Enteroviruses 

  • Author: Alexander Velazquez, MD; Chief Editor: Burke A Cunha, MD   more...
 
Updated: Nov 18, 2010
 

Background

The human enteroviruses are ubiquitous viruses that are transmitted from person to person via direct contact with virus shed from the gastrointestinal or upper respiratory tract. The enteroviruses belong to the Picornaviridae family of viruses and are traditionally divided into 5 subgenera based on differences in host range and pathogenic potential.[1] Each subgenus contains a number of unique serotypes, which are distinguished based on neutralization by specific antisera. The subgenera include polioviruses, coxsackievirus (groups A and B), and echoviruses.

A total of 72 serotypes were originally identified by conventional methods; 64 serotypes remain after recognition of redundant serotypes. Three serotypes comprise the polioviruses, 23 serotypes comprise coxsackievirus group A, 6 serotypes comprise coxsackievirus group B, and 29 serotypes comprise the echoviruses. A new classification scheme has been adopted that divides all nonpolio enterovirus into 4 groups designated A through D based on the homology within RNA region coding for the VP1 capsid protein.[2] More recently, many new serotypes that are not included in the original classification have been characterized by molecular methods, bringing the number of known serotypes to more than 90.[3, 4]

Virology

  • The enteroviruses are icosahedral nonenveloped viruses that are approximately 30 nm in diameter.
  • They have a capsid composed of 60 subunits each formed from 4 proteins (VP1 to VP4).
  • They are stable at a pH from 3-10, distinguishing them from other picornaviruses (including rhinoviruses), which are unstable below pH 6.
  • A linear, single-strand RNA genome of about 7.5 kb is enclosed by the capsid; the translation product is a single polyprotein that is cleaved after translation by viral-coded proteases into the structural proteins (VP1 to VP4), RNA polymerase, proteases, and other nonstructural proteins.[5]
  • Enteroviruses resist lipid solvents, ether, chloroform, and alcohol. They are inactivated at temperatures above 50°C but remain infectious at refrigerator temperature.
  • Molar MgCl2 reduces thermolability at higher temperatures.
  • The viruses are inactivated by ionizing radiation, formaldehyde, and phenol.

Enteroviruses cause a wide range of infections. Poliovirus, the prototypical enterovirus, can cause a subclinical or mild illness, aseptic meningitis, or paralytic poliomyelitis, a disease that has been eradicated in the United States and other developed countries. The nonpolio viruses (group A and B coxsackieviruses, echoviruses, enteroviruses) continue to be responsible for a wide spectrum of diseases in persons of all ages, although infection and illness occur most commonly in infants.

Coxsackievirus infection is the most common cause of viral heart disease. Group A coxsackieviruses may cause flaccid paralysis, while group B coxsackieviruses cause spastic paralysis. Other diseases associated with group A coxsackievirus infections include hand-foot-and-mouth disease (HFMD) and hemorrhagic conjunctivitis, while group B coxsackievirus is associated with herpangina, pleurodynia, myocarditis, pericarditis, and meningoencephalitis. Aseptic meningitis and the common cold are associated with both groups.

Diseases caused by echoviral infections range from the common cold and fever to aseptic meningitis and acute hemorrhagic conjunctivitis (AHC).

Next

Pathophysiology

Enteroviruses are transmitted predominantly via the fecal-oral route. However, there are some exceptions, including coxsackievirus A21, which is spread mainly by respiratory secretions,[6] and enterovirus 70, which is shed in tears and spread via fingers and fomites.[7]

Upon entry into the oropharynx, the virus replicates in submucosal tissues of the distal pharynx and alimentary tract.[8] Viral particles are shed in the feces and in upper respiratory tract secretions for days prior to symptom onset. The average incubation period is 3-10 days, during which the virus migrates to regional lymphoid tissue and replicates. Minor viremia results, which is associated with the onset of symptoms and viral spread to the reticuloendothelial system (spleen, liver, bone marrow).[9]

Dissemination to target organs follows, and viral replication in target organs produces the major viremia with possible secondary seeding of the CNS. Potential target organs include the skin and CNS. Infectious virus is shed from the upper respiratory tract for 1-3 weeks and from the feces for 3-8 weeks. Enteroviruses undergoes a high rate of mutation during replication in the gastrointestinal tract, where single-site mutations can occur in the 5' noncoding region of the attenuated polioviruses; this can lead to prolonged excretion and neurovirulence.[10]

The neuropathy of paralytic diseases caused by enteroviruses is due to direct cellular destruction. Neuronal lesions occur mainly in anterior horn cells of the spinal cord. The 3 serotypes of poliovirus all bind to the cell surface receptor CD155.

Immunity and immune response

  • Immunity to enterovirus is serotype-specific. Intact humoral immunity is required for the control and eradication of enteroviral disease.
  • T lymphocytes do not contribute to viral clearance and, in coxsackievirus B3 myocarditis, may contribute to myocardial inflammation.[11]
  • Humoral immunity (antibody-mediated) mechanisms operate both in the alimentary tract (to prevent mucosal infection) and in the blood (to prevent dissemination to target organs).
  • Secretory immunoglobulin A (IgA) appears in nasal and alimentary secretions 2-4 weeks after the administration of live-attenuated oral poliovirus vaccine (OPV) and persists for at least 15 years.[12] Upon re-exposure to infectious virus, high titers of secretory IgA antibodies prevent or substantially reduce poliovirus shedding; higher secretory IgA titers lead to better immunity.[12]
  • Immunoglobulin M (IgM) antibodies appear as early as 1-3 days after enteroviral challenge and disappear after 2-3 months.[12]
  • Immunoglobulin G (IgG) antibody, which is generally detected 7-10 days after infection, is mostly of the IgG1 and IgG3 subtypes. Serum neutralizing IgG antibodies persist for life after natural enteroviral infections.[13]
  • Macrophage function is also a critical component of the immune response in enteroviral infections; ablation of macrophage function in experimental animals markedly enhances the severity of coxsackievirus B infections.[14]
Previous
Next

Epidemiology

Frequency

United States

  • Nonpolio enteroviruses are responsible for 10-20 million symptomatic infections per year and are more prevalent among children of lower socioeconomic class, probably because of crowding, poor hygiene, and opportunities for fecal contamination.
  • AHC was first recognized in the United States in 1981 during an epidemic in Florida; few cases have been reported since. The prevalence is higher in southern areas than in northern areas.
  • Between 2002 and 2004, echoviruses 9 and 30 were the most commonly reported enterovirus serotypes in the United States.[15] In contrast, other enterovirus serotypes (eg, echovirus 1, coxsackievirus B6, and enteroviruses 68 and 69) are rarely reported and appear to have little epidemic potential.[16]
  • Coxsackievirus A is likely underrepresented because only some serotypes are readily isolated in cell culture.[17]
  • National or regional outbreaks of aseptic meningitis are occasionally reported, such as the echovirus 30 outbreaks in the United States between 1989 and 1992 and in 2003 and echovirus 13 and echovirus 18 outbreaks in 2001. Aseptic meningitis is no longer a nationally notifiable disease in the United States.

International

  • Enteroviruses are distributed worldwide and are influenced by season and climate. Infections occur in summer and early fall in temperate areas, while tropical and semitropical areas bear the brunt all year.
  • AHC occurs as epidemics in tropical countries during the hot and rainy season. It was first recognized in 1969 in Ghana (Apollo disease) and Indonesia. AHC is also epidemic in India and the Far East.
  • The worldwide prevalence of poliomyelitis has decreased significantly because of improved economic conditions and availability of vaccines. The last case of wild polio in the Americas occurred in Peru in 1991. In 1994, the World Health Organization declared polio eradicated from the Western Hemisphere. In 2000, 7 cases of poliomyelitis due to a mutated polio strain related to oral polio vaccine were reported from Haiti and the Dominican Republic. Polio remains a significant disease in the developing world, and, in 2003, 6 endemic countries were identified: Afghanistan, Egypt, India, Niger, Nigeria, and Pakistan.
  • In 2008, 1,652 confirmed cases of paralytic polio were reported worldwide. Polio is endemic in 4 countries: Afghanistan, India, Nigeria, and Pakistan. In addition, 14 other previously polio-free countries (Angola, Burkina Faso, Benin, Central Africa Republic, Chad, Côte d'Ivoire, The Democratic Republic of Congo, Ghana, Ethiopia, Nepal, Niger, Sudan, Tango) have reported cases in 2008-2009 (114 cases through August 2009) as a result of importations.[18, 19] As of September 2009, 969 cases of polio (including wild polio strains and oral vaccine–derived) had been reported in endemic and nonendemic countries.[20]

Mortality/Morbidity

  • More than 90% of infections caused by the nonpolio enteroviruses are asymptomatic or result in only an undifferentiated febrile illness.[21]
  • Myopericarditis carries a mortality rate of 0%-4%. Myocarditis carries a higher mortality rate than pericarditis. Additionally, murine model studies have suggested that a deficiency of complement receptors 1 and 2 leads to increased morbidity in coxsackie B3 infections, including myocarditis, dilated cardiomyopathy, and fibrosis.[22]
  • Prior to the vaccine era, the mortality rate in polio epidemics was 5%-7%.
  • The overall risk of OPV-related disease is estimated to be 1 case per 2.6 million doses of OPV. The inactivated poliovirus vaccine (IPV) was incorporated into the routine polio vaccination in Europe and Canada in the 1980s. IPV has been used in the United States since 2000; OPV is no longer used in the United States.
  • Despite the risk of OPV-related paralysis, it is still the preferred vaccine for global polio eradication in developing nations (see Deterrence/Prevention).

Sex

  • The male-to-female ratio of myopericarditis is 2:1. The risk of cardiac involvement is higher during pregnancy and immediately postpartum.
  • The prevalence of polio infection is equal in boys and girls, although paralysis is more common in boys. Among adults, women are at increased risk of infection and the postpolio syndrome.
  • Aseptic meningitis is approximately twice as common in males as in females.

Age

  • Enteroviral infections are most common in young children. Herpangina primarily affects children aged 3 months to 16 years. Poliomyelitis is observed in children younger than 15 years. Aseptic meningitis due to enteroviral infection is more common in infants than in adults. Most cases of pleurodynia occur in children and adults younger than 30 years.
  • Myopericarditis is most prevalent in young adults, especially those who are physically active. AHC is most prevalent in adults aged 20-50 years.
  • Neonates are at high risk for severe sepsis due to enterovirus infections.
Previous
Proceed to Clinical Presentation
 
 
Contributor Information and Disclosures
Author

Alexander Velazquez, MD  Fellow, Department of Infectious Diseases, Orlando Regional Medical Center

Alexander Velazquez, MD is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Coauthor(s)

Mark R Wallace, MD, FACP, FIDSA  Clinical Professor of Medicine, Florida State University College of Medicine; Head of Infectious Disease Fellowship Program, Orlando Regional Medical Center

Mark R Wallace, MD, FACP, FIDSA is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Tropical Medicine and Hygiene, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Smeeta Sinha, MD  Staff Physician, Department of Dermatology, UMDNJ-New Jersey Medical School

Smeeta Sinha, MD is a member of the following medical societies: Alpha Omega Alpha, Phi Beta Kappa, and Sigma Xi

Disclosure: Nothing to disclose.

Rajendra Kapila, MD, MBBS  Professor of Medicine, Department of Medicine, UMDNJ, New Jersey Medical School

Rajendra Kapila, MD, MBBS is a member of the following medical societies: American College of Physicians, American Medical Association, Infectious Diseases Society of America, and Infectious Diseases Society of New Jersey

Disclosure: Nothing to disclose.

Robert A Schwartz, MD, MPH  Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi

Disclosure: Nothing to disclose.

Pratibha Dua, MD, MBBS  Staff Physician, Department of Internal Medicine, The Brooklyn Hospital Center

Pratibha Dua, MD, MBBS is a member of the following medical societies: American Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary D Nettleman, MD, MS, MACP  Professor and Chair, Department of Medicine, Michigan State University College of Human Medicine

Mary D Nettleman, MD, MS, MACP is a member of the following medical societies: American College of Physicians, Association of Professors of Medicine, Central Society for Clinical Research, Infectious Diseases Society of America, and Society of General Internal Medicine

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Senior Pharmacy Editor, eMedicine

Disclosure: eMedicine Salary Employment

Ronald A Greenfield, MD  Professor, Department of Internal Medicine, University of Oklahoma College of Medicine

Ronald A Greenfield, MD is a member of the following medical societies: American College of Physicians, American Federation for Medical Research, American Society for Microbiology, Central Society for Clinical Research, Infectious Diseases Society of America, Medical Mycology Society of the Americas, Phi Beta Kappa, Southern Society for Clinical Investigation, and Southwestern Association of Clinical Microbiology

Disclosure: Pfizer Honoraria Speaking and teaching; Gilead Honoraria Speaking and teaching; Ortho McNeil Honoraria Speaking and teaching; Abbott Honoraria Speaking and teaching; Astellas Honoraria Speaking and teaching; Cubist Honoraria Speaking and teaching

Eleftherios Mylonakis, MD  Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital

Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD  Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital

Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

References

  1. Melnick JL. The discovery of the enteroviruses and the classification of poliovirus among them. Biologicals. Dec 1993;21(4):305-9. [Medline].

  2. Oberste MS, Maher K, Kilpatrick DR, Flemister MR, Brown BA, Pallansch MA. Typing of human enteroviruses by partial sequencing of VP1. J Clin Microbiol. May 1999;37(5):1288-93. [Medline].

  3. Oberste MS, Maher K, Michele SM, Belliot G, Uddin M, Pallansch MA. Enteroviruses 76, 89, 90 and 91 represent a novel group within the species Human enterovirus A. J Gen Virol. Feb 2005;86:445-51. [Medline].

  4. Oberste MS, Maher K, Nix WA, et al. Molecular identification of 13 new enterovirus types, EV79-88, EV97, and EV100-101, members of the species Human Enterovirus B. Virus Res. Sep 2007;128(1-2):34-42. [Medline].

  5. Rueckert RR. Picornaviridae and their replication. In: Fields BN, Knipe DM, eds. Virology. 2nd ed. New York: Raven Press; 1990:507.

  6. Couch RB, Douglas RG Jr, Lindgren KM, Gerone PJ, Knight V. Airborne transmission of respiratory infection with coxsackievirus A type 21. Am J Epidemiol. Jan 1970;91(1):78-86. [Medline].

  7. Onorato IM, Morens DM, Schonberger LB, Hatch MH, Kaminski RM, Turner JP. Acute hemorrhagic conjunctivitis caused by enterovirus type 70: an epidemic in American Samoa. Am J Trop Med Hyg. Sep 1985;34(5):984-91. [Medline].

  8. Wolf JL, Rubin DH, Finberg R, et al. Intestinal M cells: a pathway for entry of reovirus into the host. Science. Apr 24 1981;212(4493):471-2. [Medline].

  9. Horstmann DM, Mccollum RW. Poliomyelitis virus in human blood during the minor illness and the asymptomatic infection. Proc Soc Exp Biol Med. Mar 1953;82(3):434-7. [Medline].

  10. Minor PD, John A, Ferguson M, Icenogle JP. Antigenic and molecular evolution of the vaccine strain of type 3 poliovirus during the period of excretion by a primary vaccinee. J Gen Virol. Apr 1986;67 ( Pt 4):693-706. [Medline].

  11. Rose NR, Wolfgram LJ, Herskowitz A, Beisel KW. Postinfectious autoimmunity: two distinct phases of coxsackievirus B3-induced myocarditis. Ann N Y Acad Sci. 1986;475:146-56. [Medline].

  12. Ogra PL, Karzon DT. Formation and function of poliovirus antibody in different tissues. Prog Med Virol. 1971;13:157.

  13. Torfason EG, Reimer CB, Keyserling HL. Subclass restriction of human enterovirus antibodies. J Clin Microbiol. Aug 1987;25(8):1376-9. [Medline].

  14. Rager-Zisman B, Allison AC. The role of antibody and host cells in the resistance of mice against infection by coxsackie B-3 virus. J Gen Virol. Jun 1973;19(3):329-38. [Medline].

  15. Centers for Disease Control and Prevention (CDC). Enterovirus surveillance--United States, 2002-2004. MMWR Morb Mortal Wkly Rep. Feb 17 2006;55(6):153-6. [Medline].

  16. Centers for Disease Control and Prevention. Enterovirus surveillance--United States, 2000-2001. MMWR Morb Mortal Wkly Rep. Nov 22 2002;51(46):1047-9. [Medline].

  17. Lipson SM, Walderman R, Costello P. Sensitivity of rhabdomyosarcoma and guinea pig embryo cell cultures to field isolates of difficult-to-cultivate group A coxsackieviruses. J Clin Microbiol. 1986;26:1298.

  18. World Health Organization – Regional Office for Eastern Mediterranean. AFP Surveillance, Polio Fax weekly bulletin. Week 36. World Health Organization – Regional Office for Eastern Mediterranean; 9/7/2009.

  19. Center for Disease Control and Prevention. Glopal Polio Erradication Program. CDC; July 2009.

  20. Global Polio Eradication Initiative. Wild Poliovirus Weekly Update. Sept 8,2009. [Full Text].

  21. Kogon A, Spigland I, Frothingham TE, Elveback L, Williams C, Hall CE. The virus watch program: a continuing surveillance of viral infections in metropolitan New York families. VII. Observations on viral excretion, seroimmunity, intrafamilial spread and illness association in coxsackie and echovirus infections. Am J Epidemiol. Jan 1969;89(1):51-61. [Medline].

  22. Fairweather D, Frisancho-Kiss S, Njoku DB, Nyland JF, Kaya Z, Yusung SA. Complement receptor 1 and 2 deficiency increases coxsackievirus B3-induced myocarditis, dilated cardiomyopathy, and heart failure by increasing macrophages, IL-1beta, and immune complex deposition in the heart. J Immunol. Mar 15 2006;176(6):3516-24. [Medline].

  23. Curnen EC, Shaw EW, Melnick JL. Disease resembling nonparalytic poliomyelitis associated with a virus pathogenic for infant mice. J Am Med Assoc. Nov 26 1949;141(13):894-901. [Medline].

  24. Weller TH, Enders JF, Buckingham M, Finn JJ Jr. The etiology of epidemic pleurodynia: a study of two viruses isolated from a typical outbreak. J Immunol. Sep 1950;65(3):337-46. [Medline].

  25. Warin JF, Davies JB, Sanders FK, Vizoso AD. Oxford epidemic of Bornholm disease, 1951. Br Med J. Jun 20 1953;1(4824):1345-51. [Medline].

  26. Narula J, Khaw BA, Dec GW Jr, et al. Brief report: recognition of acute myocarditis masquerading as acute myocardial infarction. N Engl J Med. Jan 14 1993;328(2):100-4. [Medline].

  27. Kono R. Apollo 11 disease or acute hemorrhagic conjunctivitis: a pandemic of a new enterovirus infection of the eyes. Am J Epidemiol. May 1975;101(5):383-90. [Medline].

  28. Sklar VE, Patriarca PA, Onorato IM, et al. Clinical findings and results of treatment in an outbreak of acute hemorrhagic conjunctivitis in southern Florida. Am J Ophthalmol. Jan 1983;95(1):45-54. [Medline].

  29. Arnow PM, Hierholzer JC, Higbee J. Acute hemorrhagic conjunctivitis: A mixed virus outbreak among Vietnamese refugees on Guam. Am J Epidemiol. 1977;105:69.

  30. Marier R, Rodriguez W, Chloupek RJ, Brandt CD, Kim HW, Baltimore RS. Coxsackievirus B5 infection and aseptic meningitis in neonates and children. Am J Dis Child. Mar 1975;129(3):321-5. [Medline].

  31. Berlin LE, Rorabaugh ML, Heldrich F, Roberts K, Doran T, Modlin JF. Aseptic meningitis in infants < 2 years of age: diagnosis and etiology. J Infect Dis. Oct 1993;168(4):888-92. [Medline].

  32. Rorabaugh ML, Berlin LE, Heldrich F, et al. Aseptic meningitis in infants younger than 2 years of age: acute illness and neurologic complications. Pediatrics. Aug 1993;92(2):206-11. [Medline].

  33. Huang CC, Liu CC, Chang YC, Chen CY, Wang ST, Yeh TF. Neurologic complications in children with enterovirus 71 infection. N Engl J Med. Sep 23 1999;341(13):936-42. [Medline].

  34. Cherry JL, Soriano F, Jahn CL. Search for perinatal enterovirus infection. Am J Dis Child. Sept/1968;116(3):245-50.

  35. Lukashev AN, Koroleva GA, Lashkevich VA, Mikhailov MI. [Enterovirus 71: epidemiology and diagnostics]. Zh Mikrobiol Epidemiol Immunobiol. May-Jun 2009;110-6. [Medline].

  36. Fowlkes AL, Honarmand S, Glaser C, et al. Enterovirus-associated encephalitis in the California encephalitis project, 1998-2005. J Infect Dis. Dec 1 2008;198(11):1685-91. [Medline].

  37. Roden VJ, Cantor HE, O'Connor DM, Schmidt RR, Cherry JD. Acute hemiphegia of childhood associated with Coxsackie A9 viral infection. J Pediatr. Jan 1975;86(1):56-8. [Medline].

  38. Whitley RJ, Cobbs CG, Alford CA Jr, et al. Diseases that mimic herpes simplex encephalitis. Diagnosis, presentation, and outcome. NIAD Collaborative Antiviral Study Group. JAMA. Jul 14 1989;262(2):234-9. [Medline].

  39. Barak Y, Schwartz JF. Acute transverse myelitis associated with ECHO type 5 infection. Am J Dis Child. Feb 1988;142(2):128. [Medline].

  40. Smith WG. Coxsackie B myopericarditis in adults. Am Heart J. Jul 1970;80(1):34-46. [Medline].

  41. Koontz CH, Ray CG. The role of Coxsackie group B virus infections in sporadic myopericarditis. Am Heart J. Dec 1971;82(6):750-8. [Medline].

  42. Kono R, Uchida Y. Acute hemorrhagic conjunctivitis. Ophthalmol Dig. 1977;39:14.

  43. Rotbart HA, Brennan PJ, Fife KH, et al. Enterovirus meningitis in adults. Clin Infect Dis. Oct 1998;27(4):896-8. [Medline].

  44. Modlin JF, Dagan R, Berlin LE, Virshup DM, Yolken RH, Menegus M. Focal encephalitis with enterovirus infections. Pediatrics. Oct 1991;88(4):841-5. [Medline].

  45. Begier EM, Oberste MS, Landry ML, et al. An outbreak of concurrent echovirus 30 and coxsackievirus A1 infections associated with sea swimming among a group of travelers to Mexico. Clin Infect Dis. Sep 1 2008;47(5):616-23. [Medline].

  46. Pozzetto B, Gaudin OG, Aouni M, Ros A. Comparative evaluation of immunoglobulin M neutralizing antibody response in acute-phase sera and virus isolation for the routine diagnosis of enterovirus infection. J Clin Microbiol. Apr 1989;27(4):705-8. [Medline].

  47. Trabelsi A, Grattard F, Nejmeddine M, Aouni M, Bourlet T, Pozzetto B. Evaluation of an enterovirus group-specific anti-VP1 monoclonal antibody, 5-D8/1, in comparison with neutralization and PCR for rapid identification of enteroviruses in cell culture. J Clin Microbiol. Sep 1995;33(9):2454-7. [Medline].

  48. Rotbart HA, Sawyer MH, Fast S, et al. Diagnosis of enteroviral meningitis by using PCR with a colorimetric microwell detection assay. J Clin Microbiol. Oct 1994;32(10):2590-2. [Medline].

  49. Halonen P, Rocha E, Hierholzer J, et al. Detection of enteroviruses and rhinoviruses in clinical specimens by PCR and liquid-phase hybridization. J Clin Microbiol. Mar 1995;33(3):648-53. [Medline].

  50. Archimbaud C, Chambon M, Bailly JL, et al. Impact of rapid enterovirus molecular diagnosis on the management of infants, children, and adults with aseptic meningitis. J Med Virol. Jan 2009;81(1):42-8. [Medline].

  51. Avner E, Satz J, Plotkin SA. Hypoglycorrhachia in young infants with viral meningitis. J Pediatr. 1975;87:883.

  52. Xiao XL, Wu H, Li YJ, et al. Simultaneous detection of enterovirus 70 and coxsackievirus A24 variant by multiplex real-time RT-PCR using an internal control. J Virol Methods. Jul 2009;159(1):23-8. [Medline].

  53. Garg A, Shiau J, Guyatt G. The ineffectiveness of immunosuppressive therapy in lymphocytic myocarditis: an overview. Ann Intern Med. Aug 15 1998;129(4):317-22. [Medline].

  54. Goland S, Czer LS, Siegel RJ, et al. Intravenous immunoglobulin treatment for acute fulminant inflammatory cardiomyopathy: series of six patients and review of literature. Can J Cardiol. Jul 2008;24(7):571-4. [Medline].

  55. Rotbart HA, Webster AD. Treatment of potentially life-threatening enterovirus infections with pleconaril. Clin Infect Dis. Jan 15 2001;32(2):228-35. [Medline].

  56. [Best Evidence] Mason JW, O'Connell JB, Herskowitz A, et al. A clinical trial of immunosuppressive therapy for myocarditis. The Myocarditis Treatment Trial Investigators. N Engl J Med. Aug 3 1995;333(5):269-75. [Medline].

  57. Brunetti L, DeSantis ER. Treatment of viral myocarditis caused by coxsackievirus B. Am J Health Syst Pharm. Jan 15 2008;65(2):132-7. [Medline].

  58. Quartier P, Debre M, De Blic J, et al. Early and prolonged intravenous immunoglobulin replacement therapy in childhood agammaglobulinemia: a retrospective survey of 31 patients. J Pediatr. May 1999;134(5):589-96. [Medline].

  59. Kew O, Morris-Glasgow V, Landaverde M, et al. Outbreak of poliomyelitis in Hispaniola associated with circulating type 1 vaccine-derived poliovirus. Science. Apr 12 2002;296(5566):356-9. [Medline].

  60. Combined immunization of infants with oral and inactivated poliovirus vaccines: results of a randomized trial in The Gambia, Oman, and Thailand. WHO Collaborative Study Group on Oral and Inactivated Poliovirus Vaccines. J Infect Dis. Feb 1997;175 Suppl 1:S215-27. [Medline].

  61. Sutter RW, John TJ, Jain H, Agarkhedkar S, Ramanan PV, Verma H, et al. Immunogenicity of bivalent types 1 and 3 oral poliovirus vaccine: a randomised, double-blind, controlled trial. Lancet. Nov 13 2010;376(9753):1682-8. [Medline].

  62. Wadia NH, Katrak SM, Misra VP, et al. Polio-like motor paralysis associated with acute hemorrhagic conjunctivitis in an outbreak in 1981 in Bombay, India: clinical and serologic studies. J Infect Dis. Apr 1983;147(4):660-8. [Medline].

  63. McKinney RE Jr, Katz SL, Wilfert CM. Chronic enteroviral meningoencephalitis in agammaglobulinemic patients. Rev Infect Dis. Mar-Apr 1987;9(2):334-56. [Medline].

  64. Hyoty H. Enterovirus infections and type 1 diabetes. Ann Med. 2002;34(3):138-47. [Medline].

  65. Richer MJ, Horwitz MS. Coxsackievirus infection as an environmental factor in the etiology of type 1 diabetes. Autoimmun Rev. Jun 2009;8(7):611-5. [Medline].

  66. Galama JM, de Leeuw N, Wittebol S, Peters H, Melchers WJ. Prolonged enteroviral infection in a patient who developed pericarditis and heart failure after bone marrow transplantation. Clin Infect Dis. Jun 1996;22(6):1004-8. [Medline].

  67. Chakrabarti S, Osman H, Collingham KE, Fegan CD, Milligan DW. Enterovirus infections following T-cell depleted allogeneic transplants in adults. Bone Marrow Transplant. Feb 2004;33(4):425-30. [Medline].

  68. Agre JC, Rodríquez AA, Tafel JA. Late effects of polio: critical review of the literature on neuromuscular function. Arch Phys Med Rehabil. Oct 1991;72(11):923-31. [Medline].

  69. Aston JW Jr. Post-polio syndrome. An emerging threat to polio survivors. Postgrad Med. Jul 1992;92(1):249-56, 260. [Medline].

  70. Barnard DL. Current status of anti-picornavirus therapies. Curr Pharm Des. 2006;12(11):1379-90. [Medline].

  71. Bartfeld H, Ma D. Recognizing post-polio syndrome. Hosp Pract (Minneap). May 15 1996;31(5):95-7, 101-3, 107 passim. [Medline].

  72. Cardosa MJ, Perera D, Brown BA, Cheon D, Chan HM, Chan KP. Molecular epidemiology of human enterovirus 71 strains and recent outbreaks in the Asia-Pacific region: comparative analysis of the VP1 and VP4 genes. Emerg Infect Dis. Apr 2003;9(4):461-8. [Medline].

  73. Conrad DA, Jenson HB. New recommendations for poliovirus vaccination. Combination regimen captures best effects of available vaccines. Postgrad Med. Nov 1997;102(5):45-8, 51-3, 59-60 passim. [Medline].

  74. Desmond RA, Accortt NA, Talley L, Villano SA, Soong SJ, Whitley RJ. Enteroviral meningitis: natural history and outcome of pleconaril therapy. Antimicrob Agents Chemother. Jul 2006;50(7):2409-14. [Medline].

  75. Dowdle WR, Birmingham ME. The biologic principles of poliovirus eradication. J Infect Dis. Feb 1997;175 Suppl 1:S286-92. [Medline].

  76. Honeyman M. How robust is the evidence for viruses in the induction of type 1 diabetes?. Curr Opin Immunol. Dec 2005;17(6):616-23. [Medline].

  77. Hsiung GD, Wang JR. Enterovirus infections with special reference to enterovirus 71. J Microbiol Immunol Infect. Mar 2000;33(1):1-8. [Medline].

  78. Jubelt B, Agre JC. Characteristics and management of postpolio syndrome. JAMA. Jul 26 2000;284(4):412-4. [Medline].

  79. Lönnrot M, Korpela K, Knip M, et al. Enterovirus infection as a risk factor for beta-cell autoimmunity in a prospectively observed birth cohort: the Finnish Diabetes Prediction and Prevention Study. Diabetes. Aug 2000;49(8):1314-8. [Medline].

  80. Melnick JL. Enteroviruses: polioviruses, coxsackieviruses, echoviruses, and newer enteroviruses. In: Fields Virology. 3rd ed. Philadelphia, Pa: Lippincott-Raven; 1996:655-712.

  81. Modlin JF. Introduction to Enteroviruses. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases. 6th ed. Churchill Livingstone: New York; 2005.

  82. Patriarca PA, Foege WH, Swartz TA. Progress in polio eradication. Lancet. Dec 11 1993;342(8885):1461-4. [Medline].

  83. Pesonen E, Andsberg E, Ohlin H, Puolakkainen M, Rautelin H, Sarna S. Dual role of infections as risk factors for coronary heart disease. Atherosclerosis. Jun 2007;192(2):370-5. [Medline].

  84. Pevear DC, Tull TM, Seipel ME, Groarke JM. Activity of pleconaril against enteroviruses. Antimicrob Agents Chemother. Sep 1999;43(9):2109-15. [Medline].

  85. Racaniello VR. One hundred years of poliovirus pathogenesis. Virology. Jan 5 2006;344(1):9-16. [Medline].

  86. Roivainen M. Enteroviruses and myocardial infarction. Am Heart J. Nov 1999;138(5 Pt 2):S479-83. [Medline].

  87. Russell SJ, Bell EJ. Echoviruses and carditis. Lancet. Apr 11 1970;1(7650):784-5. [Medline].

  88. Sawyer MH. Enterovirus infections: diagnosis and treatment. Pediatr Infect Dis J. Dec 1999;18(12):1033-9; quiz 1040. [Medline].

  89. Skarsvik S, Puranen J, Honkanen J, Roivainen M, Ilonen J, Holmberg H. Decreased in vitro type 1 immune response against coxsackie virus B4 in children with type 1 diabetes. Diabetes. Apr 2006;55(4):996-1003. [Medline].

  90. Smith WG. Adult heart disease due to the Coxsackie virus group B. Br Heart J. Mar 1966;28(2):204-20. [Medline].

  91. Thorsteinsson G. Management of postpolio syndrome. Mayo Clin Proc. Jul 1997;72(7):627-38. [Medline].

  92. Webster AD. Pleconaril--an advance in the treatment of enteroviral infection in immuno-compromised patients. J Clin Virol. Jan 2005;32(1):1-6. [Medline].

  93. WHO. Resurgence of wild poliovirus type 1 transmission and effect of importation into polio-free countries, 2002-2005. Wkly Epidemiol Rec. Feb 17 2006;81(7):63-8. [Medline].

  94. Woodruff JF. Viral myocarditis. A review. Am J Pathol. Nov 1980;101(2):425-84. [Medline].

  95. Zaoutis T, Klein JD. Enterovirus infections. Pediatr Rev. Jun 1998;19(6):183-91. [Medline].

 
Previous
Next
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.