Das humane Metapneumovirus als Erreger von Atemwegsinfektionen bei hospitalisierten Kindern - eine Übersicht

Zusammenfassung

Besonders bei Säuglingen im zweiten Lebenshalbjahr und bei Kleinkindern scheint das im Jahr 2001 von van den Hoogen erstmals beschriebene humane Metapneumovirus (HMPV) eine herausragende Rolle als Erreger von Atemwegsinfektionen zu spielen. Vor dem Hintergrund der bis Anfang 2005 publizierten Studien und eigener, retrospektiv analysierter Daten aus zwei konsekutiven Winterperioden (2002-2004) wird in dieser Übersicht das HMPV aus der Perspektive der klinischen Pädiatrie, das heißt mit besonderem Augenmerk auf verfügbaren Informationen zu hospitalisierten Kindern vorgestellt. Dabei bestätigt sich, dass bei hospitalisierten Kindern ein erheblicher Anteil Risikofaktoren für einen komplizierten Verlauf aufweist. Besondere bei Frühgeborenen treten vermehrt Apnoen im Verlauf der HMPV-Infektion auf. Auch wenn die erste HMPV-Infektion in der Regel später auftritt als die RSV-Primärinfektion, verlaufen HMPV-Infektionen nicht generell milder. Klinische und radiologische Zeichen lassen keine ätiologische Zuordnung zu einem bestimmten Erreger zu, was die Bedeutung der gezielten virologischen Diagnostik mittels PCR unterstreicht. HMPV kann auch segmentale und lobäre Pneumonien auslösen. Kinder mit Exazerbation eines Asthma bronchiale oder einer zystischen Fibrose sollten in den Wintermonaten nicht nur auf RSV, sondern auch auf HMPV getestet werden. Prospektive Studien zu therapeutischen Interventionen und zur Bedeutung und Prävention nosokomialer HMPVInfektionen werden erwartet. Obwohl bislang erst von einem Fall berichtet wurde, sollte bei unklarer Meningoenzephalitis auch eine HMPV-PCR durchgeführt werden.

Abstract

The human Metapneumovirus (HMPV) has been discovered by von den Hoogen et al. in 2001 and seems to play an important role as etiologic agent in childhood respiratory tract infections in particular involving infants after the 6th month of life and toddlers. Duly considering the hitherto published studies and retrospective analysis of two HMPV seasons (2002-2004) at our institution this review focuses on children, who had to be hospitalized due to HMPV infection. The analysis confirmed, that among those patients there is a high proportion of children with pre-existing risk factors for a complicated clinical course, a high proportion of children with bronchiolitis or pneumonia and a relevant proportion of children with HMPV related apnoeas, most prevalent in the prematurely born. Although the first HMPV infection takes place somewhat later in infancy, the data do not show that HMPV infection is in general milder than RSV infection in hospitalized children. Clinical symptoms and radiological signs do not permit tentative conclusions on the causative agent. This underlines the necessity of specific diagnostic efforts (in case of HMPV with PCR). HMPV may cause lobar or segmental pneumonias difficult to distinguish from bacterial lower respiratory tract infection. Children admitted to the hospital with an acute exacerbation of asthma bronchiale or cystic fibrosis should not only be tested for RSV but also for HMPV. Prospective studies investigating specific therapeutic interventions or describing the impact and prevention of nosocomial HMPV in fection are awaited for. There has been one report of a meningoencephalitis possibly related to HMPV. Thus, liquor samples in such cases should be tested for HMPV too.

Humanes Metapneumovirus - hospitalisierte Patienten - Pneumonie - Bronchiolitis

human metapneumovirus - hospitalized patients - pneumonia - bronchiolitis

Literatur

• 1 Alvarez R, Harrod KS, Shieh WJ, Zaki S, Tripp RA. Human metapneumovirus persists in BALB/c mice despite the presence of neutralizing antibodies.  J Virol. 2004;  78 14003-14011
• 2 Alvarez R, Tripp RA. The immune response to human metapneumovirus is associated with aberrant immunity and impaired virus clearance in BALB/c mice.  J Virol. 2005;  79 5971-5978
• 3 American Academy of Pediatrics, Subcommittee on Management of Acute Otitis Media . Diagnosis and management of acute otitis media.  Pediatrics. 2004;  113 1451-1465
• 4 Arruda LK, Sole D, Baena-Cagnani CE, Naspitz CK. Risk factors for asthma and atopy.  Curr Opin Allergy Clin Immunol. 2005;  5 153-159
• 5 Black CP. Systematic review of the biology and medical management of respiratory syncytial virus infection.  Respir Care. 2003;  48 209-231
• 6 Boivin G, Abed Y, Pelletier G. et al . Virological features and clinical manifestations associated with human metapneumovirus: a new paramyxovirus responsible for acute respiratory-tract infections in all age groups.  J Infect Dis. 2002;  186 1330-1334
• 7 Boivin G, De Serres G, Cote S. et al . Human metapneumovirus infections in hospitalized children.  Emerg Infect Dis. 2003;  9 634-640
• 8 Bosis S, Esposito S, Niesters HG, Crovari P, Osterhaus AD, Principi N. Impact of human metapneumovirus in childhood: comparison with respiratory syncytial virus and influenza viruses.  J Med Virol. 2005;  75 101-104
• 9 Bouscambert-Duchamp M, Lina B, Trompette A, Moret H, Motte J, Andreoletti L. 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. 2005;  43 1411-1414
• 10 Cane PA, den Hoogen BG van, Chakrabarti S, Fegan CD, Osterhaus AD. Human metapneumovirus in a haematopoietic stem cell transplant recipient with fatal lower respiratory tract disease.  Bone Marrow Transplant. 2003;  31 309-310
• 11 Crowe Jr JE. Human metapneumovirus as a major cause of human respiratory tract disease.  Pediatr Infect Dis J. 2004;  23 215-221
• 12 Cunha BA. Therapeutic implications of antibacterial resistance in community-acquired respiratory tract infections in children.  Infection. 2004;  32 98-108
• 13 Dollner H, Risnes K, Radtke A, Nordbo SA. Outbreak of human metapneumovirus infection in norwegian children.  Pediatr Infect Dis J. 2004;  23 436-440
• 14 Donnelly LF. Practical issues concerning imaging of pulmonary infection in children.  J Thorac Imaging. 2001;  16 238-250
• 15 Druce J, Tran T, Kelly H. et al . Laboratory diagnosis and surveillance of human respiratory viruses by PCR in Victoria, Australia, 2002-2003.  J Med Virol. 2005;  75 122-129
• 16 Esper F, Boucher D, Weibel C, Martinello RA, Kahn JS. Human metapneumovirus infection in the United States: clinical manifestations associated with a newly emerging respiratory infection in children.  Pediatrics. 2003;  111 1407-1410
• 17 Esper F, Martinello RA, Boucher D. et al . A 1-year experience with human metapneumovirus in children aged <5 years.  J Infect Dis. 2004;  189 1388-1396
• 18 Fitzgerald DA, Kilham HA. Bronchiolitis: assessment and evidencebased management.  Med J Aust. 2004;  180 399-404
• 19 Forster J, Ihorst G, Rieger CH. et al . Prospective population-based study of viral lower respiratory tract infections in children under 3 years of age (the PRI. DE study).  Eur J Pediatr. 2004;  163 709-716
• 20 Gern JE. Viral respiratory infection and the link to asthma.  Pediatr Infect Dis J. 2004;  23 78-86
• 21 Greensill J, McNamara PS, Dove W, Flanagan B, Smyth RL, Hart CA. Human metapneumovirus in severe respiratory syncytial virus bronchiolitis.  Emerg Infect Dis. 2003;  9 372-375
• 22 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 11-18
• 23 Heymann PW, Carper HT, Murphy DD. et al . Viral infections in relation to age, atopy, and season of admission among children hospitalized for wheezing.  J Allergy Clin Immunol. 2004;  114 239-247
• 24 Hicks KL, Chemaly RF, Kontoyiannis DP. Common community respiratory viruses in patients with cancer: more than just “common colds”.  Cancer. 2003;  97 2576-2587
• 25 Jartti T, den Hoogen B van, Garofalo RP, Osterhaus AD, Ruuskanen O. Metapneumovirus and acute wheezing in children.  Lancet. 2002;  360 1393-1394
• 26 Kashiwa H, Shimozono H, Takao S. Clinical pictures of children with human metapneumovirus infection: comparison with respiratory syncytial virus infection.  Jpn J Infect Dis. 2004;  57 80-82
• 27 King VJ, Viswanathan M, Bordley WC. et al . Pharmacologic treatment of bronchiolitis in infants and children: a systematic review.  Arch Pediatr Adolesc Med. 2004;  158 127-137
• 28 Konig B, Konig W, Arnold R, Werchau H, Ihorst G, Forster J. Prospective study of human metapneumovirus infection in children less than 3 years of age.  J Clin Microbiol. 2004;  42 4632-4635
• 29 Korppi M. Community-acquired pneumonia in children: issues in optimizing antibacterial treatment.  Paediatr Drugs. 2003;  5 821-832
• 30 Korppi M. Mixed microbial aetiology of community-acquired pneumonia in children.  Apmis. 2002;  110 515-522
• 31 Kuiken T, den Hoogen BG van, Riel DA van. et al . Experimental human metapneumovirus infection of cynomolgus macaques (Macaca fascicularis) results in virus replication in ciliated epithelial cells and pneumocytes with associated lesions throughout the respiratory tract.  Am J Pathol. 2004;  164 1893-1900
• 32 Landry ML, Ferguson D, Cohen S, Peret TC, Erdman DD. Detection of human metapneumovirus in clinical samples by immunofluorescence staining of shell vial centrifugation cultures prepared from three different cell lines.  J Clin Microbiol. 2005;  43 1950-1952
• 33 Leader S, Kohlhase K. Recent trends in severe respiratory syncytial virus (RSV) among US infants, 1997 to 2000.  J Pediatr. 2003;  143 127-132
• 34 Leung J, Esper F, Weibel C, Kahn JS. Seroepidemiology of human metapneumovirus (hMPV) on the basis of a novel enzyme-linked immunosorbent assay utilizing hMPV fusion protein expressed in recombinant vesicular stomatitis virus.  J Clin Microbiol. 2005;  43 1213-1219
• 35 Levine DA, Platt SL, Dayan PS. et al . Risk of serious bacterial infection in young febrile infants with respiratory syncytial virus infections.  Pediatrics. 2004;  113 1728-1734
• 36 Low DE, Pichichero ME, Schaad UB. Optimizing antibacterial therapy for community-acquired respiratory tract infections in children in an era of bacterial resistance.  Clin Pediatr (Phila). 2004;  43 135-151
• 37 Madhi SA, Ludewick H, Abed Y, Klugman KP, Boivin G. 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. 2003;  37 1705-1710
• 38 Maggi F, Pifferi M, Vatteroni M. et al . Human metapneumovirus associated with respiratory tract infections in a 3-year study of nasal swabs from infants in Italy.  J Clin Microbiol. 2003;  41 2987-2991
• 39 McAdam AJ, Hasenbein ME, Feldman HA. et al . Human metapneumovirus in children tested at a tertiary-care hospital.  J Infect Dis. 2004;  190 20-26
• 40 McIntosh K. Community-acquired pneumonia in children.  N Engl J Med. 2002;  346 429-437
• 41 McIntosh K, McAdam AJ. Human metapneumovirus - an important new respiratory virus.  N Engl J Med. 2004;  350 431-433
• 42 Meissner HC. Selected populations at increased risk from respiratory syncytial virus infection.  Pediatr Infect Dis J. 2003;  22 40-44
• 43 Moulin F, Raymond J, Lorrot M. et al . Procalcitonin in children admitted to hospital with community acquired pneumonia.  Arch Dis Child. 2001;  84 332-336
• 44 Mullins JA, Erdman DD, Weinberg GA. et al . Human metapneumovirus infection among children hospitalized with acute respiratory illness.  Emerg Infect Dis. 2004;  10 700-705
• 45 Noyola DE, Alpuche-Solis AG, Herrera-Diaz A, Soria-Guerra RE, Sanchez- Alvarado J, Lopez-Revilla R. Human metapneumovirus infections in Mexico: epidemiological and clinical characteristics.  J Med Microbiol. 2005;  54 969-974
• 46 Ogra PL. Respiratory syncytial virus: the virus, the disease and the immune response.  Paediatr Respir Rev. 2004;  5 ((Suppl A)) 119-126
• 47 Peiris JS, Tang WH, Chan KH. et al . Children with respiratory disease associated with metapneumovirus in Hong Kong.  Emerg Infect Dis. 2003;  9 628-633
• 48 Pelletier G, Dery P, Abed Y, Boivin G. Respiratory tract reinfections by the new human Metapneumovirus in an immunocompromised child.  Emerg Infect Dis. 2002;  8 976-978
• 49 Purcell K, Fergie J. Concurrent serious bacterial infections in 2396 infants and children hospitalized with respiratory syncytial virus lower respiratory tract infections.  Arch Pediatr Adolesc Med. 2002;  156 322-324
• 50 Rawlinson WD, Waliuzzaman Z, Carter IW, Belessis YC, Gilbert KM, Morton JR. Asthma exacerbations in children associated with rhinovirus but not human metapneumovirus infection.  J Infect Dis. 2003;  187 1314-1318
• 51 Robinson CA, Kuhn RJ, Craigmyle J, Anstead MI, Kanga JE. Susceptibility of pseudomonas aeruginosa to cefepime versus ceftazidime in patients with cystic fibrosis.  Pharmacotherapy. 2001;  21 1320-1324
• 52 Robinson JL, Lee BE, Bastien N, Li Y. Seasonality and clinical features of human metapneumovirus infection in children in Northern Alberta.  J Med Virol. 2005;  76 98-105
• 53 Sasaki A, Suzuki H, Saito R. et al . Prevalence of human metapneumovirus and influenza virus infections among Japanese children during two successive winters.  Pediatr Infect Dis J. 2005;  24 905-908
• 54 Scarfone RJ. Controversies in the treatment of bronchiolitis.  Curr Opin Pediatr. 2005;  17 62-66
• 55 Schauer U, Hoffjan S, Bittscheidt J. et al . RSV bronchiolitis and risk of wheeze and allergic sensitisation in the first year of life.  Eur Respir J. 2002;  20 1277-1283
• 56 Schildgen O, Geikowski T, Glatzel T, Schuster J, Simon A. Frequency of human metapneumovirus in the upper respiratory tract of children with symptoms of an acute otitis media.  Eur J Pediatr. 2005;  164 400-401
• 57 Schildgen O, Geikowski T, Glatzel T. et al . New variant of the human metapneumovirus (HMPV) associated with an acute and severe exacerbation of asthma bronchiale.  J Clin Virol. 2004;  31 283-288
• 58 Schildgen O, Glatzel T, Geikowski T. et al . Human metapneumovirus RNA in encephalitis patient.  Emerg Infect Dis. 2005;  11 467-470
• 59 Semple MG, Cowell A, Dove W. et al . Dual infection of infants by human metapneumovirus and human respiratory syncytial virus is strongly associated with severe bronchiolitis.  J Infect Dis. 2005;  191 382-386
• 60 Sigurs N, Gustafsson PM, Bjarnason R. et al . Severe respiratory syncytial virus bronchiolitis in infancy and asthma and allergy at age 13.  Am J Respir Crit Care Med. 2005;  171 137-141
• 61 Takao S, Shimozono H, Kashiwa H. et al . Clinical study of pediatric cases of acute respiratory diseases associated with human metapneumovirus in Japan.  Jpn J Infect Dis. 2003;  56 127-129
• 62 Toikka P, Irjala K, Juven T. et al . Serum procalcitonin, C-reactive protein and interleukin-6 for distinguishing bacterial and viral pneumonia in children.  Pediatr Infect Dis J. 2000;  19 598-602
• 63 den Hoogen BG van, de Jong JC, Groen J. et al . A newly discovered human pneumovirus isolated fromyoung children with respiratory tract disease.  Nat Med. 2001;  7 719-724
• 64 den Hoogen BG van, Osterhaus DM, Fouchier RA. Clinical impact and diagnosis of human metapneumovirus infection.  Pediatr Infect Dis J. 2004;  23 25-32
• 65 den Hoogen BG van, Doornum GJ van, Fockens JC. et al . Prevalence and clinical symptoms of human metapneumovirus infection in hospitalized patients.  J Infect Dis. 2003;  188 1571-1577
• 66 Viazov S, Ratjen F, Scheidhauer R, Fiedler M, Roggendorf M. High prevalence of human metapneumovirus infection in young children and genetic heterogeneity of the viral isolates.  J Clin Microbiol. 2003;  41 3043-3045
• 67 Linstow ML von, Henrik Larsen H, Eugen-Olsen J. et al . Human metapneumovirus and respiratory syncytial virus in hospitalized danish children with acute respiratory tract infection.  Scand J Infect Dis. 2004;  36 578-584
• 68 Weigl JA, Puppe W, Schmitt HJ. Can respiratory syncytial virus etiology be diagnosed clinically? A hospital-based case-control study in children under two years of age.  Eur J Epidemiol. 2003;  18 431-439
• 69 Wilkesmannn A, Schildgen O, Eis-Hübinger A. et al . Human Metapneumovirus infection is not milder than RSV infection.  Eur J Pediatr. , (accepted for publication)
• 70 Williams JV, Harris PA, Tollefson SJ. et al . Human metapneumovirus and lower respiratory tract disease in otherwise healthy infants and children.  N Engl J Med. 2004;  350 443-450
• 71 Williams JV, Tollefson SJ, Heymann PW, Carper HT, Patrie J, Crowe JE. Human metapneumovirus infection in children hospitalized for wheezing.  J Allergy Clin Immunol. 2005;  115 1311-1312
• 72 Wyde PR, Chetty SN, Jewell AM, Boivin G, Piedra PA. Comparison of the inhibition of human metapneumovirus and respiratory syncytial virus by ribavirin and immune serum globulin in vitro.  Antiviral Res. 2003;  60 51-59

1 Diese beiden Autoren trugen gleichermaßen zum Manuskript bei.

2 Ein vollständiges Verzeichnis aller Studien kann vom korrespondierenden

Korrespondenzadresse