Monatsschrift Kinderheilkunde

, Volume 161, Issue 2, pp 157–168

Zytomegalievirusinfektionen im ersten Lebensjahr

CME Zertifizierte Fortbildung

Zusammenfassung

Das Zytomegalievirus (CMV) gehört zu den humanen Herpesviren. CMV-Infektionen sind im ersten Lebensjahr häufig, jedoch selten behandlungsbedürftig. Wegen des epidemiologischen Überwiegens subklinischer Infektionen erfordert die Diagnose einer symptomatischen CMV-Infektion immer auch den Ausschluss anderer infektiöser und nichtinfektiöser Erkrankungen. Eine konnatale Infektion ist nur in den ersten 3 Lebenswochen oder post hoc durch positiven Befund aus der Trockenblutkarte des neonatalen Stoffwechselscreenings nachweisbar. Da CMV lebenslang im Organismus persistiert, kann das Ziel einer antiviralen Therapie nur eine (vorübergehende) Suppression der Virusreplikation sein, um dem betroffenen Kind über vulnerable Phasen zu helfen. Bezüglich der Effektivität anderer Interventionen, z. B. Hyperimmunglobulingabe bei Schwangeren mit Primärinfektion, werden laufende Studien die Evidenzlage verbessern. Bis dahin bleibt die Handhygiene im Umgang mit den Sekreten kleiner Kinder die beste prophylaktische Maßnahme.

Schlüsselwörter

Herpesviren Humanes Herpesvirus 5 Kongenitale Infektion Behandlung Prophylaxe 

Abkürzungsverzeichnis

CMV

Zytomegalievirus

dCTP

Desoxycytidin

DGPI

Deutsche Gesellschaft für pädiatrische Infektiologie

DNA

Desoxyribonukleinsäure

ESPED

Erhebungseinheit seltener pädiatrischer Erkrankungen in Deutschland

HHV

Humanes Herpesvirus

HIG

Hyperimmunglobulin

HIV

Humanes Immundefizienzvirus

IGeL

Individuellen Gesundheitsleistungen

IgG

Immunglobulin G

IgM

Immunglobulin M

KG

Körpergewicht

PCR

Polymerasekettenreaktion

SCID

„Severe combined immunodeficiency“

SGA

„Small for gestational age“

SSW

Schwangerschaftswoche

ZNS

Zentralnervensystem

Cytomegalovirus infections in the first year of life

Abstract

The cytomegalovirus (CMV) belongs to the family of herpes viruses. CMV infections in the first year of life are frequent but only rarely require treatment. Because of the predominance of subclinical infections, the diagnosis of a symptomatic CMV infection requires the exclusion of other infectious and non-infectious diseases. Diagnosis of a congenital CMV infection is only possible in the first 3 weeks of life or by analysis of blood from the neonatal screening card. As CMV persists lifelong in the host, antiviral therapy aims at suppressing viral replication during the particular neurodevelopmental vulnerability of infancy. Ongoing studies will soon provide evidence for the efficacy of other interventions, such as hyperimmune globulins, in pregnant women with primary cytomegalovirus infections. Until then, hand hygiene in case of contact with body fluids of small children remains the best prophylactic measure for pregnant CMV-negative women.

Keywords

Herpesviridae Human herpesvirus 5 Congenital infection Treatment Prophylaxis 

Literatur

  1. 1.
    Bate SL, Dollard SC, Cannon MJ (2010) Cytomegalovirus seroprevalence in the United States: the national health and nutrition examination surveys, 1988–2004. Clin Infect Dis 50(11):1439–1447PubMedCrossRefGoogle Scholar
  2. 2.
    Cannon MJ, Schmid DS, Hyde TB (2010) Review of cytomegalovirus seroprevalence and demographic characteristics associated with infection. Rev Med Virol 20(4):202–213PubMedCrossRefGoogle Scholar
  3. 3.
    Hyde TB, Schmid DS, Cannon MJ (2010) Cytomegalovirus seroconversion rates and risk factors: implications for congenital CMV. Rev Med Virol 20(5):311–326PubMedCrossRefGoogle Scholar
  4. 4.
    Lübeck PR, Doerr HW, Rabenau HF (2010) Epidemiology of human cytomegalovirus (HCMV) in an urban region of Germany: what has changed? Med Microbiol Immunol 199(1):53–60PubMedCrossRefGoogle Scholar
  5. 5.
    Sande MA van der, Kaye S, Miles DJ et al (2007) Risk factors for and clinical outcome of congenital cytomegalovirus infection in a peri-urban West-African birth cohort. PLoS One 2(6):e492PubMedCrossRefGoogle Scholar
  6. 6.
    Stowell JD, Forlin-Passoni D, Din E et al (2012) Cytomegalovirus survival on common environmental surfaces: opportunities for viral transmission. J Infect Dis 205(2):211–214PubMedCrossRefGoogle Scholar
  7. 7.
    Bhide A, Papageorghiou AT (2008) Managing primary CMV infection in pregnancy. BJOG 115:805–807PubMedCrossRefGoogle Scholar
  8. 8.
    Kenneson A, Cannon MJ (2007) Review and meta-analysis of the epidemiology of congenital cytomegalovirus (CMV) infection. Rev Med Virol 17(4):253–276PubMedCrossRefGoogle Scholar
  9. 9.
    Wang C, Zhang X, Bialek S, Cannon MJ (2011) Attribution of congenital cytomegalovirus infection to primary versus non-primary maternal infection. Clin Infect Dis 52(2):e11–e13PubMedCrossRefGoogle Scholar
  10. 10.
    Enders G, Daiminger A, Bäder U et al (2011) Intrauterine transmission and clinical outcome of 248 pregnancies with primary cytomegalovirus infection in relation to gestational age. J Clin Virol 52(3):244–246PubMedCrossRefGoogle Scholar
  11. 11.
    Revello MG, Gerna G (2004) Pathogenesis and prenatal diagnosis of human cytomegalovirus infection. J Clin Virol 29(2):71–83PubMedCrossRefGoogle Scholar
  12. 12.
    Grosse SD, Ross DS, Dollard SC (2008) Congenital cytomegalovirus (CMV) infection as a cause of permanent bilateral hearing loss: a quantitative assessment. J Clin Virol 41(2):57–62PubMedCrossRefGoogle Scholar
  13. 13.
    Dahle AJ, Fowler KB, Wright JD et al (2000) Longitudinal investigation of hearing disorders in children with congenital cytomegalovirus. J Am Acad Audiol 11(5):283–290PubMedGoogle Scholar
  14. 14.
    Nijman J, Vries LS de, Koopman-Esseboom C et al (2012) Postnatally acquired cytomegalovirus infection in preterm infants: a prospective study on risk factors and cranial ultrasound findings. Arch Dis Child Fetal Neonatal Ed 97(4):F259–F263PubMedCrossRefGoogle Scholar
  15. 15.
    Stagno S, Dworsky ME, Torres J et al (1982) Prevalence and importance of congenital cytomegalovirus infection in three different populations. J Pediatr 101(6):897–900PubMedCrossRefGoogle Scholar
  16. 16.
    Boppana SB, Ross SA, Novak Z et al (2010) Dried blood spot real-time polymerase chain reaction assays to screen newborns for congenital cytomegalovirus infection. JAMA 303(14):1375–1382PubMedCrossRefGoogle Scholar
  17. 17.
    Boppana SB, Ross SA, Shimamura M et al (2011) Saliva polymerase-chain-reaction assay for cytomegalovirus screening in newborns. N Engl J Med 364(22):2111–2118PubMedCrossRefGoogle Scholar
  18. 18.
    Yamamoto AY, Mussi-Pinhata MM, Marin LJ et al (2006) Is saliva as reliable as urine for detection of cytomegalovirus DNA for neonatal screening of congenital CMV infection? J Clin Virol 36(3):228–230PubMedCrossRefGoogle Scholar
  19. 19.
    Lazzarotto T, Varani S, Guerra B et al (2000) Prenatal indicators of congenital cytomegalovirus infection. J Pediatr 137(1):90–95PubMedCrossRefGoogle Scholar
  20. 20.
    Vries JJ de, Barbi M, Binda S, Claas EC (2012) Extraction of DNA from dried blood in the diagnosis of congenital CMV infection. Methods Mol Biol 903:169–175PubMedCrossRefGoogle Scholar
  21. 21.
    Kadambari S, Williams EJ, Luck S et al (2011) Evidence based management guidelines for the detection and treatment of congenital CMV. Early Hum Dev 87(11):723–728PubMedCrossRefGoogle Scholar
  22. 22.
    Deutsche Gesellschaft für Pädiatrische Infektiologie (2009) Zytomegalovirus-Infektionen. DGPI Handbuch, 5. Aufl. Thieme, Stuttgart New York, S 565–568Google Scholar
  23. 23.
    Kimberlin DW, Lin CY, Sánchez PJ et al (2003) Effect of ganciclovir therapy on hearing in symptomatic congenital cytomegalovirus disease involving the central nervous system: a randomized, controlled trial. J Pediatr 143(1):16–25PubMedCrossRefGoogle Scholar
  24. 24.
    Kimberlin DW, Acosta EP, Sánchez PJ et al (2008) Pharmacokinetic and pharmacodynamic assessment of oral valganciclovir in the treatment of symptomatic congenital cytomegalovirus disease. J Infect Dis 197(6):836–845PubMedCrossRefGoogle Scholar
  25. 25.
    Lombardi G, Garofoli F, Villani P et al (2009) Oral valganciclovir treatment in newborns with symptomatic congenital cytomegalovirus infection. Eur J Clin Microbiol Infect Dis 28(12):1465–1470PubMedCrossRefGoogle Scholar
  26. 26.
    Amir J, Wolf DG, Levy I (2010) Treatment of symptomatic congenital cytomegalovirus infection with intravenous ganciclovir followed by long-term oral valganciclovir. Eur J Pediatr 169(9):1061–1067PubMedCrossRefGoogle Scholar
  27. 27.
    Lurain NS, Chou S (2010) Antiviral drug resistance of human cytomegalovirus. Clin Microbiol Rev 23(4):689–712PubMedCrossRefGoogle Scholar
  28. 28.
    Hakki M, Chou S (2011) The biology of cytomegalovirus drug resistance. Curr Opin Infect Dis 24(6):605–611PubMedCrossRefGoogle Scholar
  29. 29.
    Visentin S, Manara R, Milanese L et al (2012) Early primary cytomegalovirus infection in pregnancy: maternal hyperimmunoglobulin therapy improves outcomes among infants at 1 year of age. Clin Infect Dis 55(4):497–503PubMedCrossRefGoogle Scholar
  30. 30.
    Nigro G, Adler SP, Parruti G et al (2012) Immunoglobulin therapy of fetal cytomegalovirus infection occurring in the first half of pregnancy – a case-control study of the outcome in children. J Infect Dis 205(2):215–227PubMedCrossRefGoogle Scholar
  31. 31.
    Nigro G, Adler SP, La Torre R et al (2005) Passive immunization during pregnancy for congenital cytomegalovirus infection. N Engl J Med 353(13):1350–1362PubMedCrossRefGoogle Scholar
  32. 32.
    Cannon MJ, Westbrook K, Levis D et al (2012) Awareness of and behaviors related to child-to-mother transmission of cytomegalovirus. Prev Med 54(5):351–357PubMedCrossRefGoogle Scholar
  33. 33.
    Cannon MJ, Davis KF (2005) Washing our hands of the congenital cytomegalovirus disease epidemic. BMC Public Health 5:70PubMedCrossRefGoogle Scholar
  34. 34.
    Pass RF, Zhang C, Evans A et al (2009) Vaccine prevention of maternal cytomegalovirus infection. N Engl J Med 360(12):1191–1199PubMedCrossRefGoogle Scholar
  35. 35.
    Dempsey AF, Pangborn HM, Prosser LA (2012) Cost-effectiveness of routine vaccination of adolescent females against cytomegalovirus. Vaccine 30(27):4060–4066PubMedCrossRefGoogle Scholar
  36. 36.
    Stronati M, Lombardi G, Di Comite A, Fanos V (2007) Breastfeeding and cytomegalovirus infections. J Chemother [Suppl 2] 19:49–51Google Scholar
  37. 37.
    Curtis N, Chau L, Garland S et al (2005) Cytomegalovirus remains viable in naturally infected breast milk despite being frozen for 10 days. Arch Dis Child Fetal Neonatal Ed 90(6):F529–F530PubMedCrossRefGoogle Scholar
  38. 38.
    Hamprecht K, Maschmann J, Müller D et al (2004) Cytomegalovirus (CMV) inactivation in breast milk: reassessment of pasteurization and freeze-thawing. Pediatr Res 56(4):529–535PubMedCrossRefGoogle Scholar
  39. 39.
    Sharland M, Khare M, Bedford-Russell A (2002) Prevention of postnatal cytomegalovirus infection in preterm infants. Arch Dis Child Fetal Neonatal Ed 86(2):F140PubMedCrossRefGoogle Scholar
  40. 40.
    Hassan A, Jones N, Gaspar HB, Davies EG (2010) Risk factors and outcome of cytomegalovirus infection in children with severe combined immunodeficiency. Abstract P61, XIVth meeting of the European Society for Immunodeficiencies in Istanbul, 2010. ESID, GenfGoogle Scholar
  41. 41.
    Visconti MR, Pennington J, Garner SFL et al (2004) Assessment of removal of human cytomegalovirus from blood components by leukocyte depletion filters using real-time quantitative PCR. Blood 103:1137–1139PubMedCrossRefGoogle Scholar
  42. 42.
    Bundesärztekammer Deutschland (2011) Querschnitts-Leitlinie zur Therapie mit Blutkomponenten und Plasmaderivaten, 4. Aufl. 2008, zuletzt geändert Januar 2011. http://www.bundesaerztekammer.de/page.asp?his = 0.6.3288.8906. Zugegriffen: 12.10.2012Google Scholar
  43. 43.
    Josephson CD, Castillejo MI, Caliendo AM et al (2011) Prevention of transfusion-transmitted cytomegalovirus in low-birth weight infants (≤ 1500 g) using cytomegalovirus-seronegative and leukoreduced transfusions. Transfus Med Rev 25(2):125–132PubMedCrossRefGoogle Scholar
  44. 44.
    Ehl S, Schwarz K, Enders A et al (2005) A variant of SCID with specific immune responses and predominance of gamma delta T cells. J Clin Invest 115(11):3140–3148PubMedCrossRefGoogle Scholar
  45. 45.
    Fuchs S, Rensing-Ehl A, Speckmann C et al (2011) Antiviral and regulatory T cell immunity in a patient with stromal interaction molecule 1 deficiency. J Immunol 188(3):1523–1533PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • K. Schuster
    • 1
  • P. Henneke
    • 2
  • D. Huzly
    • 3
  • C. Speckmann
    • 2
  1. 1.Zentrum für Kinderheilkunde und JugendmedizinUniversitätsklinikum FreiburgFreiburgDeutschland
  2. 2.Zentrum fuer Kinderheilkunde und Jugendmedizin, Centrum fuer Chronische Immundefizienz - CCI Universitätsklinikum FreiburgFreiburgDeutschland
  3. 3.Abteilung Virologie, Institut für Medizinische Mikrobiologie und HygieneUniversitätsklinikum FreiburgFreiburgDeutschland

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