Pediatric Drugs

, Volume 6, Issue 1, pp 1–10 | Cite as

Presentation, Diagnosis, and Management of Enterovirus Infections in Neonates

  • Mark J. Abzug
Therapy In Practice


The nonpoliovirus enteroviruses commonly infect newborns, with consequences ranging from asymptomatic infection and benign illness, to severe, life-threatening disease. Frequently occurring symptoms include fever, irritability, lethargy, anorexia, and rash. Although most illnesses are mild, severe disease develops in a subset of newborns infected in the first 2 weeks of life. Severe disease may consist of sepsis, meningoencephalitis, myocarditis, pneumonia, hepatitis, and/or coagulopathy. Substantial mortality rates have been reported, and long-term sequelae may occur among survivors. Risk factors and clinical features associated with severe disease include absence of neutralizing antibody to the infecting serotype, maternal illness prior to or at delivery, prematurity, illness onset within the first few days of life, multiorgan disease, severe hepatitis, positive serum viral culture, and specific infecting serotype (e.g. group B coxsackieviruses and echovirus 11).

Whereas the mainstay of diagnosis has traditionally been viral isolation in tissue culture, the polymerase chain reaction has been demonstrated to be more sensitive than culture, highly specific, and rapid. Immunoglobulin has been used as a therapeutic agent for neonates with enterovirus disease; however, clinical efficacy has not been proven.

Specific antiviral therapy for enteroviruses is in development. Pleconaril is an investigational agent that inhibits viral attachment to host cell receptors and uncoating of viral nucleic acid. It has broad and potent anti-enterovirus activity, excellent oral bioavailability, and is well tolerated. Some clinical trials have demonstrated benefit in children and adults with enterovirus meningitis, and in adults with upper respiratory tract infections caused by picornaviruses (rhinoviruses or enteroviruses). Data summarizing compassionate use for severe enterovirus diseases (including neonatal sepsis) also suggest possible benefit. Limited pharmacokinetic data are available in infants and neonates. A multicenter, placebo-controlled, randomized trial of pleconaril in neonates with severe hepatitis, coagulopathy, and/or myocarditis is currently being conducted.



No sources of funding were used to assist in the preparation of this manuscript. The author has no conflicts of interest that are directly relevant to the content of this manuscript.


  1. 1.
    Abzug MJ, Rotbart HA. Enterovirus infections of neonates and infants. Semin Pediatr Infect Dis 1999; 10: 169–76CrossRefGoogle Scholar
  2. 2.
    Modlin JF. Introduction to picornaviridae. In: Mandell GL, Bennett JE, Dolin R, editors. Principles and practice of infectious diseases. Philadelphia (PA): Churchill Livingstone, 2000: 1888–95Google Scholar
  3. 3.
    King AMP, Brown F, Christian P, et al. Picornaviridae. In: Wickner RB, editor. Classification and nomenclature of viruses: seventh report of the international committee on taxonomy of viruses. New York (NY): Academic Press, 1999: 657–64Google Scholar
  4. 4.
    Modlin JF. Coxsackieviruses, echoviruses, and newer enteroviruses. In: Mandell GL, Bennett JE, Dolin R, editors. Principles and practice of infectious diseases. Philadelphia (PA): Churchill Livingstone, 2000: 1904–19Google Scholar
  5. 5.
    Abzug MJ, Levin MJ, Rotbart HA. Profile of enterovirus disease in the first two weeks of life. Pediatr Infect Dis J 1993; 12: 820–4PubMedCrossRefGoogle Scholar
  6. 6.
    Modlin JF. Perinatal echovirus infection: insights from a literature review of 61 cases of serious infection and 16 outbreaks in nurseries. Rev Infect Dis 1986; 8: 918–26PubMedCrossRefGoogle Scholar
  7. 7.
    Jenista JA, Powell KR, Menegus MA. Epidemiology of neonatal enterovirus infection. J Pediatr 1984; 104: 685–90PubMedCrossRefGoogle Scholar
  8. 8.
    Kaplan MH, Klein SW, McPhee J, et al. Group B coxsackievirus infections in infants younger than three months of age: a serious childhood illness. Rev Infect Dis 1983; 5: 1019–32PubMedCrossRefGoogle Scholar
  9. 9.
    Lake AM, Lauer BA, Clark JC, et al. Enterovirus infections in neonates. J Pediatr 1976; 89: 787–91PubMedCrossRefGoogle Scholar
  10. 10.
    Modlin JF. Fatal echovirus 11 disease in premature neonates. Pediatrics 1988; 66: 775–80Google Scholar
  11. 11.
    Birenbaum E, Handsher R, Kuint J, et al. Echovirus type 22 outbreak associated with gastro-intestinal disease in a neonatal intensive care unit. Am J Perinatol 1997; 14: 469–73PubMedCrossRefGoogle Scholar
  12. 12.
    Theodoridou M, Kakourou T, Laina I, et al. Vesiculopapular rash as a single presentation in intrauterine coxsackie virus infection. Eur J Pediatr 2002; 16: 412–3CrossRefGoogle Scholar
  13. 13.
    Sauerbrei A, Gluck B, Jung K, et al. Congenital skin lesions caused by intrauterine infections with coxsackievirus B3. Infection 2000 Sep; 28: 326–8PubMedCrossRefGoogle Scholar
  14. 14.
    Verboon-Maciolek MA, Krediet TG, van Loon AM, et al. Epidemiological survey of neonatal non-polio enterovirus infection in The Netherlands. J Med Virol 2002; 66: 241–5PubMedCrossRefGoogle Scholar
  15. 15.
    Kibrick S, Benirschke K. Severe generalized disease (encephalohepatomyocarditis) occurring in the newborn period and due to infection with coxsackie virus, group B: evidence of intrauterine infection with this agent. Pediatrics 1958; 22: 857–74PubMedGoogle Scholar
  16. 16.
    Rorabaugh ML, Berlin LE, Heldrich F, et al. Aseptic meningitis in infants younger than 2 years of age: acute illness and neurologic complications. Pediatrics 1993; 92: 206–11PubMedGoogle Scholar
  17. 17.
    Haddad J, Messer J, Gut JP, et al. Neonatal echovirus encephalitis with white matter necrosis. Neuropediatrics 1990; 21: 215–7PubMedCrossRefGoogle Scholar
  18. 18.
    Goren A, Kaplan M, Glaser J, et al. Chronic neonatal coxsackie myocarditis. Arch Dis Child 1989; 64: 404–6PubMedCrossRefGoogle Scholar
  19. 19.
    Hornung TS, Bernard EJ, Howman-Giles RB, et al. Myocardial infarction complicating neonatal enterovirus myocarditis. J Paediatr Child Health 1999; 35: 309–12PubMedCrossRefGoogle Scholar
  20. 20.
    Shah SS, Hellenbrand WE, Gallagher PG. Atrial flutter complicating neonatal coxsackie B2 myocarditis. Pediatr Cardiol 1998; 19: 185–6PubMedCrossRefGoogle Scholar
  21. 21.
    Rigourd V, Dommergues MA, Ayachi A, et al. Neonatal enterovirus myocarditis. Arch Pediatr 2002; 9: 495–8PubMedCrossRefGoogle Scholar
  22. 22.
    Baker DA, Phillips CA. Maternal and neonatal infection with coxsackievirus. Obstet Gynecol 1980; 55: 12–15SCrossRefGoogle Scholar
  23. 23.
    Boyd MT, Jordan SW, Davis LE. Fatal pneumonitis from congenital echovirus type 6 infection. Pediatr Infect Dis J 1987; 6: 1138–9PubMedGoogle Scholar
  24. 24.
    Cheeseman SH, Hirsch MS, Keller EW, et al. Fatal neonatal pneumonia caused by echovirus type 9. Am J Dis Child 1977; 131: 1169PubMedGoogle Scholar
  25. 25.
    Abzug MJ. The prognosis for neonates with enterovirus hepatitis and coagulopathy. Pediatr Infect Dis J 2001 Aug; 20: 758–63PubMedCrossRefGoogle Scholar
  26. 26.
    Wang J, Atchison RW, Walpusk J, et al. Echovirus hepatic failure in infancy: report of four cases with speculation on the pathogenesis. Pediatr Dev Pathol 2001; 4: 454–60PubMedCrossRefGoogle Scholar
  27. 27.
    Abzug MJ, Johnson SM. Catastrophic intracranial hemorrhage complicating perinatal viral infections. Pediatr Infect Dis J 2000; 19: 556–9PubMedCrossRefGoogle Scholar
  28. 28.
    Ventura KC, Hawkins H, Smith MB, et al. Fatal neonatal echovirus 6 infection: autopsy case report and review of the literature. Mod Pathol 2001; 14: 85–90PubMedCrossRefGoogle Scholar
  29. 29.
    Barre V, Marret S, Mendel I, et al. Enterovirus-associated haemophagocytic syndrome in a neonate. Acta Paediatr 1998; 87: 469–71PubMedCrossRefGoogle Scholar
  30. 30.
    Tarcan A, Ozbek N, Gurakan B. Bone marrow failure with concurrent enteroviral infection in a newborn. Pediatr Infect Dis 2001 Jul; 20: 719–21CrossRefGoogle Scholar
  31. 31.
    Spector SA, Straube RC. Protean manifestations of perinatal enterovirus infections. West J Med 1983; 138: 847–51PubMedGoogle Scholar
  32. 32.
    Hoi-shan Chan S, Lun KS. Ventricular aneurysm complicating neonatal coxsackie B4 myocarditis. Pediatr Cardiol 2001; 22: 247–9PubMedCrossRefGoogle Scholar
  33. 33.
    Konen O, Rathaus V, Bauer S, et al. Progressive liver calcifications in neonatal coxsackievirus infection. Pediatr Radiol 2000; 30: 343–5PubMedCrossRefGoogle Scholar
  34. 34.
    Farmer K, MacArthur BA, Clay MM. A follow-up study of 15 cases of neonatal meningoencephalitis due to coxsackie virus B5. J Pediatr 1975; 87: 568–71PubMedCrossRefGoogle Scholar
  35. 35.
    Sells CJ, Carpenter RL, Ray CG. Sequelae of central-nervous-system enterovirus infections. N Engl J Med 1975; 293: 1–4PubMedCrossRefGoogle Scholar
  36. 36.
    Wilfert CM, Thompson RJ, Sunder TR, et al. Longitudinal assessment of children with enteroviral meningitis during the first three months of life. Pediatrics 1981; 67: 811–5PubMedGoogle Scholar
  37. 37.
    Bergman I, Painter MJ, Wald ER, et al. Outcome in children with enteroviral meningitis during the first year of life. J Pediatr 1987; 110: 705–9PubMedCrossRefGoogle Scholar
  38. 38.
    Rantakallio P, Saukkonen AL, Krause U. Follow-up study of 17 cases of neonatal coxsackie B5 meningitis and one with suspected myocarditis. Scand J Infect Dis 1970; 2: 25–8PubMedGoogle Scholar
  39. 39.
    Rorabaugh ML, Berlin LE, Rosenberg L, et al. Absence of neurodevelopmental sequelae from aseptic meningitis [abstract]. Pediatr Res 1992; 31: 177AGoogle Scholar
  40. 40.
    Brown GC, Karunas RS. Relationship of congenital anomalies and maternal infection with selected enteroviruses. Am J Epidemiol 1971; 95: 207–17Google Scholar
  41. 41.
    Cherry JD, Soriano F, Jahn CL. Search for perinatal viral infection: a prospective, clinical, virologic, and serologic study. Am J Dis Child 1968; 116: 245–50PubMedGoogle Scholar
  42. 42.
    Dagan R, Hall CB, Powell KR, et al. Epidemiology and laboratory diagnosis of infection with viral and bacterial pathogens in infants hospitalized for suspected sepsis. J Pediatr 1989; 115: 351–6PubMedCrossRefGoogle Scholar
  43. 43.
    Rosenlew M, Stenvik M, Roivainen M, et al. A population-based prospective survey of newborn infants with suspected systemic infection: occurrence of sporadic enterovirus and adenovirus infections. J Clin Virol 1999; 12: 211–9PubMedCrossRefGoogle Scholar
  44. 44.
    Shattuck KE, Chonmaitree T. The changing spectrum of neonatal meningitis over a fifteen-year period. Clin Pediatr 1992; 31: 130–6CrossRefGoogle Scholar
  45. 45.
    Byington CL, Taggart EW, Carroll KC, et al. A polymerase chain reaction-based epidemiologic investigation of the incidence of nonpolio enteroviral infections in febrile and afebrile infants 90 days and younger. Pediatrics 1999; 103: E27PubMedCrossRefGoogle Scholar
  46. 46.
    Rotbart HA, McCracken GH, Whitley RJ, et al. Clinical significance of enteroviruses in serious summer febrile illnesses of children. Pediatr Infect Dis J 1999; 18: 869–74PubMedCrossRefGoogle Scholar
  47. 47.
    Horn P. Poliomyelitis in pregnancy: a twenty-year report from Los Angeles County, California. J Am Acad Obstet Gynecol 1955; 6: 121–37Google Scholar
  48. 48.
    Jones MJ, Kolb M, Votava HJ, et al. Intrauterine echovirus type 11 infection. Mayo Clin Proc 1980; 55: 509–12PubMedGoogle Scholar
  49. 49.
    Amstey MS, Miller RK, Menegus MA, et al. Enterovirus in pregnant women and the perfused placenta. Am J Obstet Gynecol 1988; 158: 775–82PubMedGoogle Scholar
  50. 50.
    Reyes MP, Ostrea EM, Roskamp J, et al. Disseminated neonatal echovirus 11 disease following antenatal maternal infection with a virus-positive cervix and virus-negative gastrointestinal tract. J Med Virol 1983; 12: 155–9PubMedCrossRefGoogle Scholar
  51. 51.
    Reyes MP, Zalenski D, Smith F, et al. Coxsackievirus-positive cervices in women with febrile illnesses during the third trimester in pregnancy. Am J Obstet Gynecol 1986; 155: 159–61PubMedGoogle Scholar
  52. 52.
    Burch GE, Sun SC, Chu KC, et al. Interstitial and coxsackievirus B myocarditis in infants and children. JAMA 1968; 203: 1–8PubMedCrossRefGoogle Scholar
  53. 53.
    Strong BS, Young SA. Intrauterine coxsackievirus, group B type 1, infection: viral cultivation from amniotic fluid in the third trimester. Am J Perinatol 1995; 55: 509–12Google Scholar
  54. 54.
    Philip AGS, Larson EJ. Overwhelming neonatal infection with ECHO 19 virus. J Pediatr 1973; 82: 391–7PubMedCrossRefGoogle Scholar
  55. 55.
    Berkovich S, Smithwick EM. Transplacental infection due to ECHO virus type 22. J Pediatr 1968; 72: 94–6PubMedCrossRefGoogle Scholar
  56. 56.
    Garcia AGP, Basso NGDS, Fonseca MEF, et al. Congenital echo virus infection: morphological and virological study of fetal and placental tissue. J Pathol 1990; 160: 123–7PubMedCrossRefGoogle Scholar
  57. 57.
    Skeels MR, Williams JJ, Ricker FM. Perinatal echovirus infection [letter]. N Engl J Med 1981; 305: 1529CrossRefGoogle Scholar
  58. 58.
    Batcup G, Holt P, Hambling MH, et al. Placental and fetal pathology in coxsackie virus A9 infection: a case report. Histopathology 1985; 9: 1227–35PubMedCrossRefGoogle Scholar
  59. 59.
    Garcia AGP, Basso NGDS, Fonseca MEF, et al. Enterovirus associated placental morphology: a light, virological, electron microscopic and immunohistologic study. Placenta 1991; 12: 533–47PubMedCrossRefGoogle Scholar
  60. 60.
    Nielsen JL, Berryman GK, Hankins GDV. Intrauterine fetal death and the isolation of echovirus 27 from amniotic fluid. J Infect Dis 1988; 158: 501–2PubMedCrossRefGoogle Scholar
  61. 61.
    Brightman VJ, McNair Scott TF, Westphal M, et al. An outbreak of coxsackie B-5 virus infection in a newborn nursery. J Pediatr 1966; 69: 179–92PubMedCrossRefGoogle Scholar
  62. 62.
    Kinney JS, McCray E, Kaplan JE, et al. Risk factors associated with echovirus 11 infection in a hospital nursery. Pediatr Infect Dis J 1986; 5: 192–7CrossRefGoogle Scholar
  63. 63.
    Nagington J, Wreghitt TG, Gandy G, et al. Fatal echovirus 11 infections in outbreak in special-care baby unit. Lancet 1978; II: 725–8CrossRefGoogle Scholar
  64. 64.
    Rabkin CS, Telzak EE, Ho MS, et al. Outbreak of echovirus 11 infection in hospitalized neonates. Pediatr Infect Dis J 1988; 7: 186–90PubMedGoogle Scholar
  65. 65.
    Jankovic B, Pasic S, Kanjuh B, et al. Severe neonatal echovirus 17 infection during a nursery outbreak. Pediatr Infect Dis J 1999; 18: 393–4PubMedCrossRefGoogle Scholar
  66. 66.
    Pasic S, Jankovic B, Abinun M, et al. Intravenous immunoglobulin prophylaxis in an echovirus 6 and echovirus 4 nursery outbreak. Pediatr Infect Dis J 1997; 16: 718–20PubMedCrossRefGoogle Scholar
  67. 67.
    Modlin JF, Polk BF, Horton P, et al. Perinatal echovirus infection: risk of transmission during a community outbreak. N Engl J Med 1981; 305: 368–71PubMedCrossRefGoogle Scholar
  68. 68.
    Lonnrot M, Knip M, Roivainen M, et al. Onset of type 1 diabetes mellitus in infancy after enterovirus infections. Diabet Med 1998; 15: 431–4PubMedCrossRefGoogle Scholar
  69. 69.
    Abzug MJ, Keyserling HL, Lee ML, et al. Neonatal enterovirus infection: virology, serology, and effects of intravenous immune globulin. Clin Infect Dis 1995; 20: 1201–6PubMedCrossRefGoogle Scholar
  70. 70.
    Sawada T, Kohno Y, Ikegami H, et al. Detection of coxsackie B2 virus myocarditis in a neonate using T1-201 and I-123 BMIPP myocardial imaging. Clin Nucl Med 2000 Jan; 25: 77–8PubMedCrossRefGoogle Scholar
  71. 71.
    Dagan R, Jenista JA, Prather SL, et al. Viremia in hospitalized children with enterovirus infections. J Pediatr 1985; 106: 397–401PubMedCrossRefGoogle Scholar
  72. 72.
    Dahlquist GG, Boman JE, Juto P. Enteroviral RNA and IgM antibodies in early pregnancy and risk for childhood-onset IDDM in offspring. Diabetes Care 1999; 22: 364–5PubMedCrossRefGoogle Scholar
  73. 73.
    Terletskaia-Ladwig E, Metzger C, Schalasta G, et al. Evaluation of enterovirus serological tests IgM-EIA and complement fixation in patients with meningitis, confirmed by detection of enteroviral RNA by RT-PCR in cerebrospinal fluid. J Med Virol 2000; 61: 221–7PubMedCrossRefGoogle Scholar
  74. 74.
    Terletskaia-Ladwig E, Metzger C, Schalasta G, et al. A new enzyme immunoassay for the detection of enteroviruses in faecal specimens. J Med Virol 2000; 60: 439–45PubMedCrossRefGoogle Scholar
  75. 75.
    Bourlet T, Gharbi J, Omar S, et al. Comparison of a rapid culture method combining an immunoperoxidase test and a group specific anti-VP1 monoclonal antibody with conventional virus isolation techniques for routine detection of enteroviruses in stools. J Med Virol 1998; 54: 204–9PubMedCrossRefGoogle Scholar
  76. 76.
    Rotbart HA. Diagnosis of enteroviral meningitis with the polymerase chain reaction. J Pediatr 1990; 117: 85–9PubMedCrossRefGoogle Scholar
  77. 77.
    Sawyer MH, Holland D, Aintablian N, et al. Diagnosis of enteroviral central nervous system infection by polymerase chain reaction during a large community outbreak. Pediatr Infect Dis J 1994; 13: 177–82PubMedCrossRefGoogle Scholar
  78. 78.
    Rotbart HA, Ahmed A, Hickey S, et al. Diagnosis of enterovirus infection by polymerase chain reaction of multiple specimen types. Pediatr Infect Dis J 1997; 16: 409–11PubMedCrossRefGoogle Scholar
  79. 79.
    Ahmed A, Brito F, Goto C, et al. Clinical utility of the polymerase chain reaction for diagnosis of enteroviral meningitis in infancy. J Pediatr 1997; 131: 393–7PubMedCrossRefGoogle Scholar
  80. 80.
    Schlessinger Y, Sawyer MH, Storch GA. Enteroviral meningitis in infancy: potential role for polymerase chain reaction in patient management. Pediatrics 1994; 94: 157–62Google Scholar
  81. 81.
    Rice SK, Heinl RE, Thornton LL, et al. Clinical characteristics, management strategies, and cost implications of a statewide outbreak of enterovirus meningitis. Clin Infect Dis 1995; 20: 931–7PubMedCrossRefGoogle Scholar
  82. 82.
    Romero JR, Hinrich SH, Cavalieri SJ, et al. Potential health care cost savings from PCR-based rapid diagnosis of enteroviral meningitis [abstract]. Pediatr Res 1996; 39: 139ACrossRefGoogle Scholar
  83. 83.
    Abzug MJ, Loeffelholz M, Rotbart HA. Diagnosis of neonatal enterovirus infection by polymerase chain reaction. J Pediatr 1995; 26: 447–50Google Scholar
  84. 84.
    Yoshio H, Yamada M, Yokoi Y, et al. Diagnosis of neonatal enterovirus meningitis by reverse transcription-polymerase chain reaction. Kansenshogaku Zasshi 1997; 71: 1046–50PubMedGoogle Scholar
  85. 85.
    Chambon M, Delage C, Bailly JL, et al. Fatal hepatic necrosis in a neonate with echovirus 20 infection: use of the polymerase chain reaction to detect enterovirus in liver tissue. Clin Infect Dis 1997; 24: 523–4PubMedCrossRefGoogle Scholar
  86. 86.
    Austin BJ, Croxson MC, Powell KF, et al. The successful containment of coxsackie B4 infection in a neonatal unit. J Paediatr Child Health 1999; 35: 102–4PubMedCrossRefGoogle Scholar
  87. 87.
    Chambon M, Bailly JL, Beguet A, et al. An outbreak due to echovirus type 30 in a neonatal unit in France in 1997: usefulness of PCR diagnosis. J Hosp Infect 1999; 43: 63–8PubMedCrossRefGoogle Scholar
  88. 88.
    Takami T, Kawashima H, Takei Y, et al. Usefulness of nested PCR and sequence analysis in a nosocomial outbreak of neonatal enterovirus infection. J Clin Virol 1998; 11: 67–75PubMedCrossRefGoogle Scholar
  89. 89.
    Bailly J, Beguet A, Chambon M, et al. Nosocomial transmission of echovirus 30: molecular evidence by phylogenetic analysis of the VP1 encoding sequence. J Clin Microbiol 2000; 38: 2889–92PubMedGoogle Scholar
  90. 90.
    Takami T, Sonodat S, Houjyo H, et al. Diagnosis of horizontal enterovirus infections in neonates by nested PCR and direct sequence analysis. J Hosp Infect 2000; 45: 283–7PubMedCrossRefGoogle Scholar
  91. 91.
    Syriopoulou VP, Hadjichristodoulou CH, Daikos GL, et al. Clinical and epidemiological aspects of an enterovirus outbreak in a neonatal unit. J Hosp Infect 2002; 51: 275–80PubMedCrossRefGoogle Scholar
  92. 92.
    Isacsohn M, Eidelman AI, Kaplan M, et al. Neonatal coxsackievirus group B infections: experience of a single department of neonatology. Isr J Med Sci 1994; 30: 371–4PubMedGoogle Scholar
  93. 93.
    Clavell M, Barkemeyer B, Martinez B, et al. Severe hepatitis in a newborn with coxsackievirus B5 infection. Clin Pediatr 1999; 38: 739–41CrossRefGoogle Scholar
  94. 94.
    Chuang E, Maller ES, Hoffman MA, et al. Successful treatment of fulminant echovirus 11 infection in a neonate by orthotopic liver transplantation. J Pediatr Gastroenterol Nutr 1993; 17: 211–4PubMedCrossRefGoogle Scholar
  95. 95.
    Van Saene HKF, Stoutenbeek CP, Faber-Nijholt R, et al. Selective decontamination of the digestive tract contributes to the control of disseminated intravascular coagulation in severe liver impairment. J Pediatr Gastroenterol Nutr 1986; 5: 476–80CrossRefGoogle Scholar
  96. 96.
    Gilliam GL, Stokes KB, McLellan J, et al. Fulminant hepatic failure with intractable ascites due to an echovirus 11 infection successfully managed with a peritoneo-venous (LeVeen) shunt. J Pediatr Gastroenterol Nutr 1986; 5: 476–80CrossRefGoogle Scholar
  97. 97.
    Nagington J. Echovirus 11 infection and prophylactic antiserum [letter]. Lancet 1982; II: 446CrossRefGoogle Scholar
  98. 98.
    Dagan R, Prather S, Powell K, et al. Neutralizing antibodies to non-polio enteroviruses in human immune serum globulin. Pediatr Infect Dis J 1983; 2: 454–6CrossRefGoogle Scholar
  99. 99.
    Hammond GW, Lukes H, Wells B, et al. Maternal and neonatal neutralizing antibody titers to selected enteroviruses. Pediatr Infect Dis J 1985; 4: 32–5CrossRefGoogle Scholar
  100. 100.
    Wong SN, Tam AYC, Ng TH, et al. Fatal coxsackie B1 virus infection in neonates. Pediatr Infect Dis J 1989; 8: 638–41PubMedCrossRefGoogle Scholar
  101. 101.
    Black S. Treatment of overwhelming neonatal ECHO 5 virus infection with intravenous gamma globulin [abstract no. 314]. In: American Society for Microbiology: program and abstracts of the 23rd Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington (DC): American Society for Microbiology, 1983: 140Google Scholar
  102. 102.
    Johnston JM, Overall JC. Intravenous immunoglobulin in disseminated neonatal echovirus 11 infection. Pediatr Infect Dis J 1989; 8: 254–6PubMedGoogle Scholar
  103. 103.
    Valduss D, Murray DL, Kama P. Use of intravenous immunoglobulin in twin neonates with disseminated coxsackie B1 infection. Clin Pediatr 1993; 32: 561–3CrossRefGoogle Scholar
  104. 104.
    Kimura H, Minakami H, Harigaya A, et al. Treatment of neonatal infection caused by coxsackievirus B3. J Perinatal 1999; 19: 388–90CrossRefGoogle Scholar
  105. 105.
    Jantausch BA, Luban NL, Duffy L, et al. Maternal plasma transfusion in the treatment of disseminated neonatal echovirus 11 infection. Pediatr Infect Dis J 1995; 14: 154–5PubMedCrossRefGoogle Scholar
  106. 106.
    Rotbart HA. Antiviral therapy for enteroviral infections. Pediatr Infect Dis J 1999; 18: 632–3PubMedCrossRefGoogle Scholar
  107. 107.
    Sawyer MH. Enterovirus infections: diagnosis and treatment. Pediatr Infect Dis J 1999 Dec; 18: 1033–40PubMedCrossRefGoogle Scholar
  108. 108.
    Groarke JM, Pevear DC. Attenuated virulence of pleconaril-resistant coxsackievirus B3 variants. J Infect Dis 1999; 179: 1538–41PubMedCrossRefGoogle Scholar
  109. 109.
    Pevear DC, Tull TM, Seipel ME. Activity of pleconaril against enteroviruses. Antimicrob Agents Chemother 1999; 43: 2109–15PubMedGoogle Scholar
  110. 110.
    Schiff GM, Sherwood JR. Clinical activity of pleconaril in an experimentally induced coxsackievirus A21 respiratory infection. J Infect Dis 2000; 181: 20–6PubMedCrossRefGoogle Scholar
  111. 111.
    Shafran SD, Halota W, Gilbert D, et al. Pleconaril is effective for enteroviral meningitis in adolescents and adults: a randomized placebo-controlled multi-center trial [abstract no. 1904]. In: American Society for Microbiology: programs and abstracts of the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington (DC): American Society for Microbiology, 1999: 436Google Scholar
  112. 112.
    Beer K, ViroPharma Inc. ViroPharma announces results of viral respiratory infection and viral meningitis studies [online]. Available from URL: [Accessed 2002 Dec 31]
  113. 113.
    Sawyer MH, Saez-Llorenz X, Aviles CL, et al. Oral pleconaril reduces the duration and severity of enterovirus meningitis in children [abstract no. 1012]. Pediatr Res 1999 Apr; 45(4): 173ACrossRefGoogle Scholar
  114. 114.
    Beer K, ViroPharma Inc. ViroPharma Incorporated announces successful viral respiratory infection program with pleconaril [online]. Available from URL: [Accessed 2002 Dec 31]
  115. 115.
    Beer K, ViroPharma Inc. Picovir™ (pleconaril) is first antiviral drug candidate shown in pivotal studies to treat the cause and symptoms of viral respiratory infection [online]. Available from URL: [Accessed 2002 Dec 31]
  116. 116.
    Rotbart HA, Webster AD. Treatment of potentially life-threatening enterovirus infections with pleconaril. Clin Infect Dis 2001; 32: 228–35PubMedCrossRefGoogle Scholar
  117. 117.
    Abzug MJ, Cloud G, Bradley J, et al. Double-blind, placebo-controlled trial of pleconaril in infants with enterovirus meningitis. Pediatr Infect Dis J 2003 Apr; 22: 335–40PubMedGoogle Scholar
  118. 118.
    Kearns GL, Bradley JS, Jacobs RJ, et al. Single dose pharmacokinetics of pleconaril in neonates. Pediatr Infect Dis J 2000; 19: 833–9PubMedCrossRefGoogle Scholar
  119. 119.
    Bauer S, Gottesman G, Sirota L, et al. Severe coxsackie virus B infection in preterm newborns treated with pleconaril. Eur J Pediatr 2002; 161: 491–3PubMedCrossRefGoogle Scholar
  120. 120.
    Aradottir E, Alonso EM, Shulman ST. Severe neonatal enteroviral hepatitis treated with pleconaril. Pediatr Infect Dis 2001 Apr; 20: 457–9CrossRefGoogle Scholar
  121. 121.
    Beer K, ViroPharma Inc. ViroPharma provides further update on Picovir™ NDA [online]. Available from URL: [Accessed 2002 Dec 31]
  122. 122.
    Wilson CW, Stevenson DK, Arvin AM. A concurrent epidemic of respiratory syncytial virus and echovirus 7 infections in an intensive care nursery. Pediatr Infect Dis J 1989; 8: 24–9PubMedCrossRefGoogle Scholar
  123. 123.
    Carolane DJ, Long AM, McKeever PA, et al. Prevention of spread of echovirus 6 in a special care baby unit. Arch Dis Child 1985; 60: 674–6PubMedCrossRefGoogle Scholar
  124. 124.
    Nagington J, Walker J, Gandy G. Use of normal immunoglobulin in an echovirus 11 outbreak in a special-care baby unit. Lancet 1983; II: 443–6CrossRefGoogle Scholar

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© Adis Data Information BV 2004

Authors and Affiliations

  • Mark J. Abzug
    • 1
  1. 1.Department of Pediatrics, Pediatric Infectious DiseasesUniversity of Colorado School of Medicine and The Children’s HospitalDenverUSA

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