EC Paediatrics

Introduction: Although neonatal herpes infection is relatively uncommon, neonatal HSV causes serious morbidity and mortality, and survivors may need to live with permanent sequelae.

Aim of Work: In this review, we will discuss the most recent evidence regarding neonatal herpes simplex virus, methods of diagnosis, and management.

Methodology: We did a thorough search for most recent available evidence regarding the diagnosis and management of herpes simplex virus (HSV) in neonate.

Conclusion: The disease is classified clinically to three main types: SEM, CNS herpes simplex virus; disseminated HSV infection. Physicians’ high index of suspicion is essential to consider neonatal HSV. Polymerase chain reaction (PCR) is more sensitive than viral culture for CSF samples. However, false negative results could be seen and should not exclude the diagnosis in case of high sus- picion. The Adequate Neonatal HSV management consists of support measures and antiviral therapy. Supporting steps are especially important for CNS involvement and for disseminated HSV. Acyclovir have led to sharp decrease in the mortality rate and considered the drug of choice. Ganciclovir IV was suggested to be the first-line alternative to acyclovir.

keywords: Neonatal Herpes Simplex Virus; Neonatal HSV; Complication of HSV; Pregnant with HSV; Simplex with CNS Involvement.

1. Jones CA., et al. “Neonatal HSVSI, Contributors to the Australian Paediatric Surveillance U (2014) Population-based surveillance of neonatal herpes simplex virus infection in Australia, 1997-2011”. Clinical Infectious Diseases4 (2014): 525-531.
2. Corey L and Wald A. “Maternal and neonatal herpes simplex virus infections”. The New England Journal of Medicine 361 (2009): 1376.
3. Mahnert N., et al. “The incidence of neonatal herpes infection”. American Journal of Obstetrics and Gynecology 196 (2007): e55.
4. Roberts S. “Herpes simplex virus: incidence of neonatal herpes simplex virus, maternal screening, management during pregnancy, and HIV”. Current Opinion in Obstetrics and Gynecology 21 (2009): 124.
5. Flagg EW and Weinstock H. “Incidence of neonatal herpes simplex virus infections in the United States, 2006”. Pediatrics 127 (2011): e1.
6. Brown ZA., et al. “Effect of serologic status and cesarean delivery on transmission rates of herpes simplex virus from mother to infant”. The Journal of the American Medical Association 289 (2003): 203.
7. Kimberlin DW. “Neonatal herpes simplex infection”. Clinical Microbiology Reviews 17 (2004): 1.
8. Caviness AC., et al. “Cost-effectiveness analysis of herpes simplex virus testing and treatment strategies in febrile neonates”. The Archives of Pediatrics and Adolescent Medicine 162 (2008): 665.
9. Davis KL., et al. “Why are young infants tested for herpes simplex virus?” Pediatric Emergency Care 24 (2008): 673.
10. Ambroggio L., et al. “Congenital anomalies and resource utilization in neonates infected with herpes simplex virus”. Sexually Transmitted Diseases 36 (2009): 680.
11. Kimberlin DW. “Herpes simplex virus infections of the newborn”. Seminars in Perinatology 31 (2007): 19.
12. Caviness AC., et al. “Clinical and laboratory features of neonatal herpes simplex virus infection: a case-control study”. The Pediatric Infectious Disease Journal 27 (2008): 425.
13. Kimberlin DW., et al. “Natural history of neonatal herpes simplex virus infections in the acyclovir era”. Pediatrics 108 (2001): 223.
14. Whitley R., et al. “Predictors of morbidity and mortality in neonates with herpes simplex virus infections. The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group”. The New England Journal of Medicine 324 (1991): 450.
15. Jones CA., et al. “Neonatal HSV Study Investigators and Contributors to the Australian Paediatric Surveillance Unit. Population-based surveillance of neonatal herpes simplex virus infection in Australia, 1997-2011”. Clinical Infectious Diseases
16. American Academy of Pediatrics. Herpes simplex. In: Red Book: 2018-2021 Report of the Committee on Infectious Diseases, 31st edition, Kimberlin DW (Edition), American Academy of Pediatrics, Elk Grove Village, IL (2018): 437.
17. Malik AN., et al. “Bilateral macular scars following intrauterine herpes simplex virus type 2 infection”. Journal of AAPOS 12 (2008): 305.
18. Granerod J., et al. “Causes of encephalitis and differences in their Clinical Presentations in England: A Multicentre, Population-Based Prospective Study” (2010).
19. Huppatz C., et al. “Etiology of encephalitis in Australia, 1990-2007”. Emerging Infectious Diseases 9 (2009):1359-1365.
20. Whitley RJ. “Herpes simplex encephalitis: adolescents and adults”. Antiviral Research2-3 (2006): 141- 148.
21. Whitley RJ. “Viral encephalitis”. The New England Journal of Medicine4 (1990): 242-250.
22. Levitz RE. “Herpes simplex encephalitis: a review”. Heart Lung3 (1998): 209-212.
23. Hjalmarsson A., et al. “Herpes simplex encephalitis in Sweden, 1990-2001: incidence, morbidity, and mortality”. Clinical Infectious Diseases 7 (2007): 875-880.
24. Corey L., et al. “Difference between herpes simplex virus type 1 and type 2 neonatal encephalitis in neurological outcome”. Lancet 8575-6 (1988): 1-4.
25. Pinninti SG and Kimberlin DW. “Management of neonatal herpes simplex virus infection and exposure”. Archives of Disease in Childhood. Fetal and Neonatal Edition3 (2014): F240-F244.
26. Toth C., et al. “Neonatal herpes encephalitis: a case series and review of clinical presentation”. The Canadian Journal of Neurological Sciences 30 (2003): 36.
27. Corey L., et al. “Difference between herpes simplex virus type 1 and type 2 neonatal encephalitis in neurological outcome”. Lancet 1 (1988): 1.
28. Caviness AC., et al. “The prevalence of neonatal herpes simplex virus infection compared with serious bacterial illness in hospitalized neonates”. The Journal of Pediatrics 153 (2008): 164.
29. Long SS. “In defense of empiric acyclovir therapy in certain neonates”. The Journal of Pediatrics 153 (2008): 157.
30. Kimberlin DW. “When should you initiate acyclovir therapy in a neonate?” The Journal of Pediatrics 153 (2008): 155.
31. Kimberlin DW and Gutierrez KM. “Herpes simplex virus infections”. In: Remington and Klein’s infectious diseases of the fetus and newborn infant, 8th, Wilson CB, Nizet V, Maldonado YA, Remington JS, Klein JO (Editions), Saunders, Phildelphia, PA (2016): 843.
32. Riediger C., et al. “Herpes simplex virus sepsis and acute liver failure”. Clinical Transplantation 21 (2009): 37.
33. Meyer TA and Warner BW. “Extracorporeal life support for the treatment of viral pneumonia: collective experience from the ELSO registry. Extracorporeal Life Support Organization”. Journal of Pediatric Surgery 32 (1997): 232.
34. Cantey JB., et al. “Use of blood polymerase chain reaction testing for diagnosis of herpes simplex virus infection”. The Journal of Pediatrics 161 (2012): 357.
35. Fidler KJ., et al. “Could neonatal disseminated herpes simplex virus infections be treated earlier?” Journal of Infection 49 (2004): 141.
36. LaRocco MT. “Evaluation of an enzyme-linked viral inducible system for the rapid detection of Herpes simplex virus”. European Journal of Clinical Microbiology and Infectious Diseases 19 (2000): 233.
37. Verano L and Michalski FJ. “Comparison of a direct antigen enzyme immunoassay, Herpchek, with cell culture for detection of herpes simplex virus from clinical specimens”. Journal of Clinical Microbiology 33 (1995): 1378.
38. Troendle-Atkins J., et al. “Rapid diagnosis of herpes simplex virus encephalitis by using the polymerase chain reaction”. The Journal of Pediatrics 123 (1993): 376.
39. Kimura H., et al. “Detection of viral DNA in neonatal herpes simplex virus infections: frequent and prolonged presence in serum and cerebrospinal fluid”. The Journal of Infectious Diseases 164 (1991): 289.
40. Malm G and Forsgren M. “Neonatal herpes simplex virus infections: HSV DNA in cerebrospinal fluid and serum”. Archives of Disease in Childhood. Fetal and Neonatal Edition 81 (1999): F24.
41. Kimberlin DW., et al. “Application of the polymerase chain reaction to the diagnosis and management of neonatal herpes simplex virus disease. National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group”. The Journal of Infectious Diseases6 (1996):1162-1167.
42. Slomka MJ., et al. “A comparison of PCR with virus isolation and direct antigen detection for diagnosis and typing of genital herpes”. Journal of Medical Virology 55 (1998): 177.
43. Espy MJ., et al. “Diagnosis of herpes simplex virus infections in the clinical laboratory by LightCycler PCR”. Journal of Clinical Microbiology 38 (2000): 795.
44. Frenkel LM. “Challenges in the diagnosis and management of neonatal herpes simplex virus encephalitis”. Pediatrics 115 (2005): 795.
45. Mejías A., et al. “Persistence of herpes simplex virus DNA in cerebrospinal fluid of neonates with herpes simplex virus encephalitis”. Journal of Perinatology 29 (2009): 290.
46. No Melvin AJ., et al. “Plasma and cerebrospinal fluid herpes simplex virus levels at diagnosis and outcome of neonatal infection”. The Journal of Pediatrics 166 (2015): 827.
47. Reina J., et al. “Evaluation of a direct immunofluorescence cytospin assay for the detection of herpes simplex virus in clinical samples”. European Journal of Clinical Microbiology and Infectious Diseases 16 (1997): 851.
48. Mizrahi EM and Tharp BR. “A characteristic EEG pattern in neonatal herpes simplex encephalitis”. Neurology 32 (1982): 1215.
49. American Academy of Pediatrics. Transmission of infectious agents via human milk. In: Red Book: 2018-2021 Report of the Committee on Infectious Diseases, 31st edition, Kimberlin DW, Brady MT, Jackson MA, Long SS (Editions), American Academy of Pediatrics, Itasca, I.
50. Kimberlin DW., et al. “Safety and efficacy of high-dose intravenous acyclovir in the management of neonatal herpes simplex virus infections”. Pediatrics 108 (2001): 230.
51. Gutierrez KM., et al. “Herpes simplex virus infections”. In: Infectious Diseases of the Fetus and Newborn Infant, 7th edition, Remington JS, Klein JO, Wilson CB, et al (Editions), Elsevier Saunders, Philadelphia (2011): 813.
52. Whitley RJ., et al. “Vidarabine therapy of neonatal herpes simplex virus infection”. Pediatrics 66 (1980): 495.
53. Whitley R., et al. “A controlled trial comparing vidarabine with acyclovir in neonatal herpes simplex virus infection. Infectious Diseases Collaborative Antiviral Study Group”. The New England Journal of Medicine 324 (1991): 444.
54. Workowski KA and Bolan GA. “Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines”. MMWR Recommendations and Reports 64 (2015): 1.
55. Jones CA., et al. “Antiviral agents for treatment of herpes simplex virus infection in neonates”. The Cochrane Database of Systematic Reviews (2009): CD004206.
56. Whitley RJ., et al. “Changing presentation of herpes simplex virus infection in neonates”. The Journal of Infectious Diseases 158 (1988): 109.
57. Shortage of intravenous acyclovir. Red Book Online Special Alert (2012).
58. Kimberlin DW. “Ganciclovir may be used during intravenous acyclovir shortage”. AAP News 30 (2009): 10.
59. Current Drug Shortages. US Food and Drug Administration (2012).