Clinical Characteristics and Comparison of the Various Methods Used for the Diagnosis of the New Influenza A Pandemic in Korea

Min Jung Kwon; Chang Kyu Lee; Kyoung Ho Roh; Myung Hyun Nam; Soo Young Yoon; Chae Seung Lim; Yun Jung Cho; Young Kee Kim; Kap No Lee

doi:10.3343/lmo.2011.1.1.5

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Kwon, Lee, Roh, Nam, Yoon, Lim, Cho, Kim, and Lee: Clinical Characteristics and Comparison of the Various Methods Used for the Diagnosis of the New Influenza A Pandemic in Korea

Original Article

Clinical Microbiology

Laboratory Medicine Online

Laboratory Medicine Online 2011; 1(1): 26-34.

Published online: 1 January 2011

DOI: https://doi.org/10.3343/lmo.2011.1.1.5

Clinical Characteristics and Comparison of the Various Methods Used for the Diagnosis of the New Influenza A Pandemic in Korea

Min Jung Kwon, Chang Kyu Lee, Kyoung Ho Roh, Myung Hyun Nam, Soo Young Yoon, Chae Seung Lim, Yun Jung Cho, Young Kee Kim, Kap No Lee

Department of Laboratory Medicine, Korea University College of Medicine, Seoul, Korea.

Corresponding author: Chang Kyu Lee. Department of Laboratory Medicine, Korea University College of Medicine, Anam-dong 5-ga, Seongbuk-gu, Seoul 136-705, Korea. Tel: +82-2-920-5784, Fax: +82-2-920-5538, cklee@korea.ac.kr

Received 1 October 2010 Revised 23 October 2010 Accepted 25 October 2010

(open-access):

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Laboratory diagnosis of new influenza A (H1N1) is crucial for managing patients and establishing control and prevention measures. We compared the diagnostic accuracies of the real time RT-PCR (rRT-PCR) test recommended for the confirmation of the new flu and the viral culture method used conventionally for viral disease with that of the rapid antigen test (RAT).

Methods

We performed RAT, R-mix culture, and real-time PCR by using 861 respiratory samples collected from December 2009 to January 2010 and evaluated the abilities of these methods to detect new influenza A. The relationship among the positive rates of RAT, grades of culture, and the cycle threshold (Ct) values of rRT-PCR was also evaluated.

Results

Of the 861 patients, 308 (35.8%) were diagnosed with new influenza A. The sensitivities, specificities, positive predictive values, and negative predictive values of the tests were respectively as follows: 59.7%, 99.5%, 98.4%, and 81.6% for RAT; 93.2%, 100%, 100%, and 96.3% for R-mix culture; and 95.8%, 100%, 100%, and 97.7% for rRT-PCR. Samples with weak positive grade in culture and those with Ct values of 30-37 in rRT-PCR showed positivities as low as 25.3% and 2.3% in RAT, respectively. The hospitalization rate and death rate of the confirmed patients were 3.2% and 0.3%, respectively, and gastrointestinal symptoms were observed in 7.2% of the patients.

Conclusions

R-mix culture and rRT-PCR tests showed excellent reliability in the diagnosis of new influenza A and could be very useful, especially for samples with low viral load.

Keywords: New influenza, Rapid antigen test, Culture, Real-time RT-PCR

Figures and Tables

Table 1

Demograpnic and clinical characteristics of 308 patients with confirmed new influenza A (H1N1)

^*High-risk group includs patients with age above 65 yr, age below 5 yr, malignancy, pregnancy, chronic diseaes of liver, kindey and lung.

Table 2

Performance of three tests for new influenza A (H1N1)

^*Positive confirmation for new influenza A (H1N1) was made when the specimen was positive in either realtime RT-PCR or culture. Negative confirmaton for new influenza A (H1N1) was made when the specimen was negative in both real-time RT-PCR and culture.

Abbreviations: PPV, positive predictive value; NPV, negative predictive value.

Table 3

Summary of results from rRT-PCR, R-mix culture and rapid antigen test

Abbreviations: RAT, rapid antigen test; PPV, positive predictive value; NPV, negative predictive value.

Table 4

Comparison of R-mix culture and rapid antigen test results based on Ct values of rRT-PCR among the confirmed new influenza A patients

^*The culture test results in this group are composed of two cases of 1+ grade and one case of 2+ grade; ^†The culture test results in this group are composed of eleven cases of 1+ grade, 2 cases of 1+ grade and 2 cases of 2+ grade.

Table 5

Comparison of rRT-PCR and rapid antiten test results based on the grades of R-mix culture results among the confirmed new influenza A patients

^*There were 21 cases of negative culture results, though not presented in the table. Among these cases, all 21 were positive by rRT-PCR and only 1 tested positive by rapid antigen test.

Notes

This article is available from http://www.labmedonline.org

References

1. Kim WJ. Epidemiology, clinical manifestations, and management of pandemic novel influenza A (H1N1). Korean J Med. 2009. 77:157–164.

2. Taubenberger JK, Morens DM. The pathology of influenza virus infections. Annu Rev Pathol. 2008. 3:499–522.

3. Neuzil KM, Zhu Y, Griffin MR, Edwards KM, Thompson JM, Tollefson SJ, et al. Burden of interpandemic influenza in children younger than 5 years: a 25-year prospective study. J Infect Dis. 2002. 185:147–152.

4. McBean AM, Babish JD, Warren JL. The impact and cost of influenza in the elderly. Arch Intern Med. 1993. 153:2105–2111.

5. Treanor JJ. Richman DD, Whitley RJ, editors. Respiratory infections. Clinical Virology. 2002. 2nd ed. Washington D.C.: ASM press.

6. Barenfanger J, Drake C, Mueller T, Troutt T, O'Brien J, Guttman K. R-Mix cells are faster, at least as sensitive and marginally more costly than conventional cell lines for the detection of respiratory viruses. J Clin Virol. 2001. 22:101–110.

7. Human infection with pandemic (H1N1) 2009 virus: updated interim WHO guidance on global surveillance. WHO. Updated on July 2009. http://www.who.int/csr/disease/swineflu/WHO_case_definition_swine_flu_2009_04_29.pdf.

8. Garten RJ, Davis CT, Russell CA, Shu B, Lindstrom S, Balish A, et al. Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans. Science. 2009. 325:197–201.

9. Herzum I, Lutz T, Koch F, Geisel R, Gehrt A. Diagnostic performance of rapid influenza antigen assays in patients infected with the new influenza A (H1N1) virus. Clin Chem Lab Med. 2010. 48:53–56.

10. Biggs C, Walsh P, Overmyer CL, Gonzalez D, Feola M, Mordechai E, et al. Performance of influenza rapid antigen testing in influenza in emergency department patients. Emerg Med J. 2010. 27:5–7.

11. Hwang YS, Kim KH, Lee MA. Evaluation of the efficacies of rapid antigen test, multiplex PCR, and real-time PCR for the detection of a novel influenza A (H1N1) virus. Korean J Lab Med. 2010. 30:147–152.

12. Hancock K, Veguilla V, Lu X, Zhong W, Butler EN, et al. Cross-reactive antibody response to the 2009 pandemic H1N1 influenza virus. N Engl J Med. 2009. 361:1945–1952.

13. Perez-Padilla R, de la Rosa-Zamboni D, Ponce de Leon S, Hernandez M, Quinones-Falconi F, Bautista E, et al. Pneumonia and respiratory failure from swine-origin influenza A (H1N1) in Mexico. N Engl J Med. 2009. 361:680–689.

14. Peltola VT, McCullers JA. Respiratory viruses predisposing to bacterial infections: role of neuraminidase. Pediatr Infect Dis J. 2004. 23:S87–S97.

15. Hament JM, Kimpen JL, Fleer A, Wolfs TF. Respiratory viral infection predisposing for bacterial disease: a concise review. FEMS Immunol Med Microbiol. 1999. 26:189–195.

16. Flahault A. First estimation of direct H1N1pdm virulence: From reported non consolidated data from Mauritius and New Caledonia. PLoS Curr. 2009. 1:RRN1010.

17. Garske T, Legrand J, Donnelly CA, Ward H, Cauchemez S, Fraser C, et al. Assessing the severity of the novel influenza A/H1N1 pandemic. BMJ. 2009. 339:b2840.

18. Ginocchio CC, Zhang F, Manji R, Arora S, Bornfreund M, Falk L, et al. Evaluation of multiple test methods for the detection of the novel 2009 influenza A (H1N1) during the New York City outbreak. J Clin Virol. 2009. 45:191–195.

19. Chan KH, Lai ST, Poon LL, Guan Y, Yuen KY, Peiris JS. Analytical sensitivity of rapid influenza antigen detection tests for swine-origin influenza virus (H1N1). J Clin Virol. 2009. 45:205–207.

20. Yoo Y, Sohn JW, Park DW, Kim JY, Shin HK, Lee Y, et al. Clinical evaluation of the SD Bioline influenza virus antigen test for rapid detection of influenza viruses A and B in children and adults during the influenza season. Clin Vaccine Immunol. 2007. 14:1050–1052.

21. Weinberg A, Mettenbrink CJ, Ye D, Yang CF. Sensitivity of diagnostic tests for influenza varies with the circulating strains. J Clin Virol. 2005. 33:172–175.

22. Mackie PL, McCormick EM, Williams C. Evaluation of Binax NOW RSV as an acute point-of-care screening test in a paediatric accident and emergency unit. Commun Dis Public Health. 2004. 7:328–330.

23. Daisy JA, Lief FS, Friedman HM. Rapid diagnosis of influenza A infection by direct immunofluorescence of nasopharyngeal aspirates in adults. J Clin Microbiol. 1979. 9:688–692.

24. Gavin PJ, Thomson RB. Review of rapid diagnostic tests for influenza. Clin Applied Immunol Rev. 2004. 4:151–172.

25. St George K, Patel NM, Hartwig RA, Scholl DR, Jollick JA, Kauffmann LM, et al. Rapid and sensitive detection of respiratory virus infections for directed antiviral treatment using R-Mix cultures. J Clin Virol. 2002. 24:107–115.

26. Mackay IM, editor. Real-time PCR in microbiology from diagnosis to characterization. 2007. 1st ed. Norkolk: Caister Academic Press;101–269.

27. Ashihara Y, Kasahara Y, Nakamura RM. McPherson RA, Pincus MR, et al. Immunoassay and immunochemistry. Henry's clinical diagnosis and management by laboratory methods. 2007. 21th ed. Philadelphia: WB Saunders;812–814.

28. Interim guidance for the detection of novel influenza A virus using rapid influenza diagnostic tests. CDC. Updated on Aug 2009. http://www.cdc.gov/h1n1flu/guidance/rapid_testing.htm.

29. Yuen KY, Chan PK, Peiris M, Tsang DN, Que TL, Shortridge KF, et al. Clinical features and rapid viral diagnosis of human disease associated with avian influenza A H5N1 virus. Lancet. 1998. 351:467–471.

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