The role of the NxTAG® respiratory pathogen panel assay and other multiplex platforms in clinical practice

Expert Review of Molecular Diagnostics

Volumn 17, Issue 1, 2017, Pages 9-17

  Esposito, Susanna ^a   Principi, Nicola ^a  

^a UNIVERSITY OF MILAN   (Italy)

Author keywords

Atypical bacteria; multiplex assays; NxTAG RPP; respiratory pathogen; respiratory virus

Indexed keywords

ANTIBIOTIC AGENT;

ANTIBIOTIC THERAPY; ARTICLE; BACTERIUM IDENTIFICATION; CLINICAL PRACTICE; DRUG USE; EPIDEMIOLOGICAL DATA; HOSPITALIZATION; HUMAN; LENGTH OF STAY; MULTIPLEX POLYMERASE CHAIN REACTION; NONHUMAN; POLYMERASE CHAIN REACTION SYSTEM; RANDOMIZED CONTROLLED TRIAL (TOPIC); REAL TIME POLYMERASE CHAIN REACTION; RESPIRATORY DIAGNOSTIC DEVICE; RESPIRATORY PATHOGEN PANEL ASSAY; RESPIRATORY SYSTEM; RESPIRATORY TRACT DISEASE; SENSITIVITY AND SPECIFICITY; VIRUS IDENTIFICATION; DEVICES; GENETICS; PROCEDURES; RESPIRATORY TRACT INFECTIONS;

HUMANS; MULTIPLEX POLYMERASE CHAIN REACTION; RESPIRATORY TRACT INFECTIONS;

EID: 85004072426     PISSN: 14737159     EISSN: 17448352     Source Type: Journal    
DOI: 10.1080/14737159.2017.1266260     Document Type: Article

References (84)

1. Esposito S, Daleno C, Prunotto G, et al. Impact of viral infections in children with community-acquired pneumonia:results of a study of17 respiratory viruses. Influenza Other Respir Viruses. 2013;7:18–26.
2. Brown RJ, Nguipdop-Djomo P, Zhao H, et al. Mycoplasma pneumoniae epidemiology in England and Wales:a national perspective. Front Microbiol. 2016;7:157.• An interesting summary of the investigations of patients with suspected Mycoplasma pneumoniae infection that have been undertaken in England since the early 1970s.
3. Esposito S, Principi N., Unsolved problems in the approach to pediatric communityacquired pneumonia. Curr Opin Infect Dis. 2012;25:286–291.
4. Principi N, Esposito S. Emerging role of Mycoplasma pneumoniae and Chlamydia pneumoniae in pediatric respiratory-tract infections. Lancet Infect Dis. 2001;1:334–344.
5. Brodzinski H, Ruddy RM. Review of new and newly discovered respiratory tract viruses in children. Pediatr Emerg Care. 2009;25:352–353.
6. Hodinka RL. Point:is the era of viral culture over in the clinical microbiology laboratory? J Clin Microbiol. 2013;51:2–4.
7. Ginocchio CC. Detection of respiratory viruses using non-molecular based methods. J Clin Virol. 2007;40 Suppl 1(Suppl. 1):SS11-4.
8. Buchan BW, Ledeboer NA. Emerging technologies for the clinical microbiology laboratory. Clin Microbiol Rev. 2014;27:783–822.
9. Miller MB, Tang YW. Basic concepts of microarrays and potential applications in clinical microbiology. Clin Microbiol Rev. 2009;22:611–633.
10. Krunic N, Yager TD, Himsworth D, et al. xTAG RVP assay:analytical and clinical performance. J Clin Virol. 2007;40(Suppl. 1):S39–S46.
11. Mahony J, Chong S, Merante F, et al. Development of a respiratory virus panel test for detection of twenty human respiratory viruses by use of multiplex PCR and a fluid microbead-based assay. J Clin Microbiol. 2007;45:2965–2970.
12. Pabbaraju K, Tokaryk KL, Wong S, et al. Comparison of the Luminex xTAG respiratory viral panel with in-house nucleic acid amplification tests for diagnosis of respiratory virus infections. J Clin Microbiol. 2008;46:3056–3062.
13. Choudhary ML, Anand SP, Tikhe SA, et al. Comparison of the conventional multiplex RT-PCR, real time RT-PCR and Luminex xTAG® RVP fast assay for the detection of respiratory viruses. J Med Virol. 2016;88:51–57.
14. Esposito S, Scala A, Bianchini S, et al. Identification of human adenovirus in respiratory samples with Luminex Respiratory Virus Panel Fast V2 assay and real-time polymerase chain reaction. Int J Mol Sci. 2016;17:297.•• A study showing that the RVP Fast v2 assay has limitations for the detection of hADV and cannot be used to evaluate whether hADVs are the main etiologic agent responsible for an outbreak or when epidemiological studies are performed.
15. Babady NE, Mead P, Stiles J, et al. Comparison of the Luminex xTAG RVP Fast assay and the Idaho Technology FilmArray RP assay for detection of respiratory viruses in pediatric patients at a cancer hospital. J Clin Microbiol. 2012;50:2282–2288.
16. Rand KH, Rampersaud H, Houck HJ. Comparison of two multiplex methods for detection of respiratory viruses:FilmArray RP and xTAG RVP. J Clin Microbiol. 2011;49:2449–2453.
17. Beckmann C, Hirsch HH. Comparing Luminex NxTAG-Respiratory Pathogen Panel and RespiFinder-22 for multiplex detection of respiratory pathogens. J Med Virol. 2016;88:1319–1324.
18. Biomerieux, BioFire FilmArray®. [cited 2016 Aug 15]. Available from:http://www.biomerieux-usa.com/clinical/biofire-film-array.
19. Chen JH, Lam HY, Yip CC, et al. Clinical evaluation of the new high-throughput Luminex NxTAG Respiratory Pathogen Panel Assay for multiplex respiratory pathogen detection. J Clin Microbiol. 2016;54:1820–1825.• This study showed that NxTAG RPP assay demonstrated good diagnostic performance for most respiratory pathogens. The high sample throughput with reasonable turnaround time of this new assay makes it a suitable multiplex platform for routine screening of respiratory specimens in hospital-based laboratories.
20. Tang YW, Gonsalves S, Sun JY, et al. Clinical Evaluation of the Luminex NxTAG Respiratory Pathogen Panel. J Clin Microbiol. 2016;54:1912–1914.• A study showing that the Luminex NxTAG RPP Assay had clinical sensitivities and specificities compared to those of the reference methods that were 80.0–100.0% and 98.9–100.0%, respectively.
21. Pathofinder®. RespiFinder22. [cited 2016 Aug 15]. Available from:http://www.pathofinder.com/products/multifinder/respifinder-22
22. Esposito S, Scala A, Bianchini S, et al. Partial comparison of the NxTAG Respiratory Pathogen Panel Assay with the Luminex xTAG Respiratory Panel Fast Assay V2 and singleplex real-time polymerase chain reaction for detection of respiratory pathogens. Diagn Microbiol Infect Dis. 2016;86:53–57.•• An interesting study showing that the NxTAG RPP assay overcomes some of the limitations of previous Luminex assays, although further studies are needed for a more complete evaluation of the new assay.
23. Malmström K, Pitkäranta A, Carpen O, et al. Human rhinovirus in bronchial epithelium of infants with recurrent respiratory symptoms. J Allergy Clin Immunol. 2006;118:591–596.
24. Simons E, Schroth MK, Gern JE. Analysis of tracheal secretions for rhinovirus during natural colds. Pediatr Allergy Immunol. 2005;16:276–278.
25. Thavagnanam S, Christie SN, Doherty GM, et al. Respiratory viral infection in lower airways of asymptomatic children. Acta Paediatr. 2010;99:394–398.
26. Lahti E, Peltola V, Waris M, et al. Induced sputum in the diagnosis of childhood community-acquired pneumonia. Thorax. 2009;64:252–257.
27. Mathisen M, Strand TA, Valentiner-Branth P, et al. Respiratory viruses in Nepalese children with and without pneumonia:a case-control study. Pediatr Infect Dis J. 2010;29:731–735.
28. Rhedin S, Lindstrand A, Rotzén-Östlund M, et al. Clinical utility of PCR for common viruses in acute respiratory illness. Pediatrics. 2014;133:e538–e545.
29. Esposito S, Daleno C, Tagliabue C, et al. Impact of rhinoviruses on pediatric community-acquired pneumonia. Eur J Clin Microbiol Infect Dis. 2012;31:1637–1645.
30. Principi N, Daleno C, Esposito S. Human rhinoviruses and severe respiratory infections:is it possible to identify at-risk patients early? Expert Rev Anti-Infect Ther. 2014;12:423–430.
31. Parker LC, Stokes CA, Sabroe I. Rhinoviral infection and asthma:the detection and management of rhinoviruses by airway epithelial cells. Clin Exp Allergy. 2014;44:20–28.
32. Shalhoub S, Husain S. Community-acquired respiratory viral infections in lung transplant recipients. Curr Opin Infect Dis. 2013;26:302–308.
33. Jacobs SE, Soave R, Shore TB, et al. Human rhinovirus infections of the lower respiratory tract in hematopoietic stem cell transplant recipients. Transpl Infect Dis. 2013;15:474–486.
34. Johnston SL, Sanderson G, Pattemore PK, et al. Use of polymerase chain reaction for diagnosis of picornavirus infection in subjects with and without respiratory symptoms. J Clin Microbiol. 1993;31:111–117.
35. Van Benten I, Koopman L, Niesters B, et al. Predominance of rhinovirus in the nose of symptomatic and asymptomatic infants. Pediatr Allergy Immunol. 2003;14:363–370.
36. Van Gageldonk-Lafeber AB, Heijnen ML, Bartelds AI, et al. A case-control study of acute respiratory tract infection in general practice patients in The Netherlands. Clin Infect Dis. 2005;41:490–497.
37. Fry AM, Lu X, Olsen SJ, et al. Human rhinovirus infections in rural Thailand:epidemiological evidence for rhinovirus as both pathogen and bystander. PLoS One. 2011;6:e17780.
38. Peltola V, Waris M, Kainulainen L, et al. Virus shedding after human rhinovirus infection in children, adults and patients with hypogammaglobulinaemia. Clin Microbiol Infect. 2013;19:E322–E327.
39. Principi N, Zampiero A, Gambino M, et al. Prospective evaluation of rhinovirus infection in healthy young children. J Clin Virol. 2015;66:83–89.
40. Fox JP, Hall CE, Cooney MK. The Seattle Virus Watch. VII. Observations of adenovirus infections. Am J Epidemiol. 1977;105:362–386.
41. Brandt CD, Kim HW, Vargosko AJ, et al. Infections in 18,000 infants and children in a controlled study of respiratory tract disease. I. Adenovirus pathogenicity in relation to serologic type and illness syndrome. Am J Epidemiol. 1969;90:484–500.
42. Edwards KM, Thompson J, Paolini J, et al. Adenovirus infections in young children. Pediatrics. 1985;76:420–424.
43. Tabain I, Ljubin-Sternak S, Cepin-Bogovic J, et al. Adenovirus respiratory infections in hospitalized children:clinical findings in relation to species and serotypes. Pediatr Infect Dis J. 2012;31:680–684.
44. Fairchok MP, Martin ET, Chambers S, et al. Epidemiology of viral respiratory tract infections in a prospective cohort of infants and toddlers attending daycare. J Clin Virol. 2010;49:16–20.
45. Colvin JM, Muenzer JT, Jaffe DM, et al. Detection of viruses in young children with fever without an apparent source. Pediatrics. 2012;130:e1455–e1462.
46. Kalu SU, Loeffelholz M, Beck E, et al. Persistence of adenovirus nucleic acids in nasopharyngeal secretions:a diagnostic conundrum. Pediatr Infect Dis J. 2010;29:746–750.
47. Jartti T, Hedman K, Jartti L, et al. Human bocavirus-the first 5 years. Rev Med Virol. 2012;22:46–64.
48. Jartti T, Lehtinen P, Vuorinen T, et al. Bronchiolitis:age and previous wheezing episodes are linked to viral etiology and atopic characteristics. Pediatr Infect Dis J. 2009;28:311–317.
49. Brand HK, De Groot R, Galama JM, et al. Infection with multiple viruses is not associated with increased disease severity in children with bronchiolitis. Pediatr Pulmonol. 2012;47:393–400.
50. Principi N, Piralla A, Zampiero A, et al. Bocavirus Infection in Otherwise Healthy Children with Respiratory Disease. PLoS One. 2015;10:e0135640.• This study shows that hBoV is a relatively uncommon but stable infectious agent in children and that hBoV1 seems to be the only strain detected in Italy in respiratory samples. From a clinical point of view, hBoV1 seems to have in the majority of healthy children relatively low clinical relevance. Moreover, the viral load influences only the duration of hospitalization and the use of aerosol therapy without any association with the site of the respiratory disease.
51. Esposito S, Zampiero A, Bianchini S, et al. Epidemiology and Clinical Characteristics of Respiratory Infections Due to Adenovirus in Children Living in Milan, Italy, during 2013 and 2014. PLoS One. 2016;11:e0152375.• This study has shown that hADV infections are diagnosed more commonly than usually thought and that hADVs are stable infectious agents that do not frequently cause severe diseases. A trend toward more complex disease in cases due to hADV species C and in those with higher viral load was demonstrated.
52. Daleno C, Piralla A, Scala A, et al. Phylogenetic analysis of human rhinovirus isolates collected from otherwise healthy children with community-acquired pneumonia during five successive years. PLoS One. 2013;8:e80614.
53. Esposito S, Piralla A, Zampiero A, et al. Characteristics and their clinical relevance of respiratory syncytial virus types and genotypes circulating in Northern Italy in five consecutive winter seasons. PLoS One. 2015;10:e0129369.• This study shows that RSV has complex patterns of circulation characterized by the periodical replacement of the predominant genotypes and indicates that the circulation and pathogenic role of the different RSV strains should be investigated as each may have a different impact on the host.
54. Ramirez JA, Ahkee S, Tolentino A, et al. Diagnosis of Legionella pneumophila, Mycoplasma pneumoniae, or Chlamydia pneumoniae lower respiratory infection using the polymerase chain reaction on a single throat swab specimen. Diagn Microbiol Infect Dis. 1996;24:7–14.
55. Bridge JA, Edelstein PH. Oropharyngeal colonization with Legionella pneumophila. J Clin Microbiol. 1983;18:1108–1112.
56. Meyer Sauteur PM, Unger WW, Nadal D, et al. Infection with and carriage of Mycoplasma pneumoniae in children. Front Microbiol. 2016;7:329.• This review focuses on the characteristics of M. pneumoniae infections in children and exemplifies that simple clinical decision rules may help identifying children at high risk for pneumonia due to M. pneumoniae. This may aid physicians in prescribing appropriate first-line antibiotics, since current diagnostic tests for M. pneumoniae infection are not reliably predictive.
57. Spuesens EB, Fraaij PL, Visser EG, et al. Carriage of Mycoplasma pneumoniae in the upper respiratory tract of symptomatic and asymptomatic children:an observational study. PLoS Med. 2013;10:e1001444.
58. Wood PR, Hill VL, Burks ML, et al. Mycoplasma pneumoniae in children with acute and refractory asthma. Ann Allergy Asthma Immunol. 2013;110:328–334.
59. Miyashita N, Obase Y, Fukuda M, et al. Evaluation of the diagnostic usefulness of real-time PCR for detection of Chlamydophila pneumoniae in acute respiratory infections. J Infect Chemother. 2007;13:183–187.
60. Esposito S, Principi N. Oseltamivir for influenza infection in children:risks and benefits. Expert Rev Respir Med. 2016;10:79–87.• This review highlights that to avoid the risk that children with mild influenza or patients suffering from different viral infections receive oseltamivir, oseltamivir treatment should be recommended only in severe influenza cases, especially if confirmed by reliable laboratory tests.
61. Mazur NI, Martinón-Torres F, Baraldi E, et al. Lower respiratory tract infection caused by respiratory syncytial virus:current management and new therapeutics. Lancet Respir Med. 2015;3:888–900.
62. Esposito S, Bosis S, Begliatti E, et al. Acute tonsillopharyngitis associated with atypical bacterial infection in children:natural history and impact of macrolide therapy. Clin Infect Dis. 2006;43:206–209.
63. Esposito S, Cohen R, Domingo JD, et al. Antibiotic therapy for pediatric community-acquired pneumonia:do we know when, what and for how long to treat? Pediatr Infect Dis J. 2012;3:e78–85.
64. Kohlhoff SA, Hammerschlag MR. Treatment of Chlamydial infections:2014 update. Expert Opin Pharmacother. 2015;16:205–212.
65. Spuesens EB, Meyer Sauteur PM, Vink C, et al. Mycoplasma pneumoniae infections - does treatment help? J Infect. 2014;69(Suppl. 1):S42–46.
66. Gardiner SJ, Gavranich JB, Chang AB. Antibiotics for community-acquired lower respiratory tract infections secondary to Mycoplasma pneumoniae in children. Cochrane Database Syst Rev. 2015;1:CD004875.
67. Principi N, Esposito S. Macrolide-resistant Mycoplasma pneumoniae:its role in respiratory infection. J Antimicrob Chemother. 2013;68:506–511.
68. Noyola DE, Demmler GJ. Effect of rapid diagnosis on management of influenza A infections. Pediatr Infect Dis J. 2000;19:303–307.
69. Esposito S, Marchisio P, Morelli P, et al. Effect of a rapid influenza diagnosis. Arch Dis Child. 2003;88:525–526.
70. Ozkaya E, Cambaz N, Coşkun Y, et al. The effect of rapid diagnostic testing for influenza on the reduction of antibiotic use in paediatric emergency department. Acta Paediatr. 2009;98:1589–1592.
71. Abanses JC, Dowd MD, Simon SD, et al. Impact of rapid influenza testing at triage on management of febrile infants and young children. Pediatr Emerg Care. 2006;22:145–149.
72. Nicholson KG, Abrams KR, Batham S, 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;18:1–274.
73. Doan Q, Enarson P, Kissoon N, et al. Rapid viral diagnosis for acute febrile respiratory illness in children in the Emergency Department.Cochrane. Database Syst Rev. 2014;9:CD006452.
74. Wishaupt JO, Russcher A, Smeets LC, et al. Clinical impact of RT-PCR for pediatric acute respiratory infections:a controlled clinical trial. Pediatrics. 2011;128:e1113–1120.
75. Oosterheert JJ, Van Loon AM, Schuurman R, et al. Impact of rapid detection of viral and atypical bacterial pathogens by real-time polymerase chain reaction for patients with lower respiratory tract infection. Clin Infect Dis. 2005;41:1438–1444.
76. Svensson MJ, Lind I, Wirgart BZ, et al. Performance of the Simplexa™ Flu A/B & RSV Direct Kit on respiratory samples collected in saline solution Scand J Infect Dis. 2014;46:825–831.
77. Selvaraju SB, Tierney D, Leber AL, et al. Influenza and respiratory syncytial virus detection in clinical specimens without nucleic acid extraction using FOCUS direct disc assay is substantially equivalent to the traditional methods and the FOCUS nucleic acid extraction-dependent RT-PCR assay. Diagn Microbiol Infect Dis. 2014;78:232–236.
78. Esposito S, Scala A, Tagliabue C, et al. Evaluation of a multiplex real-time polymerase chain reaction assay for the detection of influenza and respiratory syncytial viruses. Diagn Microbiol Infect Dis. 2016;84:40–42.• Nasopharyngeal swabs from 424 children were used to compare the performances of the new multiplex real-time polymerase chain reaction (RT-PCR) RIDA® GENE Flu & RSV kit and monospecific RT-PCR assays in detecting respiratory syncytial and influenza viruses. The easy-to-use kit was highly sensitive and specific and is recommended for routine practice.
79. Lou Z, Sun Y, Rao Z. Current progress in antiviral strategies.Trends. Pharmacol Sci. 2014;35:86–102.
80. Aguilar HC, Lee B. Emerging paramyxoviruses:molecular mechanisms and antiviral strategies. Med. 2011 Feb;24(13):e6.
81. Martínez-Aguado P, Serna-Gallego A, Marrugal-Lorenzo JA, et al. Antiadenovirus drug discovery:potential targets and evaluation methodologies. Drug Discov Today. 2015 Oct;20(10):1235–1242.
82. Liu Q, Zhou YH, Ye F, et al. Antivirals for Respiratory Viral Infections:Problems and Prospects. Semin Respir Crit Care Med. 2016;37:640–646.
83. Gasparini R, Amicizia D, Lai PL, et al. Compounds with anti-influenza activity:present and future of strategies for the optimal treatment and management of influenza Part II:Future compounds against influenza virus. J Prev Med Hyg. 2014;55:109–129.
84. Mejias A, Ramilo O. New options in the treatment of respiratory syncytial virus disease. J Infect. 2015;71(Suppl 1):SS80-7.