Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Clinical manifestations and diagnosis of enterovirus and parechovirus infections

John F Modlin, MD
Section Editors
Martin S Hirsch, MD
Morven S Edwards, MD
Deputy Editor
Allyson Bloom, MD


The human enteroviruses and parechoviruses are ubiquitous viruses found throughout the world, and are transmitted from person to person through fecal-oral contact [1]. Polioviruses, the prototypic enteroviruses, are the cause of paralytic poliomyelitis, a disease that has been eradicated in the United States and other developed countries (except for very rare cases that are attributable to live, attenuated polio vaccine viruses), and that is targeted for worldwide eradication.

The non-polio enteroviruses (group A and B coxsackieviruses, echoviruses, and enteroviruses) and parechoviruses continue to be responsible for a wide spectrum of disease in persons of all ages, although infection and illness occur most commonly in infants and young children.

The clinical manifestations and laboratory diagnosis of enterovirus and parechovirus infections will be reviewed here. The microbiology, epidemiology, pathogenesis, treatment, and prevention of these infections are discussed separately. (See "Epidemiology, pathogenesis, treatment, and prevention of enterovirus and parechovirus infections" and "Poliovirus vaccination".)


More than 90 percent of infections caused by the non-polio enteroviruses are asymptomatic or result only in an undifferentiated febrile illness [2]. When disease occurs, the spectrum and severity of clinical manifestations vary with the age, gender, and immune status of the host. Some clinical syndromes (viral meningitis and some exanthems) are caused by many enterovirus serotypes; others are predominantly caused by certain enterovirus subgroups (eg, pleurodynia and myocarditis due to the group B coxsackieviruses).

The spectrum of diseases attributed to parechoviruses is similar to that of the echoviruses, including fever, respiratory tract infections, exanthems, viral meningitis, encephalitis, myocarditis, and serious neonatal infections [3-10].


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Sep 2016. | This topic last updated: Sep 30, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
  1. Ooi MH, Wong SC, Lewthwaite P, et al. Clinical features, diagnosis, and management of enterovirus 71. Lancet Neurol 2010; 9:1097.
  2. Kogon A, Spigland I, Frothingham TE, et al. 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 1969; 89:51.
  3. Joki-Korpela P, Hyypiä T. Parechoviruses, a novel group of human picornaviruses. Ann Med 2001; 33:466.
  4. Harvala H, Robertson I, McWilliam Leitch EC, et al. Epidemiology and clinical associations of human parechovirus respiratory infections. J Clin Microbiol 2008; 46:3446.
  5. Verboon-Maciolek MA, Krediet TG, Gerards LJ, et al. Severe neonatal parechovirus infection and similarity with enterovirus infection. Pediatr Infect Dis J 2008; 27:241.
  6. Wolthers KC, Benschop KS, Schinkel J, et al. Human parechoviruses as an important viral cause of sepsislike illness and meningitis in young children. Clin Infect Dis 2008; 47:358.
  7. Abed Y, Boivin G. Human parechovirus types 1, 2 and 3 infections in Canada. Emerg Infect Dis 2006; 12:969.
  8. Harvala H, Wolthers KC, Simmonds P. Parechoviruses in children: understanding a new infection. Curr Opin Infect Dis 2010; 23:224.
  9. Levorson RE, Jantausch BA. Human parechoviruses. Pediatr Infect Dis J 2009; 28:831.
  10. Khatami A, McMullan BJ, Webber M, et al. Sepsis-like disease in infants due to human parechovirus type 3 during an outbreak in Australia. Clin Infect Dis 2015; 60:228.
  11. Bell EJ, Ross CA, Grist NR. ECHO 9 infection in pregnant women with suspected rubella. J Clin Pathol 1975; 28:267.
  12. LERNER AM, KLEIN JO, LEVIN HS, FINLAND M. Infections due to Coxsackie virus group A, type 9, in Boston, 1959, with special reference to exanthems and pneumonia. N Engl J Med 1960; 263:1265.
  13. SABIN AB, KRUMBIEGEL ER, WIGAND R. ECHO type 9 virus disease. AMA J Dis Child 1958; 96:197.
  14. NEVA FA. A second outbreak of Boston exanthem disease in Pittsburgh during 1954. N Engl J Med 1956; 254:838.
  15. NEVA FA, FEEMSTER RF, GORBACH IJ. Clinical and epidemiological features of an usual epidemic exanthem. J Am Med Assoc 1954; 155:544.
  16. Adler JL, Mostow SR, Mellin H, et al. Epidemiologic investigation of hand, foot, and mouth disease. Infection caused by coxsackievirus A 16 in Baltimore, June through September 1968. Am J Dis Child 1970; 120:309.
  17. Flett K, Youngster I, Huang J, et al. Hand, foot, and mouth disease caused by coxsackievirus a6. Emerg Infect Dis 2012; 18:1702.
  18. Stewart CL, Chu EY, Introcaso CE, et al. Coxsackievirus A6-induced hand-foot-mouth disease. JAMA Dermatol 2013; 149:1419.
  19. Chung WH, Shih SR, Chang CF, et al. Clinicopathologic analysis of coxsackievirus a6 new variant induced widespread mucocutaneous bullous reactions mimicking severe cutaneous adverse reactions. J Infect Dis 2013; 208:1968.
  20. Alexander JP Jr, Baden L, Pallansch MA, Anderson LJ. Enterovirus 71 infections and neurologic disease--United States, 1977-1991. J Infect Dis 1994; 169:905.
  21. Lum LC, Wong KT, Lam SK, et al. Fatal enterovirus 71 encephalomyelitis. J Pediatr 1998; 133:795.
  22. Huang CC, Liu CC, Chang YC, et al. Neurologic complications in children with enterovirus 71 infection. N Engl J Med 1999; 341:936.
  23. Chan KP, Goh KT, Chong CY, et al. Epidemic hand, foot and mouth disease caused by human enterovirus 71, Singapore. Emerg Infect Dis 2003; 9:78.
  24. Jiang M, Wei D, Ou WL, et al. Autopsy findings in children with hand, foot, and mouth disease. N Engl J Med 2012; 367:91.
  25. Cherry JD, Jahn CL. Herpangina: the etiologic spectrum. Pediatrics 1965; 36:632.
  26. FROTHINGHAM TE. ECHO virus type 9 associated with three cases simulating meningococcemia. N Engl J Med 1958; 259:484.
  27. CHERRY JD, LERNER AM, KLEIN JO, FINLAND M. Coxsackie A9 infections with exanthems, with particular reference to urticaria. Pediatrics 1963; 31:819.
  28. Marier R, Rodriguez W, Chloupek RJ, et al. Coxsackievirus B5 infection and aseptic meningitis in neonates and children. Am J Dis Child 1975; 129:321.
  29. Wilfert CM, Lauer BA, Cohen M, et al. An epidemic of echovirus 18 meningitis. J Infect Dis 1975; 131:75.
  30. 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.
  31. Huang C, Morse D, Slater B, et al. Multiple-year experience in the diagnosis of viral central nervous system infections with a panel of polymerase chain reaction assays for detection of 11 viruses. Clin Infect Dis 2004; 39:630.
  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 1993; 92:206.
  33. Rotbart HA, Brennan PJ, Fife KH, et al. Enterovirus meningitis in adults. Clin Infect Dis 1998; 27:896.
  34. Fowlkes AL, Honarmand S, Glaser C, et al. Enterovirus-associated encephalitis in the California encephalitis project, 1998-2005. J Infect Dis 2008; 198:1685.
  35. Hayward JC, Gillespie SM, Kaplan KM, et al. Outbreak of poliomyelitis-like paralysis associated with enterovirus 71. Pediatr Infect Dis J 1989; 8:611.
  36. Nagy G, Takátsy S, Kukán E, et al. Virological diagnosis of enterovirus type 71 infections: experiences gained during an epidemic of acute CNS diseases in Hungary in 1978. Arch Virol 1982; 71:217.
  37. Shindarov LM, Chumakov MP, Voroshilova MK, et al. Epidemiological, clinical, and pathomorphological characteristics of epidemic poliomyelitis-like disease caused by enterovirus 71. J Hyg Epidemiol Microbiol Immunol 1979; 23:284.
  38. Ho M, Chen ER, Hsu KH, et al. An epidemic of enterovirus 71 infection in Taiwan. Taiwan Enterovirus Epidemic Working Group. N Engl J Med 1999; 341:929.
  39. Xu J, Qian Y, Wang S, et al. EV71: an emerging infectious disease vaccine target in the Far East? Vaccine 2010; 28:3516.
  40. McMinn P, Stratov I, Nagarajan L, Davis S. Neurological manifestations of enterovirus 71 infection in children during an outbreak of hand, foot, and mouth disease in Western Australia. Clin Infect Dis 2001; 32:236.
  41. Chang LY, Tsao KC, Hsia SH, et al. Transmission and clinical features of enterovirus 71 infections in household contacts in Taiwan. JAMA 2004; 291:222.
  42. Chang LY, Huang LM, Gau SS, et al. Neurodevelopment and cognition in children after enterovirus 71 infection. N Engl J Med 2007; 356:1226.
  43. Kreuter JD, Barnes A, McCarthy JE, et al. A fatal central nervous system enterovirus 68 infection. Arch Pathol Lab Med 2011; 135:793.
  44. Ayscue P, Van Haren K, Sheriff H, et al.. Acute Flaccid Paralysis with Anterior Myelitis — California, June 2012–June 2014. MMWR Morb Mortal Wkly Rep 2014; 63 (Early Release):1.
  45. Greninger AL, Naccache SN, Messacar K, et al. A novel outbreak enterovirus D68 strain associated with acute flaccid myelitis cases in the USA (2012-14): a retrospective cohort study. Lancet Infect Dis 2015; 15:671.
  46. Pastula DM, Aliabadi N, Haynes AK, et al.. Acute Neurologic Illness of Unknown Etiology in Children — Colorado, August–September 2014. MMWR Morb Mortal Wkly Rep 2014; 63 (Early Release):1.
  47. Messacar K, Schreiner TL, Maloney JA, et al. A cluster of acute flaccid paralysis and cranial nerve dysfunction temporally associated with an outbreak of enterovirus D68 in children in Colorado, USA. Lancet 2015; 385:1662.
  48. 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 1983; 95:45.
  49. WARIN JF, DAVIES JB, SANDERS FK, VIZOSO AD. Oxford epidemic of Bornholm disease, 1951. Br Med J 1953; 1:1345.
  50. CURNEN EC, SHAW EW, MELNICK JL. Disease resembling nonparalytic poliomyelitis associated with a virus pathogenic for infant mice. J Am Med Assoc 1949; 141:894.
  51. 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 1950; 65:337.
  52. Bell EJ, Grist NR. ECHO viruses, carditis, and acute pleurodynia. Am Heart J 1971; 82:133.
  53. Smith WG. Adult heart disease due to the Coxsackie virus group B. Br Heart J 1966; 28:204.
  54. Verma NA, Zheng XT, Harris MU, et al. Outbreak of life-threatening coxsackievirus B1 myocarditis in neonates. Clin Infect Dis 2009; 49:759.
  55. Freund MW, Kleinveld G, Krediet TG, et al. Prognosis for neonates with enterovirus myocarditis. Arch Dis Child Fetal Neonatal Ed 2010; 95:F206.
  56. Centers for Disease Control and Prevention (CDC). Clusters of acute respiratory illness associated with human enterovirus 68--Asia, Europe, and United States, 2008-2010. MMWR Morb Mortal Wkly Rep 2011; 60:1301.
  57. Midgley CM, Jackson MA, Selvarangan R, et al.. Severe Respiratory Illness Associated with Enterovirus D68 — Missouri and Illinois, 2014. MMWR Morb Mortal Wkly Rep 2014; 63:1.
  58. Modlin JF. Enterovirus déjà vu. N Engl J Med 2007; 356:1204.
  59. Amstey MS, Miller RK, Menegus MA, di Sant 'Agnese PA. Enterovirus in pregnant women and the perfused placenta. Am J Obstet Gynecol 1988; 158:775.
  60. Johansson ME, Holmström S, Abebe A, et al. Intrauterine fetal death due to echovirus 11. Scand J Infect Dis 1992; 24:381.
  61. Modlin JF. Fatal echovirus 11 disease in premature neonates. Pediatrics 1980; 66:775.
  62. Brown GC, Karunas RS. Relationship of congenital anomalies and maternal infection with selected enteroviruses. Am J Epidemiol 1972; 95:207.
  63. Elizan TS, Ajero-Froehlich L, Fabiyi A, et al. Viral infection in pregnancy and congenital CNS malformations in man. Arch Neurol 1969; 20:115.
  64. Gauntt CJ, Gudvangen RJ, Brans YW, Marlin AE. Coxsackievirus group B antibodies in the ventricular fluid of infants with severe anatomic defects in the central nervous system. Pediatrics 1985; 76:64.
  65. Kinney JS, McCray E, Kaplan JE, et al. Risk factors associated with echovirus 11' infection in a hospital nursery. Pediatr Infect Dis 1986; 5:192.
  66. 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.
  67. Modlin JF, Kinney JS. Perinatal enterovirus infections. In: Advances in Pediatric Infectious Diseases, Aronoff SC, Hughes WT, Kohl S, et al (Eds), Year Book Medical Publishers, Chicago 1987.
  68. Lake AM, Lauer BA, Clark JC, et al. Enterovirus infections in neonates. J Pediatr 1976; 89:787.
  69. 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.
  70. 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.
  71. Jones MJ, Kolb M, Votava HJ, et al. Case reports. Intrauterine echovirus type II infection. Mayo Clin Proc 1980; 55:509.
  72. Reyes MP, Ostrea EM Jr, Roskamp J, Lerner AM. 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.
  73. YOSHIOKA I, HORSTMANN DM. Viremia infection due to ECHO virus type 9. N Engl J Med 1960; 262:224.
  74. Berry PJ, Nagington J. Fatal infection with echovirus 11. Arch Dis Child 1982; 57:22.
  75. Modlin JF, Bowman M. Perinatal transmission of coxsackievirus B3 in mice. J Infect Dis 1987; 156:21.
  76. Kaplan MH, Klein SW, McPhee J, Harper RG. Group B coxsackievirus infections in infants younger than three months of age: a serious childhood illness. Rev Infect Dis 1983; 5:1019.
  78. Gear JH, Measroch V. Coxsackievirus infections of the newborn. Prog Med Virol 1973; 15:42.
  79. 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.
  80. Georgieff MK, Johnson DE, Thompson TR, et al. Fulminant hepatic necrosis in an infant with perinatally acquired echovirus 21 infection. Pediatr Infect Dis J 1987; 6:71.
  81. Spector SA, Straube RC. Protean manifestations of perinatal enterovirus infections. West J Med 1983; 138:847.
  82. Speer ME, Yawn DH. Fatal hepatoadrenal necrosis in the neonate associated with echovirus types 11 and 12 presenting as a surgical emergency. J Pediatr Surg 1984; 19:591.
  83. Wreghitt TG, Gandy GM, King A, Sutehall G. Fatal neonatal echo 7 virus infection. Lancet 1984; 2:465.
  84. Johnston JM, Overall JC Jr. Intravenous immunoglobulin in disseminated neonatal echovirus 11 infection. Pediatr Infect Dis J 1989; 8:254.
  85. McKinney RE Jr, Katz SL, Wilfert CM. Chronic enteroviral meningoencephalitis in agammaglobulinemic patients. Rev Infect Dis 1987; 9:334.
  86. Sutter RW, Prevots DR. Vaccine-associated paralytic poliomyelitis among immunodeficient persons. Infect Med 1994; 11:426.
  87. Centers for Disease Control and Prevention (CDC). Prolonged poliovirus excretion in an immunodeficient person with vaccine-associated paralytic poliomyelitis. MMWR Morb Mortal Wkly Rep 1997; 46:641.
  88. O'Neil KM, Pallansch MA, Winkelstein JA, et al. Chronic group A coxsackievirus infection in agammaglobulinemia: demonstration of genomic variation of serotypically identical isolates persistently excreted by the same patient. J Infect Dis 1988; 157:183.
  89. Rotbart HA, Webster AD, Pleconaril Treatment Registry Group. Treatment of potentially life-threatening enterovirus infections with pleconaril. Clin Infect Dis 2001; 32:228.
  90. Aquino VM, Farah RA, Lee MC, Sandler ES. Disseminated coxsackie A9 infection complicating bone marrow transplantation. Pediatr Infect Dis J 1996; 15:1053.
  91. Biggs DD, Toorkey BC, Carrigan DR, et al. Disseminated echovirus infection complicating bone marrow transplantation. Am J Med 1990; 88:421.
  92. Galama JM, de Leeuw N, Wittebol S, et al. Prolonged enteroviral infection in a patient who developed pericarditis and heart failure after bone marrow transplantation. Clin Infect Dis 1996; 22:1004.
  93. MELNICK JL, SHAW EW, CURNEN EC. A virus isolated from patients diagnosed as non-paralytic poliomyelitis or aseptic meningitis. Proc Soc Exp Biol Med 1949; 71:344.
  94. GORDON RB, LENNETTE EH, SANDROCK RS. The varied clinical manifestations of Coxsackie virus infections: observations and comments on an outbreak in California. AMA Arch Intern Med 1959; 103:63.
  95. Trabelsi A, Grattard F, Nejmeddine M, et al. 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 1995; 33:2454.
  96. Dagan R, Menegus MA. A combination of four cell types for rapid detection of enteroviruses in clinical specimens. J Med Virol 1986; 19:219.
  97. Rotbart HA, Sawyer MH, Fast S, et al. Diagnosis of enteroviral meningitis by using PCR with a colorimetric microwell detection assay. J Clin Microbiol 1994; 32:2590.
  98. 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.
  99. Nolte FS. Case studies in cost effectiveness of molecular diagnostics for infectious diseases: pulmonary tuberculosis, enteroviral meningitis, and BK virus nephropathy. Clin Infect Dis 2006; 43:1463.
  100. Pozo F, Casas I, Tenorio A, et al. Evaluation of a commercially available reverse transcription-PCR assay for diagnosis of enteroviral infection in archival and prospectively collected cerebrospinal fluid specimens. J Clin Microbiol 1998; 36:1741.
  101. Yerly S, Gervaix A, Simonet V, et al. Rapid and sensitive detection of enteroviruses in specimens from patients with aseptic meningitis. J Clin Microbiol 1996; 34:199.
  102. 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.
  103. Mirand A, Henquell C, Archimbaud C, et al. Prospective identification of enteroviruses involved in meningitis in 2006 through direct genotyping in cerebrospinal fluid. J Clin Microbiol 2008; 46:87.
  104. Bell EJ, McCartney RA, Basquill D, Chaudhuri AK. Mu-antibody capture ELISA for the rapid diagnosis of enterovirus infections in patients with aseptic meningitis. J Med Virol 1986; 19:213.
  105. 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 1989; 27:705.
  106. Oberste MS, Maher K, Kilpatrick DR, et al. Typing of human enteroviruses by partial sequencing of VP1. J Clin Microbiol 1999; 37:1288.