Advertisement

Cytomegalovirus Infection

  • Andrea Ronchi
  • Lorenza Pugni
  • Fabio Mosca
Chapter

Abstract

Cytomegalovirus (CMV) is the leading cause of congenital infection in humans and constitutes a major public health problem. Congenitally infected infants, both symptomatic and asymptomatic at birth, are at risk for sequelae including sensorineural hearing loss. The virus can be transmitted to the fetus following either a primary or a non-primary maternal infection during pregnancy. Even though the transmission rate is much higher in primary infected mothers than in mothers with preconceptional immunity, routine CMV screening of pregnant women is not recommended today because no consensus exists on prenatal treatment options. Intravenous ganciclovir or oral valganciclovir are used to treat neonates with symptoms at birth. Valganciclovir treatment for 6 months is recommended for congenitally infected neonates with moderately to severely symptomatic disease. All infants with congenital CMV infection, both symptomatic and asymptomatic at birth, need a follow-up evaluation to detect sequelae promptly. For several years, a universal screening for congenital CMV infection has been suggested by many authors for early detection of sequelae and timely intervention. A real-time PCR assay of saliva specimens seems to offer the best characteristics for use in screening.

Keywords

Cytomegalovirus Congenital infection Neonate Valganciclovir Breast milk 

References

  1. 1.
    Plosa EJ, Esbenshade JC, Fuller MP, Weitkamp JH. Cytomegalovirus infection. Pediatr Rev. 2012;33:156–63.CrossRefPubMedGoogle Scholar
  2. 2.
    Ross SA, Arora N, Novak Z, Fowler KB, Britt WJ, Boppana SB. Cytomegalovirus reinfections in healthy seroimmune women. J Infect Dis. 2010;201:386–9.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Lanzieri TM, Kruszon-Moran D, Gambhir M, Bialek SR. Influence of parity and sexual history on cytomegalovirus seroprevalence among women aged 20-49 years in the USA. Int J Gynaecol Obstet. 2016;135:82–5.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Bate SL, Dollard SC, Cannon MJ. Cytomegalovirus seroprevalence in the United States: the national health and nutrition examination surveys, 1988-2004. Clin Infect Dis. 2010;50:1439–47.CrossRefPubMedGoogle Scholar
  5. 5.
    Lanzieri TM, Dollard SC, Bialek SR, Grosse SD. Systematic review of the birth prevalence of congenital cytomegalovirus infection in developing countries. Int J Infect Dis. 2014;22:44–8.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Cannon MJ, Stowell JD, Clark R, et al. Repeated measures study of weekly and daily cytomegalovirus shedding patterns in saliva and urine of healthy cytomegalovirus-seropositive children. BMC Infect Dis. 2014;14:569.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Hyde TB, Schmid DS, Cannon MJ. Cytomegalovirus seroconversion rates and risk factors: implications for congenital CMV. Rev Med Virol. 2010;20:311–26.CrossRefPubMedGoogle Scholar
  8. 8.
    Cantey JB, Sanchez PJ. Overview of congenital infections: the prominence of cytomegalovirus. Infect Disord Drug Targets. 2011;11:426–31.CrossRefPubMedGoogle Scholar
  9. 9.
    Boppana SB, Ross SA, Shimamura M, et al. Saliva polymerase-chain-reaction assay for cytomegalovirus screening in newborns. N Engl J Med. 2011;364:2111–8.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Manicklal S, Emery VC, Lazzarotto T, Boppana SB, Gupta RK. The “silent” global burden of congenital cytomegalovirus. Clin Microbiol Rev. 2013;26:86–102.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Josephson CD, Caliendo AM, Easley KA, et al. Blood transfusion and breast milk transmission of cytomegalovirus in very low-birth-weight infants: a prospective cohort study. JAMA Pediatr. 2014;168:1054–62.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Kagan KO, Hamprecht K. Cytomegalovirus infection in pregnancy. Arch Gynecol Obstet. 2017;296:15–26.CrossRefPubMedGoogle Scholar
  13. 13.
    Boppana SB, Ross SA, Fowler KB. Congenital cytomegalovirus infection: clinical outcome. Clin Infect Dis. 2013;57:S178–81.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Boppana SB, Pass RF, Britt WJ, Stagno S, Alford CA. Symptomatic congenital cytomegalovirus infection: neonatal morbidity and mortality. Pediatr Infect Dis J. 1992;11:93–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Rawlinson WD, Boppana SB, Fowler KB, et al. Congenital cytomegalovirus infection in pregnancy and the neonate: consensus recommendations for prevention, diagnosis, and therapy. Lancet Infect Dis. 2017;17:177–88.CrossRefGoogle Scholar
  16. 16.
    Fowler KB, McCollister FP, Dahle AJ, et al. Progressive and fluctuating sensorineural hearing loss in infants with asymptomatic congenital cytomegalovirus infection. J Pediatr. 1997;130:624–30.CrossRefPubMedGoogle Scholar
  17. 17.
    Goderis J, De Leenheer E, Smets K, Van Hoecke H, Keymeulen A, Dhooge I. Hearing loss and congenital CMV infection: a systematic review. Pediatrics. 2014;134:972–82.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Kenna MA. Acquired hearing loss in children. Otolaryngol Clin N Am. 2015;48:933–53.CrossRefGoogle Scholar
  19. 19.
    Fowler KB. Congenital cytomegalovirus infection: audiologic outcome. Clin Infect Dis. 2013;57:S182–4.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Gunkel J, de Vries LS, Johngmans M, et al. Outcome of preterm infants with postnatal cytomegalovirus infection. Pediatrics. 2018;141:e20170635.CrossRefPubMedGoogle Scholar
  21. 21.
    Mosca F, Pugni L. Cytomegalovirus infection: the state of the art. J Chemother. 2007;19:46–8.CrossRefPubMedGoogle Scholar
  22. 22.
    Kaneko M, Ohhashi M, Minematsu T, Muraoka J, Kusumoto K, Sameshima H. Maternal immunoglobulin G avidity as a diagnostic tool to identify pregnant women at risk of congenital cytomegalovirus infection. J Infect Chemother. 2017;23:173–6.CrossRefPubMedGoogle Scholar
  23. 23.
    Goegebuer T, Van Meensel B, Beuselinck K, et al. Clinical predictive value of real-time PCR quantification of human cytomegalovirus DNA in amniotic fluid samples. J Clin Microbiol. 2009;47:660–5.CrossRefPubMedGoogle Scholar
  24. 24.
    Stehel EK, Shoup AG, Owen KE, et al. Newborn hearing screening and detection of congenital cytomegalovirus infection. Pediatrics. 2008;121(5):970.CrossRefPubMedGoogle Scholar
  25. 25.
    Duryea EL, Sanchez PJ, Sheffield JS, et al. Maternal human immunodeficiency virus infection and congenital transmission of cytomegalovirus. Pediatr Infect Dis J. 2010;29:915–8.CrossRefPubMedGoogle Scholar
  26. 26.
    Nigro G, Adler SP, La Torre R, Best AM. Passive immunization during pregnancy for congenital cytomegalovirus infection. N Engl J Med. 2005;353:1350–62.CrossRefPubMedGoogle Scholar
  27. 27.
    Revello MG, Lazzarotto T, Guerra B, et al. A randomized trial of hyperimmune globulin to prevent congenital cytomegalovirus. N Engl J Med. 2014;370:1316–26.CrossRefPubMedGoogle Scholar
  28. 28.
    Kimberlin DW, Jester PM, Sánchez PJ, et al. Valganciclovir for symptomatic congenital cytomegalovirus disease. N Engl J Med. 2015;372:933–43.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Kimberlin DW, Lin CY, Sánchez PJ, et al. Effect of ganciclovir therapy on hearing in symptomatic congenital cytomegalovirus disease involving the central nervous system: a randomized, controlled trial. J Pediatr. 2003;143:16–25.CrossRefPubMedGoogle Scholar
  30. 30.
    Lim Y, Lyall H. Congenital cytomegalovirus – who, when, what-with, and why to treat? J Infect. 2017;74:S89–94.CrossRefPubMedGoogle Scholar
  31. 31.
    Gunkel J, Wolfs TF, de Vries LS, Nijman J. Predictors of severity for postnatal cytomegalovirus infection in preterm infants and implications for treatment. Expert Rev Anti-Infect Ther. 2014;12:1345–55.CrossRefPubMedGoogle Scholar
  32. 32.
    Schleiss MR, Permar SR, Plotkin SA. Progress toward development of a vaccine against congenital cytomegalovirus infection. Clin Vaccine Immunol. 2017;24:e00268-17.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Jeon J, Victor M, Adler SP, et al. Knowledge and awareness of congenital cytomegalovirus among women. Infect Dis Obstet Gynecol. 2006;2006:80383.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Vauloup-Fellous C, Picone O, Cordier AG, et al. Does hygiene counseling have an impact on the rate of CMV primary infection during pregnancy? Results of a 3-year prospective study in a French hospital. J Clin Virol. 2009;46:S49–53.CrossRefPubMedGoogle Scholar
  35. 35.
    Hamprecht K, Goelz R. Postnatal cytomegalovirus infection through human milk in preterm infants: transmission, clinical presentation, and prevention. Clin Perinatol. 2017;44:121–30.CrossRefPubMedGoogle Scholar
  36. 36.
    American Academy of Pediatrics, Policy Statement. Breastfeeding and the use of human milk. Pediatrics. 2012;129:827–41.CrossRefGoogle Scholar
  37. 37.
    Amir J, Schwarz M, Levy I, Haimi-Cohen Y, Pardo J. Is lenticulostriated vasculopathy a sign of central nervous system insult in infants with congenital CMV infection? Arch Dis Child. 2011;96:846–50.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Neonatal Intensive Care Unit, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoUniversità degli Studi di MilanoMilanoItaly

Personalised recommendations