Efficacy and Tolerability of Valganciclovir 6 Months vs 6 Weeks in Symptomatic Cytomegalovirus Infection in Infants: An Open Level Randomized Controlled Trial



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Submitted Aug 26, 2021
Published Jan 11, 2022
10.24018/clinicmed.2022.3.1.122

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Congenital cytomegalovirus (CMV) infection is the most common transplacental infection affecting neurodevelopment in infant, commonly hearing and cognitive impairment. This study aimed to compare 6 weeks with 6 months duration of oral valganciclovir in respect of efficacy and tolerability. This randomized controlled trial was conducted in both outpatient and inpatient pediatrics department of a tertiary hospital, on123 infants aged 0-12 months with polymerase chain reaction proven congenital CMV infection over a period of 18 months. The children were divided into two groups, according to the treatment group they belonged to, one is 6 weeks group and other is 6 months group. The children were followed up for 12 months at 3-month interval to compare the virological clearance, psychological, visual, and hearing status, and side effects of drug. The viral load assessment was done at 6 weeks, 6 months, and 12 months of the initial treatment. Mean age of the infants of 6 weeks group is 7.33±1.74months and that of 6 months group is 6.70±2.23 months. Primary outcome is the clearance of virus, exhibited in both groups significantly at 12 weeks of follow up but 100% clearance of virus observed in 6 months group at 6 months of follow up. Whereas 5 patients at 12 weeks and 3 patients at 6 months have shown non clearance of virus among the 6 weeks treatment group. Total 50(80.6%) patients hearing return to normal at 12 months follow up in 6 months treatment group compared to 31(50.8%) in 6 weeks group (p=0.001). Visual improvement also observed among 58(93.5%) patients of 6 months group and 48(78.7%) in 6 weeks group and this difference is statistically significant (p=0.01). At 12 months of follow up 6 months group had shown better neurodevelopmental outcome (p=0.00). Both groups exhibit good tolerance to drug.

Conclusion: 6 months duration treatment of valganciclovir in symptomatic CMV infection have shown better neurodevelopmental outcome and visual, auditory improvement compared to 6 weeks duration.

Keywords: Cytomegalovirus, neurodevelopment, valganciclovir

References

  1. Kenneson A, Cannon MJ. Review and metaanalysis of the epidemiology of congenital cytomegalivirus (CMV) infection. Review Med Virol. 2007; 17: 253-76.
     Google Scholar
  2. Bhattacharya D, Panigrahi I, Chowdhury C. Clinical profile of sypmtomatic congenital cytomegalovirus infection: Cases from a tertiary hospital in north India. Tropical Doctor. 2020; 0(0): 1-3.
     Google Scholar
  3. Orney A, Citrin OD. Fetal effects of primary and secondary cytomegalovirus infection in pregnancy. Reproductive Toxicology. 2006; 21: 399-409.
     Google Scholar
  4. Gargouri J, Ellueuch H, Rekik H, Hammani A. Prevalence of anti-CMV antibodies in blood donors in the Sfax region. Tunis Med. 2000; 78: 512-7.
     Google Scholar
  5. Pultoo A, Meetoo G, Pydiah MN, Khittoo G. Seroprevalence of cytomegalovirus infection in Mauritian volunteer blood donors. Indian J Med Sci. 2001; 55: 73-8.
     Google Scholar
  6. Schopfer K, Lauber E, Krech U. Congenital cytomegalovirus infection in newborn infants of mothers infected before pregnancy. Arch Dis Child. 1978; 53: 536-9.
     Google Scholar
  7. Stagno S, Reynolds DW, Huang ES. Congenital cytomegalovirus infection: occurrence in an immune population. N Engl J Med. 1977; 296: 1254-8.
     Google Scholar
  8. Muller WJ. Treatment of perinatal viral infections to improve neurologic outcomes. Pediatr Res. 2017; 81: 162-9.
     Google Scholar
  9. Leung AKC, Sauve RS, Davies HD. Congenital Cytomegalovirus. J Natl Med Assoc. 2003; 95(3): 213-8.
     Google Scholar
  10. Naing ZW, Scott GM, Shand A, Hamilton ST, Zuylen WJ, Basha J, et al. Congenital cytomegalovirus infection in pregnancy: a review of prevalence, clinical features, diagnosis, and prevention. Aust N Z L Obstet Gynaecol. 2016; 56: 9-18.
     Google Scholar
  11. Stagno S. Breastfeeding and transmission of cytomegalovirus infections. Ital J Pediatr. 2002; 28: 275-80.
     Google Scholar
  12. Nassetta L, Kimberlin D, Whitley R. Treatment of congenital cytomegalovirus infection: implications for future therapeutic strategies. Journal of Antimicrobial Chemotherapy 2009; 63: 862-7.
     Google Scholar
  13. James SH, Kimberlin DW. Advances in the prevention and treatment of congenital cytomegalovirus infection. Curr Opin Pediatr. 2016; 28: 81-85.
     Google Scholar
  14. Bialas KM, Geeta K, Swamy GK, Permar SR. Perinatal cytomegalovirus and varicella zoster virus infections: Epidemiology, Prevention and Treatment. Clin Perinatal. 2015; 42: 61-75.
     Google Scholar
  15. Dollard SC, Grosse SD, Ross DS. New estimates of the prevalence of neurological and sensory sequelae and mortality associated with congenital cytomegalovirus infection. Rev Med Virol. 2007; 17: 255-63.
     Google Scholar
  16. Marsico C, Kimberlin DW. Congenital cytomegalovirus infection: advances and challenges in diagnosis, prevention, and treatment. Italian Journal of Periatrics. 2017; 43: 38.
     Google Scholar
  17. Rausseau T, Douvier S, Reynaud I, Laurent N, Bour JB, Durand C, et al. Severe fatal cytomegalic inclusion disease after documented mental reactivation of cytomegalovirus infection during pregnancy. Prenat Diag. 2000; 20: 333-6.
     Google Scholar
  18. Gaytant MA, Rours GI, Steegers EA, Galama JM, Semmekrot BA. Congenital cytomegalovirus infection after recurrent infection case reports and review of the literature. Eur J Pediatr. 2003; 162: 248-53.
     Google Scholar
  19. Bounsenso D, Serranti D, Gargiullo L, Cecarelli M, Ranno O, Vlentini P. Congenital cytomegalovirus infection: current strategies and future perspectives. Eur Rev Med Pharmacol Sci. 2012; 16(7): 919-35.
     Google Scholar
  20. Foulon I, Naessens A, Foulon W, Casteels A, Gordts F. A 10-year prospective study of sensorineural hearing loss in children with congenital cytomegalovirus infection. J Pediatr. 2008; 153: 84-8.
     Google Scholar
  21. Fowler KB, McCollister FP, Dahle AJ, Boppana S, Britt WJ, Pass RF. Progressive and fluctuating sensorineural hearing loss in children with asymptomatic congenital cytomegalovirus infection. J Pediatr 1997; 130: 624-30.
     Google Scholar
  22. Mocarski ES, Shenk T, Pass RF. Cytomegalovirus. Virology 5th edn. Philadelphia: Lippincott Williams and Wilkins, 2007: 2701-72.
     Google Scholar
  23. Kimberlin DW, Acosta EP, Sanchez PJ, Sood S, Agrawal V, Homans J, et al. Pharmacokinetic and pharmacodynamic assessment of oral valganciclovir in the treatment of symptomatic congenital cytomegalovirus disease. J Infect Dis. 2008; 197: 836-45.
     Google Scholar
  24. Acosta EP, Brundage RC, King JR, Sanchez PJ, Sood S, Agrawal V, et al. Ganciclovir population pharmacokinetics in neonates following intravenous administration of ganciclovir and oral administration of a liquid valganciclovir formulation. Clin Pharmacol Ther. 2007; 81: 867-72.
     Google Scholar
  25. Kimberlin DW, Lin CY, Sanchez PJ, Kiell JM, Soong SJ, Whitley RJ, 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.
     Google Scholar
  26. Meine Jansen CF, Toet MC, Rademaker CM, Ververs TF, Gerards LJ, Van Loon AM. Treatment of symptomatic congenital cytomegalovirus infection with valganciclovir. J Perinat Med. 2005; 33: 364-6.
     Google Scholar
  27. Mullar A, Eis-Hubinger AM, Brandhorst G, Heep A, Bartmann P, Franz AR. Oral valganciclovir for symptomatic congenital cytomegalovirus infection in an extremely low birth weight infant. J Perinatol. 2008; 28: 74-76.
     Google Scholar
  28. Shoji K, Ito N, Ito Y, Inoue N, Adachi S, Fujimaru T, et al. Is a 6 week course of gamciclovir therapy effective for chorioretinitis in infants with congenital cytomegalovirus infection? J Pediatr. 2010; 157: 331-3.
     Google Scholar
  29. Kashiwagi Y, Kawashima H, Nakajima J, Ishida Y, Nishimata S, Miyajima T, et al. Efficacy of prolonged valganciclovir therapy for congenital cytomegalovirus infection. J Infect Chemother. 2011; 17: 538-40.
     Google Scholar
  30. Tanaka-Kitajima N, Sugaya N, Futatani T, Kanegane H, Suzuki C, Oshiro M, et al. Ganciclovir therapy for congenital cytomegalovirus infection in six infants. Pediatr Infect Dis J. 2005; 24: 782-5.
     Google Scholar
  31. Fatema K, Rahman MM, Akhtar S, Shefa J. Efficacy of Valganciclovir versus Ganciclovir in treatment of symptomatic cytomegalovirus infection in infants: An open level randomized controlled trial. Journal of International Child Neurology Association. 2019.
     Google Scholar
  32. Munro SC, Hall B, Whybin LR, Leader L, Robertson P, Maine GT, et al. Diagnosis of and screening for cytomegalovirus infection in pregnant woman. J Clin Microbiol. 2005; 43: 4713-18.
     Google Scholar
  33. Seale H, Macintyre CR, Gidding HF, Backhouse JL, Dwyer DE, Gilbert I. National serosurvey of cytomegalovirus in Australia. Clin Vaccine Immunol. 2006; 13: 1181-84.
     Google Scholar
  34. Yashinago-Itano C, Sedey AL, Coulter DK, Mehl AL. Language of early and later identified children with hearing loss. Pediatrics. 1998; 102: 1161-71.
     Google Scholar
  35. Yasuhiro S, Yasuhisa T, Yukiko M, Keiko Y, Masanori N. Epilepsy in patients with congenital cytomegalovirus infection. Brain and Development. 2008; 30: 420-24
     Google Scholar
  36. Gallach ADJ, Albert MA, Harnandez AVM, Gonzalez NB, Badia MC, Vila MT. Neurological sequelae in patients with congenital cytomegalovirus. An Pediatr(Brac). 2020; 93: 111-17.
     Google Scholar
  37. Plosa EJ, Esbenshade JC, Fuller MP, Weitkamp JH. Cytomegalovirus infection. Pediatrics in Review. 2012; 33: 156-63.
     Google Scholar
  38. Sakiko F, Satoshi I, Shin-ya N, Hideaki M, Shin-ichi U. Clinical profile of hearing loss in children with congenital cytomegalovirus (CMV) infection: CMV DNA diagnosis using preserved umbilical cord. Acta Oto-Laryngologica. 2011; 131: 976-82.
     Google Scholar
  39. Kimberlin WD, Penelope M, Jester BSN, Sanchez PJ, Ahmed A, Boger RA, et al. Valganciclovir for symptomatic congenital cytomegalovirus disease. N Engl J Med. 2015; 372: 933-43.
     Google Scholar
  40. Van der Knapp MS, Vermeulen G, Barkhof F, Hart AAM, Loeber JG, Weel JFL. Pattern of white matter at MR imaging: use of polymerase chain reaction testing of Guthrie cards to link pattern with congenital cytomegalovirus infection. Radiology. 2004; 230: 529-36.
     Google Scholar
  41. Moore KR, Jones BV, Vezina G, Koch BL, Raybaud C, Grant PE, et al. Diagnostic imaging: pediatric neuroradiology. Diagnostic Imaging Pediatric Neuroradiology. 2017: 82-85.
     Google Scholar
  42. Hayward JC, Titelbaum DS, Clancy RR, Zimmerman RA. Lissencephaly-pachygyria associated with congenital cytomegalovirus infection. J Child Neurol. 1991; 6: 109-14.
     Google Scholar
  43. Arpino C, Gattinara GC, Rosso M, Pelliccia A, Fariello G, Curatolo P. Cortical maldevelopment in congenital cytomegalovirus infection transmitted by a woman with preexisting immuniity. J Neurovirol. 2008; 14: 173-6.
     Google Scholar
  44. Zucca C, Binda S, Borgatti R, Triulzi F, Radice L, Butte C, et al. Retrospective diagnosis of congenital cytomegalovirus infection and cortical maldevelopment. Neurology. 2003; 61: 710-12.
     Google Scholar
  45. Iannetti P, Nigro G, Spalice A, Faiella A, Boncinelli E. Cytomegalovirus infection and scizencephaly. Annals of Neurology.1998; 43: 123-7.
     Google Scholar
  46. Lombardi G, Garofoli F, Villani I, Tizzoni M, Angelini M, Cusato M. Oral valganciclovir treatment in newborns with symptomatic congenital cytomegalovirus infection. Eur J Clin Microbiol Infect Dis. 2009; 28: 1465-70.
     Google Scholar
  47. Ohyama S, Morioka I, Fukushima S, Yamana K, Nishida K, Iwatani S, et al. Efficacy of valganciclovir treatment depends on the severity on the hearing dysfunction in symptomatic infants with congenital cytomegalovirus infection. International Journal of Molecular Sciences. 2019; 20: 1388.
     Google Scholar
  48. Goderis J, De Leenheer E, Smets K, Van Hoecke H, Keymeulen A, Dhooge I. Hearing loss and congenital CMV infection: a systemic review. Pediatrics. 2014; 134: 972-82.
     Google Scholar
  49. Bilavsky E, Shahar-Nissan K, Pardo J, Attias J, Amir J. Hearing outcome of infants with congenital cytomegalovirus and hearing impairment. Arch Dis Child. 2016; 101: 433-8.
     Google Scholar
  50. Boppana SB, Ross SA, Fowler KB. Congenital cytomegalovirus infection: clinical outcome. Clin Infect Dis. 2013; 57: 178-81.
     Google Scholar
  51. Plosa EJ, Esbenshade JC, Fuller MP, Weitkamp JH. Cytomegalovirus infection. Pediatrics in Review. 2012; 33: 156-63.
     Google Scholar
  52. Whitly RJ, Cloud G, Gruber W, Storch GA, Demmler GJ, Jacobs RF, et al. Ganciclovir treatment of symptomatic congenital cytomegalovirus infection: results of a phase II study. National institute of allergy and infectious diseases collaborative antiviral study group. J Infect Dis. 1997; 175: 1080-86.
     Google Scholar
  53. Amir J, Wolf DG, Levy I. Treatment of symptomatic congenital cytomegalovirus infection with intravenous ganciclovir followed by long term oral valganciclovir. European J Pediatr. 2010; 169: 1061-67.
     Google Scholar
  54. Oliver S, Cloud G, Sanchez P, Demmler G, Dankner W, Shelton M, et al. Neurodevelopmental outcomes following ganciclovir therapy in symptomatic congenital cytomegalovirus infections involving central nervous system. J Clin Virol. 2009; 46: 22-26.
     Google Scholar


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