Abstract
Several new viruses have recently been described in children, including human metapneumovirus (hMPV) and human bocavirus (HBoV). hMPV has been established as a common cause of upper and lower respiratory tract infections in children, often second only to respiratory syncytial virus as a cause of bronchiolitis in infants. Diagnostic tools have been developed for the clinician and effective treatment and prevention strategies are being investigated. HBoV was more recently identified. Although it was initially identified in the airway of children, high rates of codetection of other viral pathogens and detection of the virus in the stool have raised questions about the true role of HBoV as a cause of respiratory infections. A focus on epidemiology, pathogenesis, clinical features, and diagnostic techniques for hMPV and HBoV is presented.
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Abbreviations
- CPE:
-
cytopathologic effects
- DFA:
-
direct fluorescent antigen detection
- FDA:
-
food and drug administration
- HBoV:
-
human bocavirus
- hMPV:
-
human metapneumovirus
- IgG:
-
immunoglobulin G
- LRI:
-
lower respiratory tract infection
- LRT:
-
lower respiratory tract
- RSV:
-
respiratory syncytial virus
- URI:
-
upper respiratory tract infection
- VLP:
-
virus-like particle
References
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: 719–724
Williams JV, Harris PA, Tollefson SJ, Halburnt-Rush LL, Pingsterhaus JM, Edwards KM, Wright PF, Crowe JE Jr 2004 Human metapneumovirus and lower respiratory tract disease in otherwise healthy infants and children. N Engl J Med 350: 443–450
Cilla G, Onate E, Perez-Yarza EG, Montes M, Vicente D, Perez-Trallero E 2009 Hospitalization rates for human metapneumovirus infection among 0- to 3-year-olds in Gipuzkoa (Basque Country), Spain. Epidemiol Infect 137: 66–72
Madhi SA, Ludewick H, Abed Y, Klugman KP, Boivin G 2003 Human metapneumovirus-associated lower respiratory tract infections among hospitalized human immunodeficiency virus type 1 (HIV-1)-infected and HIV-1-uninfected African infants. Clin Infect Dis 37: 1705–1710
Robinson JL, Lee BE, Bastien N, Li Y 2005 Seasonality and clinical features of human metapneumovirus infection in children in Northern Alberta. J Med Virol 76: 98–105
Galiano M, Videla C, Puch SS, Martinez A, Echavarria M, Carballal G 2004 Evidence of human metapneumovirus in children in Argentina. J Med Virol 72: 299–303
Bouscambert-Duchamp M, Lina B, Trompette A, Moret H, Motte J, Andreoletti L 2005 Detection of human metapneumovirus RNA sequences in nasopharyngeal aspirates of young French children with acute bronchiolitis by real-time reverse transcriptase PCR and phylogenetic analysis. J Clin Microbiol 43: 1411–1414
Viazov S, Ratjen F, Scheidhauer R, Fiedler M, Roggendorf M 2003 High prevalence of human metapneumovirus infection in young children and genetic heterogeneity of the viral isolates. J Clin Microbiol 41: 3043–3045
Peiris JS, Tang WH, Chan KH, Khong PL, Guan Y, Lau YL, Chiu SS 2003 Children with respiratory disease associated with metapneumovirus in Hong Kong. Emerg Infect Dis 9: 628–633
Carr MJ, McCormack GP, Crowley B 2005 Human metapneumovirus-associated respiratory tract infections in the Republic of Ireland during the influenza season of 2003–2004. Clin Microbiol Infect 11: 366–371
Wolf DG, Zakay-Rones Z, Fadeela A, Greenberg D, Dagan R 2003 High seroprevalence of human metapneumovirus among young children in Israel. J Infect Dis 188: 1865–1867
Ebihara T, Endo R, Kikuta H, Ishiguro N, Ishiko H, Hara M, Takahashi Y, Kobayashi K 2004 Human metapneumovirus infection in Japanese children. J Clin Microbiol 42: 126–132
Werno AM, Anderson TP, Jennings LC, Jackson PM, Murdoch DR 2004 Human metapneumovirus in children with bronchiolitis or pneumonia in New Zealand. J Paediatr Child Health 40: 549–551
Esper F, Boucher D, Weibel C, Martinello RA, Kahn JS 2003 Human metapneumovirus infection in the United States: clinical manifestations associated with a newly emerging respiratory infection in children. Pediatrics 111: 1407–1410
van den Hoogen BG, van Doornum GJ, Fockens JC, Cornelissen JJ, Beyer WE, de Groot R, Osterhaus AD, Fouchier RA 2003 Prevalence and clinical symptoms of human metapneumovirus infection in hospitalized patients. J Infect Dis 188: 1571–1577
Lambert SB, Allen KM, Druce JD, Birch CJ, Mackay IM, Carlin JB, Carapetis JR, Sloots TP, Nissen MD, Nolan TM 2007 Community epidemiology of human metapneumovirus, human coronavirus NL63, and other respiratory viruses in healthy preschool-aged children using parent-collected specimens. Pediatrics 120: e929–e937
Gerna G, Campanini G, Rovida F, Sarasini A, Lilleri D, Paolucci S, Marchi A, Baldanti F, Revello MG 2005 Changing circulation rate of human metapneumovirus strains and types among hospitalized pediatric patients during three consecutive winter-spring seasons. Brief report. Arch Virol 150: 2365–2375
van den Hoogen BG, Herfst S, Sprong L, Cane PA, Forleo-Neto E, de Swart RL, Osterhaus AD, Fouchier RA 2004 Antigenic and genetic variability of human metapneumoviruses. Emerg Infect Dis 10: 658–666
Vicente D, Montes M, Cilla G, Perez-Yarza EG, Perez-Trallero E 2006 Differences in clinical severity between genotype A and genotype B human metapneumovirus infection in children. Clin Infect Dis 42: e111–e113
Hamelin ME, Yim K, Kuhn KH, Cragin RP, Boukhvalova M, Blanco JC, Prince GA, Boivin G 2005 Pathogenesis of human metapneumovirus lung infection in BALB/c mice and cotton rats. J Virol 79: 8894–8903
Ebihara T, Endo R, Ishiguro N, Nakayama T, Sawada H, Kikuta H 2004 Early reinfection with human metapneumovirus in an infant. J Clin Microbiol 42: 5944–5946
Williams JV, Wang CK, Yang CF, Tollefson SJ, House FS, Heck JM, Chu M, Brown JB, Lintao LD, Quinto JD, Chu D, Spaete RR, Edwards KM, Wright PF, Crowe JE Jr 2006 The role of human metapneumovirus in upper respiratory tract infections in children: a 20-year experience. J Infect Dis 193: 387–395
Douville RN, Bastien N, Li Y, Pochard P, Simons FE, HayGlass KT 2006 Human metapneumovirus elicits weak IFN-gamma memory responses compared with respiratory syncytial virus. J Immunol 176: 5848–5855
Laham FR, Israele V, Casellas JM, Garcia AM, Lac Prugent CM, Hoffman SJ, Hauer D, Thumar B, Name MI, Pascual A, Taratutto N, Ishida MT, Balduzzi M, Maccarone M, Jackli S, Passarino R, Gaivironsky RA, Karron RA, Polack NR, Polack FP 2004 Differential production of inflammatory cytokines in primary infection with human metapneumovirus and with other common respiratory viruses of infancy. J Infect Dis 189: 2047–2056
Greensill J, McNamara PS, Dove W, Flanagan B, Smyth RL, Hart CA 2003 Human metapneumovirus in severe respiratory syncytial virus bronchiolitis. Emerg Infect Dis 9: 372–375
Vicente D, Cilla G, Montes M, Perez-Trallero E 2003 Human metapneumovirus and community-acquired respiratory illness in children. Emerg Infect Dis 9: 602–603
Freymouth F, Vabret A, Legrand L, Eterradossi N, Lafay-Delaire F, Brouard J, Guillois B 2003 Presence of the new human metapneumovirus in French children with bronchiolitis. Pediatr Infect Dis J 22: 92–94
Rawlinson WD, Waliuzzaman Z, Carter IW, Belessis YC, Gilbert KM, Morton JR 2003 Asthma exacerbations in children associated with rhinovirus but not human metapneumovirus infection. J Infect Dis 187: 1314–1318
Semple MG, Cowell A, Dove W, Greensill J, McNamara PS, Halfhide C, Shears P, Smyth RL, Hart CA 2005 Dual infection of infants by human metapneumovirus and human respiratory syncytial virus is strongly associated with severe bronchiolitis. J Infect Dis 191: 382–386
Paranhos-Baccala G, Komurian-Pradel F, Richard N, Vernet G, Lina B, Floret D 2008 Mixed respiratory virus infections. J Clin Virol 43: 407–410
Ebihara T, Endo R, Kikuta H, Ishiguro N, Ishiko H, Kobayashi K 2004 Comparison of the seroprevalence of human metapneumovirus and human respiratory syncytial virus. J Med Virol 72: 304–306
Ebihara T, Endo R, Kikuta H, Ishiguro N, Yoshioka M, Ma X, Kobayashi K 2003 Seroprevalence of human metapneumovirus in Japan. J Med Virol 70: 281–283
Cane PA, van den Hoogen BG, Chakrabarti S, Fegan CD, Osterhaus AD 2003 Human metapneumovirus in a haematopoietic stem cell transplant recipient with fatal lower respiratory tract disease. Bone Marrow Transplant 31: 309–310
Kamble RT, Bollard C, Demmler G, LaSala PR, Carrum G 2007 Human metapneumovirus infection in a hematopoietic transplant recipient. Bone Marrow Transplant 40: 699–700
Pelletier G, Dery P, Abed Y, Boivin G 2002 Respiratory tract reinfections by the new human metapneumovirus in an immunocompromised child. Emerg Infect Dis 8: 976–978
Kumar D, Erdman D, Keshavjee S, Peret T, Tellier R, Hadjiliadis D, Johnson G, Ayers M, Siegal D, Humar A 2005 Clinical impact of community-acquired respiratory viruses on bronchiolitis obliterans after lung transplant. Am J Transplant 5: 2031–2036
Schildgen O, Glatzel T, Geikowski T, Scheibner B, Matz B, Bindl L, Born M, Viazov S, Wilkesmann A, Knopfle G, Roggendorf M, Simon A 2005 Human metapneumovirus RNA in encephalitis patient. Emerg Infect Dis 11: 467–470
Glaser CA, Honarmand S, Anderson LJ, Schnurr DP, Forghani B, Cossen CK, Schuster FL, Christie LJ, Tureen JH 2006 Beyond viruses: clinical profiles and etiologies associated with encephalitis. Clin Infect Dis 43: 1565–1577
Hata M, Ito M, Kiyosawa S, Kimpara Y, Tanaka S, Yamashita T, Hasegawa A, Kobayashi S, Koyama N, Minagawa H 2007 A fatal case of encephalopathy possibly associated with human metapneumovirus infection. Jpn J Infect Dis 60: 328–329
Arnold JC, Singh KK, Spector SA, Sawyer MH 2008 Undiagnosed respiratory viruses in children. Pediatrics 121: e631–e637
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
Ebihara T, Endo R, Ma X, Ishiguro N, Kikuta H 2005 Detection of human metapneumovirus antigens in nasopharyngeal secretions by an immunofluorescent-antibody test. J Clin Microbiol 43: 1138–1141
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
Endo R, Ebihara T, Ishiguro N, Teramoto S, Ariga T, Sakata C, Hayashi A, Ishiko H, Kikuta H 2008 Detection of four genetic subgroup-specific antibodies to human metapneumovirus attachment (G) protein in human serum. J Gen Virol 89: 1970–1977
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: 249–253
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: 51–59
Deffrasnes C, Hamelin ME, Prince GA, Boivin G 2008 Identification and evaluation of a highly effective fusion inhibitor for human metapneumovirus. Antimicrob Agents Chemother 52: 279–287
Allander T, Tammi MT, Eriksson M, Bjerkner A, Tiveljung-Lindell A, Andersson B 2005 Cloning of a human parvovirus by molecular screening of respiratory tract samples. Proc Natl Acad Sci U S A 102: 12891–12896
Lin F, Guan W, Cheng F, Yang N, Pintel D, Qiu J 2008 ELISAs using human bocavirus VP2 virus-like particles for detection of antibodies against HBoV. J Virol Methods 149: 110–117
Kantola K, Hedman L, Allander T, Jartti T, Lehtinen P, Ruuskanen O, Hedman K, Soderlund-Venermo M 2008 Serodiagnosis of human bocavirus infection. Clin Infect Dis 46: 540–546
Endo R, Ishiguro N, Kikuta H, Teramoto S, Shirkoohi R, Ma X, Ebihara T, Ishiko H, Ariga T 2007 Seroepidemiology of human bocavirus in Hokkaido prefecture. Jpn J Clin Microbiol 45: 3218–3223
Chieochansin T, Chutinimitkul S, Payungporn S, Hiranras T, Samransamruajkit R, Theamboolers A, Poovorawan Y 2007 Complete coding sequences and phylogenetic analysis of human bocavirus (HBoV). Virus Res 129: 54–57
Chieochansin T, Samransamruajkit R, Chutinimitkul S, Payungporn S, Hiranras T, Theamboonlers A, Poovorawan Y 2008 Human bocavirus (HBoV) in Thailand: clinical manifestations in a hospitalized pediatric patient and molecular virus characterization. J Infect 56: 137–142
Allander T 2008 Human bocavirus. J Clin Virol 41: 29–33
Bastien N, Brandt K, Dust K, Ward D, Li Y 2006 Human Bocavirus infection, Canada. Emerg Infect Dis 12: 848–850
Catalano-Pons C, Bue M, Laude H, Cattan F, Moulin F, Menager C, Cosnes-Lambe C, Chalumeau M, Giraud C, Meritet JF, Rozenberg F, Lebon P, Gendrel D 2007 Human bocavirus infection in hospitalized children during winter. Pediatr Infect Dis J 26: 959–960
Kaplan NM, Dove W, Abu-Zeid AF, Shamoon HE, Abd-Eldayem SA, Hart CA 2006 Human bocavirus infection among children, Jordan. Emerg Infect Dis 12: 1418–1420
Lin F, Zeng A, Yang N, Lin H, Yang E, Wang S, Pintel D, Qiu J 2007 Quantification of human bocavirus in lower respiratory tract infections in China. Infect Agent Cancer 2: 3
Ma X, Endo R, Ishiguro N, Ebihara T, Ishiko H, Ariga T, Kikuta H 2006 Detection of human bocavirus in Japanese children with lower respiratory tract infections. J Clin Microbiol 44: 1132–1134
Monteny M, Niesters HG, Moll HA, Berger MY 2007 Human bocavirus in febrile children, The Netherlands. Emerg Infect Dis 13: 180–182
Pozo F, Garcia-Garcia ML, Calvo C, Cuesta I, Perez-Brena P, Casas I 2007 High incidence of human bocavirus infection in children in Spain. J Clin Virol 40: 224–228
Redshaw N, Wood C, Rich F, Grimwood K, Kirman JR 2007 Human bocavirus in infants, New Zealand. Emerg Infect Dis 13: 1797–1799
Sloots TP, McErlean P, Speicher DJ, Arden KE, Nissen MD, Mackay IM 2006 Evidence of human coronavirus HKU1 and human bocavirus in Australian children. J Clin Virol 35: 99–102
Smuts H, Hardie D 2006 Human bocavirus in hospitalized children, South Africa. Emerg Infect Dis 12: 1457–1458
Thanasugarn W, Samransamruajkit R, Vanapongtipagorn P, Prapphal N, Van den Hoogen B, Osterhaus AD, Poovorawan Y 2003 Human metapneumovirus infection in Thai children. Scand J Infect Dis 35: 754–756
Villa L, Melon S, Suarez S, Alvarez-Arguelles ME, Gonzalez D, Morilla A, Boga JA, Rodriguez J, de Ona M 2008 Detection of human bocavirus in Asturias, Northern Spain. Eur J Clin Microbiol Infect Dis 27: 237–239
Fry AM, Lu X, Chittaganpitch M, Peret T, Fischer J, Dowell SF, Anderson LJ, Erdman D, Olsen SJ 2007 Human bocavirus: a novel parvovirus epidemiologically associated with pneumonia requiring hospitalization in Thailand. J Infect Dis 195: 1038–1045
Kesebir D, Vazquez M, Weibel C, Shapiro ED, Ferguson D, Landry ML, Kahn JS 2006 Human bocavirus infection in young children in the United States: molecular epidemiological profile and clinical characteristics of a newly emerging respiratory virus. J Infect Dis 194: 1276–1282
Christensen A, Nordbo SA, Krokstad S, Rognlien AG, Dollner H 2008 Human bocavirus commonly involved in multiple viral airway infections. J Clin Virol 41: 34–37
Vicente D, Cilla G, Montes M, Perez-Yarza EG, Perez-Trallero E 2007 Human bocavirus, a respiratory and enteric virus. Emerg Infect Dis 13: 636–637
Esposito S, Bosis S, Niesters HG, Tremolati E, Sabatini C, Porta A, Fossali E, Osterhaus AD, Principi N 2008 Impact of human bocavirus on children and their families. J Clin Microbiol 46: 1337–1342
Garbino J, Inoubli S, Mossdorf E, Weber R, Tamm M, Soccal P, Aubert JD, Bridevaux PO, Tapparel C, Kaiser L 2008 Respiratory viruses in HIV-infected patients with suspected respiratory opportunistic infection. AIDS 22: 701–705
Albuquerque MC, Rocha LN, Benati FJ, Soares CC, Maranhao AG, Ramirez ML, Erdman D, Santos N 2007 Human bocavirus infection in children with gastroenteritis, Brazil. Emerg Infect Dis 13: 1756–1758
Lau SK, Yip CC, Que TL, Lee RA, Au-Yeung RK, Zhou B, So LY, Lau YL, Chan KH, Woo PC, Yuen KY 2007 Clinical and molecular epidemiology of human bocavirus in respiratory and fecal samples from children in Hong Kong. J Infect Dis 196: 986–993
Allander T, Jartti T, Gupta S, Niesters HG, Lehtinen P, Osterback R, Vuorinen T, Waris M, Bjerkner A, Tiveljung-Lindell A, van den Hoogen BG, Hyypia T, Ruuskanen O 2007 Human bocavirus and acute wheezing in children. Clin Infect Dis 44: 904–910
Manning A, Willey SJ, Bell JE, Simmonds P 2007 Comparison of tissue distribution, persistence, and molecular epidemiology of parvovirus B19 and novel human parvoviruses PARV4 and human bocavirus. J Infect Dis 195: 1345–1352
Lu X, Gooding LR, Erdman DD 2008 Human bocavirus in tonsillar lymphocytes. Emerg Infect Dis 14: 1332–1334
Chung JY, Han TH, Kim JS, Kim SW, Park CG, Hwang ES 2008 Th1 and Th2 cytokine levels in nasopharyngeal aspirates from children with human bocavirus bronchiolitis. J Clin Virol 43: 223–225
Arnold JC, Singh KK, Spector SA, Sawyer MH 2006 Human bocavirus: prevalence and clinical spectrum at a children's hospital. Clin Infect Dis 43: 283–288
Choi EH, Lee HJ, Kim SJ, Eun BW, Kim NH, Lee JA, Lee JH, Song EK, Kim SH, Park JY, Sung JY 2006 The association of newly identified respiratory viruses with lower respiratory tract infections in Korean children 2000–2005. Clin Infect Dis 43: 585–592
Chung JY, Han TH, Kim CK, Kim SW 2006 Bocavirus infection in hospitalized children, South Korea. Emerg Infect Dis 12: 1254–1256
Foulongne V, Olejnik Y, Perez V, Elaerts S, Rodiere M, Segondy M 2006 Human bocavirus in French children. Emerg Infect Dis 12: 1251–1253
Maggi F, Andreoli E, Pifferi M, Meschi S, Rocchi J, Bendinelli M 2007 Human bocavirus in Italian patients with respiratory diseases. J Clin Virol 38: 321–325
Naghipour M, Cuevas LE, Bakhshinejad T, Dove W, Hart CA 2007 Human bocavirus in Iranian children with acute respiratory infections. J Med Virol 79: 539–543
Qu XW, Duan ZJ, Qi ZY, Xie ZP, Gao HC, Liu WP, Huang CP, Peng FW, Zheng LS, Hou YD 2007 Human bocavirus infection, People's Republic of China. Emerg Infect Dis 13: 165–168
Volz S, Schildgen O, Klinkenberg D, Ditt V, Muller A, Tillmann RL, Kupfer B, Bode U, Lentze MJ, Simon A 2007 Prospective study of human bocavirus (HBoV) infection in a pediatric university hospital in Germany 2005/2006. J Clin Virol 40: 229–235
Schildgen O, Muller A, Simon A 2007 Human bocavirus and gastroenteritis. Emerg Infect Dis 13: 1620–1621
Schenk T, Strahm B, Kontny U, Hufnagel M, Neumann-Haefelin D, Falcone V 2007 Disseminated bocavirus infection after stem cell transplant. Emerg Infect Dis 13: 1425–1427
Koskenvuo M, Mottonen M, Waris M, Allander T, Salmi TT, Ruuskanen O 2008 Human bocavirus in children with acute lymphoblastic leukemia. Eur J Pediatr 167: 1011–1015
Kainulainen L, Waris M, Soderlund-Venermo M, Allander T, Hedman K, Ruuskanen O 2008 Hepatitis and human bocavirus primary infection in a child with T-cell deficiency. J Clin Microbiol 46: 4104–4105
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Milder, E., Arnold, J. Human Metapneumovirus and Human Bocavirus in Children. Pediatr Res 65, 78–83 (2009). https://doi.org/10.1203/PDR.0b013e31819db90c
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DOI: https://doi.org/10.1203/PDR.0b013e31819db90c
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