Main Article Content
Abstract
Introduction: Congenital cytomegalovirus (CMV) infection is the most common viral infection transmitted via the placenta, causing significant neurodevelopmental impairment in infants and children. Gancyclovir and Valgancyclovir are two drugs used in the treatment of symptomatic CMV infected case which have limited comparative study. This study compared the efficacy and tolerability of these two drugs on symptomatic CMV infected infants.
Methodology: This was an open-label randomized controlled trial done to compare oral valganciclovir(VGCV) with injectable ganciclovir (GCV) in the treatment of symptomatic congenital CMV infected infants. A total of 72 patients were included; 12 patients discontinued the treatment due to noncompliance or side effects. Pre and post-treatment CMV virus levels and adverse effects were monitored. Psychological, visual, and hearing assessments were performed at baseline and six months post-treatment.
Results: The mean age of the infants in VGCV and GCV group was 7.10±3.58 and 7.50±3.99 months, respectively. Nineteen infants presented with developmental delay, 13 with seizure, 4 with a movement disorder. Twenty-one percent of the infants were preterm, and 38% were low birth weight. Eighteen infants had a neonatal seizure. Twenty-eight infants of VGCV and 24 infants of the GCV group showed clearance of the virus after six weeks of treatment. No statistical difference was found in virus clearance. Regarding ophthalmological assessment, infants had chorioretinitis, optic atrophy, squint, and cortical blindness. On hearing assessment, none of the infants deteriorated after drug administration, while some showed improved hearing. None of the infants showed deterioration of cognition, while some of the infants showed
improvement in cognitive assessment, but there was no significant difference in two groups. The side effects of GCV were significantly greater than VGCV (P<0.05). Conclusion: In symptomatic congenital CMV infection in infants, VGCV is as efficient as GCV, and the former has fewer side effects.
Keywords
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References
Albanna, E. A. E., El-Latif, R. S. A., Sharaf, H. A., Gohar, M. K., & Ibrahim, B. M. (2013). Diagnosis of congenital cytomegalovirus infection in high risk neonates. Mediterranean Journal of Hematology and Infectious Diseases, 5(1), e2013049. https://doi.org/10.4084/MJHID.2013.049
Amir, J., Wolf, D. G., & Levy, I. (2010). Treatment of symptomatic congenital cytomegalovirus infection with intravenous ganciclovir followed by long-term oral valganciclovir. European Journal of Pediatrics, 169(9), 1061–1067. https://doi.org/10.1007/s00431-010-1176-9
Bialas, K. M., Swamy, G. K., & Permar, S. R. (2015). Perinatal cytomegalovirus and varicella zoster virus infections: epidemiology, prevention, and treatment. Clinics in Perinatology, 42(1), 61–75, viii. https://doi.org/10.1016/j.clp.2014.10.006
Biron, K. K. (2006). Antiviral drugs for cytomegalovirus diseases. Antiviral Research, 71(2–3), 154–163. https://doi.org/10.1016/j.antiviral.2006.05.002
Boppana, S. B., Fowler, K. B., Pass, R. F., Rivera, L. B., Bradford, R. D., Lakeman, F. D., & Britt, W. J. (2005). Congenital cytomegalovirus infection: association between virus burden in infancy and hearing loss. The Journal of Pediatrics, 146(6), 817–823. https://doi.org/10.1016/j.jpeds.2005.01.059
Boppana, S. B., Ross, S. A., & Fowler, K. B. (2013). Congenital cytomegalovirus infection: clinical outcome. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America, 57 Suppl 4, S178-81. https://doi.org/10.1093/cid/cit629
Buonsenso, D., Serranti, D., Gargiullo, L., Ceccarelli, M., Ranno, O., & Valentini, P. (2012). Congenital cytomegalovirus infection: current strategies and future perspectives. European Review for Medical and Pharmacological Sciences, 16(7), 919–935. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/22953641
Busca, A., de Fabritiis, P., Ghisetti, V., Allice, T., Mirabile, M., Gentile, G., … Falda, M. (2007). Oral valganciclovir as preemptive therapy for cytomegalovirus infection post allogeneic stem cell transplantation. Transplant Infectious Disease : An Official Journal of the Transplantation Society, 9(2), 102–107. https://doi.org/10.1111/j.1399-3062.2006.00183.x
Cheeran, M. C.-J., Lokensgard, J. R., & Schleiss, M. R. (2009). Neuropathogenesis of congenital cytomegalovirus infection: disease mechanisms and prospects for intervention. Clinical Microbiology Reviews, 22(1), 99–126, Table of Contents. https://doi.org/10.1128/CMR.00023-08
Crowley, B. (2002). Ganciclovir treatment of symptomatic congenital cytomegalovirus infection. The Journal of Antimicrobial Chemotherapy, 50(3), 435–436; author reply 436. https://doi.org/10.1093/jac/dkf144
Dahle, A. J., Fowler, K. B., Wright, J. D., Boppana, S. B., Britt, W. J., & Pass, R. F. (2000). Longitudinal investigation of hearing disorders in children with congenital cytomegalovirus. Journal of the American Academy of Audiology, 11(5), 283–290.
Foulon, I., Naessens, A., Foulon, W., Casteels, A., & Gordts, F. (2008). A 10-year prospective study of sensorineural hearing loss in children with congenital cytomegalovirus infection. The Journal of Pediatrics, 153(1), 84–88. https://doi.org/10.1016/j.jpeds.2007.12.049
Griffiths, P. D. (2002). The 2001 Garrod lecture. The treatment of cytomegalovirus infection. The Journal of Antimicrobial Chemotherapy, 49(2), 243–253. https://doi.org/10.1093/jac/49.2.243
James, S. H., & Kimberlin, D. W. (2016). Advances in the prevention and treatment of congenital cytomegalovirus infection. Current Opinion in Pediatrics, 28(1), 81–85. https://doi.org/10.1097/MOP.0000000000000305
Kimberlin, D. W. (2002). Antiviral therapy for cytomegalovirus infections in pediatric patients. Seminars in Pediatric Infectious Diseases, 13(1), 22–30. https://doi.org/10.1053/spid.2002.29754
Kimberlin, D. W., Acosta, E. P., Sánchez, P. J., Sood, S., Agrawal, V., Homans, J., … National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. (2008). Pharmacokinetic and pharmacodynamic assessment of oral valganciclovir in the treatment of symptomatic congenital cytomegalovirus disease. The Journal of Infectious Diseases, 197(6), 836–845. https://doi.org/10.1086/528376
Kimberlin, D. W., Jester, P. M., Sánchez, P. J., Ahmed, A., Arav-Boger, R., Michaels, M. G., … National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. (2015). Valganciclovir for symptomatic congenital cytomegalovirus disease. The New England Journal of Medicine, 372(10), 933–943. https://doi.org/10.1056/NEJMoa1404599
Leung, A. K. C., Sauve, R. S., & Davies, H. D. (2003). Congenital cytomegalovirus infection. Journal of the National Medical Association, 95(3), 213–218. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/12749681
Kimberlin, D. W., Lin, C.-Y., Sánchez, P. J., Demmler, G. J., Dankner, W., Shelton, M., … National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. (2003). Effect of ganciclovir therapy on hearing in symptomatic congenital cytomegalovirus disease involving the central nervous system: a randomized, controlled trial. The Journal of Pediatrics, 143(1), 16–25. https://doi.org/10.1016/s0022-3476(03)00192-6
Lombardi, G., Garofoli, F., Villani, P., Tizzoni, M., Angelini, M., Cusato, M., … Stronati, M. (2009). Oral valganciclovir treatment in newborns with symptomatic congenital cytomegalovirus infection. European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology, 28(12), 1465–1470. https://doi.org/10.1007/s10096-009-0806-5
Macy, K., Staal, W., Kraper, C., Steiner, A., Spencer, T. D., Kruse, L., … Scahill, L. D. (2013). Bayley Scales of Infants Development-II. In Encyclopedia of Autism Spectrum Disorders (pp. 399–400). https://doi.org/10.1007/978-1-4419-1698-3_284
Mahbub, M., Azam, M., & Khan, N. Z. (2012). Neurodevelopmental Outcome of Treatment of Symptomatic CMV Infection with Ganciclovir. Bangladesh Journal of Child Health, 35(3), 97–101. https://doi.org/10.3329/bjch.v35i3.10498
McDonald, J. M., Raghuveer, T. S., & D’Alessandro, M. P. (2001). Can congenital CMV infection lead to intracranial hemorrhage? Journal of Perinatology : Official Journal of the California Perinatal Association, 21(6), 402–404. https://doi.org/10.1038/sj.jp.7200516
Miura, C. S., Miura, E., Mombach, A. B., & Cheskya, M. (2006). Prevalência de infecção congênita por citomegalovírus em recém-nascidos de uma unidade de tratamento intensivo de um hospital público. Jornal de Pediatria, 82(1). https://doi.org/10.1590/S0021-75572006000100010
Morgan, M. A., El-Ghany, el-S. M. A., Khalifa, N. A., Sherif, A., & Rasslan, L. R. A. (2003). Prevalence of cytomegalovirus (CMV) infection among neonatal intensive care unit (NICU) and healthcare workers. The Egyptian Journal of Immunology, 10(2), 1–8. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/15719606
Muller, W. J. (2017). Treatment of perinatal viral infections to improve neurologic outcomes. Pediatric Research, 81(1–2), 162–169. https://doi.org/10.1038/pr.2016.191
Naing, Z. W., Scott, G. M., Shand, A., Hamilton, S. T., van Zuylen, W. J., Basha, J., … Rawlinson, W. D. (2016). Congenital cytomegalovirus infection in pregnancy: a review of prevalence, clinical features, diagnosis and prevention. The Australian & New Zealand Journal of Obstetrics & Gynaecology, 56(1), 9–18. https://doi.org/10.1111/ajo.12408
Nassetta, L., Kimberlin, D., & Whitley, R. (2009). Treatment of congenital cytomegalovirus infection: implications for future therapeutic strategies. The Journal of Antimicrobial Chemotherapy, 63(5), 862–867. https://doi.org/10.1093/jac/dkp083
Numazaki, K., & Fujikama, T. (2004). Chronological changes of incidence and prognosis of children with asymptomatic congenital cytomegalovirus infection in Sapporo, Japan. BMC Infectious Diseases, 4, 1–5. https://doi.org/10.1186/1471-2334-4-22
Nyholm, J. L., & Schleiss, M. R. (2010). Prevention of maternal cytomegalovirus infection: current status and future prospects. International Journal of Women’s Health, 2, 23–35. https://doi.org/10.2147/ijwh.s5782
Oliver, S. E., Cloud, G. A., Sánchez, P. J., Demmler, G. J., Dankner, W., Shelton, M., … National Institute of Allergy, I. D. C. A. S. G. (2009). Neurodevelopmental outcomes following ganciclovir therapy in symptomatic congenital cytomegalovirus infections involving the central nervous system. Journal of Clinical Virology : The Official Publication of the Pan American Society for Clinical Virology, 46 Suppl 4, S22-6. https://doi.org/10.1016/j.jcv.2009.08.012
Ornoy, A., & Diav-Citrin, O. (2006). Fetal effects of primary and secondary cytomegalovirus infection in pregnancy. Reproductive Toxicology (Elmsford, N.Y.), 21(4), 399–409. https://doi.org/10.1016/j.reprotox.2005.02.002
Pass, R. F. (2002). Cytomegalovirus Infection. Pediatrics in Review, 23(5), 163–170. https://doi.org/10.1542/pir.23-5-163
Pearl, K. N., Preece, P. M., Ades, A., & Peckham, C. S. (1986). Neurodevelopmental assessment after congenital cytomegalovirus infection. Archives of Disease in Childhood, 61(4), 323–326. https://doi.org/10.1136/adc.61.4.323
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