Respiratory Syncytial Virus and Human Metapneumovirus*

N. Esther Babady; Yi-Wei Tang

doi:10.1128/9781555817381.ch86

Chapter 86 : Respiratory Syncytial Virus and Human Metapneumovirus*

Authors: N. Esther Babady, Yi-Wei Tang

Content Type: Reference

Publication Year: 2015

Category: Clinical Microbiology

Book DOI: 10.1128/9781555817381

Chapter DOI: 10.1128/9781555817381.ch86

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Respiratory Syncytial Virus and Human Metapneumovirus*, Page 1 of 2

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Abstract:

Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are recognized as the most serious causes of severe acute lower respiratory tract illnesses in young children and infants. Rapid and accurate detection and characterization of RSV is important in the clinical management of individual patients because of the availability of specific antiviral drugs. Early detection of RSV and HMPV infections is also necessary for cohorting of infected patients to prevent nosocomial spread. Tube and shell viral cultures remain the gold standard for RSV and HMPV detection, but they are time consuming and require attention to transport and prompt inoculation. Quite a few of rapid viral antigen tests are commercially available, which yield results within 1 hour after specimen collection. However, their sensitivity is limited and negative results usually require a more sensitive back-up test such as a molecular assay or culture. With the increased number of multiplexed molecular Food and Drug Administration (FDA)-approved assays, simultaneous detection and identification of common viral pathogens is becoming the main tool for detection and identification of RSV and MPHV.

Citation: Babady N, Tang Y. 2015. Respiratory Syncytial Virus and Human Metapneumovirus*, p 1498-1518. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch86

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Respiratory Syncytial Virus and Human Metapneumovirus*

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FIGURE 1

Tomography of A2 HRSV virions. Virion morphology ranges from completely filamentous (A) to completely spherical (C) with intermediate forms (B and D) that have some tubularly curved parts but are otherwise spherically curved. Spherical particles are highly deformable when in the proximity of other particles and the membrane proximal to the neighboring particle is free of glycoprotein spikes (E). (F) Virions in panels A through E are illustrated schematically in alphabetical order. Black arrows: side views of the RNP; white arrows: top views of the RNP; green arrows: secondary density layer under the membrane in a spherical particle (bar, 100 nm). Tomographic slices are 3.8 nm thick. Reprinted from reference 9 with permission. doi:10.1128/9781555817381.ch86.f1

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FIGURE 1

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FIGURE 2

Distribution of RSV peak month by geographic zone (n = 96 locations). The black histogram represents observations while the red curve illustrates the fit of a Gaussian density kernel. Reprinted from reference 20 with permission. doi:10.1128/9781555817381.ch86.f2

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FIGURE 2

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FIGURE 3

Microscopic detection of RSV and hMPV. (A) RSV-infected HEp-2 cells have fused, forming large syncytia. (B) Direct immunofluorescence of RSV on a nasopharyngeal swab specimen. (C) Indirect immunofluorescence of HMPV-infected LLC-MK2 centrifugation culture stained with monoclonal antibody MAb-8 ( 142 ). Images courtesy of http://www.virology.org/hpphoto3.html (A) and David Ferguson and Marie Landry (B and C). doi:10.1128/9781555817381.ch86.f3

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FIGURE 3

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FIGURE 4

Seasonal distribution of HMPV infections. HMPV-positive specimens by week in Cincinnati Children’s Hospital, University of Rochester Medical Center, and Vanderbilt University Medical Center from 2003 through 2009. Reprinted from reference 123 with permission. doi:10.1128/9781555817381.ch86.f4

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FIGURE 4

References

/content/book/10.1128/9781555817381.mcm11.ch86

1. Easton AJ,, Domachowske JB,, Rosenberg HF. 2004. Animal pneumoviruses: molecular genetics and pathogenesis. Clin Microbiol Rev 17: 390– 412.

2. Pringle CR,, Easton AJ. 1997. Monopartite negative strand RNA genomes. Semin Virol 8: 49– 57.

3. Blount RE Jr.,, Morris JA,, Savage RE. 1956. Recovery of cytopathogenic agent from chimpanzees with coryza. Proc Soc Exp Biol Med 92( 3): 544– 549.

4. Chanock R,, Roizman B,, Myers R. 1957. Recovery from infants with respiratory illness of a virus related to chimpanzee coryza agent (CCA). I. Isolation, properties and characterization. Am J Hyg 66( 3): 281– 290.

5. Collins PL,, Crowe JEJ,. 2007. Respiratory syncytial virus and metapneumovirus, p. 1601– 1646. In Knipe DM,, Howley PM ( ed), Fields Virology, 5th ed. Lippincott Williams & Wilkins, Philadelphia, PA.

6. Williams JV,, Piedra PA,, Englund JA,. 2009. Respiratory syncytial virus, human metapneumovirus, and parainfluenza viruses, p 1443– 1486. In Richman DD,, Whitley RJ,, Hayden FG ( ed), Clinical Virology. ASM Press, Washington, DC.

7. Sullender WM. 2000. Respiratory syncytial virus genetic and antigenic diversity. Clin Microbiol Rev 13: 1– 15.

8. Tan L,, Coenjaerts FE,, Houspie L,, Viveen MC,, van Bleek GM,, Wiertz EJ,, Martin DP,, Lemey P. 2013. The comparative genomics of human respiratory syncytial virus subgroups a and B: genetic variability and molecular evolutionary dynamics. J Virol 87: 8213– 8226.

9. Liljeroos L,, Krzyzaniak MA,, Helenius A,, Butcher SJ. 2013. Architecture of respiratory syncytial virus revealed by electron cryotomography. Proc Natl Acad Sci USA 110( 27): 11133– 11138.

10. Li D,, Jans DA,, Bardin PG,, Meanger J,, Mills J,, Ghildyal R. 2008. Association of respiratory syncytial virus M protein with viral nucleocapsids is mediated by the M2-1 protein. J Virol 82: 8863– 8870.

11. Bitko V,, Shulyayeva O,, Mazumder B,, Musiyenko A,, Ramaswamy M,, Look DC,, Barik S. 2007. Nonstructural proteins of respiratory syncytial virus suppress premature apoptosis by an NF-kappaB-dependent, interferon-independent mechanism and facilitate virus growth. J Virol 81: 1786– 1795.

12. Spann KM,, Tran KC,, Collins PL. 2005. Effects of nonstructural proteins NS1 and NS2 of human respiratory syncytial virus on interferon regulatory factor 3, NF-kappaB, and proinflammatory cytokines. J Virol 79: 5353– 5362.

13. Mufson MA,, Orvell C,, Rafnar B,, Norrby E. 1985. Two distinct subtypes of human respiratory syncytial virus. J Gen Virol 66( Pt 10): 2111– 2124.

14. Hall CB,, Walsh EE,, Schnabel KC,, Long CE,, McConnochie KM,, Hildreth SW,, Anderson LJ. 1990. Occurrence of groups A and B of respiratory syncytial virus over 15 years: associated epidemiologic and clinical characteristics in hospitalized and ambulatory children. J Infect Dis 162( 6): 1283– 1290.

15. Tran DN,, Pham TM,, Ha MT,, Tran TT,, Dang TK,, Yoshida LM,, Okitsu S,, Hayakawa S,, Mizuguchi M,, Ushijima H. 2013. Molecular epidemiology and disease severity of human respiratory syncytial virus in Vietnam. PLoS One 8( 1): e45436. 10.1371/journal.pone.0045436.

16. Hall CB,, McCarthy CA,. 2005. Respiratory syncytial virus, p 2009– 2021. In Mandell GL,, Bennett JE, Dolan R ( ed), Principles and Practice of Infectious Diseases, 2nd ed. Churchill Livingstone, Philadelphia, PA.

17. Hall CB,, Douglas RG Jr.,, Schnabel KC,, Geiman JM. 1981. Infectivity of respiratory syncytial virus by various routes of inoculation. Infect Immun 33: 779– 783.

18. Wright M,, Piedimonte G. 2011. Respiratory syncytial virus prevention and therapy: past, present, and future. Pediatr Pulmonol 46( 4): 324– 347.

19. Pica N,, Bouvier NM. 2012. Environmental factors affecting the transmission of respiratory viruses. Curr Opin Virol 2( 1): 90– 95.

20. Bloom-Feshbach K,, Alonso WJ,, Charu V,, Tamerius J,, Simonsen L,, Miller MA,, Viboud C. 2013. Latitudinal variations in seasonal activity of influenza and respiratory syncytial virus (RSV): a global comparative review. PLoS One 8( 2): e54445. 10.1371/journal.pone.0054445.

21. Jafri HS,, Wu X,, Makari D,, Henrickson KJ. 2013. Distribution of respiratory syncytial virus subtypes A and B among infants presenting to the emergency department with lower respiratory tract infection or apnea. Pediatr Infect Dis J 32( 4): 335– 340.

22. Prifert C,, Streng A,, Krempl CD,, Liese J,, Weissbrich B. 2013. Novel respiratory syncytial virus a genotype, Germany, 2011–2012. Emerg Infect Dis 19( 6): 1029– 1030.

23. Zhang ZY,, Du LN,, Chen X,, Zhao Y,, Liu EM,, Yang XQ,, Zhao XD. 2010. Genetic variability of respiratory syncytial viruses (RSV) prevalent in Southwestern China from 2006 to 2009: emergence of subgroup B and A RSV as dominant strains. J Clin Microbiol 48: 1201– 1207.

24. Nair H,, Nokes DJ,, Gessner BD,, Dherani M,, Madhi SA,, Singleton RJ,, O’Brien KL,, Roca A,, Wright PF,, Bruce N,, Chandran A,, Theodoratou E,, Sutanto A,, Sedyaningsih ER,, Ngama M,, Munywoki PK,, Kartasasmita C,, Simoes EA,, Rudan I,, Weber MW,, Campbell H. 2010. Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis. Lancet 375( 9725): 1545– 1555.

25. Hall CB,, Weinberg GA,, Iwane MK,, Blumkin AK,, Edwards KM,, Staat MA,, Auinger P,, Griffin MR,, Poehling KA,, Erdman D,, Grijalva CG,, Zhu Y,, Szilagyi P. 2009. The burden of respiratory syncytial virus infection in young children. N Engl J Med 360( 6): 588– 598.

26. Zlateva KT,, Vijgen L,, Dekeersmaeker N,, Naranjo C,, Van Ranst M. 2007. Subgroup prevalence and genotype circulation patterns of human respiratory syncytial virus in Belgium during ten successive epidemic seasons. J Clin Microbiol 45: 3022– 3030.

27. Thorburn K,, Kerr S,, Taylor N,, van Saene HK. 2004. RSV outbreak in a paediatric intensive care unit. J Hosp Infect 57( 3): 194– 201.

28. Macartney KK,, Gorelick MH,, Manning ML,, Hodinka RL,, Bell LM. 2000. Nosocomial respiratory syncytial virus infections: the cost-effectiveness and cost-benefit of infection control. Pediatrics 106( 3): 520– 526.

29. Hall CB. 2001. Respiratory syncytial virus and parainfluenza virus. N Engl J Med 344( 25): 1917– 1928.

30. Lessler J,, Reich NG,, Brookmeyer R,, Perl TM,, Nelson KE,, Cummings DA. 2009. Incubation periods of acute respiratory viral infections: a systematic review. Lancet Infect Dis 9( 5): 291– 300.

31. Libster R,, Bugna Hortoneda J,, Laham FR,, Casellas JM,, Israele V,, Polack NR,, Delgado MF,, Klein MI,, Polack FP. 2009. Breastfeeding prevents severe disease in full term female infants with acute respiratory infection. Pediatr Infect Dis J 28( 2): 131– 134.

32. Colosia AD,, Masaquel A,, Hall CB,, Barrett AM,, Mahadevia PJ,, Yogev R. 2012. Residential crowding and severe respiratory syncytial virus disease among infants and young children: a systematic literature review. BMC Infect Dis 12: 95.

33. DeVincenzo JP,, El Saleeby CM,, Bush AJ. 2005. Respiratory syncytial virus load predicts disease severity in previously healthy infants. J Infect Dis 191( 11): 1861– 1868.

34. Henderson FW,, Collier AM,, Clyde WA Jr.,, Denny FW. 1979. Respiratory-syncytial-virus infections, reinfections and immunity. A prospective, longitudinal study in young children. N Engl J Med 300( 10): 530– 534.

35. Falsey AR,, Walsh EE. 2000. Respiratory syncytial virus infection in adults. Clin Microbiol Rev 13( 3): 371– 384.

36. Falsey AR,, Hennessey PA,, Formica MA,, Cox C,, Walsh EE. 2005. Respiratory syncytial virus infection in elderly and high-risk adults. N Engl J Med 352( 17): 1749– 1759.

37. Widmer K,, Zhu Y,, Williams JV,, Griffin MR,, Edwards KM,, Talbot HK. 2012. Rates of hospitalizations for respiratory syncytial virus, human metapneumovirus, and influenza virus in older adults. J Infect Dis 206( 1): 56– 62.

38. Renaud C,, Campbell AP. 2011. Changing epidemiology of respiratory viral infections in hematopoietic cell transplant recipients and solid organ transplant recipients. Curr Opin Infect Dis 24( 4): 333– 343.

39. Avetisyan G,, Mattsson J,, Sparrelid E,, Ljungman P. 2009. Respiratory syncytial virus infection in recipients of allogeneic stem-cell transplantation: a retrospective study of the incidence, clinical features, and outcome. Transplantation 88( 10): 1222– 1226.

40. Chemaly RF,, Ghosh S,, Bodey GP,, Rohatgi N,, Safdar A,, Keating MJ,, Champlin RE,, Aguilera EA,, Tarrand JJ,, Raad II. 2006. Respiratory viral infections in adults with hematologic malignancies and human stem cell transplantation recipients: a retrospective study at a major cancer center. Medicine (Baltimore) 85( 5): 278– 287.

41. Peck AJ,, Corey L,, Boeckh M. 2004. Pretransplantation respiratory syncytial virus infection: impact of a strategy to delay transplantation. Clin Infect Dis 39( 5): 673– 680.

42. Ariza-Heredia EJ,, Fishman JE,, Cleary T,, Smith L,, Razonable RR,, Abbo L. 2012. Clinical and radiological features of respiratory syncytial virus in solid organ transplant recipients: a single-center experience. Transpl Infect Dis 14( 1): 64– 71.

43. Krinzman S,, Basgoz N,, Kradin R,, Shepard JA,, Flieder DB,, Wright CD,, Wain JC,, Ginns LC. 1998. Respiratory syncytial virus-associated infections in adult recipients of solid organ transplants. J Heart Lung Transplant 17( 2): 202– 210.

44. Palmer SM Jr.,, Henshaw NG,, Howell DN,, Miller SE,, Davis RD,, Tapson VF. 1998. Community respiratory viral infection in adult lung transplant recipients. Chest 113( 4): 944– 950.

45. Singhal S,, Muir DA,, Ratcliffe DA,, Shirley JA,, Cane PA,, Hastings JG,, Pillay D,, Mutimer DJ. 1999. Respiratory viruses in adult liver transplant recipients. Transplantation 68( 7): 981– 984.

46. Hynicka LM,, Ensor CR. 2012. Prophylaxis and treatment of respiratory syncytial virus in adult immunocompromised patients. Ann Pharmacother 46( 4): 558– 566.

47. Feltes TF,, Cabalka AK,, Meissner HC,, Piazza FM,, Carlin DA,, Top FH Jr.,, Connor EM,, Sondheimer HM. 2003. Palivizumab prophylaxis reduces hospitalization due to respiratory syncytial virus in young children with hemodynamically significant congenital heart disease. J Pediatr 143( 4): 532– 540.

48. Carbonell-Estrany X,, Simoes EA,, Dagan R,, Hall CB,, Harris B,, Hultquist M,, Connor EM,, Losonsky GA, Motavizumab Study Group. 2010. Motavizumab for prophylaxis of respiratory syncytial virus in high-risk children: a noninferiority trial. Pediatrics 125( 1): e35– e51.

49. Feltes TF,, Sondheimer HM,, Tulloh RM,, Harris BS,, Jensen KM,, Losonsky GA,, Griffin MP,, Motavizumab Cardiac Study Group. 2011. A randomized controlled trial of motavizumab versus palivizumab for the prophylaxis of serious respiratory syncytial virus disease in children with hemodynamically significant congenital heart disease. Pediatr Res 70( 2): 186– 191.

50. Shah DP,, Ghantoji SS,, Shah JN,, El Taoum KK,, Jiang Y,, Popat U,, Hosing C,, Rondon G,, Tarrand JJ,, Champlin RE,, Chemaly RF. 2013. Impact of aerosolized ribavirin on mortality in 280 allogeneic haematopoietic stem cell transplant recipients with respiratory syncytial virus infections. J Antimicrob Chemother 68( 8): 1872– 1880.

51. Englund JA,, Piedra PA,, Jewell A,, Patel K,, Baxter BB,, Whimbey E. 1996. Rapid diagnosis of respiratory syncytial virus infections in immunocompromised adults. J Clin Microbiol 34: 1649– 1653.

52. Blaschke AJ,, Allison MA,, Meyers L,, Rogatcheva M,, Heyrend C,, Mallin B,, Carter M,, Lafleur B,, Barney T,, Poritz MA,, Daly JA,, Byington CL. 2011. Non-invasive sample collection for respiratory virus testing by multiplex PCR. J Clin Virol 52: 210– 214.

53. Falsey AR,, Formica MA,, Walsh EE. 2012. Yield of sputum for viral detection by reverse transcriptase PCR in adults hospitalized with respiratory illness. J Clin Microbiol 50: 21– 24.

54. Munywoki PK,, Hamid F,, Mutunga M,, Welch S,, Cane P,, Nokes DJ. 2011. Improved detection of respiratory viruses in pediatric outpatients with acute respiratory illness by real-time PCR using nasopharyngeal flocked swabs. J Clin Microbiol 49: 3365– 3367.

55. Spyridaki IS,, Christodoulou I,, de Beer L,, Hovland V,, Kurowski M,, Olszewska-Ziaber A,, Carlsen KH,, Lodrup-Carlsen K,, van Drunen CM,, Kowalski ML,, Molenkamp R,, Papadopoulos NG. 2009. Comparison of four nasal sampling methods for the detection of viral pathogens by RT-PCR-A GA(2)LEN project. J Virol Methods 156( 1-2): 102– 106.

56. Abu-Diab A,, Azzeh M,, Ghneim R,, Ghneim R,, Zoughbi M,, Turkuman S,, Rishmawi N,, Issa AE,, Siriani I,, Dauodi R,, Kattan R,, Hindiyeh MY. 2008. Comparison between pernasal flocked swabs and nasopharyngeal aspirates for detection of common respiratory viruses in samples from children. J Clin Microbiol 46: 2414– 2417.

57. Daley P,, Castriciano S,, Chernesky M,, Smieja M. 2006. Comparison of flocked and rayon swabs for collection of respiratory epithelial cells from uninfected volunteers and symptomatic patients. J Clin Microbiol 44: 2265– 2267.

58. Macfarlane P,, Denham J,, Assous J,, Hughes C. 2005. RSV testing in bronchiolitis: which nasal sampling method is best? Arch Dis Child 90( 6): 634– 635.

59. Chan KH,, Peiris JS,, Lim W,, Nicholls JM,, Chiu SS. 2008. Comparison of nasopharyngeal flocked swabs and aspirates for rapid diagnosis of respiratory viruses in children. J Clin Virol 42( 1): 65– 69.

60. Robinson JL,, Lee BE,, Kothapalli S,, Craig WR,, Fox JD. 2008. Use of throat swab or saliva specimens for detection of respiratory viruses in children. Clin Infect Dis 46( 7): e61– e64.

61. Cheng FW,, Lee V,, Shing MM,, Li CK. 2008. Prolonged shedding of respiratory syncytial virus in immunocompromised children: implication for hospital infection control. J Hosp Infect 70( 4): 383– 385.

62. King JC Jr.,, Burke AR,, Clemens JD,, Nair P,, Farley JJ,, Vink PE,, Batlas SR,, Rao M,, Johnson JP. 1993. Respiratory syncytial virus illnesses in human immunodeficiency virus- and noninfected children. Pediatr Infect Dis J 12( 9): 733– 739.

63. Buckingham SC,, Bush AJ,, Devincenzo JP. 2000. Nasal quantity of respiratory syncytial virus correlates with disease severity in hospitalized infants. Pediatr Infect Dis J 19( 2): 113– 117.

64. Perkins SM,, Webb DL,, Torrance SA,, El Saleeby C,, Harrison LM,, Aitken JA,, Patel A,, DeVincenzo JP. 2005. Comparison of a real-time reverse transcriptase PCR assay and a culture technique for quantitative assessment of viral load in children naturally infected with respiratory syncytial virus. J Clin Microbiol 43: 2356– 2362.

65. DeVincenzo JP,, Wilkinson T,, Vaishnaw A,, Cehelsky J,, Meyers R,, Nochur S,, Harrison L,, Meeking P,, Mann A,, Moane E,, Oxford J,, Pareek R,, Moore R,, Walsh E,, Studholme R,, Dorsett P,, Alvarez R,, Lambkin-Williams R. 2010. Viral load drives disease in humans experimentally infected with respiratory syncytial virus. Am J Respir Crit Care Med 182( 10): 1305– 1314.

66. Walsh EE,, Peterson DR,, Kalkanoglu AE,, Lee FE,, Falsey AR. 2013. Viral shedding and immune responses to respiratory syncytial virus infection in older adults. J Infect Dis 207( 9): 1424– 1432.

67. Prendergast C,, Papenburg J. 2013. Rapid antigen-based testing for respiratory syncytial virus: moving diagnostics from bench to bedside? Future Microbiol 8( 4): 435– 444.

68. Goodrich JS,, Miller MB. 2007. Comparison of Cepheid’s analyte-specific reagents with BD directigen for detection of respiratory syncytial virus. J Clin Microbiol 45: 604– 606.

69. Ohm-Smith MJ,, Nassos PS,, Haller BL. 2004. Evaluation of the Binax NOW, BD Directigen, and BD Directigen EZ assays for detection of respiratory syncytial virus. J Clin Microbiol 42: 2996– 2999.

70. Ginocchio CC. 2007. Detection of respiratory viruses using non-molecular based methods. J Clin Virol 40( Suppl 1): S11– S14.

71. Aslanzadeh J,, Zheng X,, Li H,, Tetreault J,, Ratkiewicz I,, Meng S,, Hamilton P,, Tang YW. 2008. Prospective evaluation of rapid antigen tests for diagnosis of respiratory syncytial virus and human metapneumovirus infections. J Clin Microbiol 46: 1682– 1685.

72. Henrickson KJ,, Hall CB. 2007. Diagnostic assays for respiratory syncytial virus disease. Pediatr Infect Dis J. 26( Suppl 11): S36– S40.

73. Casiano-Colon AE,, Hulbert BB,, Mayer TK,, Walsh EE,, Falsey AR. 2003. Lack of sensitivity of rapid antigen tests for the diagnosis of respiratory syncytial virus infection in adults. J Clin Virol 28( 2): 169– 174.

74. Leland DS,, Ginocchio CC. 2007. Role of cell culture for virus detection in the age of technology. Clin Microbiol Rev 20: 49– 78.

75. Borek AP,, Clemens SH,, Gaskins VK,, Aird DZ,, Valsamakis A. 2006. Respiratory syncytial virus detection by Remel Xpect, Binax RSV, direct immunofluorescent staining, and tissue culture. J Clin Microbiol 44: 1105– 1107.

76. Kuroiwa Y,, Nagai K,, Okita L,, Ukae S,, Mori T,, Hotsubo T,, Tsutsumi H. 2004. Comparison of an immunochromatography test with multiplex reverse transcription-PCR for rapid diagnosis of respiratory syncytial virus infections. J Clin Microbiol 42: 4812– 4814.

77. Shirato K,, Nishimura H,, Saijo M,, Okamoto M,, Noda M,, Tashiro M,, Taguchi F. 2007. Diagnosis of human respiratory syncytial virus infection using reverse transcription loop-mediated isothermal amplification. J Virol Methods 139( 1): 78– 84.

78. Gregson D,, Lloyd T,, Buchan S,, Church D. 2005. Comparison of the RSV respi-strip with direct fluorescent-antigen detection for diagnosis of respiratory syncytial virus infection in pediatric patients. J Clin Microbiol 43: 5782– 5783.

79. Ginocchio CC,, Swierkosz E,, McAdam AJ,, Marcon M,, Storch GA,, Valsamakis A,, Juretschko S,, Romero J,, Yen-Lieberman B. 2010. Multicenter study of clinical performance of the 3MRapid Detection RSV test. J Clin Microbiol 48: 2337– 2343.

80. Bentzen EL,, House F,, Utley TJ,, Crowe JE Jr.,, Wright DW. 2005. Progression of respiratory syncytial virus infection monitored by fluorescent quantum dot probes. Nano Lett 5( 4): 591– 595.

81. Tripp RA,, Alvarez R,, Anderson B,, Jones L,, Weeks C,, Chen W. 2007. Bioconjugated nanoparticle detection of respiratory syncytial virus infection. Int J Nanomedicine 2( 1): 117– 124.

82. Irmen KE,, Kelleher JJ. 2000. Use of monoclonal antibodies for rapid diagnosis of respiratory viruses in a community hospital. Clin Diagn Lab Immunol 7( 3): 396– 403.

83. Fong CK,, Lee MK,, Griffith BP. 2000. Evaluation of R-Mix FreshCells in shell vials for detection of respiratory viruses. J Clin Microbiol 38: 4660– 4662.

84. Landry ML,, Ferguson D. 2000. SimulFluor respiratory screen for rapid detection of multiple respiratory viruses in clinical specimens by immunofluorescence staining. J Clin Microbiol 38: 708– 711.

85. Ivaska L,, Niemela J,, Heikkinen T,, Vuorinen T,, Peltola V. 2013. Identification of respiratory viruses with a novel point-of-care multianalyte antigen detection test in children with acute respiratory tract infection. J Clin Virol 57( 2): 136– 140.

86. Loeffelholz M,, Chonmaitree T. 2010. Advances in diagnosis of respiratory virus infections. Int J Microbiol 2010: 126049.

87. Borg I,, Rohde G,, Loseke S,, Bittscheidt J,, Schultze-Werninghaus G,, Stephan V,, Bufe A. 2003. Evaluation of a quantitative real-time PCR for the detection of respiratory syncytial virus in pulmonary diseases. Eur Respir J 21( 6): 944– 951.

88. Brunstein JD,, Cline CL,, McKinney S,, Thomas E. 2008. Evidence from multiplex molecular assays for complex multipathogen interactions in acute respiratory infections. J Clin Microbiol 46: 97– 102.

89. Hymas WC,, Hillyard DR. 2009. Evaluation of Nanogen MGB Alert Detection Reagents in a multiplex real-time PCR for influenza virus types A and B and respiratory syncytial virus. J Virol Methods 156( 1-2): 124– 128.

90. Legoff J,, Kara R,, Moulin F,, Si-Mohamed A,, Krivine A,, Belec L,, Lebon P. 2008. Evaluation of the one-step multiplex real-time reverse transcription-PCR ProFlu-1 assay for detection of influenza A and influenza B viruses and respiratory syncytial viruses in children. J Clin Microbiol 46: 789– 791.

91. Li H,, McCormac MA,, Estes RW,, Sefers SE,, Dare RK,, Chappell JD,, Erdman DD,, Wright PF,, Tang YW. 2007. Simultaneous detection and high-throughput identification of a panel of RNA viruses causing respiratory tract infections. J Clin Microbiol 45: 2105– 2109.

92. Mahony J,, Chong S,, Merante F,, Yaghoubian S,, Sinha T,, Lisle C,, Janeczko R. 2007. 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 45: 2965– 2970.

93. Raymond F,, Carbonneau J,, Boucher N,, Robitaille L,, Boisvert S,, Wu WK,, De Serres G,, Boivin G,, Corbeil J. 2009. Comparison of automated microarray detection with real-time PCR assays for detection of respiratory viruses in specimens obtained from children. J Clin Microbiol 47: 743– 750.

94. Deiman B,, Schrover C,, Moore C,, Westmoreland D,, van de Wiel P. 2007. Rapid and highly sensitive qualitative real-time assay for detection of respiratory syncytial virus A and B using NASBA and molecular beacon technology. J Virol Methods 146( 1-2): 29– 35.

95. Moore C,, Valappil M,, Corden S,, Westmoreland D. 2006. Enhanced clinical utility of the NucliSens EasyQ RSV A+B Assay for rapid detection of respiratory syncytial virus in clinical samples. Eur J Clin Microbiol Infect Dis 25( 3): 167– 174.

96. Ushio M,, Yui I,, Yoshida N,, Fujino M,, Yonekawa T,, Ota Y,, Notomi T,, Nakayama T. 2005. Detection of respiratory syncytial virus genome by subgroups-A, B specific reverse transcription loop-mediated isothermal amplification (RT-LAMP). J Med Virol 77( 1): 121– 127.

97. Reijans M,, Dingemans G,, Klaassen CH,, Meis JF,, Keijdener J,, Mulders B,, Eadie K,, van Leeuwen W,, van Belkum A,, Horrevorts AM,, Simons G. 2008. RespiFinder: a new multiparameter test to differentially identify fifteen respiratory viruses. J Clin Microbiol 46: 1232– 1240.

98. Babady NE,, Mead P,, Stiles J,, Brennan C,, Li H,, Shuptar S,, Stratton CW,, Tang YW,, Kamboj M. 2012. 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 50: 2282– 2288.

99. Pabbaraju K,, Wong S,, Tokaryk KL,, Fonseca K Drews SJ. 2011. Comparison of the Luminex xTAG respiratory viral panel with xTAG respiratory viral panel fast for diagnosis of respiratory virus infections. J Clin Microbiol 49: 1738– 1744.

100. Pierce VM,, Elkan M,, Leet M,, McGowan KL,, Hodinka RL. 2012. Comparison of the Idaho Technology FilmArray system to real-time PCR for detection of respiratory pathogens in children. J Clin Microbiol 50: 364– 371.

101. Couturier MR,, Barney T,, Alger G,, Hymas WC,, Stevenson JB,, Hillyard D,, Daly JA. 2013. Evaluation of the FilmArray(R) Respiratory Panel for clinical use in a large children’s hospital. J Clin Lab Anal 27( 2): 148– 154.

102. Xu M,, Qin X,, Astion ML,, Rutledge JC,, Simpson J,, Jerome KR,, Englund JA,, Zerr DM,, Migita RT,, Rich S,, Childs JC,, Cent A,, Del Beccaro MA. 2013. Implementation of filmarray respiratory viral panel in a core laboratory improves testing turnaround time and patient care. Am J Clin Pathol 139( 1): 118– 123.

103. Hawkinson D,, Abhyankar S,, Aljitawi O,, Ganguly S,, McGuirk JP,, Horvat R. 2013. Delayed RSV diagnosis in a stem cell transplant population due to mutations that result in negative polymerase chain reaction. Diagn Microbiol Infect Dis 75( 4): 426– 430.

104. Barenfanger J,, Drake C,, Mueller T,, Troutt T,, O’Brien J,, Guttman K. 2001. 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 22( 1): 101– 110.

105. St George K,, Patel NM,, Hartwig RA,, Scholl DR,, Jollick JA Jr.,, Kauffmann LM,, Evans MR,, Rinaldo CR Jr. 2002. Rapid and sensitive detection of respiratory virus infections for directed antiviral treatment using R-Mix cultures. J Clin Virol 24( 1-2): 107– 115.

106. LaSala PR,, Bufton KK,, Ismail N,, Smith MB. 2007. Prospective comparison of R-mix shell vial system with direct antigen tests and conventional cell culture for respiratory virus detection. J Clin Virol 38( 3): 210– 216.

107. Kim JS,, Kim SH,, Bae SY,, Lim CS,, Kim YK,, Lee KN,, Lee CK. 2008. Enhanced detection of respiratory viruses using cryopreserved R-Mix ReadyCells. J Clin Virol 42( 3): 264– 267.

108. Cane PA,, Pringle CR. 1991. Respiratory syncytial virus heterogeneity during an epidemic: analysis by limited nucleotide sequencing (SH gene) and restriction mapping (N gene). J Gen Virol 72( Pt 2): 349– 357.

109. Sullender WM,, Sun L,, Anderson LJ. 1993. Analysis of respiratory syncytial virus genetic variability with amplified cDNAs. J Clin Microbiol 31: 1224– 1231.

110. Gaunt ER,, Jansen RR,, Poovorawan Y,, Templeton KE,, Toms GL,, Simmonds P. 2011. Molecular epidemiology and evolution of human respiratory syncytial virus and human metapneumovirus. PLoS One 6( 3): e17427. 10 .1371/journal.pone.0017427.

111. Sato M,, Saito R,, Sakai T,, Sano Y,, Nishikawa M,, Sasaki A,, Shobugawa Y,, Gejyo F.,, Suzuki H. 2005. Molecular epidemiology of respiratory syncytial virus infections among children with acute respiratory symptoms in a community over three seasons. J Clin Microbiol 43: 36– 40.

112. Venter M,, Madhi SA,, Tiemessen CT,, Schoub BD. 2001. Genetic diversity and molecular epidemiology of respiratory syncytial virus over four consecutive seasons in South Africa: identification of new subgroup A and B genotypes. J Gen Virol. 82( Pt 9): 2117– 2124.

113. Okiro EA,, Sande C,, Mutunga M,, Medley GF,, Cane PA,, Nokes DJ. 2008. Identifying infections with respiratory syncytial virus by using specific immunoglobulin G (IgG) and IgA enzyme-linked immunosorbent assays with oral-fluid samples. J Clin Microbiol 46: 1659– 1662.

114. Walsh EE,, Falsey AR. 2004. Humoral and mucosal immunity in protection from natural respiratory syncytial virus infection in adults. J Infect Dis 190( 2): 373– 378.

115. Taggart EW,, Hill HR,, Martins TB,, Litwin CM. 2006. Comparison of complement fixation with two enzyme-linked immunosorbent assays for the detection of antibodies to respiratory viral antigens. Am J Clin Pathol 125( 3): 460– 466.

116. Piedra PA,, Jewell AM,, Cron SG,, Atmar RL,, Glezen WP. 2003. Correlates of immunity to respiratory syncytial virus (RSV) associated-hospitalization: establishment of minimum protective threshold levels of serum neutralizing antibodies. Vaccine 21( 24): 3479– 3482.

117. Zhao X,, Chen FP,, Megaw AG,, Sullender WM. 2004. Variable resistance to palivizumab in cotton rats by respiratory syncytial virus mutants. J Infect Dis 190( 11): 1941– 1946.

118. DeVincenzo JP,, Hall CB,, Kimberlin DW,, Sanchez PJ,, Rodriguez WJ,, Jantausch BA,, Corey L,, Kahn JS,, Englund JA,, Suzich JA,, Palmer-Hill FJ,, Branco L,, Johnson S,, Patel NK,, Piazza FM. 2004. Surveillance of clinical isolates of respiratory syncytial virus for palivizumab (Synagis)-resistant mutants. J Infect Dis 190( 5): 975– 978.

119. van den Hoogen BG,, de Jong JC,, Groen J,, Kuiken T,, de Groot R,, Fouchier RA,, Osterhaus AD. 2001. A newly discovered human pneumovirus isolated from young children with respiratory tract disease. Nat Med 7( 6): 719– 724.

120. Schildgen V,, van den Hoogen B,, Fouchier R,, Tripp RA,, Alvarez R,, Manoha C,, Williams J,, Schildgen O. 2011. Human Metapneumovirus: lessons learned over the first decade. Clin Microbiol Rev 24( 4): 734– 754.

121. Cox RG,, Livesay SB,, Johnson M,, Ohi MD,, Williams JV. 2012. The human metapneumovirus fusion protein mediates entry via an interaction with RGD-binding integrins. J Virol 86: 12148– 12160.

122. Chang A,, Masante C,, Buchholz UJ,, Dutch RE. 2012. Human metapneumovirus (HMPV) binding and infection are mediated by interactions between the HMPV fusion protein and heparan sulfate. J Virol 86: 3230– 3243.

123. Edwards KM,, Zhu Y,, Griffin MR,, Weinberg GA,, Hall CB,, Szilagyi PG,, Staat MA,, Iwane M,, Prill MM,, Williams JV. 2013. Burden of human metapneumovirus infection in young children. N Engl J Med 368( 7): 633– 643.

124. Spaeder MC,, Custer JW,, Bembea MM,, Aganga DO,, Song X,, Scafidi S. 2013. A multicenter outcomes analysis of children with severe viral respiratory infection due to human metapneumovirus. Pediatr Crit Care Med 14( 3): 268– 272.

125. Aberle JH,, Aberle SW,, Redlberger-Fritz M,, Sandhofer MJ,, Popow-Kraupp T. 2010. Human metapneumovirus subgroup changes and seasonality during epidemics. Pediatr Infect Dis J 29( 11): 1016– 1018.

126. Lamson DM,, Griesemer S,, Fuschino M,, St George K. 2012. Phylogenetic analysis of human metapneumovirus from New York State patients during February through April 2010. J Clin Virol 53( 3): 256– 258.

127. Zhang C,, Du LN,, Zhang ZY,, Qin X,, Yang X,, Liu P,, Chen X,, Zhao Y,, Liu EM,, Zhao XD. 2012. Detection and genetic diversity of human metapneumovirus in hospitalized children with acute respiratory infections in Southwest China. J Clin Microbiol 50: 2714– 2719.

128. Kim S,, Sung H,, Im HJ,, Hong SJ,, Kim MN. 2009. Molecular epidemiological investigation of a nosocomial outbreak of human metapneumovirus infection in a pediatric hemato-oncology patient population. J Clin Microbiol 47: 1221– 1224.

129. Degail MA,, Hughes GJ,, Maule C,, Holmes C,, Lilley M,, Pebody R,, Bonnet J,, Bermingham A,, Bracebridge S. 2012. A human metapneumovirus outbreak at a community hospital in England, July to September 2010. Euro Surveill 17( 15): 20145.

130. Hamada N,, Hara K,, Matsuo Y,, Imamura Y,, Kashiwagi T,, Nakazono Y,, Gotoh K,, Ohtsu Y,, Ohtaki E,, Motohiro T,, Watanabe H. 2014. Performance of a rapid human metapneumovirus antigen test during an outbreak in a long-term care facility. Epidemiol Infect 142( 2): 424– 427.

131. Liao RS,, Appelgate DM,, Pelz RK. 2012. An outbreak of severe respiratory tract infection due to human metapneumovirus in a long-term care facility for the elderly in Oregon. J Clin Virol 53( 2): 171– 173.

132. Falsey AR,, Erdman D,, Anderson LJ,, Walsh EE. 2003. Human metapneumovirus infections in young and elderly adults. J Infect Dis 187( 5): 785– 790.

133. Renaud C,, Xie H,, Seo S,, Kuypers J,, Cent A,, Corey L,, Leisenring W,, Boeckh M,, Englund JA. 2013. Mortality rates of human metapneumovirus and respiratory syncytial virus lower respiratory tract infections in hematopoietic cell transplantation recipients. Biol Blood Marrow Transplant 19( 8): 1220– 1226.

134. Kitanovski L,, Kopriva S,, Pokorn M,, Dolnicar MB,, Rajic V,, Stefanovic M,, Jazbec J. 2013. Treatment of severe human metapneumovirus (hMPV) pneumonia in an immunocompromised child with oral ribavirin and IVIG. J Pediatr Hematol Oncol 35( 7): e311– e313.

135. DeVincenzo JP,, Hirsch RL,, Fuentes RJ,, Top FH Jr. 2000. Respiratory syncytial virus immune globulin treatment of lower respiratory tract infection in pediatric patients undergoing bone marrow transplantation - a compassionate use experience. Bone Marrow Transplant 25( 2): 161– 165.

136. Shahda S,, Carlos WG,, Kiel PJ,, Khan BA,, Hage CA. 2011. The human metapneumovirus: a case series and review of the literature. Transpl Infect Dis 13( 3): 324– 328.

137. Park SY,, Baek S,, Lee SO,, Choi SH,, Kim YS,, Woo JH,, Sung H,, Kim MN,, Kim DY,, Lee JH,, Lee JH,, Lee KH,, Kim SH. 2013. Efficacy of oral ribavirin in hematologic disease patients with paramyxovirus infection: analytic strategy using propensity scores. Antimicrob Agents Chemother 57: 983– 989.

138. Levy C,, Aerts L,, Hamelin ME,, Granier C,, Szecsi J,, Lavillette D,, Boivin G,, Cosset FL. 2013. Virus-like particle vaccine induces cross-protection against human metapneumovirus infections in mice. Vaccine 31( 25): 2778– 2785.

139. Semple MG,, Booth JA,, Ebrahimi B. 2007. Most human metapneumovirus and human respiratory syncytial virus in infant nasal secretions is cell free. J Clin Virol 40( 3): 241– 244.

140. Debyle C,, Bulkow L,, Miernyk K,, Chikoyak L,, Hummel KB,, Hennessy T,, Singleton R. 2012. Comparison of nasopharyngeal flocked swabs and nasopharyngeal wash collection methods for respiratory virus detection in hospitalized children using real-time polymerase chain reaction. J Virol Methods 185( 1): 89– 93.

141. Tollefson SJ,, Cox RG,, Williams JV. 2010. Studies of culture conditions and environmental stability of human metapneumovirus. Virus Res 151( 1): 54– 59.

142. Landry ML,, Ferguson D,, Cohen S,, Peret TC,, Erdman DD. 2005. Detection of human metapneumovirus in clinical samples by immunofluorescence staining of shell vial centrifugation cultures prepared from three different cell lines. J Clin Microbiol 43: 1950– 1952.

143. Kikuta H,, Sakata C,, Gamo R,, Ishizaka A,, Koga Y,, Konno M,, Ogasawara Y,, Sawada H,, Taguchi Y,, Takahashi Y,, Yasuda K,, Ishiguro N,, Hayashi A,, Ishiko H,, Kobayashi K. 2008. Comparison of a lateral-flow immunochromatography assay with real-time reverse transcription-PCR for detection of human metapneumovirus. J Clin Microbiol 46: 928– 932.

144. Kukavica-Ibrulj I,, Boivin G. 2009. Detection of human metapneumovirus antigens in nasopharyngeal aspirates using an enzyme immunoassay. J Clin Virol 44( 1): 88– 90.

145. Fuenzalida L,, Fabrega J,, Blanco S,, Del Mar Martinez M,, Prat C,, Perez M,, Ramil C,, Dominguez J,, Ausina V,, Rodrigo C. 2010. Usefulness of two new methods for diagnosing metapneumovirus infections in children. Clin Microbiol Infect 16( 11): 1663– 1668.

146. Matsuzaki Y,, Takashita E,, Okamoto M,, Mizuta K,, Itagaki T,, Katsushima F,, Katsushima Y,, Nagai Y,, Nishimura H. 2009. Evaluation of a new rapid antigen test using immunochromatography for detection of human metapneumovirus in comparison with real-time PCR assay. J Clin Microbiol 47: 2981– 2984.

147. Vinh DC,, Newby D,, Charest H,, McDonald J. 2008. Evaluation of a commercial direct fluorescent-antibody assay for human metapneumovirus in respiratory specimens. J Clin Microbiol 46: 1840– 1841.

148. Percivalle E,, Sarasini A,, Visai L,, Revello MG,, Gerna G. 2005. Rapid detection of human metapneumovirus strains in nasopharyngeal aspirates and shell vial cultures by monoclonal antibodies. J Clin Microbiol 43: 3443– 3446.

149. Landry ML,, Cohen S,, Ferguson D. 2008. Prospective study of human metapneumovirus detection in clinical samples by use of light diagnostics direct immunofluorescence reagent and real-time PCR. J Clin Microbiol 46: 1098– 1100.

150. Cote S,, Abed Y,, Boivin G. 2003. Comparative evaluation of real-time PCR assays for detection of the human metapneumovirus. J Clin Microbiol 41: 3631– 3635.

151. Maertzdorf J,, Wang CK,, Brown JB,, Quinto JD,, Chu M,, de Graaf M,, van den Hoogen BG,, Spaete R,, Osterhaus AD,, Fouchier RA. 2004. Real-time reverse transcriptase PCR assay for detection of human metapneumoviruses from all known genetic lineages. J Clin Microbiol 42: 981– 986.

152. Scheltinga SA,, Templeton KE,, Beersma MF,, Claas EC. 2005. Diagnosis of human metapneumovirus and rhinovirus in patients with respiratory tract infections by an internally controlled multiplex real-time RNA PCR. J Clin Virol 33: 306– 311.

153. Dare R,, Sanghavi S,, Bullotta A,, Keightley MC,, George KS,, Wadowsky RM,, Paterson DL,, McCurry KR,, Reinhart TA,, Husain S,, Rinaldo CR. 2007. Diagnosis of human metapneumovirus infection in immunosuppressed lung transplant recipients and children evaluated for pertussis. J Clin Microbiol 45: 548– 552.

154. Rand KH,, Rampersaud H,, Houck HJ. 2011. Comparison of two multiplex methods for detection of respiratory viruses: FilmArray RP and xTAG RVP. J Clin Microbiol 49: 2449– 3453.

155. Kim SR,, Ki CS,, Lee NY. 2009. Rapid detection and identification of 12 respiratory viruses using a dual priming oligonucleotide system-based multiplex PCR assay. J Virol Methods 156( 1-2): 111– 116.

156. Chen KF,, Rothman RE,, Ramachandran P,, Blyn L,, Sampath R,, Ecker DJ,, Valsamakis A,, Gaydos CA. 2011. Rapid identification viruses from nasal pharyngeal aspirates in acute viral respiratory infections by RT-PCR and electrospray ionization mass spectrometry. J Virol Methods 173( 1): 60– 66.

157. Pierce VM,, Hodinka RL. 2012. Comparison of the GenMark Diagnostics eSensor respiratory viral panel to real-time PCR for detection of respiratory viruses in children. J Clin Microbiol 50: 3458– 3465.

158. Yan Y,, Zhang S,, Tang YW. 2011. Molecular assays for the detection and characterization of respiratory viruses. Semin Respir Crit Care Med 32( 4): 512– 526.

159. Caliendo AM. 2011. Multiplex PCR and emerging technologies for the detection of respiratory pathogens. Clin Infect Dis 52( Suppl 4): S326– S330.

160. Martin ET,, Kuypers J,, Wald A,, Englund JA. 2012. Multiple versus single virus respiratory infections: viral load and clinical disease severity in hospitalized children. Influenza Other Respi Viruses 6( 1): 71– 77.

161. Deng J,, Ma Z,, Huang W,, Li C,, Wang H,, Zheng Y,, Zhou R,, Tang YW. 2013. Respiratory virus multiplex RT-PCR assay sensitivities and influence factors in hospitalized children with lower respiratory tract infections. Virol Sin 28( 2): 97– 102.

162. Utokaparch S,, Marchant D,, Gosselink JV,, McDonough JE,, Thomas EE,, Hogg JC,, Hegele RG. 2011. The relationship between respiratory viral loads and diagnosis in children presenting to a pediatric hospital emergency department. Pediatr Infect Dis J 30( 2): e18– e23.

163. Tiwari A,, Patnayak DP,, Chander Y,, Goyal SM. 2006. Permissibility of different cell types for the growth of avian metapneumovirus. J Virol Methods 138( 1-2): 80– 84.

164. Reina J,, Ferres F,, Alcoceba E,, Mena A,, de Gopegui ER,, Figuerola J. 2007. Comparison of different cell lines and incubation times in the isolation by the shell vial culture of human metapneumovirus from pediatric respiratory samples. J Clin Virol 40( 1): 46– 49.

165. Li J,, Ren L,, Guo L,, Xiang Z,, Paranhos-Baccala G,, Vernet G,, Wang J. 2012. Evolutionary dynamics analysis of human metapneumovirus subtype A2: genetic evidence for its dominant epidemic. PLoS One 7( 3): e34544. doi:10.1371/journal.pone.0034544.

166. Hamelin ME,, Boivin G. 2005. Development and validation of an enzyme-linked immunosorbent assay for human metapneumovirus serology based on a recombinant viral protein. Clin Diagn Lab Immunol 12( 2): 249– 253.

167. Sastre P,, Ruiz T,, Schildgen O,, Schildgen V,, Vela C,, Rueda P. 2012. Seroprevalence of human respiratory syncytial virus and human metapneumovirus in healthy population analyzed by recombinant fusion protein-based enzyme linked immunosorbent assay. Virol J 9: 130.

168. Te Wierik MJ,, Nguyen DT,, Beersma MF,, Thijsen SF,, Heemstra KA. 2012. An outbreak of severe respiratory tract infection caused by human metapneumovirus in a residential care facility for elderly in Utrecht, the Netherlands, January to March 2010. Euro Surveill 17( 13): 20132.

169. Biacchesi S,, Skiadopoulos MH,, Yang L,, Murphy BR,, Collins PL,, Buchholz UJ. 2005. Rapid human metapneumovirus microneutralization assay based on green fluorescent protein expression. J Virol Methods 128: 192– 197.

170. Luchsinger V,, Ruiz M,, Zunino E,, Martinez MA,, Machado C,, Piedra PA,, Fasce R,, Ulloa MT,, Fink MC,, Lara P,, Gebauer M,, Chavez F,, Avendano LF. 2013. Community-acquired pneumonia in Chile: the clinical relevance in the detection of viruses and atypical bacteria. Thorax 68( 11): 1000– 1006.

171. Feikin DR,, Njenga MK,, Bigogo G,, Aura B,, Gikunju S,, Balish A,, Katz MA,, Erdman D,, Breiman RF. 2013. Additional diagnostic yield of adding serology to PCR in diagnosing viral acute respiratory infections in Kenyan patients 5 years of age and older. Clin Vaccine Immunol 20( 1): 113– 114.

172. Wyde PR,, Chetty SN,, Jewell AM,, Boivin G,, Piedra PA. 2003. Comparison of the inhibition of human metapneumovirus and respiratory syncytial virus by ribavirin and immune serum globulin in vitro. Antiviral Res 60( 1): 51– 59.

173. Sadeghi CD,, Aebi C,, Gorgievski-Hrisoho M,, Muhlemann K,, Barbani MT. 2011. Twelve years’ detection of respiratory viruses by immunofluorescence in hospitalised children: impact of the introduction of a new respiratory picornavirus assay. BMC Infect Dis 11: 41.

174. Hayashi K,, Uchiyama T,, Iwat M,, Sano K,, Yanai M,, Kumasaka K,, Inamo Y. 2005. [The clinical usefulness of a newly rapid diagnosis kit, detection of respiratory syncytial virus]. Kansenshogaku Zasshi 79( 4): 276– 283.

175. Alby K,, Popowitch EB,, Miller MB. 2013. Comparative evaluation of the Nanosphere Verigene RV+ assay and the Simplexa Flu A/B & RSV kit for detection of influenza and respiratory syncytial viruses. J Clin Microbiol 51: 352– 353.

176. Hindiyeh M,, Kolet L,, Meningher T,, Weil M,, Mendelson E,, Mandelboim M. 2013. Evaluation of Simplexa Flu A/B & RSV for direct detection of influenza viruses (A and B) and respiratory syncytial virus in patient clinical samples. J Clin Microbiol 51: 2421– 2424.

177. Pabbaraju K,, Tokaryk KL,, Wong S,, Fox JD. 2008. Comparison of the Luminex xTAG respiratory viral panel with in-house nucleic acid amplification tests for diagnosis of respiratory virus infections. J Clin Microbiol 46: 3056– 3062.

178. Dabisch-Ruthe M,, Vollmer T,, Adams O,, Knabbe C,, Dreier J. 2012. Comparison of three multiplex PCR assays for the detection of respiratory viral infections: evaluation of xTAG respiratory virus panel fast assay, RespiFinder 19 assay and RespiFinder SMART 22 assay. BMC Infect Dis 12: 163.

179. Nolte FS,, Marshall DJ,, Rasberry C,, Schievelbein S,, Banks GG,, Storch GA,, Arens MQ,, Buller RS,, Prudent JR. 2007. MultiCode-PLx System for multiplexed detection of seventeen respiratory viruses. J Clin Microbiol 45: 2779– 2786.

Tables

Respiratory Syncytial Virus and Human Metapneumovirus*

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TABLE 1

Commercial RSV and hMPV DFA reagents and their performance

TABLE 1

Commercial RSV and hMPV DFA reagents and their performance

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TABLE 2

Main commercially available RSV rapid antigen products and their performance characteristics

TABLE 2

Main commercially available RSV rapid antigen products and their performance characteristics

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TABLE 3

Commercial NAATs for detection and identification of RSV and hMPV a

TABLE 3

Commercial NAATs for detection and identification of RSV and hMPV a