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Evaluation of a rapid antigen detection point-of-care test for respiratory syncytial virus and influenza in a pediatric hospitalized population in the Netherlands
Diagnostic Microbiology and Infectious Disease 80 (2014) 292–293
Contents lists available at ScienceDirect
Diagnostic Microbiology and Infectious Disease journal homepage: www.elsevier.com/locate/diagmicrobio
Evaluation of a rapid antigen detection point-of-care test for respiratory syncytial virus and influenza in a pediatric hospitalized population in the Netherlands Andrea H.L. Bruning a,⁎,1, Karin van Dijk b,1, Hetty W.M. van Eijk c, Gerrit Koen c, Job B.M. van Woensel a, Frea H. Kruisinga a, Dasja Pajkrt a,2, Katja C. Wolthers c,2 a b c
Department of Pediatrics, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands Department of Medical Microbiology and Infection Control, VU University Medical Center, De Boelelaan 1118, 1081 HZ Amsterdam, The Netherlands Laboratory of Clinical Virology, Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands
a r t i c l e
i n f o
Article history: Received 12 July 2014 Received in revised form 20 August 2014 Accepted 25 August 2014 Available online 30 August 2014
a b s t r a c t This pilot study evaluates the diagnostic performance of Sofia RSV Fluorescent Immunoassay Analyzer (FIA) and Sofia Influenza A + B FIA for rapid detection of respiratory syncytial virus and influenza A and B. Sofia had a lower-than-expected sensitivity for all viruses and a high rate of false-positive results for influenza B virus. © 2014 Elsevier Inc. All rights reserved.
Keywords: Rapid testing Respiratory infection Antigen detection Point-of-care Children
Respiratory viral infections are a serious public health concern and the most common cause for hospital admission of children in developed countries (Tregoning and Schwarze, 2010). Rapid and sensitive diagnosis of respiratory infections is needed to initiate timely and specific treatment, prevent misuse of antibiotics, and avoid infection transmission by optimizing infection control measures (Ivaska et al., 2013; Mills et al., 2011). Due to its high sensitivity and high specificity, polymerase chain reaction (PCR) has become the reference method for diagnosing viral infections. However, performance of PCR is relatively expensive and may delay treatment as it requires technical expertise, and highly skilled laboratory personnel and equipment are not always directly available. As a result, rapid antigen detection tests or ‘pointof-care tests’ (POCTs) are a promising alternative as a time-saving method for viral detection (Brotons et al., 2014). Sofia Fluorescent Immunoassay Analyzer (FIA) (Quidel, San Diego, CA) is a rapid fluorescence-based lateral flow immunoassay in which results are analyzed by a compact instrument (Sofia Analyzer). Sofia FIA is designed to be operated by both trained laboratory staff as well as bedside pediatric residents. In this pilot study, we evaluated the performance of Sofia FIA for detection of respiratory syncytial virus (RSV) and influenza viruses ⁎ Corresponding author. Tel.: +31-205668668; fax: +31-206912231. E-mail address: [email protected] (A.H.L. Bruning). 1 Equal contribution as first authors. 2 Equal contribution as last authors. http://dx.doi.org/10.1016/j.diagmicrobio.2014.08.010 0732-8893/© 2014 Elsevier Inc. All rights reserved.
compared to routinely used PCR and Binax blot, a rapid in vitro immunochromatographic assay for detection of RSV. Based on previously published results and information provided by the company, we expected sensitivity and specificity of Sofia FIA for RSV and Influenza in the order of 80% compared to PCR, which would be valued as acceptable (Lee et al., 2012). Secondly, we evaluated practical implementation and forthcoming clinical consequences of Sofia FIA testing. The study was conducted at the pediatric intensive care unit (PICU) and infant ward (IW) of the Academic Medical Center (AMC), a university hospital located in Amsterdam, The Netherlands. After laboratory validation, samples were collected from children (aged 0–16 years old) with symptoms of respiratory illness admitted to either PICU or IW from December 2013 until February 2014. Nasopharyngeal swabs (Copan) were collected at the PICU, and nasopharyngeal aspirates were taken at the IW. After collection, samples were immediately tested for RSV using Sofia RSV FIA and Binax and for Influenza using Sofia Influenza A + B FIA. An internally controlled multiplex real-time PCR was performed within 24 hours after sample collection using the same material (Jansen et al., 2011). Two Sofia analyzers were provided by the manufacturers during study period for evaluation. Binax and PCR facilities were already operational at the AMC. Sofia testing was performed in accordance with the manufacturer's instructions. Study sites were instructed to follow the package insert, and the Sofia analyzer was used in compliance with the manufacturer's user manual. After diagnosis, pediatric residents and laboratory staff were asked to fill in a questionnaire to evaluate the practical benefits and limitations of Sofia FIA.
A.HL. Bruning et al. / Diagnostic Microbiology and Infectious Disease 80 (2014) 292–293 Table 1 Sensitivity and specificity calculations for Sofia FIA and Binax Blot, RSV. RSV
PCR+
Sofia+
18
PCR− 1
Total 19
Sofia−
6
39
45
Sofia invalid Total Binax+
1 25 20
1 41 0
2 66 20
Binax− Total
5 25
41 41
46 66
Sensitivity Sofia: 18/(18 + 6) = 75% (95% CI: 57.7–92.3%) Specificity Sofia: 39/(39 + 1) = 97.5% (95% CI: 92.7–100%)
Sensitivity Binax: 20/(20 + 5) = 80% (95% CI: 64.3–95.7%) Specificity Binax: 41/(41 + 0) = 100%
Influence of diagnosis on changes in isolation measures, discontinuation of antibiotics, and initiation of antiviral agents were monitored. Sixty-six samples were tested for RSV. Twenty-five were positive for RSV by PCR, 19 were positive by Sofia, and 20 were positive by Binax. One sample (2.5%) was false positive using Sofia, and 1 was invalid. As compared to PCR results, Sofia had a sensitivity of 75% (95% confidence interval [CI]: 57.7–92.3%) and a specificity of 97.5% (95% CI: 92.7–100%), and Binax had a sensitivity of 80% (95% CI: 64.3–95.7%) and a specificity of 100% (Table 1). Seventy-three samples were tested using Sofia Influenza A + B FIA. For Influenza A, 10 were positive by PCR, and 8 were positive by Sofia. Two samples (3.4%) were false positive using Sofia, and 5 were invalid. Compared to PCR, Sofia had a sensitivity of 66.7% (95% CI: 35.9–97.5%) and a specificity of 96.6% (95% CI: 92.0–100%) for Influenza A. For Influenza B, 11 of the 73 samples tested were positive by PCR, and 10 were positive by Sofia. Six samples (10.2%) were false positive for Sofia, and 5 were invalid. Compared to PCR, Sofia had a sensitivity of 40% (95% CI: 9.6–70.4%) and a specificity of 89.7% (95% CI: 81.8–97.5%) (Table 2). Thirty questionnaires on clinical benefits and limitations were completed by pediatric residents. In 8 (26.6%), test result had consequences on isolation measures. In 1 case (3.3%), duration of administering antibiotics was reduced. Our results show that performance of Sofia FIA, above all for sensitivity, is poorer than expected from other studies (Hazelton et al., 2014). Furthermore, rate of false positives is high, in particular for Influenza B. As mentioned by Olsen et al. (2014) and Dunn et al. (2014), the manufacturer of Sofia issued a recall on specific lots on December 3, 2012, due to issues with false-positive results (Dunn et al., 2014; Olsen et al., 2014; US Federal Drug Administration, 2013). Despite that we used lots that were produced after the recall, our results demonstrate that there still might be problems. Evaluation of Sofia by laboratory technicians showed as main limitation the numerous and time-consuming proceedings to perform the test, in contrast to Binax. Furthermore, additional material needed for on-site test implementation, e.g., vortex, clock and tube container, not routinely present on a medical ward, was not supplied. According to pediatric residents who were instructed by the company to perform the tests, Sofia was time consuming and difficult to perform. However, availability of a POCT was highly appreciated. POCTs are a promising alternative as a simple, potentially timesaving, and cheaper method for viral testing. However, due to insufficient performance, POCT testing with Sofia FIA is not yet implemented at our center. For implementation of a POCT at a medical ward or emergency room, several logistic difficulties have to be overcome. Our advice for future implementation of POCTs is 3-fold. First, when implementing a POCT, a laboratory validation of the POCT is necessary. Second, it is strongly advised to provide sufficient training moments for both
293
Table 2 Sensitivity and specificity calculations for Sofia FIA, Influenza A + B. Sensitivity and specificity calculations for Sofia FIA, Influenza A Flu A PCR+ PCR− Total Sofia+ 6 2 8 Sensitivity Sofia: 6/(6 + 3) = 66.7% (95% CI: 35.9 – 97.5%) Sofia− 3 57 60 Specificity Sofia: 57/(57 + 2) = 96.6% (95% CI: 92.0 – 100%) Sofia invalid 1 4 5 Total 10 63 73 Sensitivity and specificity calculations for Sofia FIA, Influenza B Flu B PCR+ PCR− Total Sofia+ 4 6 10 Sensitivity Sofia: 4/(4 + 6) = 40% (95% CI: 9.6–70.4%) Sofia− 6 52 58 Specificity Sofia: 52/(52 + 6) = 89.7% (95% CI: 81.8–97.5%) Sofia invalid 1 4 5 Total 11 62 73
laboratory staff as well as other personnel involved in using the test to prevent problems with performing and interpreting test results. Third, confirmation of negative POCT results by more sensitive methods such as PCR would be a recommendable practice, and awareness for falsepositive-results is necessary. Conflict of interest During the study period, 2 Sofia analyzers were provided by the distributor (ITK Diagnostics) for evaluation. ITK Diagnostics had no involvement in the study design, data interpretation, or preparation of the manuscript. References Brotons P, Launes C, Iňigo M, Peris N, Selva L, Muñoz-Almagro C. Performance of a rapid multi-analyte 2-photon excitation assay in children with acute respiratory infection. Diagn Microbiol Infect Dis 2014;79(2):190–3. http://dx.doi.org/10.1016/j. diagmicrobio.2014.02.005. Dunn J, Obuekwe J, Baun T, Rogers J, Patel T, Snow L. Prompt detection of influenza A and B viruses using the BD Veritor™ System Flu A + B, Quidel® Sofia ® Influenza A + B FIA, and Alere BinaxNow®Influenza A&B compared to real-time reversie transcription-polymerase chain reaction (RT-PCR). Diagn Microbiol Infect Dis 2014; 79(1):10–3. http://dx.doi.org/10.1016/j.diagmicrobio.2014.01.018. Hazelton B, Nedeljkovic G, Ratnamohan VM, Dwyer DE, Kok J. Evaluation of the Sofia Influenza A + B fluorescent immunoassay for the rapid diagnosis of influenza A and B. J Med Virol 2014. http://dx.doi.org/10.1002/jmv.23976. Ivaska L, Niemelä J, Heikkinen T, Vuorinen T, Peltola V. Identification of respiratory viruses with a novel point-of-care multianalyte antigen detection test in children with acute respiratory tract infection. J Clin Virol 2013;57(2):136–40. http://dx.doi.org/10.1016/ j.jcv.2013.02.011. Jansen RR, Schinkel J, Koekkoek S, Pajkrt D, Beld M, de Jong MD. Development and evaluation of a four-tube real time multiplex PCR assay covering fourteen respiratory viruses, and comparison to its corresponding single target counterparts. J Clin Virol 2011;51(3):179–85. http://dx.doi.org/10.1016/j.jcv.2011.04.010. Lee CK, Cho CH, Woo MK, Nyeck AE, Lim CS, Kim WJ. Evaluation of Sofia fluorescent immunoassay analyzer for influenza A/B virus. J Clin Virol 2012;55(3):236–43. http:// dx.doi.org/10.1016/j.jcv.2012.07.008. Mills JM, Harper J, Broomfield D, Templeton KE. Rapid testing for respiratory syncytial virus in a paediatric emergency department: benefits for infection control and bed management. J Hosp Infect 2011;77(3):248–51. http://dx.doi.org/10.1016/j.jhin. 2010.11.019. Olsen SJ, Kittikraisak W, Fernandez S, Suntarattiwong P, Chotpitayasunondh T. Challenges with new rapid influenza diagnostic tests. Pediatr Infect Dis J 2014;33(1):117–8. http://dx.doi.org/10.1097/INF.0000000000000089. Tregoning JS, Schwarze J. Respiratory viral infections in infants: causes, clinical symptoms, virology, and immunology. Clin Microbiol Rev 2010;23(1):74–98. http://dx.doi.org/ 10.1128/CMR.00032-09. US Federal Drug Administration. Class 2 recall Sofia influenza A + B FIA, Kit#2028;2013. Available at: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfRes/res.cfm?ID= 115438. [Accessed July 11, 2014].
Contents lists available at ScienceDirect
Diagnostic Microbiology and Infectious Disease journal homepage: www.elsevier.com/locate/diagmicrobio
Evaluation of a rapid antigen detection point-of-care test for respiratory syncytial virus and influenza in a pediatric hospitalized population in the Netherlands Andrea H.L. Bruning a,⁎,1, Karin van Dijk b,1, Hetty W.M. van Eijk c, Gerrit Koen c, Job B.M. van Woensel a, Frea H. Kruisinga a, Dasja Pajkrt a,2, Katja C. Wolthers c,2 a b c
Department of Pediatrics, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands Department of Medical Microbiology and Infection Control, VU University Medical Center, De Boelelaan 1118, 1081 HZ Amsterdam, The Netherlands Laboratory of Clinical Virology, Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands
a r t i c l e
i n f o
Article history: Received 12 July 2014 Received in revised form 20 August 2014 Accepted 25 August 2014 Available online 30 August 2014
a b s t r a c t This pilot study evaluates the diagnostic performance of Sofia RSV Fluorescent Immunoassay Analyzer (FIA) and Sofia Influenza A + B FIA for rapid detection of respiratory syncytial virus and influenza A and B. Sofia had a lower-than-expected sensitivity for all viruses and a high rate of false-positive results for influenza B virus. © 2014 Elsevier Inc. All rights reserved.
Keywords: Rapid testing Respiratory infection Antigen detection Point-of-care Children
Respiratory viral infections are a serious public health concern and the most common cause for hospital admission of children in developed countries (Tregoning and Schwarze, 2010). Rapid and sensitive diagnosis of respiratory infections is needed to initiate timely and specific treatment, prevent misuse of antibiotics, and avoid infection transmission by optimizing infection control measures (Ivaska et al., 2013; Mills et al., 2011). Due to its high sensitivity and high specificity, polymerase chain reaction (PCR) has become the reference method for diagnosing viral infections. However, performance of PCR is relatively expensive and may delay treatment as it requires technical expertise, and highly skilled laboratory personnel and equipment are not always directly available. As a result, rapid antigen detection tests or ‘pointof-care tests’ (POCTs) are a promising alternative as a time-saving method for viral detection (Brotons et al., 2014). Sofia Fluorescent Immunoassay Analyzer (FIA) (Quidel, San Diego, CA) is a rapid fluorescence-based lateral flow immunoassay in which results are analyzed by a compact instrument (Sofia Analyzer). Sofia FIA is designed to be operated by both trained laboratory staff as well as bedside pediatric residents. In this pilot study, we evaluated the performance of Sofia FIA for detection of respiratory syncytial virus (RSV) and influenza viruses ⁎ Corresponding author. Tel.: +31-205668668; fax: +31-206912231. E-mail address: [email protected] (A.H.L. Bruning). 1 Equal contribution as first authors. 2 Equal contribution as last authors. http://dx.doi.org/10.1016/j.diagmicrobio.2014.08.010 0732-8893/© 2014 Elsevier Inc. All rights reserved.
compared to routinely used PCR and Binax blot, a rapid in vitro immunochromatographic assay for detection of RSV. Based on previously published results and information provided by the company, we expected sensitivity and specificity of Sofia FIA for RSV and Influenza in the order of 80% compared to PCR, which would be valued as acceptable (Lee et al., 2012). Secondly, we evaluated practical implementation and forthcoming clinical consequences of Sofia FIA testing. The study was conducted at the pediatric intensive care unit (PICU) and infant ward (IW) of the Academic Medical Center (AMC), a university hospital located in Amsterdam, The Netherlands. After laboratory validation, samples were collected from children (aged 0–16 years old) with symptoms of respiratory illness admitted to either PICU or IW from December 2013 until February 2014. Nasopharyngeal swabs (Copan) were collected at the PICU, and nasopharyngeal aspirates were taken at the IW. After collection, samples were immediately tested for RSV using Sofia RSV FIA and Binax and for Influenza using Sofia Influenza A + B FIA. An internally controlled multiplex real-time PCR was performed within 24 hours after sample collection using the same material (Jansen et al., 2011). Two Sofia analyzers were provided by the manufacturers during study period for evaluation. Binax and PCR facilities were already operational at the AMC. Sofia testing was performed in accordance with the manufacturer's instructions. Study sites were instructed to follow the package insert, and the Sofia analyzer was used in compliance with the manufacturer's user manual. After diagnosis, pediatric residents and laboratory staff were asked to fill in a questionnaire to evaluate the practical benefits and limitations of Sofia FIA.
A.HL. Bruning et al. / Diagnostic Microbiology and Infectious Disease 80 (2014) 292–293 Table 1 Sensitivity and specificity calculations for Sofia FIA and Binax Blot, RSV. RSV
PCR+
Sofia+
18
PCR− 1
Total 19
Sofia−
6
39
45
Sofia invalid Total Binax+
1 25 20
1 41 0
2 66 20
Binax− Total
5 25
41 41
46 66
Sensitivity Sofia: 18/(18 + 6) = 75% (95% CI: 57.7–92.3%) Specificity Sofia: 39/(39 + 1) = 97.5% (95% CI: 92.7–100%)
Sensitivity Binax: 20/(20 + 5) = 80% (95% CI: 64.3–95.7%) Specificity Binax: 41/(41 + 0) = 100%
Influence of diagnosis on changes in isolation measures, discontinuation of antibiotics, and initiation of antiviral agents were monitored. Sixty-six samples were tested for RSV. Twenty-five were positive for RSV by PCR, 19 were positive by Sofia, and 20 were positive by Binax. One sample (2.5%) was false positive using Sofia, and 1 was invalid. As compared to PCR results, Sofia had a sensitivity of 75% (95% confidence interval [CI]: 57.7–92.3%) and a specificity of 97.5% (95% CI: 92.7–100%), and Binax had a sensitivity of 80% (95% CI: 64.3–95.7%) and a specificity of 100% (Table 1). Seventy-three samples were tested using Sofia Influenza A + B FIA. For Influenza A, 10 were positive by PCR, and 8 were positive by Sofia. Two samples (3.4%) were false positive using Sofia, and 5 were invalid. Compared to PCR, Sofia had a sensitivity of 66.7% (95% CI: 35.9–97.5%) and a specificity of 96.6% (95% CI: 92.0–100%) for Influenza A. For Influenza B, 11 of the 73 samples tested were positive by PCR, and 10 were positive by Sofia. Six samples (10.2%) were false positive for Sofia, and 5 were invalid. Compared to PCR, Sofia had a sensitivity of 40% (95% CI: 9.6–70.4%) and a specificity of 89.7% (95% CI: 81.8–97.5%) (Table 2). Thirty questionnaires on clinical benefits and limitations were completed by pediatric residents. In 8 (26.6%), test result had consequences on isolation measures. In 1 case (3.3%), duration of administering antibiotics was reduced. Our results show that performance of Sofia FIA, above all for sensitivity, is poorer than expected from other studies (Hazelton et al., 2014). Furthermore, rate of false positives is high, in particular for Influenza B. As mentioned by Olsen et al. (2014) and Dunn et al. (2014), the manufacturer of Sofia issued a recall on specific lots on December 3, 2012, due to issues with false-positive results (Dunn et al., 2014; Olsen et al., 2014; US Federal Drug Administration, 2013). Despite that we used lots that were produced after the recall, our results demonstrate that there still might be problems. Evaluation of Sofia by laboratory technicians showed as main limitation the numerous and time-consuming proceedings to perform the test, in contrast to Binax. Furthermore, additional material needed for on-site test implementation, e.g., vortex, clock and tube container, not routinely present on a medical ward, was not supplied. According to pediatric residents who were instructed by the company to perform the tests, Sofia was time consuming and difficult to perform. However, availability of a POCT was highly appreciated. POCTs are a promising alternative as a simple, potentially timesaving, and cheaper method for viral testing. However, due to insufficient performance, POCT testing with Sofia FIA is not yet implemented at our center. For implementation of a POCT at a medical ward or emergency room, several logistic difficulties have to be overcome. Our advice for future implementation of POCTs is 3-fold. First, when implementing a POCT, a laboratory validation of the POCT is necessary. Second, it is strongly advised to provide sufficient training moments for both
293
Table 2 Sensitivity and specificity calculations for Sofia FIA, Influenza A + B. Sensitivity and specificity calculations for Sofia FIA, Influenza A Flu A PCR+ PCR− Total Sofia+ 6 2 8 Sensitivity Sofia: 6/(6 + 3) = 66.7% (95% CI: 35.9 – 97.5%) Sofia− 3 57 60 Specificity Sofia: 57/(57 + 2) = 96.6% (95% CI: 92.0 – 100%) Sofia invalid 1 4 5 Total 10 63 73 Sensitivity and specificity calculations for Sofia FIA, Influenza B Flu B PCR+ PCR− Total Sofia+ 4 6 10 Sensitivity Sofia: 4/(4 + 6) = 40% (95% CI: 9.6–70.4%) Sofia− 6 52 58 Specificity Sofia: 52/(52 + 6) = 89.7% (95% CI: 81.8–97.5%) Sofia invalid 1 4 5 Total 11 62 73
laboratory staff as well as other personnel involved in using the test to prevent problems with performing and interpreting test results. Third, confirmation of negative POCT results by more sensitive methods such as PCR would be a recommendable practice, and awareness for falsepositive-results is necessary. Conflict of interest During the study period, 2 Sofia analyzers were provided by the distributor (ITK Diagnostics) for evaluation. ITK Diagnostics had no involvement in the study design, data interpretation, or preparation of the manuscript. References Brotons P, Launes C, Iňigo M, Peris N, Selva L, Muñoz-Almagro C. Performance of a rapid multi-analyte 2-photon excitation assay in children with acute respiratory infection. Diagn Microbiol Infect Dis 2014;79(2):190–3. http://dx.doi.org/10.1016/j. diagmicrobio.2014.02.005. Dunn J, Obuekwe J, Baun T, Rogers J, Patel T, Snow L. Prompt detection of influenza A and B viruses using the BD Veritor™ System Flu A + B, Quidel® Sofia ® Influenza A + B FIA, and Alere BinaxNow®Influenza A&B compared to real-time reversie transcription-polymerase chain reaction (RT-PCR). Diagn Microbiol Infect Dis 2014; 79(1):10–3. http://dx.doi.org/10.1016/j.diagmicrobio.2014.01.018. Hazelton B, Nedeljkovic G, Ratnamohan VM, Dwyer DE, Kok J. Evaluation of the Sofia Influenza A + B fluorescent immunoassay for the rapid diagnosis of influenza A and B. J Med Virol 2014. http://dx.doi.org/10.1002/jmv.23976. Ivaska L, Niemelä J, Heikkinen T, Vuorinen T, Peltola V. Identification of respiratory viruses with a novel point-of-care multianalyte antigen detection test in children with acute respiratory tract infection. J Clin Virol 2013;57(2):136–40. http://dx.doi.org/10.1016/ j.jcv.2013.02.011. Jansen RR, Schinkel J, Koekkoek S, Pajkrt D, Beld M, de Jong MD. Development and evaluation of a four-tube real time multiplex PCR assay covering fourteen respiratory viruses, and comparison to its corresponding single target counterparts. J Clin Virol 2011;51(3):179–85. http://dx.doi.org/10.1016/j.jcv.2011.04.010. Lee CK, Cho CH, Woo MK, Nyeck AE, Lim CS, Kim WJ. Evaluation of Sofia fluorescent immunoassay analyzer for influenza A/B virus. J Clin Virol 2012;55(3):236–43. http:// dx.doi.org/10.1016/j.jcv.2012.07.008. Mills JM, Harper J, Broomfield D, Templeton KE. Rapid testing for respiratory syncytial virus in a paediatric emergency department: benefits for infection control and bed management. J Hosp Infect 2011;77(3):248–51. http://dx.doi.org/10.1016/j.jhin. 2010.11.019. Olsen SJ, Kittikraisak W, Fernandez S, Suntarattiwong P, Chotpitayasunondh T. Challenges with new rapid influenza diagnostic tests. Pediatr Infect Dis J 2014;33(1):117–8. http://dx.doi.org/10.1097/INF.0000000000000089. Tregoning JS, Schwarze J. Respiratory viral infections in infants: causes, clinical symptoms, virology, and immunology. Clin Microbiol Rev 2010;23(1):74–98. http://dx.doi.org/ 10.1128/CMR.00032-09. US Federal Drug Administration. Class 2 recall Sofia influenza A + B FIA, Kit#2028;2013. Available at: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfRes/res.cfm?ID= 115438. [Accessed July 11, 2014].