Abstract
Even with the approaching worldwide eradication of the polioviruses, the nonpolio enteroviruses remain major pathogens of the central nervous system. Our understanding of this important group of viral pathogens has increased dramatically in the past decade. The advent of molecular virology has yielded information that has been vital to the development of molecular diagnostic techniques for the detection of the enteroviruses and for the design of novel antienteroviral drugs. Advances in molecular diagnostics have allowed for a better definition of the diseases they cause and have impacted on patient care. This review discusses recent developments in the diagnosis and treatment of enterovirus infections of the central nervous system, including an overview of the molecular virology of the enteroviruses as it pertains to taxonomy, diagnosis, and treatment.
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References and Recommended Reading
Racaniello VR: Picornaviridae: the viruses and their replication. In Fields Virology, edn 4. Edited by Knipe DM, Howley PM. Philadelphia: Lippincott Williams & Wilkins; 2001:685–722.
Cherry JD: Enteroviruses: coxsackieviruses, enteroviruses, and polioviruses. In Textbook of Pediatric Infectious Diseases, edn 4. Edited by Feigin RD Cherry JD. Philadelphia: WB Saunders Co.; 1998:1787–1839.
Oberste MS, Maher K, Flemister MR, et al.: Comparison of classic and molecular approaches for the identification of untypeable enteroviruses. J Clin Microbiol 2000, 38:1170–1174.
Centers for Disease Control and Prevention: Progress toward global eradication of poliomyelitis, 2001. Morb Mortal Wkly Rep 2002, 51:253–256. Reviews the current status of global eradication of the PV.
Byington CL, Taggart EW, Carroll KC, Hillyard DR: 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:E27.
Chambon M, Archimbaud C, Bailly JL, et al.: Circulation of enteroviruses and persistence of meningitis cases in the winter of 1999–2000. J Med Virol 2001, 65:340–347.
Rotbart HA: Viral meningitis. Semin Neurol 2000, 20:277–292.
Centers for Disease Control and Prevention: Enterovirus surveillance-United States, 1997–1999. Morb Mortal Wkly Rep 2000, 49:913.
Rotbart HA: Enteroviral infections of the central nervous system. Clin Infect Dis 1995, 20:971–981.
Centers for Disease Control and Prevention: Echovirus type 13-United States, 2001. Morb Mortal Wkly Rep 2001, 50:777–780.
Dietz V, Andrus J, Olive JM, et al.: Epidemiology and clinical characteristics of acute flaccid paralysis associated with nonpolio enterovirus isolation: the experience in the Americas. Bull World Health Organ 1995, 73:597–603.
Chaves SS, Lobo S, Kennett M, Black J: Coxsackie virus A24 infection presenting as acute flaccid paralysis. Lancet 2001, 357:605.
Gear JH: Nonpolio causes of polio-like paralytic syndromes. Rev Infect Dis 1984, 6(suppl 2):S379-S384.
Huang CC, Liu CC, Chang YC, et al.: Neurologic complications in children with enterovirus 71 infection. N Engl J Med 1999, 341:936–942. A detailed presentation of neurologic syndromes (meningitis, rhombencephalitis, acute flaccid paralysis) associated with EV71 infection during an epidemic in Taiwan.
Melnick JL: Enterovirus type 71 infections: a varied clinical pattern sometimes mimicking paralytic poliomyelitis. Rev Infect Dis 1984, 6(Suppl 2):S387-S390.
Berlin LE, Rorabaugh ML, Heldrich F, et al.: Aseptic meningitis in infants < 2 years of age: diagnosis and etiology. J Infect Dis 1993, 168:888–892.
Modlin JF: Enterovirus infection in infants and children. Adv Pediatr Infect Dis 1996, 12:155–180.
McKinney RE Jr, Katz SL, Wilfert CM: Chronic enteroviral meningoencephalitis in agammaglobulinemic patients. Rev Infect Dis 1987, 9:334–356.
Cunningham CK, Bonville CA, Ochs HD, et al.: Enteroviral meningoencephalitis as a complication of X-linked hyper IgM syndrome. J Pediatr 1999, 134:584–588.
Fischmeister G, Wiesbauer P, Holzmann HM, et al.: Enteroviral meningoencephalitis in immunocompromised children after matched unrelated donor-bone marrow transplantation. Pediatr Hematol Oncol 2000, 17:393–399.
Webster AD, Rotbart HA, Warner T, et al.: Diagnosis of enterovirus brain disease in hypogammaglobulinemic patients by polymerase chain reaction. Clin Infect Dis 1993, 17:657–661.
Modlin JF, Dagan R, Berlin LE, et al.: Focal encephalitis with enterovirus infections. Pediatrics 1991, 88:841–845.
Hosoya M, Sato M, Honzumi K, et al.: Association of nonpolio enteroviral infection in the central nervous system of children with febrile seizures. Pediatrics 2001, 107:E12.
Romero JR: Reverse transcription-polymerase chain reaction detection of the enteroviruses: overview and clinical utility in pediatric enteroviral infections. Arch Pathol Lab Med 1999, 123:1161–1169.
Oberste MS, Maher K, Kilpatrick DR, et al.: Typing of human enteroviruses by partial sequencing of VP1. J Clin Microbiol 1999, 37:1288–1293.
Oberste SM, Schnurr D, Maher K, et al.: Molecular identification of new picornaviruses and characterization of a proposed enterovirus 73 serotype. J Gen Virol 2001, 82:409–416.
International Committee on Taxonomy of Viruses. Family Picornaviridae. In Virus Taxonomy. Classification and Nomenclature of Viruses. Edited by Regenmortel MHV, Fauquate CM, Bishop HL, et al. San Diego: Academic Press; 2000:657–683.
McKinlay MA, Pevear DC, Rossmann MG: Treatment of the picornavirus common cold by inhibitors of viral uncoating and attachment. Ann Rev Microbiol 1992, 46:635–654.
Abzug MJ: Perinatal enterovirus infections. In Human Enterovirus Infections. Edited by Rotbart HA. Washington DC: ASM; 1995:239–254.
Rotbart HA, Brennan PJ, Fife KH, et al.: Enterovirus meningitis in adults. Clin Infect Dis 1998, 27:896–898. An excellent prospective observational report of the clinical findings and associated morbidity of EV meningitis in adults.
Nielsen HE, Andersen EA, Andersen J, et al.: Diagnostic assessment of haemorrhagic rash and fever. Arch Dis Child 2001, 85:160–165.
Ho M: Enerovirus 71: the virus, its infections and outbreaks. J Microbiol Immunol Infect 2000, 33:205–216.
Chen CY, Chang YC, Huang CC, et al.: Acute flaccid paralysis in infants and young children with enterovirus 71 infection: MR imaging findings and clinical correlates. AJNR Am J Neuroradiol 2001, 22:200–205.
Malzberg MS, Rogg JM, Tate CA, et al.: Poliomyelitis: Hyperintensity of the anterior horn cells on MR images of the spinal cord. AJR Am J Roentgenol 1993, 161:863–865.
Lum LC, Chua KB, McMinn PC, et al.: Echovirus 7 associated encephalomyelitis. J Clin Virol 2002, 23:153–160.
Romero JR, Rotbart HA: Enteroviruses. In Manual of Clinical Microbiology, edn 8. Edited by Murray PR, Baron EJ, Pfaller MA, et al. Washington, DC: American Society for Microbiology; In press.
Van Doornum GJ, De Jong JC: Rapid shell vial culture technique for detection of enteroviruses and adenoviruses in fecal specimens: comparison with conventional virus isolation method. J Clin Microbiol 1998, 36:2865–2868.
Ramers C, Billman G, Hartin M, et al.: Impact of a diagnostic cerebrospinal fluid enterovirus polymerase chain reaction test on patient management. JAMA 2000, 283:2680–2685. This report documents that the use RT-PCR for rapid diagnosis of EV meningitis can reduce the use of antibiotics, lead to fewer ancillary tests, and promote rapid discharge of hospitalized patients.
Abzug MJ, Keyserling HL, Lee ML, et al.: Neonatal enterovirus infection: virology, serology, and effects of intravenous immune globulin. Clin Infect Dis 1995, 20:1201–1206.
Rogers JM, Diana GD, MCKinlay MA: Pleconaril. A broad spectrum antipicornaviral agent. Adv Exp Med Biol 1999, 458:69–76.
Romero JR: Pleconaril: a novel antipicornaviral drug. Exp Opin Invest Drug 2001, 10:369–379. A review of pleconaril including its mechanism of action, spectrum of activity, and pharmacokinetics in all age groups, and summaries of available clinical trials.
Pevear DC, Tull TM, Seipel ME, Groarke JM: Activity of pleconaril against enteroviruses. Antimicrob Agents Chemother 1999, 43:2109–2115. This report describes the activity of pleconaril against the prototypic and clinical strains of the most common EVs. Its protective activity in animal models of lethal EV infection is also presented.
Abdel-Rahman SM, Kearns GL: Single-dose pharmacokinetics of a pleconaril (VP63843) oral solution and effect of food. Antimicrob Agents Chemother 1998, 42:2706–2709.
Abdel-Rahman SM, Kearns GL: Single oral dose escalation pharmacokinetics of pleconaril (VP 63843) capsules in adults. J Clin Pharmacol 1999, 39:613–618.
Kearns GL, Abdel-Rahman SM, James LP, et al.: Single-dose pharmacokinetics of a pleconaril (VP63843) oral solution in children and adolescents. Antimicrob Agents Chemother 1999, 43:634–638.
Kearns GL, Bradley JS, Jacobs RF, et al.: Single dose pharmacokinetics of pleconaril in neonates. Pediatr Infect Dis J 2000, 19:833–839.
Rotbart HA, Webster AD: Treatment of potentially life-threatening enterovirus infections with pleconaril. Clin Infect Dis 2001, 32:228–235. This report discusses the outcomes of 38 patients treated with pleconaril on a compassionate use basis for life-threatening EV infections (CEMA, neonatal sepsis, myocarditis, bone marrow transplant recipients, encephalitis, VAPP, poliomyelitis, ALS). A favorable clinical response was observed in the majority of patients treated.
Romero JR, Gross T, Abromowitch M, Jung L: Pleconaril treatment of vaccine-acquired poliovirus [abstract]. Pediatr Res 1999, 45(part 2):173A.
Sawyer MH, Saez-Llorenz X, Aviles CL, et al.: Oral pleconaril reduces the duration and severity of enteroviral meningitis in children [abstract]. Pediatr Res 1999, 45(part 2):173A.
Shafran SD, Halota W, Gilbert E, et al.: Pleconaril is effective for enteroviral meningitis in adolescents and adults: a randomized placebo-controlled multicenter trial [abstract 1904]. Program and Abstracts of the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy. San Francisco. September 26–29, 1999.
Bradrick SS, Romero JR: Polioviruses.In Encyclopedia of Life Sciences. London: Nature Publishing Group. 2001:1–7.
Rotbart HA: Enteroviruses: overview of treatments, current and future. Infect Med 1999, 16(Suppl D):11–20.
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Romero, J.R. Diagnosis and management of enteroviral infections of the central nervous system. Curr Infect Dis Rep 4, 309–316 (2002). https://doi.org/10.1007/s11908-002-0023-1
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DOI: https://doi.org/10.1007/s11908-002-0023-1