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Prevention and Therapy: More than Trial and Error

  • Gabriele Halwachs-Baumann
Chapter

Abstract

Given the importance of congenital CMV as a potentially preventable cause of disability in children, it is logical to consider it for potential inclusion in public health newborn screening [1]. This statement is in polar opposite to an opinion published 2 years before, concluding that no screening program for congenital cytomegalovirus infection is justified [2]. These two examples stand for two groups of scientists, the one being optimistic seeing a benefit in promoting CMV awareness in the community and the other being afraid to open Pandora’s box [1–4]. It is written: “For in much wisdom is much grief: and he that increases the knowledge increases the sorrow” (Ecclesiastes 1:18). But it is also written: “The simple believes everything, but the prudent looks where he is going.” (Proverbs 14:15). In the absence of proven therapeutic options, prevention of CMV infection in women of reproductive age is an important strategy to reduce the rate of congenital CMV infection. And the easiest way to prevent congenital cytomegalovirus is the teaching and implementation of hygiene interventions [4]. We now know the risk factors for congenital cytomegalovirus infection. Caring for preschool children is one of them [5–7]. The problem is the lack of knowledge and awareness of congenital cytomegalovirus among women. Only 13–22% of women had heard of congenital CMV (and only 7% of men), compared to 98% who had heard of HIV/AIDS [8, 9]. Thereby seroconversion rates consistently decrease as cytomegalovirus education and support increases [10, 11]. Hygienic practices to reduce risk of CMV infection for women who are pregnant or planning to become pregnant are simple [8]:

References

  1. 1.
    Grosse SD, Dollard S, Ross DS, Cannon M (2009) Newborn screening for congenital cytomegalovirus: options for hospital-based and public health programs. J Clin Virol 46S:S32–S36CrossRefGoogle Scholar
  2. 2.
    Schlesinger Y (2007) Routine screening for CMV in pregnancy: opening the pandora box? Isr Med Assoc J 9:395–397PubMedGoogle Scholar
  3. 3.
    Cahill AG, Odibo AO, Stamilio DM, Macones GA (2009) Screening and treating for primary cytomegalovirus infection in pregnancy: where do we stand? A decision-analytic and economic analysis. Am J Obstet Gynecol 201:466.e1–466.e7CrossRefGoogle Scholar
  4. 4.
    Demmler-Harrison GJ (2009) J Clin Virol 46S:S1–S5CrossRefGoogle Scholar
  5. 5.
    Fowler KB, Pass RF (2006) Risk factors for congenital cytomegalovirus infection in the offspring of young women: exposure to young children and recent onset of sexual activity. Pediatrics 118:e286–e292PubMedCrossRefGoogle Scholar
  6. 6.
    Adler SP, Finney JW, Manganello AM, Best AM (2004) Prevention of child-to-mother transmission of cytomegalovirus among pregnant women. J Pediatr 145:485–491PubMedCrossRefGoogle Scholar
  7. 7.
    Marshall BC, Adler SP (2009) The frequency of pregnancy and exposure to cytomegalovirus (CMV) infections among women with a young child in day care. Am J Obstet Gynecol 200(2):163.e1–163.e5CrossRefGoogle Scholar
  8. 8.
    Jeon J, Victor M, Adler SP, Arwady A, Demmler G, Fowler K, Goldfarb J, Keyserling H, Massoudi M, Richards K, Staras SAS, Cannon MJ (2006) Knowledge and awareness of congenital cytomegalovirus among women. Infect Dis Obstet Gynecol 2006:1–7CrossRefGoogle Scholar
  9. 9.
    Cannon MJ, Westbrook K, Levis D, Schleiss MR, Thackeray R, Pass RF (2012) Awareness of and behaviors related to child-to-mother transmission of cytomegalovirus. Prev Med 54(5):351–357PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Harvey J, Dennis CL (2008) Hygiene interventions for prevention of cytomegalovirus infection among childbearing women: systematic review. J Adv Nurs 63(5):440–450PubMedCrossRefGoogle Scholar
  11. 11.
    Valoup-Fellous C, Picone O, Cordier AG, Parent-du-Chatelet I, Senat MV, Frydman R, Grangeot-Keros L (2009) Does hygiene counselling have an impact on the rate of CMV primary infection during pregnancy? Results of a 3-year prospective study in French hospital. J Clin Virol 46S:S49–S53CrossRefGoogle Scholar
  12. 12.
    Pass RF, Arav-Boger R (2018) Maternal and fetal cytomegalovirus infection: diagnosis, management, and prevention. F1000Res 7:255PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Revello MG, Tibaldi C, Masuelli G et al (2015) Prevention of primary cytomegalovirus infection in pregnancy. EBioMedicine 2:1205–1210PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    van Zuylen WJ, Hamilton ST, Naing Z, Hall B, Shand A, Rawlinson WD (2014) Congenital cytomegalovirus infection: clinical presentation, epidemiology, diagnosis and prevention. Obstet Med 7(4):140–146PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Stowell JD, Forlin-Passoni D, Radford K et al (2014) Cytomegalovirus survival and transferability and the effectiveness of common hand-washing agents against cytomegalovirus on live human hands. Appl Environ Microbiol 80(2):455–461PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Burny W, Liesnard C, Donner C, Marchant A (2004) Epidemiology, pathogenesis and prevention of congenital cytomegalovirus infection. Expert Rev Anti-Infect Ther 2(6):881–894PubMedCrossRefGoogle Scholar
  17. 17.
    Mercorelli B, Sinigalia E, Loregian A, Palu G (2008) Human cytomegalovirus DNA replication: antiviral targets and drugs. Rev Med Virol 18:177–210PubMedCrossRefGoogle Scholar
  18. 18.
    Fiddian P, Sabin CA, Griffiths PD (2002) Valacyclovir provides optimum acyclovir exposure for prevention of cytomegalovirus and related outcomes after organ transplantation. J Infect Dis 186(Suppl 1):S110–S115PubMedCrossRefGoogle Scholar
  19. 19.
    Talarico CL, Burnette TC, Miller WH et al (1999) Acyclovir is phosphorylated by the human cytomegalovirus UL97 protein. Antimicrob Agents Chemother 43(8):1941–1946PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Nigro G, Sali E, Anceschi MM, Mazzocco M, Maranghi L, Clerico A, Castello MA (2004) Foscarnet therapy for congenital cytomegalovirus liver fibrosis following prenatal ascites. J Matern Fetal Neonatal Med 15(5):325–329PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Nassetta L, Kimberlin D, Whitley R (2009) Treatment of congenital cytomegalovirus infection: implications for future therapeutic strategies. J Antimicrob Chemother 63:862–867PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Marshall BC, Koch WC (2009) Antivirals for cytomegalovirus infection in neonates and infants: focus on pharmacokinetics, formulations, dosing, and adverse events. Paediatr Drugs 11(5):309–321PubMedCrossRefGoogle Scholar
  23. 23.
    Trang JM, Kidd L, Gruber W, Storch G, Demmler G, Jacobs R, Dankner W, Starr S, Pass R, Stagno S, Alford C, Song SJ, Whitley RJ, Sommadossi JP (1993) Linear single-dose pharmacokinetics of ganciclovir in newborns with congenital cytomegalovirus infection. Clin Pharmacol Ther 53:15–21PubMedCrossRefGoogle Scholar
  24. 24.
    Kimberlin DW, Acosta EP, Sanchez PJ, Sood S, Agrawal V, Homans J, Jacobs RF, Lang D, Romero JR, Grifin J, Cloud GA, Lakeman FD, Whitley RJ (2008) Pharmacokinetic and pharmacodynamic assessment of oral valganciclovir in the treatment of symptomatic congenital cytomegalovirus disease. J Infect Dis 197:836–845PubMedCrossRefGoogle Scholar
  25. 25.
    Galli L, Novelli A, Chiappini E, Gervaso P, Cassetta MI, Fallani S, Martino M (2007) Valganciclovir for congenital CMV infection: a pilot study on plasma concentration in newborns and infants. J Pediatr Infect Dis 26(5):451–453CrossRefGoogle Scholar
  26. 26.
    Jacquemard F, Yamamoto M, Costa JM, Romand S, Jaqz-Aigrain E, Dejean A, Daffos F, Ville Y (2007) Maternal administration of valaciclovir in symptomatic intrauterine cytomegalovirus infection. BJOG 114:1113–1121PubMedCrossRefGoogle Scholar
  27. 27.
    Pacifici GM (2005) Transfer of antivirals across the human placenta. Early Hum Dev 81:647–654PubMedCrossRefGoogle Scholar
  28. 28.
    Leruez-Ville M, Ghout I, Bussières L et al (2016) In utero treatment of congenital cytomegalovirus infection with valacyclovir in a multicentre, open-label, phase II study. Am J Obstet Gynecol 215:462.e1–462.e10CrossRefGoogle Scholar
  29. 29.
    Seidel V, Feiterna-Sperling C, Siedentopf JP et al (2017) Intrauterine therapy of cytomegalovirus infection with valganciclovir: review of the literature. Med Microbiol Immunol 206:347–354PubMedCrossRefGoogle Scholar
  30. 30.
    Rawlinson WD, Boppana SB, Fowler KB et al (2017) Congenital cytomegalovirus infection in pregnancy and the neonate: consensus recommendations for prevention, diagnosis, and therapy. Lancet Infect Dis 17:e177–e188PubMedCrossRefPubMedCentralGoogle Scholar
  31. 31.
    Rezanka E, Ploier R, Emhofer B, Emhofer J (1993) Congenital, generalized cytomegalovirus infection. Follow-up and therapeutic strategy with ganciclovir. Padiatr Padol 28(6):153–155PubMedPubMedCentralGoogle Scholar
  32. 32.
    Junker AK, Matheson D, Tingle AT, Thomas EE (1991) Immune responses after ganciclovir and immunoglobulin therapy of infants. J Pediatr Infect Dis 10(3):256–258CrossRefGoogle Scholar
  33. 33.
    Muntean W, Lackner H, Stünzner D, Ebner F (1989) 9 Wochen alter Säugling mit konnataler Zytomegalievirusinfection und Therapie mit Ganciclovir. Wien Klin Wochenschr 101:554–557PubMedPubMedCentralGoogle Scholar
  34. 34.
    Nigro G, Scholz H, Bartmann U (1994) Ganciclovir therapy for symptomatic congenital cytomegalovirus infection in infants: a two-regimen experience. J Pediatr 124:318–322PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Whitley RJ, Cloud G, Gruber W, Storch GA, Demmler GJ, Jacobs RF, Dankner W, Spector SA, Starr S, Pass RF, Stagno S, Britt WJ, Alford C, Soong SJ, Zhou XJ, Sherrill L, FitzGerald JM, Sommadossi JP (1997) Ganciclovir treatment of symptomatic congenital cytomegalovirus infection: results of a phase II study. J Infect Dis 175:1080–1086PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Halwachs-Baumann G, Genser B, Pailer S, Engele H, Rosegger H, Schalk A, Kessler HH, Truschnig-Wilders M (2002) Human cytomegalovirus load in various body fluids of congenitally infected newborns. J Clin Virol 25(Suppl 3):S81–S87PubMedCrossRefGoogle Scholar
  37. 37.
    Michaels MG, Greenberg DP, Sabo DL, Wald ER (2003) Treatment of children with congenital cytomegalovirus infection with ganciclovir. Pediatr Infect Dis J 22:504–505PubMedPubMedCentralGoogle Scholar
  38. 38.
    Kimberlin DW, Lin CY, Sanches PJ, Demmler GJ, Dankner W, Shelton M, Jacobs RF, Vaudry W, Pass RF, Kiell JM, Soong SJ, Whitley RJ (2003) Effect of ganciclovir therapy on hearing in symptomatic congenital cytomegalovirus disease involving the central nervous system: a randomized, controlled trial. J Pediatr 143:16–25PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Kimberlin DW, Jester PM, Sánchez PJ et al (2015) Valganciclovir for symptomatic congenital cytomegalovirus disease. N Engl J Med 372(10):933–943PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Oliver SE, Cloud G a, Sanchez PJ, Demmler GJ, Dankner W, Shelton M, Jacobs RF, Vaudry W, Pass RF, Soong SJ, Whitley RJ, Kimberlin DW (2009) Neurodevelopmental outcomes following ganciclovir therapy in symptomatic congenital cytomegalovirus infections involving the central nervous system. J Clin Virol 46S:S22–S26CrossRefGoogle Scholar
  41. 41.
    Weng YH, Chu SM, Lien RI, Chou YH, Lin TY (2003) Clinical experience with ganciclovir and anti-cytomegalovirus immunoglobulin treatment for a severe case of congenital cytomegalovirus infection. Chang Gung Med J 26:128–132PubMedPubMedCentralGoogle Scholar
  42. 42.
    Shoji K, Ito N, Ito Y, Inoue N, Adachi S, Fujimaru T, Nakamura T, Nishina S, Azuma N, Saitoh A (2010) Is a 6-week course of ganciclovir therapy effective for chorioretinitis in infants with congenital cytomegalovirus infection? J Pediatr 157(2):331–333PubMedCrossRefPubMedCentralGoogle Scholar
  43. 43.
    Yilmaz CD, Vardar F (2011) Effect on hearing of oral valganciclovir for asymptomatic congenital cytomegalovirus infection. J Trop Pediatr 57(2):132–134CrossRefGoogle Scholar
  44. 44.
    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):1061–1067.  https://doi.org/10.1007/s00431-010-1176-9CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Gandhi RS, Fernandez-Alvarez JR, Rabe H (2010) Management of congenital cytomegalovirus infection: an evidence-based approach. Acta Paediatr 99:509–515PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Luck S, Sharland M, Griffiths P (2007) Ganciclovir therapy for neonates with congenital cytomegalovirus infection. Eur J Pediatr 166:633–634PubMedCrossRefPubMedCentralGoogle Scholar
  47. 47.
    Smets K, De Coen K, Dhooge I, Standaert L, Laroche S, Mahieu L, Logghe N, Cossey V, Boudewyns A (2006) Selecting neonates with congenital cytomegalovirus infection for ganciclovir therapy. Eur J Pediatr 165:885–890PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    Prober C g, Enright AM (2003) Congenital cytomegalovirus (CMV) infections: hats off to Alabama. J Pediatr 143:4–6PubMedCrossRefPubMedCentralGoogle Scholar
  49. 49.
    Michaels MG (2007) Treatment of congenital cytomegalovirus: where are we now? Expert Rev Anti-Infect Ther 5(3):441–448PubMedCrossRefPubMedCentralGoogle Scholar
  50. 50.
    Demmler GJ (2003) Congenital cytomegalovirus infection treatment. Pediatr Infect Dis J 22:1003–1006CrossRefGoogle Scholar
  51. 51.
    Dahle AJ, fowler KB, Wright JD, Boppana SB, Britt WJ, Pass RF (2000) Longitudinal investigation of hearing disorders in children with congenital cytomegalovirus. J Am Acad Audiol 11(5):283–290PubMedGoogle Scholar
  52. 52.
    Fowler KB, McCollister FP, Dahle AJ, Boppana S, Britt WJ, Pass RF (1997) Progressive and fluctuating sensorineural hearing loss in children with asymptomatic congenital cytomegalovirus infection. J Pediatr 130:624–630PubMedCrossRefGoogle Scholar
  53. 53.
    Lackner A, Acham A, Alborno T, Moser M, Engele H, Raggam RB, Halwachs-Baumann G, Kapitan M, Walch C (2009) Effect on hearing of ganciclovir therapy for asymptomatic congenital cytomegalovirus infection: four to 10 year follow up. J Laryngol Otol 123(4):391–396PubMedCrossRefGoogle Scholar
  54. 54.
    James SH, Kimberlin DW (2016) Advances in the prevention and treatment of congenital cytomegalovirus infection. Curr Opin Pediatr 28(1):81–85PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    James SH, Kimberlin DW, Whitley RJ (2009) Antiviral therapy for herpesvirus central nervous system infections: neonatal herpes simplex virus infection, herpes simplex encephalitis, and congenital cytomegalovirus infection. Antivir Res 83:207–213PubMedCrossRefPubMedCentralGoogle Scholar
  56. 56.
    Clark AL, Gall SA (1997) Clinical uses of intravenous immunoglobulin in pregnancy. Am J Obstet Gynecol 176:241–253PubMedCrossRefPubMedCentralGoogle Scholar
  57. 57.
    Clark AL (1999) Clinical uses of intravenous immunoglobulin in pregnancy. Clin Obstet Gynecol 42(2):368–380PubMedCrossRefPubMedCentralGoogle Scholar
  58. 58.
    Adler SP, Nigro G (2009) Findings and conclusions from CMV hyperimmune globulin treatment trials. J Clin Virol 46S:S54–S57CrossRefGoogle Scholar
  59. 59.
    Keller MA, Stiehm ER (2000) Passive immunity I prevention and treatment of infectious diseases. Clin Microbial Rev 13(4):602–614CrossRefGoogle Scholar
  60. 60.
    Chang MH (2007) Hepatitis B virus infection. Semin Fetal Neonatal Med 12:160–167PubMedCrossRefGoogle Scholar
  61. 61.
    Rhiner J, Pfister R, Tschopp YN, Bucher H (2007) Ul. Selective immunisation strategy to protect newborns at risk for transmission of hepatitis B: retrospective audit of vaccine uptake. Swiss Med Wkly 137:531–535PubMedGoogle Scholar
  62. 62.
    (1990) Protection against viral hepatitis. Recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR Recomm Rep 9:1–26Google Scholar
  63. 63.
    Heininger U, Vaudaux B, Nidecker M, Pfister RE, Posfay-Barbe KM, Bachofner M, Hoigne I, Gnehm HE (2010) Evaluation of the compliance with recommended procedures in newborns exposed to HBsAg-positive mothers: a multicenter collaborative study. Pediatr Infect Dis J 29(3):248–250PubMedCrossRefGoogle Scholar
  64. 64.
    (1990) NIH Consensus Conference. Intravenus immunoglobulin. Prevention and treatment of disease. J Am Med Assoc 264:3189–3193Google Scholar
  65. 65.
    Lories RJU, Maertens JA, Ceuppens JL, Peetermans WE (2000) The use of polyclonal intravenous immunoglobulins in the prevention and treatment of infectious diseases. Acta Clin Belg 55(3):163–169PubMedCrossRefGoogle Scholar
  66. 66.
    Von Muralt G, Sidiropoulos D (1988) Prenatal and postnatal prophylaxis of infections in preterm neonates. Pediatr Infect Dis J 7(5):S072–S078Google Scholar
  67. 67.
    Jauniaux E, Jurkovic D, Gulbis B, Liesnard C, Lees C, Campbell S (1995) Materno-fetal immunoglobulin transfer and passive immunity during the first trimester of human pregnancy. Hum Reprod 10(2):3297–3300PubMedCrossRefGoogle Scholar
  68. 68.
    Adler SP, Starr SE, Plotkin SA, Hempfling SH, Buis J, Manning ML, Best AM (1995) Immunity induced by primary human cytomegalovirus infection protects against secondary infection among women of childbearing age. J Infect Dis 171(1):26–32PubMedCrossRefGoogle Scholar
  69. 69.
    Cui X, Meza BP, Adler SP, McVoy MA (2008) Cytomegalovirus vaccines fail to induce epithelial entry neutralizing antibodies comparable to natural infection. Vaccine 26(45):5760–5766PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Cekinovic D, Golemac M, Pugel EP, Tomac J, Cicin-Sain L, Slavuljica I, Bradford R, Misch S, Winkler TH, Mach M, Britt WJ, Jonjic S (2008) Passive immunization reduces murine cytomegalovirus-induced brain pathology in newborn mice. J Virol 82(24):12172–12180PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Negishi H, Yamada H, Hirayama E, Okuyama K, Sagawa T, Matsumoto Y, Fujimoto S (1998) Intraperitoneal administration of cytomegalovirus hyperimmunoglobulin to the cytomegalovirus infected fetus. J Perinatol 18(6):466–469PubMedGoogle Scholar
  72. 72.
    Breindl A, Lassmann R (1989) Zytomegalie-Infektion bei Zwillingsschwangerschaft – Reversibilität eines Hydrops fetalis nach Behandlung mit Humanimmunglobulin (Cytotect®). Gynecologie 12:339–341Google Scholar
  73. 73.
    Moxley K, Knudtson EJ (2008) Resolution of hydrops secondary to cytomegalovirus after naternal and fetal treatment with human cytomegalovirus hyperimmune globulin. Obstet Gynecol 111(2):524–526PubMedCrossRefGoogle Scholar
  74. 74.
    Nigro G, La Torre R, Anceschi MM, Mazzocco M, Cosmi EV (1999) Hyperimmunoglobulin therapy for a twin fetus with cytomegalovirus infection and growth restriction. Am J Obstet Gynecol 180:1222–1226PubMedCrossRefGoogle Scholar
  75. 75.
    Nigro G, Adler SP, La Torre R, Best AM (2005) Passive immunization during pregnancy for congenital cytomegalovirus infection. N Engl J Med 29:1350–1362CrossRefGoogle Scholar
  76. 76.
    La Torre R, Nigro G, Mazzocco M, Best AB, Adler SP (2006) Placental enlargement in women with primary maternal cytomegalovirus infection is associated with fetal and neonatal disease. Clin Infect Dis 43:994–1000PubMedCrossRefPubMedCentralGoogle Scholar
  77. 77.
    Schleiss MR (2006) The role of the placenta in the pathogenesis of congenital cytomegalovirus infection: is the benefit of cytomegalovirus immune globulin for the newborn mediated through improved placental health and function? Clin Infect Dis 43:1001–1003PubMedCrossRefPubMedCentralGoogle Scholar
  78. 78.
    Duff P (2005) Immunotherapy for congenital cytomegalovirus infection. N Engl J Med 353:1402–1404PubMedCrossRefGoogle Scholar
  79. 79.
    Silverman NS, Puliyanda D, Lehman D (2005) Passive immunization against cytomegalovirus during pregnancy. N Engl J Med 353:2818PubMedCrossRefGoogle Scholar
  80. 80.
    Carbillon L (2005) Passive immunization against cytomegalovirus during pregnancy. N Engl J Med 353:2828–2818Google Scholar
  81. 81.
    Revello MG (2005) Passive immunization against cytomegalovirus during pregnancy. N Engl J Med 353:2819Google Scholar
  82. 82.
    Nigro G, Adler S (2005) Passive immunization against cytomegalovirus during pregnancy. N Engl J Med 353:2819–2820CrossRefGoogle Scholar
  83. 83.
    Adler SP (2008) The importance of cytomegalovirus-specific antibodies for the prevention of fetal cytomegalovirus infection or disease. Herpesviridae 15(2):24–27Google Scholar
  84. 84.
    Adler SP, Nigro G, Pereira L (2007) Recent advances in the prevention and treatment of congenital cytomegalovirus infections. Semin Perinatol 31:10–18PubMedCrossRefGoogle Scholar
  85. 85.
    Nigro G (2009) Maternal-fetal cytomegalovirus infection: from diagnosis to therapy. J Matern Fetal Neonatal Med 22(2):169–174PubMedCrossRefGoogle Scholar
  86. 86.
    Revello MG, Lazzarotto T, Guerra B et al (2014) A randomized trial of hyperimmune globulin to prevent congenital cytomegalovirus. N Engl J Med 370:1316–1326PubMedCrossRefGoogle Scholar
  87. 87.
    Blázquez-Gamero D, Galindo Izquierdo A, Del Rosal T et al (2017) Prevention and treatment of fetal cytomegalovirus infection with cytomegalovirus hyperimmune globulin: a multicentre study in Madrid. J Matern Fetal Neonatal Med 26:1–9Google Scholar
  88. 88.
    Nigro G, Capretti I, Manganello AM, Best AM, Adler SP (2015) Primary maternal cytomegalovirus infections during pregnancy: association of CMV hyperimmune globulin with gestational age at birth and birth weight. J Matern Fetal Neonatal Med 28(2):168–171PubMedCrossRefGoogle Scholar
  89. 89.
    Delle Chiaie L, Neuberger P, Vochem M, Lihs A, Karck U, Enders M (2018) No evidence of obstetrical adverse events after hyperimmune globulin application for primary cytomegalovirus infection in pregnancy: experience from a single centre. Arch Gynecol Obstet 297(6):1389–1395.  https://doi.org/10.1007/s00404-018-4703-yCrossRefGoogle Scholar
  90. 90.
    Jückstock J, Rothenburger M, Friese K, Traunbüller F (2015) Passive immunization against congenital cytomegalovirus infection: current state of knowledge. Pharmacology 95:209–217PubMedCrossRefGoogle Scholar
  91. 91.
    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. CID 55:497–503CrossRefGoogle Scholar
  92. 92.
    Pass RF, Burke RL (2002) Development of cytomegalovirus vaccines: prospects for prevention of congenital CMV infection. Semin Pediatr Infect Dis 13(3):196–204PubMedCrossRefGoogle Scholar
  93. 93.
    Griffiths PD, McLean A, Emery VC (2001) Encouraging prospects for immunisation against primary cytomegalovirus infection. Vaccine 19:1356–1362PubMedCrossRefGoogle Scholar
  94. 94.
    Schleiss MR, Bourne N, Jensen NJ, Bravo F, Bernstein DI (2000) Immunogenicity evaluation of DNA vaccines that target guinea pig cytomegalovirus proteins glycoprotein B and UL83. Viral Immunol 13(2):155–167PubMedCrossRefGoogle Scholar
  95. 95.
    Pass RF, Duliege AM, Boppana S, Sekulovich R, Percell S, Britt W, Burke RL (1999) A subunit cytomegalovirus vaccine based on recombinant envelope glycoprotein B and a new adjuvant. J Infect Dis 180:970–975PubMedCrossRefGoogle Scholar
  96. 96.
    Adler SP (1996) Current prospects for immunization against cytomegaloviral disease. Infect Agents Dis 5:29–35PubMedGoogle Scholar
  97. 97.
    Harrison CJ, Britt WJ, Chapman NM, Mullican J, Tracy S (1995) Reduced congenital cytomegalovirus (CMV) infection after maternal immunization with a guinea pig CMV glycoprotein before gestational primary CMV infection in the guinea pig model. J Infect Dis 172:1212–1220PubMedCrossRefGoogle Scholar
  98. 98.
    Bourne N, Schleiss MR, Bravo FJ, Bernstein DI (2001) Preconception immunization with a cytomegalovirus (CMV) glycoprotein vaccine improves pregnancy outcome in a guinea pig model of congenital CMV infection. J Infect Dis 183:59–64PubMedCrossRefGoogle Scholar
  99. 99.
    Schleiss MR (2009) Cytomegalovirus vaccines: at last, a major step forward. Herpesviridae 15:44–45Google Scholar
  100. 100.
    Adler SP (2008) Human CMV vaccine trials: what if CMV caused a rash? J Clin Virol 41:231–236PubMedCrossRefGoogle Scholar
  101. 101.
    Schleiss MR, Heineman TC (2005) Progress toward an elusive goal: current status of cytomegalovirus vaccines. Expert Rev Vaccines 4(3):381–406PubMedCrossRefPubMedCentralGoogle Scholar
  102. 102.
    Schleiss MR, Permar SR, Plotkin SA (2017) Progress toward development of a vaccine against congenital cytomegalovirus infection. Clin Vaccine Immunol 24(12):e00268–e00217PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Schleiss M (2005) Progress in cytomegalovirus vaccine development. Herpesviridae 12(3):66–75Google Scholar
  104. 104.
    Schleiss MR (2010) Cytomegalovirus vaccines and methods of production (WO20009049138): the emerging recognition of the importance of virus neutralization at the epithelial/endothelial interface. Expert Opin Ther Pat 20(4):597–602PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Gerna G, Sarasini A, Patrone M, Percivalle E, Fiorina L, Campanini G, Gallina A, Baldanti F, Revello MG (2008) Human cytomegalovirus serum neutralizing antibodies block virus infection of endothelial/epithelial cells, but not fibroblasts, early during primary infection. J Gen Virol 89:853–865PubMedCrossRefPubMedCentralGoogle Scholar
  106. 106.
    Pass RF, Zhang C, Evans A, Simpson T, Andrews W, Huang ML, Corey L, Hill J, Davis E, Flanigan C, Cloud G (2009) Vaccine prevention of maternal cytomegalovirus infection. N Engl J Med 360(12):1191–1199PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Dekker CL, Arvin AM (2009) One step closer to a CMV vaccine. N Engl J Med 360(12):1250–1252PubMedCrossRefPubMedCentralGoogle Scholar
  108. 108.
    Pass RF (2009) Development and evidence for efficacy of CM glycoprotein B vaccine with MF59 adjuvant. J Clin Virol 46(Suppl 4):S73–S76.  https://doi.org/10.1016/j.jcv.2009.07.002CrossRefPubMedPubMedCentralGoogle Scholar
  109. 109.
    Jacobson MA, Adler SP, Sinclair E, Black D, Smith A, Chu A, Moss RB, Wloch MK (2009) A CMV DNA vaccine primes for memory immune responses to live-attenuated CMV (Towne strain). Vaccine 15:1540–1548CrossRefGoogle Scholar
  110. 110.
    Clumpler MM, Choi KY, McVoy MA, Schleiss MR (2009) A live guinea pig cytomegalovirus vaccine deleted of three putative immune evasion genes is highly attenuated but remains immunogenic in a vaccine/challenge model of congenital cytomegalovirus infection. Vaccine 27:4209–4218CrossRefGoogle Scholar
  111. 111.
    Heineman TC, Schleiss M, Bernstein DI, Spaete RR, Yan L, Dukle G, Prichard M, Wang Z, Yan Q, Sharp MA, Klein N, Arvin AM, Kemble G (2006) A phase I study of 4 live, recombinant human cytomegalovirus Towne/Toledo chimeric vaccines. J Infect Dis 193:1350–1360PubMedCrossRefGoogle Scholar
  112. 112.
    Griffiths PD (2009) CMV vaccine trial endpoints. J Clin Virol 46S:S64–S67CrossRefGoogle Scholar

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© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Department of Laboratory MedicineRegional Hospital SteyrSteyrAustria

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