Semin Respir Crit Care Med 2016; 37(04): 538-554
DOI: 10.1055/s-0036-1584798
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Parainfluenza Virus Infection

Angela R. Branche
1   Department of Medicine, University of Rochester, Rochester, New York
,
Ann R. Falsey
1   Department of Medicine, University of Rochester, Rochester, New York
2   Department of Medicine, Rochester General Hospital, Rochester, New York
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Publikationsverlauf

Publikationsdatum:
03. August 2016 (online)

Abstract

Human parainfluenza viruses (HPIVs) are single-stranded, enveloped RNA viruses of the Paramyoviridaie family. There are four serotypes which cause respiratory illnesses in children and adults. HPIVs bind and replicate in the ciliated epithelial cells of the upper and lower respiratory tract and the extent of the infection correlates with the location involved. Seasonal HPIV epidemics result in a significant burden of disease in children and account for 40% of pediatric hospitalizations for lower respiratory tract illnesses (LRTIs) and 75% of croup cases. Parainfluenza viruses are associated with a wide spectrum of illnesses which include otitis media, pharyngitis, conjunctivitis, croup, tracheobronchitis, and pneumonia. Uncommon respiratory manifestations include apnea, bradycardia, parotitis, and respiratory distress syndrome and rarely disseminated infection. Immunity resulting from disease in childhood is incomplete and reinfection with HPIV accounts for 15% of respiratory illnesses in adults. Severe disease and fatal pneumonia may occur in elderly and immunocompromised adults. HPIV pneumonia in recipients of hematopoietic stem cell transplant (HSCT) is associated with 50% acute mortality and 75% mortality at 6 months. Though sensitive molecular diagnostics are available to rapidly diagnose HPIV infection, effective antiviral therapies are not available. Currently, treatment for HPIV infection is supportive with the exception of croup where the use of corticosteroids has been found to be beneficial. Several novel drugs including DAS181 appear promising in efforts to treat severe disease in immunocompromised patients, and vaccines to decrease the burden of disease in young children are in development.

 
  • References

  • 1 Glezen WP, Frank AL, Taber LH, Kasel JA. Parainfluenza virus type 3: seasonality and risk of infection and reinfection in young children. J Infect Dis 1984; 150 (6) 851-857
  • 2 Glezen WP, Loda FA, Clyde Jr WA , et al. Epidemiologic patterns of acute lower respiratory disease of children in a pediatric group practice. J Pediatr 1971; 78 (3) 397-406
  • 3 Denny FW, Murphy TF, Clyde Jr WA, Collier AM, Henderson FW. Croup: an 11-year study in a pediatric practice. Pediatrics 1983; 71 (6) 871-876
  • 4 Henrickson KJ, Kuhn SM, Savatski LL. Epidemiology and cost of infection with human parainfluenza virus types 1 and 2 in young children. Clin Infect Dis 1994; 18 (5) 770-779
  • 5 Knott AM, Long CE, Hall CB. Parainfluenza viral infections in pediatric outpatients: seasonal patterns and clinical characteristics. Pediatr Infect Dis J 1994; 13 (4) 269-273
  • 6 Marx A, Török TJ, Holman RC, Clarke MJ, Anderson LJ. Pediatric hospitalizations for croup (laryngotracheobronchitis): biennial increases associated with human parainfluenza virus 1 epidemics. J Infect Dis 1997; 176 (6) 1423-1427
  • 7 Lewis VA, Champlin R, Englund J , et al. Respiratory disease due to parainfluenza virus in adult bone marrow transplant recipients. Clin Infect Dis 1996; 23 (5) 1033-1037
  • 8 McCann S, Byrne JL, Rovira M , et al; Infectious Diseases Working Party of the EBMT. Outbreaks of infectious diseases in stem cell transplant units: a silent cause of death for patients and transplant programmes. Bone Marrow Transplant 2004; 33 (5) 519-529
  • 9 Wendt CH, Weisdorf DJ, Jordan MC, Balfour Jr HH, Hertz MI. Parainfluenza virus respiratory infection after bone marrow transplantation. N Engl J Med 1992; 326 (14) 921-926
  • 10 Chemaly RF, Ghosh S, Bodey GP , et al. Respiratory viral infections in adults with hematologic malignancies and human stem cell transplantation recipients: a retrospective study at a major cancer center. Medicine (Baltimore) 2006; 85 (5) 278-287
  • 11 Henrickson KJ. Parainfluenza viruses. Clin Microbiol Rev 2003; 16 (2) 242-264
  • 12 Karron RA, Collins P. Parainfluenza viruses. In: Knipe D, Howley PM, , eds. Fields Virology. 5th ed. Philadelphia, PA: Lippincott, Williams & Wilkins; 2006: 1497
  • 13 Moscona A. Entry of parainfluenza virus into cells as a target for interrupting childhood respiratory disease. J Clin Invest 2005; 115 (7) 1688-1698
  • 14 Heilman CA. From the National Institute of Allergy and Infectious Diseases and the World Health Organization. Respiratory syncytial and parainfluenza viruses. J Infect Dis 1990; 161 (3) 402-406
  • 15 Huberman K, Peluso RW, Moscona A. Hemagglutinin-neuraminidase of human parainfluenza 3: role of the neuraminidase in the viral life cycle. Virology 1995; 214 (1) 294-300
  • 16 Moscona A. Interaction of human parainfluenza virus type 3 with the host cell surface. Pediatr Infect Dis J 1997; 16 (10) 917-924
  • 17 Schomacker H, Schaap-Nutt A, Collins PL, Schmidt AC. Pathogenesis of acute respiratory illness caused by human parainfluenza viruses. Curr Opin Virol 2012; 2 (3) 294-299
  • 18 Ray R, Duncan J, Quinn R, Matsuoka Y. Distinct hemagglutinin and neuraminidase epitopes involved in antigenic variation of recent human parainfluenza virus type 2 isolates. Virus Res 1992; 24 (1) 107-113
  • 19 Komada H, Orstavik I, Ito Y, Norrby E. Strain variation in parainfluenza virus type 4. J Gen Virol 1990; 71 (Pt 7) 1581-1583
  • 20 Henrickson KJ. Monoclonal antibodies to human parainfluenza virus type 1 detect major antigenic changes in clinical isolates. J Infect Dis 1991; 164 (6) 1128-1134
  • 21 Ison MG. Parainfluenza viruses. In: Bennett JE, Dolin R, Blaser MJ, , eds. Principles and Practice of Infectious Diseases. 8th ed. Philadelphia, PA: Elsevier Saunders; 2015: 1937-1941
  • 22 Castleman WL, Northrop PJ, McAllister PK. Replication of parainfluenza type-3 virus and bovine respiratory syncytial virus in isolated bovine type-II alveolar epithelial cells. Am J Vet Res 1991; 52 (6) 880-885
  • 23 Castleman WL, Brundage-Anguish LJ, Kreitzer L, Neuenschwander SB. Pathogenesis of bronchiolitis and pneumonia induced in neonatal and weanling rats by parainfluenza (Sendai) virus. Am J Pathol 1987; 129 (2) 277-286
  • 24 Welliver RC, Wong DT, Sun M, McCarthy N. Parainfluenza virus bronchiolitis. Epidemiology and pathogenesis. Am J Dis Child 1986; 140 (1) 34-40
  • 25 Welliver RC, Wong DT, Middleton Jr E, Sun M, McCarthy N, Ogra PL. Role of parainfluenza virus-specific IgE in pathogenesis of croup and wheezing subsequent to infection. J Pediatr 1982; 101 (6) 889-896
  • 26 Porter DD, Prince GA, Hemming VG, Porter HG. Pathogenesis of human parainfluenza virus 3 infection in two species of cotton rats: Sigmodon hispidus develops bronchiolitis, while Sigmodon fulviventer develops interstitial pneumonia. J Virol 1991; 65 (1) 103-111
  • 27 Bower J, McBride JT. Croup in children (acute laryngotracheobronchitis). In: Bennett JE, Dolin R, Blaser MJ, , eds. Principles and Practices of Infectious Disease. 8th ed. Philadelphia, PA: Elsevier Saunders; 2015: 762-766
  • 28 Matsuse H, Kondo Y, Saeki S , et al. Naturally occurring parainfluenza virus 3 infection in adults induces mild exacerbation of asthma associated with increased sputum concentrations of cysteinyl leukotrienes. Int Arch Allergy Immunol 2005; 138 (3) 267-272
  • 29 Smith CB, Purcell RH, Bellanti JA, Chanock RM. Protective effect of antibody to parainfluenza type 1 virus. N Engl J Med 1966; 275 (21) 1145-1152
  • 30 Spriggs MK, Murphy BR, Prince GA, Olmsted RA, Collins PL. Expression of the F and HN glycoproteins of human parainfluenza virus type 3 by recombinant vaccinia viruses: contributions of the individual proteins to host immunity. J Virol 1987; 61 (11) 3416-3423
  • 31 Ray R, Matsuoka Y, Burnett TL, Glaze BJ, Compans RW. Human parainfluenza virus induces a type-specific protective immune response. J Infect Dis 1990; 162 (3) 746-749
  • 32 Henderson FW. Pulmonary cell-mediated cytotoxicity in hamsters with parainfluenza virus type 3 pneumonia. Am Rev Respir Dis 1979; 120 (1) 41-47
  • 33 Hou S, Doherty PC, Zijlstra M, Jaenisch R, Katz JM. Delayed clearance of Sendai virus in mice lacking class I MHC-restricted CD8+ T cells. J Immunol 1992; 149 (4) 1319-1325
  • 34 Dave VP, Allan JE, Slobod KS , et al. Viral cross-reactivity and antigenic determinants recognized by human parainfluenza virus type 1-specific cytotoxic T-cells. Virology 1994; 199 (2) 376-383
  • 35 Kasel JA, Frank AL, Keitel WA, Taber LH, Glezen WP. Acquisition of serum antibodies to specific viral glycoproteins of parainfluenza virus 3 in children. J Virol 1984; 52 (3) 828-832
  • 36 Chanock RM. Association of a new type of cytopathogenic myxovirus with infantile croup. J Exp Med 1956; 104 (4) 555-576
  • 37 Chanock RM, Parrott RH, Bell JA, Rowe WP, Huebner RJ. New viruses observed in children with respiratory diseases. Public Health Rep 1958; 73 (3) 193-195
  • 38 Fry AM, Curns AT, Harbour K, Hutwagner L, Holman RC, Anderson LJ. Seasonal trends of human parainfluenza viral infections: United States, 1990-2004. Clin Infect Dis 2006; 43 (8) 1016-1022
  • 39 Ansari SA, Springthorpe VS, Sattar SA, Rivard S, Rahman M. Potential role of hands in the spread of respiratory viral infections: studies with human parainfluenza virus 3 and rhinovirus 14. J Clin Microbiol 1991; 29 (10) 2115-2119
  • 40 Chew FT, Doraisingham S, Ling AE, Kumarasinghe G, Lee BW. Seasonal trends of viral respiratory tract infections in the tropics. Epidemiol Infect 1998; 121 (1) 121-128
  • 41 Gardner SD. The isolation of parainfluenza 4 subtypes A and B in England and serological studies of their prevalence. J Hyg (Lond) 1969; 67 (3) 545-550
  • 42 Lindquist SW, Darnule A, Istas A, Demmler GJ. Parainfluenza virus type 4 infections in pediatric patients. Pediatr Infect Dis J 1997; 16 (1) 34-38
  • 43 Vachon ML, Dionne N, Leblanc E, Moisan D, Bergeron MG, Boivin G. Human parainfluenza type 4 infections, Canada. Emerg Infect Dis 2006; 12 (11) 1755-1758
  • 44 Canchola JG, Chanock RM, Jeffries BC , et al. Recovery and identification of human myxoviruses. Bacteriol Rev 1965; 29 (4) 496-503
  • 45 Canchola J, Vargosko AJ, Kim HW , et al. Antigenic variation among newly isolated strains of parainfluenza type 4 virus. Am J Hyg 1964; 79: 357-364
  • 46 Berman S. Epidemiology of acute respiratory infections in children of developing countries. Rev Infect Dis 1991; 13 (Suppl. 06) S454-S462
  • 47 Denny Jr FW. The clinical impact of human respiratory virus infections. Am J Respir Crit Care Med 1995; 152 (4, Pt 2) S4-S12
  • 48 Kim MR, Lee HR, Lee GM. Epidemiology of acute viral respiratory tract infections in Korean children. J Infect 2000; 41 (2) 152-158
  • 49 McIntosh K. Pathogenesis of severe acute respiratory infections in the developing world: respiratory syncytial virus and parainfluenza viruses. Rev Infect Dis 1991; 13 (Suppl. 06) S492-S500
  • 50 Denny FW, Clyde Jr WA. Acute lower respiratory tract infections in nonhospitalized children. J Pediatr 1986; 108 (5, Pt 1) 635-646
  • 51 Wright PF. Parainfluenza viruses. In: Mandell GL, , ed. Principles and Practices of Infectious Diseases. Philadelphia, PA: Churchill Livingston; 2000: 1770-1776
  • 52 Fiore AE, Iverson C, Messmer T , et al. Outbreak of pneumonia in a long-term care facility: antecedent human parainfluenza virus 1 infection may predispose to bacterial pneumonia. J Am Geriatr Soc 1998; 46 (9) 1112-1117
  • 53 Reed G, Jewett PH, Thompson J, Tollefson S, Wright PF. Epidemiology and clinical impact of parainfluenza virus infections in otherwise healthy infants and young children < 5 years old. J Infect Dis 1997; 175 (4) 807-813
  • 54 Weinberg GA, Hall CB, Iwane MK , et al; New Vaccine Surveillance Network. Parainfluenza virus infection of young children: estimates of the population-based burden of hospitalization. J Pediatr 2009; 154 (5) 694-699
  • 55 Hemming VG. Viral respiratory diseases in children: classification, etiology, epidemiology, and risk factors. J Pediatr 1994; 124 (5, Pt 2): S13-S16
  • 56 Counihan ME, Shay DK, Holman RC, Lowther SA, Anderson LJ. Human parainfluenza virus-associated hospitalizations among children less than five years of age in the United States. Pediatr Infect Dis J 2001; 20 (7) 646-653
  • 57 Lee MS, Walker RE, Mendelman PM. Medical burden of respiratory syncytial virus and parainfluenza virus type 3 infection among US children. Implications for design of vaccine trials. Hum Vaccin 2005; 1 (1) 6-11
  • 58 Hall CB. Respiratory syncytial virus and parainfluenza virus. N Engl J Med 2001; 344 (25) 1917-1928
  • 59 Gilca R, Amini R, Douville-Fradet M , et al. Other respiratory viruses are important contributors to adult respiratory hospitalizations and mortality even during peak weeks of the influenza season. Open Forum Infect Dis 2014; 1 (2) ofu086
  • 60 Falsey AR, Walsh EE. Viral pneumonia in older adults. Clin Infect Dis 2006; 42 (4) 518-524
  • 61 Nisii C, Meschi S, Selleri M , et al. Frequency of detection of upper respiratory tract viruses in patients tested for pandemic H1N1/09 viral infection. J Clin Microbiol 2010; 48 (9) 3383-3385
  • 62 Osiowy C. Direct detection of respiratory syncytial virus, parainfluenza virus, and adenovirus in clinical respiratory specimens by a multiplex reverse transcription-PCR assay. J Clin Microbiol 1998; 36 (11) 3149-3154
  • 63 Gaunt ER, Harvala H, McIntyre C, Templeton KE, Simmonds P. Disease burden of the most commonly detected respiratory viruses in hospitalized patients calculated using the disability adjusted life year (DALY) model. J Clin Virol 2011; 52 (3) 215-221
  • 64 Johnstone J, Majumdar SR, Fox JD, Marrie TJ. Viral infection in adults hospitalized with community-acquired pneumonia: prevalence, pathogens, and presentation. Chest 2008; 134 (6) 1141-1148
  • 65 Angeles Marcos M, Camps M, Pumarola T , et al. The role of viruses in the aetiology of community-acquired pneumonia in adults. Antivir Ther 2006; 11 (3) 351-359
  • 66 Greenberg SB, Allen M, Wilson J, Atmar RL. Respiratory viral infections in adults with and without chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000; 162 (1) 167-173
  • 67 Glezen WP, Greenberg SB, Atmar RL, Piedra PA, Couch RB. Impact of respiratory virus infections on persons with chronic underlying conditions. JAMA 2000; 283 (4) 499-505
  • 68 Kherad O, Rutschmann OT. Viral infections as a cause of chronic obstructive pulmonary disease (COPD) exacerbation [in German]. Praxis (Bern 1994) 2010; 99 (4) 235-240
  • 69 Hutchinson AF, Ghimire AK, Thompson MA , et al. A community-based, time-matched, case-control study of respiratory viruses and exacerbations of COPD. Respir Med 2007; 101 (12) 2472-2481
  • 70 Parainfluenza infections in the elderly 1976-82. Br Med J (Clin Res Ed) 1983; 287 (6405) 1619
  • 71 Anonymous Parainfluenza outbreaks in extended-care facilities–United States. MMWR Morb Mortal Wkly Rep 1978; 27: 475-476
  • 72 Falsey AR, Treanor JJ, Betts RF, Walsh EE. Viral respiratory infections in the institutionalized elderly: clinical and epidemiologic findings. J Am Geriatr Soc 1992; 40 (2) 115-119
  • 73 Glasgow KW, Tamblyn SE, Blair G. A respiratory outbreak due to parainfluenza virus type 3 in a home for the aged—Ontario. Can Commun Dis Rep 1995; 21 (7) 57-61
  • 74 Arroyo JC, Jordan W, Milligan L. Upper respiratory tract infection and serum antibody responses in nursing home patients. Am J Infect Control 1988; 16 (4) 152-158
  • 75 Gross PA, Rodstein M, LaMontagne JR , et al. Epidemiology of acute respiratory illness during an influenza outbreak in a nursing home. A prospective study. Arch Intern Med 1988; 148 (3) 559-561
  • 76 Falsey AR, McCann RM, Hall WJ , et al. Acute respiratory tract infection in daycare centers for older persons. J Am Geriatr Soc 1995; 43 (1) 30-36
  • 77 Marcolini JA, Malik S, Suki D, Whimbey E, Bodey GP. Respiratory disease due to parainfluenza virus in adult leukemia patients. Eur J Clin Microbiol Infect Dis 2003; 22 (2) 79-84
  • 78 Nichols WG, Corey L, Gooley T, Davis C, Boeckh M. Parainfluenza virus infections after hematopoietic stem cell transplantation: risk factors, response to antiviral therapy, and effect on transplant outcome. Blood 2001; 98 (3) 573-578
  • 79 Hodson A, Kasliwal M, Streetly M, MacMahon E, Raj K. A parainfluenza-3 outbreak in a SCT unit: sepsis with multi-organ failure and multiple co-pathogens are associated with increased mortality. Bone Marrow Transplant 2011; 46 (12) 1545-1550
  • 80 Vilchez RA, McCurry K, Dauber J , et al. The epidemiology of parainfluenza virus infection in lung transplant recipients. Clin Infect Dis 2001; 33 (12) 2004-2008
  • 81 Vilchez R, McCurry K, Dauber J , et al. Influenza and parainfluenza respiratory viral infection requiring admission in adult lung transplant recipients. Transplantation 2002; 73 (7) 1075-1078
  • 82 Billings JL, Hertz MI, Savik K, Wendt CH. Respiratory viruses and chronic rejection in lung transplant recipients. J Heart Lung Transplant 2002; 21 (5) 559-566
  • 83 Vesa S, Kleemola M, Blomqvist S, Takala A, Kilpi T, Hovi T. Epidemiology of documented viral respiratory infections and acute otitis media in a cohort of children followed from two to twenty-four months of age. Pediatr Infect Dis J 2001; 20 (6) 574-581
  • 84 Henrickson KJ, Hoover S, Kehl KS, Hua W. National disease burden of respiratory viruses detected in children by polymerase chain reaction. Pediatr Infect Dis J 2004; 23 (1, Suppl): S11-S18
  • 85 Johnson D. Croup. Clin Evid 2005; 14: 310-327
  • 86 Rosychuk RJ, Klassen TP, Metes D, Voaklander DC, Senthilselvan A, Rowe BH. Croup presentations to emergency departments in Alberta, Canada: a large population-based study. Pediatr Pulmonol 2010; 45 (1) 83-91
  • 87 Sofer S, Dagan R, Tal A. The need for intubation in serious upper respiratory tract infection in pediatric patients (a retrospective study). Infection 1991; 19 (3) 131-134
  • 88 Tan AK, Manoukian JJ. Hospitalized croup (bacterial and viral): the role of rigid endoscopy. J Otolaryngol 1992; 21 (1) 48-53
  • 89 McEniery J, Gillis J, Kilham H, Benjamin B. Review of intubation in severe laryngotracheobronchitis. Pediatrics 1991; 87 (6) 847-853
  • 90 Westley CR, Cotton EK, Brooks JG. Nebulized racemic epinephrine by IPPB for the treatment of croup: a double-blind study. Am J Dis Child 1978; 132 (5) 484-487
  • 91 Thompson M, Vodicka TA, Blair PS, Buckley DI, Heneghan C, Hay AD ; TARGET Programme Team. Duration of symptoms of respiratory tract infections in children: systematic review. BMJ 2013; 347: f7027
  • 92 Hasegawa K, Tsugawa Y, Brown DF, Mansbach JM, Camargo Jr CA. Trends in bronchiolitis hospitalizations in the United States, 2000-2009. Pediatrics 2013; 132 (1) 28-36
  • 93 Swingler GH, Hussey GD, Zwarenstein M. Duration of illness in ambulatory children diagnosed with bronchiolitis. Arch Pediatr Adolesc Med 2000; 154 (10) 997-1000
  • 94 Williams DJ, Shah SS. Community-acquired pneumonia in the Conjugate Vaccine Era. J Pediatric Infect Dis Soc 2012; 1 (4) 314-328
  • 95 Jain S, Finelli L ; CDC EPIC Study Team. Community-acquired pneumonia among U.S. children. N Engl J Med 2015; 372 (22) 2167-2168
  • 96 Slavin KA, Passaro DJ, Hacker JK, Hendry RM, Kohl S. Parainfluenza virus type 4: case report and review of the literature. Pediatr Infect Dis J 2000; 19 (9) 893-896
  • 97 Cooney MK, Fox JP, Hall CE. The Seattle Virus Watch. VI. Observations of infections with and illness due to parainfluenza, mumps and respiratory syncytial viruses and Mycoplasma pneumoniae. Am J Epidemiol 1975; 101 (6) 532-551
  • 98 Nicholson KG, Baker DJ, Farquhar A, Hurd D, Kent J, Smith SH. Acute upper respiratory tract viral illness and influenza immunization in homes for the elderly. Epidemiol Infect 1990; 105 (3) 609-618
  • 99 Gwaltney Jr JM, Scheld WM, Sande MA, Sydnor A. The microbial etiology and antimicrobial therapy of adults with acute community-acquired sinusitis: a fifteen-year experience at the University of Virginia and review of other selected studies. J Allergy Clin Immunol 1992; 90 (3, Pt 2) 457-461 , discussion 462
  • 100 Fransén H, Wolontis S. Infections with viruses, Mycoplasma pneumoniae and bacteria in acute respiratory illness. A study of hospitalized patients, patients treated at home, and healthy subjects. Scand J Infect Dis 1969; 1 (1) 31-37
  • 101 Monto AS, Sullivan KM. Acute respiratory illness in the community. Frequency of illness and the agents involved. Epidemiol Infect 1993; 110 (1) 145-160
  • 102 Stanek J, Heinz F. On the epidemiology and etiology of pneumonia in adults. J Hyg Epidemiol Microbiol Immunol 1988; 32 (1) 31-38
  • 103 Talbot HK, Falsey AR. The diagnosis of viral respiratory disease in older adults. Clin Infect Dis 2010; 50 (5) 747-751
  • 104 Falsey AR, Becker KL, Swinburne AJ , et al. Bacterial complications of respiratory tract viral illness: a comprehensive evaluation. J Infect Dis 2013; 208 (3) 432-441
  • 105 Buscho RO, Saxtan D, Shultz PS, Finch E, Mufson MA. Infections with viruses and Mycoplasma pneumoniae during exacerbations of chronic bronchitis. J Infect Dis 1978; 137 (4) 377-383
  • 106 Hudgel DW, Langston Jr L, Selner JC, McIntosh K. Viral and bacterial infections in adults with chronic asthma. Am Rev Respir Dis 1979; 120 (2) 393-397
  • 107 Dimopoulos G, Lerikou M, Tsiodras S , et al. Viral epidemiology of acute exacerbations of chronic obstructive pulmonary disease. Pulm Pharmacol Ther 2012; 25 (1) 12-18
  • 108 Hansbro NG, Horvat JC, Wark PA, Hansbro PM. Understanding the mechanisms of viral induced asthma: new therapeutic directions. Pharmacol Ther 2008; 117 (3) 313-353
  • 109 Carilli AD, Gohd RS, Gordon W. A virologic study of chronic bronchitis. N Engl J Med 1964; 270: 123-127
  • 110 Johnston NW. The similarities and differences of epidemic cycles of chronic obstructive pulmonary disease and asthma exacerbations. Proc Am Thorac Soc 2007; 4 (8) 591-596
  • 111 Whimbey E, Vartivarian SE, Champlin RE, Elting LS, Luna M, Bodey GP. Parainfluenza virus infection in adult bone marrow transplant recipients. Eur J Clin Microbiol Infect Dis 1993; 12 (9) 699-701
  • 112 Chemaly RF, Hanmod SS, Rathod DB , et al. The characteristics and outcomes of parainfluenza virus infections in 200 patients with leukemia or recipients of hematopoietic stem cell transplantation. Blood 2012; 119 (12) 2738-2745 , quiz 2969
  • 113 Luján-Zilbermann J, Benaim E, Tong X, Srivastava DK, Patrick CC, DeVincenzo JP. Respiratory virus infections in pediatric hematopoietic stem cell transplantation. Clin Infect Dis 2001; 33 (7) 962-968
  • 114 Srinivasan A, Wang C, Yang J, Shenep JL, Leung WH, Hayden RT. Symptomatic parainfluenza virus infections in children undergoing hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2011; 17 (10) 1520-1527
  • 115 Ison MG. Respiratory viral infections in transplant recipients. Antivir Ther 2007; 12 (4, Pt B): 627-638
  • 116 Ferguson PE, Sorrell TC, Bradstock K, Carr P, Gilroy NM. Parainfluenza virus type 3 pneumonia in bone marrow transplant recipients: multiple small nodules in high- resolution lung computed tomography scans provide a radiological clue to diagnosis. Clin Infect Dis 2009; 48 (7) 905-909
  • 117 Herzog KD, Dunn SP, Langham Jr MR, Marmon LM. Association of parainfluenza virus type 3 infection with allograft rejection in a liver transplant recipient. Pediatr Infect Dis J 1989; 8 (8) 534-536
  • 118 DeFabritus AM, Riggio RR, David DS, Senterfit LB, Cheigh JS, Stenzel KH. Parainfluenza type 3 in a transplant unit. JAMA 1979; 241 (4) 384-386
  • 119 Palmer Jr SM, Henshaw NG, Howell DN, Miller SE, Davis RD, Tapson VF. Community respiratory viral infection in adult lung transplant recipients. Chest 1998; 113 (4) 944-950
  • 120 Matar LD, McAdams HP, Palmer SM , et al. Respiratory viral infections in lung transplant recipients: radiologic findings with clinical correlation. Radiology 1999; 213 (3) 735-742
  • 121 Frank Jr JA, Warren RW, Tucker JA, Zeller J, Wilfert CM. Disseminated parainfluenza infection in a child with severe combined immunodeficiency. Am J Dis Child 1983; 137 (12) 1172-1174
  • 122 Bloom H, Johnson K, Jacobsen R, Chanock R. Recovery of parainfluenza viruses from adults with upper respiratory tract illnesses. Am J Epi 1961; 74: 50-59
  • 123 Zhao H, De BP, Das T, Banerjee AK. Inhibition of human parainfluenza virus-3 replication by interferon and human MxA. Virology 1996; 220 (2) 330-338
  • 124 Seidman DS, Nass D, Mendelson E, Shehtman I, Mashiach S, Achiron R. Prenatal ultrasonographic diagnosis of fetal hydrocephalus due to infection with parainfluenza virus type 3. Ultrasound Obstet Gynecol 1996; 7 (1) 52-54
  • 125 Singh-Naz N, Willy M, Riggs N. Outbreak of parainfluenza virus type 3 in a neonatal nursery. Pediatr Infect Dis J 1990; 9 (1) 31-33
  • 126 Meissner HC, Murray SA, Kiernan MA, Snydman DR, McIntosh K. A simultaneous outbreak of respiratory syncytial virus and parainfluenza virus type 3 in a newborn nursery. J Pediatr 1984; 104 (5) 680-684
  • 127 McCarthy VP, Carlile JR, Reichelderfer PS, Clark JS. Parainfluenza type 3 in newborns. Pediatr Infect Dis J 1987; 6 (2) 217-218
  • 128 MacDonald NE, Wolfish N, McLaine P, Phipps P, Rossier E. Role of respiratory viruses in exacerbations of primary nephrotic syndrome. J Pediatr 1986; 108 (3) 378-382
  • 129 Wilks D, Burns SM. Myopericarditis associated with parainfluenza virus type 3 infection. Eur J Clin Microbiol Infect Dis 1998; 17 (5) 363-365
  • 130 Bitnun A, Ford-Jones EL, Petric M , et al. Acute childhood encephalitis and Mycoplasma pneumoniae. Clin Infect Dis 2001; 32 (12) 1674-1684
  • 131 Downham MA, McQuillin J, Gardner PS. Diagnosis and clinical significance of parainfluenza virus infections in children. Arch Dis Child 1974; 49 (1) 8-15
  • 132 Vreede RW, Schellekens H, Zuijderwijk M. Isolation of parainfluenza virus type 3 from cerebrospinal fluid. J Infect Dis 1992; 165 (6) 1166
  • 133 Wong VK, Steinberg E, Warford A. Parainfluenza virus type 3 meningitis in an 11-month-old infant. Pediatr Infect Dis J 1988; 7 (4) 300-301
  • 134 Arguedas A, Stutman HR, Blanding JG. Parainfluenza type 3 meningitis. Report of two cases and review of the literature. Clin Pediatr (Phila) 1990; 29 (3) 175-178
  • 135 Román G, Phillips CA, Poser CM. Parainfluenza virus type 3: isolation from CSF of a patient with Guillain-Barré syndrome. JAMA 1978; 240 (15) 1613-1615
  • 136 Munywoki PK, Hamid F, Mutunga M, Welch S, Cane P, Nokes DJ. Improved detection of respiratory viruses in pediatric outpatients with acute respiratory illness by real-time PCR using nasopharyngeal flocked swabs. J Clin Microbiol 2011; 49 (9) 3365-3367
  • 137 Branche AR, Walsh EE, Formica MA, Falsey AR. Detection of respiratory viruses in sputum from adults by use of automated multiplex PCR. J Clin Microbiol 2014; 52 (10) 3590-3596
  • 138 Herrmann Jr EC, Hable KA. Experiences in laboratory diagnosis of parainfluenza viruses in routine medical practice. Mayo Clin Proc 1970; 45 (3) 177-188
  • 139 Leland DS, Ginocchio CC. Role of cell culture for virus detection in the age of technology. Clin Microbiol Rev 2007; 20 (1) 49-78
  • 140 Olsen MA, Shuck KM, Sambol AR, Flor SM, O'Brien J, Cabrera BJ. Isolation of seven respiratory viruses in shell vials: a practical and highly sensitive method. J Clin Microbiol 1993; 31 (2) 422-425
  • 141 Miall F, Rye A, Fraser M, Hunter A, Snowden JA. Human parainfluenza type 4 infection: a case report highlighting pathogenicity and difficulties in rapid diagnosis in the post-transplant setting. Bone Marrow Transplant 2002; 29 (6) 541-542
  • 142 Hirsch HH, Martino R, Ward KN, Boeckh M, Einsele H, Ljungman P. Fourth European Conference on Infections in Leukaemia (ECIL-4): guidelines for diagnosis and treatment of human respiratory syncytial virus, parainfluenza virus, metapneumovirus, rhinovirus, and coronavirus. Clin Infect Dis 2013; 56 (2) 258-266
  • 143 Fan J, Henrickson KJ, Savatski LL. Rapid simultaneous diagnosis of infections with respiratory syncytial viruses A and B, influenza viruses A and B, and human parainfluenza virus types 1, 2, and 3 by multiplex quantitative reverse transcription-polymerase chain reaction-enzyme hybridization assay (Hexaplex). Clin Infect Dis 1998; 26 (6) 1397-1402
  • 144 Babady NE. The FilmArray® respiratory panel: an automated, broadly multiplexed molecular test for the rapid and accurate detection of respiratory pathogens. Expert Rev Mol Diagn 2013; 13 (8) 779-788
  • 145 Kuypers J, Wright N, Ferrenberg J , et al. Comparison of real-time PCR assays with fluorescent-antibody assays for diagnosis of respiratory virus infections in children. J Clin Microbiol 2006; 44 (7) 2382-2388
  • 146 Kuypers J, Campbell AP, Cent A, Corey L, Boeckh M. Comparison of conventional and molecular detection of respiratory viruses in hematopoietic cell transplant recipients. Transpl Infect Dis 2009; 11 (4) 298-303
  • 147 Kadmon G, Levy I, Mandelboim M , et al. Polymerase-chain-reaction-based diagnosis of viral pulmonary infections in immunocompromised children. Acta Paediatr 2013; 102 (6) e263-e268
  • 148 Weinberg GA, Erdman DD, Edwards KM , et al; New Vaccine Surveillance Network Study Group. Superiority of reverse-transcription polymerase chain reaction to conventional viral culture in the diagnosis of acute respiratory tract infections in children. J Infect Dis 2004; 189 (4) 706-710
  • 149 Pabbaraju K, Tokaryk KL, Wong S, Fox JD. 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 (9) 3056-3062
  • 150 Ruggiero P, McMillen T, Tang YW, Babady NE. Evaluation of the BioFire FilmArray respiratory panel and the GenMark eSensor respiratory viral panel on lower respiratory tract specimens. J Clin Microbiol 2014; 52 (1) 288-290
  • 151 Templeton KE, Scheltinga SA, Beersma MF, Kroes AC, Claas EC. Rapid and sensitive method using multiplex real-time PCR for diagnosis of infections by influenza a and influenza B viruses, respiratory syncytial virus, and parainfluenza viruses 1, 2, 3, and 4. J Clin Microbiol 2004; 42 (4) 1564-1569
  • 152 Pabbaraju K, Wong S, Tokaryk KL, Fonseca K, Drews SJ. Comparison of the Luminex xTAG respiratory viral panel with xTAG respiratory viral panel fast for diagnosis of respiratory virus infections. J Clin Microbiol 2011; 49 (5) 1738-1744
  • 153 Julkunen I. Serological diagnosis of parainfluenza virus infections by enzyme immunoassay with special emphasis on purity of viral antigens. J Med Virol 1984; 14 (2) 177-187
  • 154 van der Logt JT, van Loon AM, Heessen FW, van der Veen J. Diagnosis of parainfluenza virus infection in children and older patients by detection of specific IgM antibody. J Med Virol 1985; 16 (2) 191-199
  • 155 Bjornson CL, Johnson DW. Croup. Lancet 2008; 371 (9609) 329-339
  • 156 Bjornson CL, Klassen TP, Williamson J , et al; Pediatric Emergency Research Canada Network. A randomized trial of a single dose of oral dexamethasone for mild croup. N Engl J Med 2004; 351 (13) 1306-1313
  • 157 Kairys SW, Olmstead EM, O'Connor GT. Steroid treatment of laryngotracheitis: a meta-analysis of the evidence from randomized trials. Pediatrics 1989; 83 (5) 683-693
  • 158 Kristjánsson S, Berg-Kelly K, Winsö E. Inhalation of racemic adrenaline in the treatment of mild and moderately severe croup. Clinical symptom score and oxygen saturation measurements for evaluation of treatment effects. Acta Paediatr 1994; 83 (11) 1156-1160
  • 159 Seo S, Xie H, Campbell AP , et al. Parainfluenza virus lower respiratory tract disease after hematopoietic cell transplant: viral detection in the lung predicts outcome. Clin Infect Dis 2014; 58 (10) 1357-1368
  • 160 Gilbert BE, Knight V. Biochemistry and clinical applications of ribavirin. Antimicrob Agents Chemother 1986; 30 (2) 201-205
  • 161 American Academy of Pediatrics Committee on Infectious Diseases. Reassessment of the indications for ribavirin therapy in respiratory syncytial virus infections. Pediatrics 1996; 97 (1) 137-140
  • 162 Picardi A, Gentilucci UV, Zardi EM, D'Avola D, Amoroso A, Afeltra A. The role of ribavirin in the combination therapy of hepatitis C virus infection. Curr Pharm Des 2004; 10 (17) 2081-2092
  • 163 Chakrabarti S, Collingham KE, Holder K, Fegan CD, Osman H, Milligan DW. Pre-emptive oral ribavirin therapy of paramyxovirus infections after haematopoietic stem cell transplantation: a pilot study. Bone Marrow Transplant 2001; 28 (8) 759-763
  • 164 Stankova J, Carret AS, Moore D , et al. Long-term therapy with aerosolized ribavirin for parainfluenza 3 virus respiratory tract infection in an infant with severe combined immunodeficiency. Pediatr Transplant 2007; 11 (2) 209-213
  • 165 Sparrelid E, Ljungman P, Ekelöf-Andström E , et al. Ribavirin therapy in bone marrow transplant recipients with viral respiratory tract infections. Bone Marrow Transplant 1997; 19 (9) 905-908
  • 166 Shima T, Yoshimoto G, Nonami A , et al. Successful treatment of parainfluenza virus 3 pneumonia with oral ribavirin and methylprednisolone in a bone marrow transplant recipient. Int J Hematol 2008; 88 (3) 336-340
  • 167 Wright JJ, O'driscoll G. Treatment of parainfluenza virus 3 pneumonia in a cardiac transplant recipient with intravenous ribavirin and methylprednisolone. J Heart Lung Transplant 2005; 24 (3) 343-346
  • 168 Chakrabarti S, Collingham KE, Holder K, Oyaide S, Pillay D, Milligan DW. Parainfluenza virus type 3 infections in hematopoetic stem cell transplant recipients: response to ribavirin therapy. Clin Infect Dis 2000; 31 (6) 1516-1518
  • 169 Casey J, Morris K, Narayana M, Nakagaki M, Kennedy GA. Oral ribavirin for treatment of respiratory syncitial virus and parainfluenza 3 virus infections post allogeneic haematopoietic stem cell transplantation. Bone Marrow Transplant 2013; 48 (12) 1558-1561
  • 170 Elizaga J, Olavarria E, Apperley J, Goldman J, Ward K. Parainfluenza virus 3 infection after stem cell transplant: relevance to outcome of rapid diagnosis and ribavirin treatment. Clin Infect Dis 2001; 32 (3) 413-418
  • 171 Kalimuddin S, Sessions OM, Hou Y , et al. Successful clearance of human parainfluenza virus type 2 viraemia with intravenous ribavirin and immunoglobulin in a patient with acute myocarditis. J Clin Virol 2013; 56 (1) 37-40
  • 172 Liu V, Dhillon GS, Weill D. A multi-drug regimen for respiratory syncytial virus and parainfluenza virus infections in adult lung and heart-lung transplant recipients. Transpl Infect Dis 2010; 12 (1) 38-44
  • 173 McIntosh K, Kurachek SC, Cairns LM, Burns JC, Goodspeed B. Treatment of respiratory viral infection in an immunodeficient infant with ribavirin aerosol. Am J Dis Child 1984; 138 (3) 305-308
  • 174 Nichols WG, Gooley T, Boeckh M. Community-acquired respiratory syncytial virus and parainfluenza virus infections after hematopoietic stem cell transplantation: the Fred Hutchinson Cancer Research Center experience. Biol Blood Marrow Transplant 2001; 7 (Suppl): 11S-15S
  • 175 Moss RB, Steigbigel RT, Sanders RL, Fang F. Perspective: emerging challenges in the treatment of influenza and parainfluenza in transplant patients. Adv Virol 2011; 2011: 910930
  • 176 Triana-Baltzer GB, Sanders RL, Hedlund M , et al. Phenotypic and genotypic characterization of influenza virus mutants selected with the sialidase fusion protein DAS181. J Antimicrob Chemother 2011; 66 (1) 15-28
  • 177 Nishino R, Ikeda K, Hayakawa T, Takahashi T, Suzuki T, Sato M. Syntheses of 2-deoxy-2,3-didehydro-N-acetylneuraminic acid analogues modified by N-sulfonylamidino groups at the C-4 position and biological evaluation as inhibitors of human parainfluenza virus type 1. Bioorg Med Chem 2011; 19 (7) 2418-2427
  • 178 Chen YB, Driscoll JP, McAfee SL , et al. Treatment of parainfluenza 3 infection with DAS181 in a patient after allogeneic stem cell transplantation. Clin Infect Dis 2011; 53 (7) e77-e80
  • 179 Jones BG, Hayden RT, Hurwitz JL. Inhibition of primary clinical isolates of human parainfluenza virus by DAS181 in cell culture and in a cotton rat model. Antiviral Res 2013; 100 (2) 562-566
  • 180 Drozd DR, Limaye AP, Moss RB , et al. DAS181 treatment of severe parainfluenza type 3 pneumonia in a lung transplant recipient. Transpl Infect Dis 2013; 15 (1) E28-E32
  • 181 Chalkias S, Mackenzie MR, Gay C , et al. DAS181 treatment of hematopoietic stem cell transplant patients with parainfluenza virus lung disease requiring mechanical ventilation. Transpl Infect Dis 2014; 16 (1) 141-144
  • 182 Waghmare A, Wagner T, Andrews R , et al. Successful treatment of parainfluenza virus respiratory tract infection with DAS181 in 4 immunocompromised children. J Pediatric Infect Dis Soc 2015; 4 (2) 114-118
  • 183 Pastey MK, Gower TL, Spearman PW, Crowe Jr JE, Graham BS. A RhoA-derived peptide inhibits syncytium formation induced by respiratory syncytial virus and parainfluenza virus type 3. Nat Med 2000; 6 (1) 35-40
  • 184 Mao H, Thakur CS, Chattopadhyay S, Silverman RH, Gudkov A, Banerjee AK. Inhibition of human parainfluenza virus type 3 infection by novel small molecules. Antiviral Res 2008; 77 (2) 83-94
  • 185 Mao H, Chattopadhyay S, Banerjee AK. N-terminally truncated C protein, CNDelta25, of human parainfluenza virus type 3 is a potent inhibitor of viral replication. Virology 2009; 394 (1) 143-148
  • 186 Watanabe M, Mishin VP, Brown SA , et al. Effect of hemagglutinin-neuraminidase inhibitors BCX 2798 and BCX 2855 on growth and pathogenicity of Sendai/human parainfluenza type 3 chimera virus in mice. Antimicrob Agents Chemother 2009; 53 (9) 3942-3951
  • 187 Alymova IV, Watanabe M, Boyd KL, Chand P, Babu YS, Portner A. Efficacy of the novel parainfluenza virus haemagglutinin-neuraminidase inhibitor BCX 2798 in mice - further evaluation. Antivir Ther 2009; 14 (7) 891-898
  • 188 Ottolini MG, Hemming VG, Piazza FM, Johnson SA, Darnell ME, Prince GA. Topical immunoglobulin is an effective therapy for parainfluenza type 3 in a cotton rat model. J Infect Dis 1995; 172 (1) 243-245
  • 189 Ottolini MG, Porter DD, Blanco JC, Prince GA. A cotton rat model of human parainfluenza 3 laryngotracheitis: virus growth, pathology, and therapy. J Infect Dis 2002; 186 (12) 1713-1717
  • 190 Prince GA, Porter DD. Treatment of parainfluenza virus type 3 bronchiolitis and pneumonia in a cotton rat model using topical antibody and glucocorticosteroid. J Infect Dis 1996; 173 (3) 598-608
  • 191 Sridhar S, Luk HK, Lau SK, Woo PC. First report of severe parainfluenza virus 4B and rhinovirus C coinfection in a liver transplant recipient treated with immunoglobulin. J Clin Virol 2014; 61 (4) 611-614
  • 192 Cotugno N, Manno EC, Stoppa F , et al. Severe parainfluenza pneumonia in a case of transient hypogammalobulinemia of infancy. BMJ Case Rep 2013; ;2013:10.1136/bcr,2013-009959
  • 193 Seo S, Xie H, Karron RA , et al. Parainfluenza virus type 3 Ab in allogeneic hematopoietic cell transplant recipients: factors influencing post-transplant Ab titers and associated outcomes. Bone Marrow Transplant 2014; 49 (9) 1205-1211
  • 194 Schmidt AC, Schaap-Nutt A, Bartlett EJ , et al. Progress in the development of human parainfluenza virus vaccines. Expert Rev Respir Med 2011; 5 (4) 515-526
  • 195 Wright PF, Karron RA, Belshe RB , et al. The absence of enhanced disease with wild type respiratory syncytial virus infection occurring after receipt of live, attenuated, respiratory syncytial virus vaccines. Vaccine 2007; 25 (42) 7372-7378
  • 196 Karron RA, Casey R, Thumar B , et al. The cDNA-derived investigational human parainfluenza virus type 3 vaccine rcp45 is well tolerated, infectious, and immunogenic in infants and young children. Pediatr Infect Dis J 2011; 30 (10) e186-e191
  • 197 Karron RA, Thumar B, Schappell E , et al. Evaluation of two chimeric bovine-human parainfluenza virus type 3 vaccines in infants and young children. Vaccine 2012; 30 (26) 3975-3981
  • 198 Bernstein DI, Malkin E, Abughali N, Falloon J, Yi T, Dubovsky F. MI-CP149 Investigators. Phase 1 study of the safety and immunogenicity of a live, attenuated respiratory syncytial virus and parainfluenza virus type 3 vaccine in seronegative children. Pediatr Infect Dis J 2012; 31 (2) 109-114
  • 199 Gomez M, Mufson MA, Dubovsky F, Knightly C, Zeng W, Losonsky G. Phase-I study MEDI-534, of a live, attenuated intranasal vaccine against respiratory syncytial virus and parainfluenza-3 virus in seropositive children. Pediatr Infect Dis J 2009; 28 (7) 655-658
  • 200 Hall CB, Geiman JM, Breese BB, Douglas Jr RG. Parainfluenza viral infections in children: correlation of shedding with clinical manifestations. J Pediatr 1977; 91 (2) 194-198
  • 201 Brady MT, Evans J, Cuartas J. Survival and disinfection of parainfluenza viruses on environmental surfaces. Am J Infect Control 1990; 18 (1) 18-23
  • 202 Muchmore HG, Parkinson AJ, Humphries JE , et al. Persistent parainfluenza virus shedding during isolation at the South Pole. Nature 1981; 289 (5794) 187-189
  • 203 Nichols WG, Erdman DD, Han A, Zukerman C, Corey L, Boeckh M. Prolonged outbreak of human parainfluenza virus 3 infection in a stem cell transplant outpatient department: insights from molecular epidemiologic analysis. Biol Blood Marrow Transplant 2004; 10 (1) 58-64
  • 204 Maziarz RT, Sridharan P, Slater S , et al. Control of an outbreak of human parainfluenza virus 3 in hematopoietic stem cell transplant recipients. Biol Blood Marrow Transplant 2010; 16 (2) 192-198
  • 205 Harvala H, Gaunt E, McIntyre C , et al. Epidemiology and clinical characteristics of parainfluenza virus 3 outbreak in a Haemato-oncology unit. J Infect 2012; 65 (3) 246-254
  • 206 Peck AJ, Englund JA, Kuypers J , et al. Respiratory virus infection among hematopoietic cell transplant recipients: evidence for asymptomatic parainfluenza virus infection. Blood 2007; 110 (5) 1681-1688
  • 207 Huang CC, Shih SL. Images in clinical medicine. Steeple sign of croup. N Engl J Med 2012; 367 (1) 66