cost about US$ 15 per test, rapid molecular influenza tests cost about US$ 25 per test, and up to US$ 45 per test if they include respiratory syncytial virus.
Ethical issues, equity and human rights issues
Consent is required to obtain a sample. Like RDTs, rapid molecular tests for influenza are accessible for use in any outpatient setting, owing to their ease of use. The typical price of US$ 25 per test may limit access in LMICs.
1. Nicholson KG, Abrams KR, Batham S, Medina MJ, Warren FC, Barer M, et al. Randomised controlled trial and health economic evaluation of the impact of diagnostic testing for influenza, respiratory syncytial virus and Streptococcus pneumoniae infection on the management of acute admissions in the elderly and high-risk 18- to 64-year olds. Health Technol Assess. 2014;18(36): 1–274,vii–viii. 2. You JHS, Tam L, Lee NLS. Cost-effectiveness of molecular point-of-care testing for influenza viruses in elderly patients at ambulatory care setting. PLoS One. 2017;12(7):e0182091. 3. 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.