Abstract
As the world prepares for the next influenza pandemic, governments have made significant funding commitments to vaccine development and antiviral stockpiling. While these are essential components to pandemic response, rapid and accurate diagnostic testing remains an often neglected cornerstone of pandemic influenza preparedness. Clinicians and Public Health Practitioners need to understand the benefits and drawbacks of different influenza tests in both seasonal and pandemic settings. Culture has been the traditional gold standard for influenza diagnosis but requires from 1–10 days to generate a positive result, compared to nucleic acid detection methods such as real time reverse transcriptase polymerase chain reaction (RT-PCR). Although the currently available rapid antigen detection kits can generate results in less than 30 minutes, their sensitivity is suboptimal and they are not recommended for the detection of novel influenza viruses. Until point-of-care (POC) tests are improved, PILPN recommends that the best option for pandemic influenza preparation is the enhancement of nucleic acid-based testing capabilities across Canada.
Key words: Pandemic influenza, seasonal influenza, point of care testing, nucleic acid amplification testing
Résumé
Tandis que le monde se prépare à la prochaine pandémie de grippe, les gouvernements se sont engagés à financer substantiellement la mise au point de vaccins et la constitution de réserves d’antiviraux. Même s’il s’agit là de volets essentiels à une intervention en cas de pandémie, le diagnostic rapide et exact demeure une pierre angulaire, souvent négligée, de la préparation à la pandémie de grippe. Les cliniciens et les praticiens en santé publique doivent comprendre les avantages et les inconvénients des différents tests de dépistage tant en saison de grippe qu’en situation de pandémie. La mise en culture est depuis longtemps le test de référence servant au diagnostic de la grippe, mais il faut de 1 à 10 jours pour obtenir un résultat positif, comparativement aux méthodes de détection des acides nucléiques telles que l’amplification par la polymérase après transcription inverse (RT-PCR) en temps réel. Bien que les trousses courantes de détection des antigènes puissent donner un résultat en moins de 30 minutes, leur sensibilité est sous-optimale, et elles ne sont pas conseillées pour déceler les nouveaux virus de la grippe. Tant que les tests au point de service ne se seront pas améliorés au Canada, le RPLPI recommande un renforcement dans tout le pays, de la capacité de dépistage du virus à l’aide d’un test d’amplification des acides nucléiques comme étant le meilleur moyen de se préparer à une pandémie de grippe.
Mots clés: grippe saisonnière, dépistage au point de service, test d’amplification des acides nucléiques
Footnotes
Members of PILPN: Nathalie Bastien, Jody Berry, Tim F. Booth, Max Chernesky, Michel Couillard, Steven Drews, Anthony Ebsworth, Margaret Fearon, Kevin Fonseca, Julie Fox, Jean-Nicolas Gagnon, Steven Guercio, Greg Horsman, Cathy Jorowski, Theodore Kuschak, Yan Li, Anna Majury, Martin Petric, Sam Ratnam, Marek Smieja, Paul Van Caeseele.
References
- 1.The Canadian Pandemic Influenza Plan for the Health Sector. Annex C: Pandemic Influenza Laboratory Preparedness Plan, 2006. Available online at: https://doi.org/www.phac-aspc.gc.ca/cpip-pclcpi/ann-c-eng.php (Accessed April 15, 2008).
- 2.Petric M, Comanor L, Petti A. The role of the laboratory in diagnosis of influenza during seasonal epidemics and potential pandemics. J Infect Dis. 2006;194(Suppl2):S98–S110. doi: 10.1086/507554. [DOI] [PubMed] [Google Scholar]
- 3.Gharabaghi F, Tellier R, Cheung R, Collins C, Broukhanski G, Drews SJ, Richardson SE. Comparison of a commercial qualitative real-time RT-PCR kit with direct immunofluorescence assay (DFA) and cell culture for detection of influenza A and B in children. J Clin Virol. 2008;42:190–93. doi: 10.1016/j.jcv.2008.01.013. [DOI] [PubMed] [Google Scholar]
- 4.van de Pol AC, van Loon AM, Wolfs TF, Jansen NJ, Nijhuis M, Breteler EK, et al. Increased detection of respiratory syncytial virus, influenza viruses, parainfluenza viruses, and adenoviruses with real-time PCR in samples from patients with respiratory symptoms. J Clin Microbiol. 2007;45:2260–62. doi: 10.1128/JCM.00848-07. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Zitterkopf NL, Leekha S, Espy MJ, Wood CM, Sampathkumar P, Smith TF. Relevance of influenza A virus detection by PCR, shell vial assay, and tube cell culture to rapid reporting procedures. J Clin Microbiol. 2006;44(9):3366–67. doi: 10.1128/JCM.00314-06. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Espy MJ, Uhl JR, Sloan LM, Buckwalter SP, Jones MF, Vetter EA, et al. Realtime PCR in clinical microbiology: Applications for routine laboratory testing. Clin Microbiol Rev. 2006;19(1):165–256. doi: 10.1128/CMR.19.1.165-256.2006. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Ellis JS, Fleming DM, Zambon MC. Multiplex reverse transcription-PCR for surveillance of influenza A and B viruses in England and Wales in 1995 and 1996. J Clin Microbiol. 1997;35:2076–82. doi: 10.1128/jcm.35.8.2076-2082.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Fiore AE, Shay DK, Broder K, Iskander JK, Uyeki TM, Mootrey G, et al. Centers for Disease Control and Prevention (CDC); Advisory Committee on Immunization Practices (ACIP). Prevention and control of influenza: Recommendations of the Advisory Committee on Immunization Practices (ACIP) MMWR Recomm Rep. 2008;57:1–60. [PubMed] [Google Scholar]
- 9.Allen UD, Aoki FY, Stiver HG. The use of antiviral drugs for influenza: Recommended guidelines for practitioners. Can J Infect Dis Med Microbiol. 2006;17(5):273–84. doi: 10.1155/2006/165940. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Weinberg A, Walker ML. Evaluation of three immunoassay kits for rapid detection of influenza virus A and B. Clin Diagn Lab Immunol. 2005;12(3):367–70. doi: 10.1128/CDLI.12.3.367-370.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Hurt AC, Alexander R, Hibbert J, Deed N, Barr IG. Performance of six influenza rapid tests in detecting human influenza in clinical specimens. J Clin Virol. 2007;39(2):132–35. doi: 10.1016/j.jcv.2007.03.002. [DOI] [PubMed] [Google Scholar]
- 12.Waner JL, Todd SJ, Shalaby H, Murphy P, Wall LV. Comparison of Directigen FLU-A with viral isolation and direct immunofluorescence for the rapid detection and identification of influenza A virus. J Clin Microbiol. 1991;29(3):479–82. doi: 10.1128/jcm.29.3.479-482.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Johnston SL, Bloy H. Evaluation of a rapid enzyme immunoassay for detection of influenza A virus. J Clin Microbiol. 1993;31(1):142–43. doi: 10.1128/jcm.31.1.142-143.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Kaiser L, Briones MS, Hayden FG. Performance of virus isolation and Directi-gen Flu A to detect influenza A virus in experimental human infection. J Clin Virol. 1999;14(3):191–97. doi: 10.1016/S1386-6532(99)00058-X. [DOI] [PubMed] [Google Scholar]
- 15.Gooskens J, Swaan CM, Claas EC, Kroes AC. Rapid molecular detection of influenza outbreaks in nursing homes. J Clin Virol. 2008;41(1):7–12. doi: 10.1016/j.jcv.2007.10.023. [DOI] [PubMed] [Google Scholar]
- 16.Reina J, Padilla E, Alonso F R D, Gopegui E, Munar M, Mari M. Evaluation of a new dot blot enzyme immunoassay (Directigen flu A+B) for simultaneous and differential detection of influenza A and B virus antigens from respiratory samples. J Clin Microbiol. 2002;40(9):3515–17. doi: 10.1128/JCM.40.9.3515-3517.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Hamilton MS, Abel DM, Ballam YJ, Otto MK, Nickell AF, Pence LM, et al. Clinical evaluation of the ZstatFlu-II test: A chemiluminescent rapid diagnostic test for influenza virus. J Clin Microbiol. 2002;40(7):2331–34. doi: 10.1128/JCM.40.7.2331-2334.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Landry ML, Cohen S, Ferguson D. Comparison of Binax NOW and Directigen for rapid detection of influenza A and B. J Clin Virol. 2004;31(2):113–15. doi: 10.1016/j.jcv.2004.04.005. [DOI] [PubMed] [Google Scholar]
- 19.Booth S, Baleriola C, Rawlinson WD. Comparison of two rapid influenza A/B test kits with reference methods showing high specificity and sensitivity for influenza A infection. J Med Virol. 2006;78(5):619–22. doi: 10.1002/jmv.20584. [DOI] [PubMed] [Google Scholar]
- 20.Rahman M, Kieke BA, Vandermause MF, Mitchell PD, Greenlee RT, Belongia EA. Performance of Directigen flu A+B enzyme immunoassay and direct fluorescent assay for detection of influenza infection during the 2004–2005 season. Diagn Microbiol Infect Dis. 2007;58(4):413–18. doi: 10.1016/j.diagmicrobio.2007.03.011. [DOI] [PubMed] [Google Scholar]
- 21.Hindiyeh M, Goulding C, Morgan H, Kenyon B, Langer J, Fox L, et al. Evaluation of BioStar FLU OIA assay for rapid detection of influenza A and B viruses in respiratory specimens. J Clin Virol. 2000;17(2):119–26. doi: 10.1016/S1386-6532(00)00081-0. [DOI] [PubMed] [Google Scholar]
- 22.Rodriguez WJ, Schwartz RH, Thorne MM. Evaluation of diagnostic tests for influenza in a pediatric practice. Pediatr Infect Dis J. 2002;21(3):193–96. doi: 10.1097/00006454-200203000-00006. [DOI] [PubMed] [Google Scholar]
- 23.Covalciuc KA, Webb KH, Carlson CA. Comparison of four clinical specimen types for detection of influenza A and B viruses by optical immunoassay (FLU OIA test) and cell culture methods. J Clin Microbiol. 1999;37(12):3971–74. doi: 10.1128/jcm.37.12.3971-3974.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Rashid H, Shafi S, Haworth E E, Bashir H, Ali KA, Memish ZA, Booy R. Value of rapid testing for influenza among Hajj pilgrims. Travel Med Infect Dis. 2007;5(5):310–13. doi: 10.1016/j.tmaid.2007.07.006. [DOI] [PubMed] [Google Scholar]
- 25.Weitzel T, Schnabel E, Dieckmann S, Börner U, Schweiger B. Evaluation of a new point-of-care test for influenza A and B virus in travelers with influenzalike symptoms. Clin Microbiol Infect. 2007;13(7):665–69. doi: 10.1111/j.1469-0691.2007.01739.x. [DOI] [PubMed] [Google Scholar]
- 26.Cruz AT, Cazacu AC, Greer JM, Demmler GJ. Rapid assays for the diagnosis of influenza A and B viruses in patients evaluated at a large tertiary care children’s hospital during two consecutive winter seasons. J Clin Virol. 2008;41(2):143–47. doi: 10.1016/j.jcv.2007.11.006. [DOI] [PubMed] [Google Scholar]
- 27.WHO recommendations on the use of rapid testing for influenza diagnosis. 2005. Available online at: https://doi.org/www.who.int/csr/disease/avian_influenza/guidelines/rapid_testing/en/index.html (Accessed April 15, 2008).
- 28.U.S. FoodDrug Administration, Office of In Vitro Diagnostic Device EvaluationSafety. Cautions in Using Rapid Tests for Detecting Influenza A Viruses. 2007. [Google Scholar]
- 29.Chan KH, Maldeis N, Pope W, Yup A, Ozinskas A, Gill J, et al. Evaluation of the Directigen FluA+B test for rapid diagnosis of influenza virus type A and B infections. J Clin Microbiol. 2002;40(5):1675–80. doi: 10.1128/JCM.40.5.1675-1680.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Fedorko DP, Nelson NA, McAuliffe JM, Subbarao K. Performance of rapid tests for detection of avian influenza A virus types H5N1 and H9N2. J Clin Micro-biol. 2006;44(4):1596–97. doi: 10.1128/JCM.44.4.1596-1597.2006. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Chan KH, Lam SY, Puthavathana P, Nguyen TD, Long HT, Pang CM, et al. Comparative analytical sensitivities of six rapid influenza A antigen detection test kits for detection of influenza A subtypes H1N1, H3N2 and H5N1. J Clin Virol. 2007;38(2):169–71. doi: 10.1016/j.jcv.2006.11.010. [DOI] [PubMed] [Google Scholar]
- 32.Abdel-Ghafar AN, Chotpitayasunondh T, Gao Z, Hayden FG, Nguyen DH, de Jong MD, et al. Writing Committee of the Second World Health Organization Consultation on Clinical Aspects of Human Infection with Avian Influenza A (H5N1) Virus. Update on avian influenza A (H5N1) virus infection in humans. N Engl J Med. 2008;358(3):261–73. doi: 10.1056/NEJMra0707279. [DOI] [PubMed] [Google Scholar]
