- Author: Martha L Muller, MD; Chief Editor: Michael Stuart Bronze, MD more...
Definitive diagnosis can be made based on isolation of the virus in cell culture. Cytopathic effect can usually be seen within 2-6 days. Samples are normally taken from the stool or rectal swabs but may be isolated from the oropharynx early in the disease course. False-positive culture results are possible, as excretion can occur for up to 8 weeks after initial infection. Serology can be difficult to interpret. Traditionally, enteroviral infections have been noted after a rise in neutralizing antibodies titer (at least a 4-fold rise in titer between acute and convalescent phase). PCR is also available, with a sensitivity of 66-90%.
The workup needs to rule out bacterial meningitis, and appropriate antibiotics should be administered until the workup is complete. Diagnosis requires cerebrospinal fluid (CSF) evaluation, which tends to show a lymphocytic predominance, normal-to-decreased glucose levels, and normal-to-slightly elevated protein levels. The virus can be isolated via cell culture (sensitivity, 30-35%) or PCR (sensitivity, 66-90%). A recent study in infants reported that routine CSF PCR for enteroviruses resulted in shorter hospital stays (by 1.54 days) and a decreased duration of antibiotic use (by 33%).
Diagnostic workup requires CSF evaluation, which yields findings similar to those of aseptic meningitis.
Diagnosis is generally circumstantial, with evidence of infection from the oropharynx, feces, or on serology.
Acute hemorrhagic conjunctivitis (AHC)
Diagnosis requires conjunctival swabs or scrapings, which are 90% successful. A rising antibody titer can be demonstrated.
Head CT scanning without contrast may be obtained upon initial presentation of meningitis and/or encephalitis to rule out hemorrhage, increased intracranial pressure, or mass lesions.
Echocardiography can be used to evaluate overall cardiac function and valvular disease in patients with myopericarditis and heart failure.
Obtain a throat culture to rule out streptococcal pharyngitis and/or tonsillitis.
HIV testing is always appropriate in patients who present with nonspecific febrile illness or rashes.
An EEG can be used to detect the presence of and localize seizure activity.
ECG changes in myopericarditis include ST-segment elevations or nonspecific ST segment, T-wave abnormalities, arrhythmia, and heart block.
Lumbar puncture is crucial in the evaluation of meningitis and/or encephalitis.
Skin biopsy may be helpful in the evaluation of nonspecific exanthems.
Obtain a Tzank smear to rule out herpes virus infection.
Intracytoplasmic viral particles may be observed, especially with skin lesions and/or rashes of HFM.
Lim BK, Ju ES, Lao DH, Yun SH, Lee YJ, Kim DK, et al. Development of a enterovirus diagnostic assay system for diagnosis of viral myocarditis in humans. Microbiol Immunol. 2013 Apr. 57(4):281-7. [Medline].
Muehlenbachs A, Bhatnagar J, Zaki SR. Tissue tropism, pathology and pathogenesis of enterovirus infection. J Pathol. 2014 Sep 11. [Medline].
Kadambari S, Bukasa A, Okike IO, Pebody R, Brown D, Gallimore C. Enterovirus infections in England and Wales, 2000-2011: the impact of increased molecular diagnostics. Clin Microbiol Infect. 2014 Jul 4. [Medline].
Khetsuriani N, Lamonte A, Oberste MS, et al. Neonatal enterovirus infections reported to the national enterovirus surveillance system in the United States, 1983-2003. Pediatr Infect Dis J. 2006 Oct. 25(10):889-93. [Medline].
Stewart CL, Chu EY, Introcaso CE, Schaffer A, James WD. Coxsackievirus A6-induced hand-foot-mouth disease. JAMA Dermatol. 2013 Dec. 149(12):1419-21. [Medline].
King RL, Lorch SA, Cohen DM, et al. Routine cerebrospinal fluid enterovirus polymerase chain reaction testing reduces hospitalization and antibiotic use for infants 90 days of age or younger. Pediatrics. 2007 Sep. 120(3):489-96. [Medline].
Schiff GM, Sherwood JR. Clinical activity of pleconaril in an experimentally induced coxsackievirus A21 respiratory infection. J Infect Dis. 2000 Jan. 181(1):20-6. [Medline].
Brunetti L, DeSantis ER. Treatment of viral myocarditis caused by coxsackievirus B. Am J Health Syst Pharm. 2008 Jan 15. 65(2):132-7. [Medline].
Yue-Chun L, LiSha G, Jiang-Hua R, Peng-Lin Y, Jia-Feng L, Ji-Fei T, et al. Protective effects of carvedilol in murine model with the coxsackievirus B3-induced viral myocarditis. J Cardiovas Pharmacol. Jan/2008. 51:92-98. [Medline].
Shi L, Xiong H, He J, et al. Antiviral activity of arbidol against influenza A virus, respiratory syncytial virus, rhinovirus, coxsackie virus and adenovirus in vitro and in vivo. Arch Virol. 2007. 152(8):1447-55. [Medline].
Ang LW, Koh BK, Chan KP, Chua LT, James L, Goh KT. Epidemiology and control of hand, foot and mouth disease in Singapore, 2001-2007. Ann Acad Med Singapore. 2009 Feb. 38(2):106-12. [Medline].
Bergman I, Painter MJ, Wald ER, et al. Outcome in children with enteroviral meningitis during the first year of life. J Pediatr. 1987 May. 110(5):705-9. [Medline].
Berlin LE, Rorabaugh ML, Heldrich F, et al. Aseptic meningitis in infants < 2 years of age: diagnosis and etiology. J Infect Dis. 1993 Oct. 168(4):888-92. [Medline].
Cheung CT, Deisher TA, Luo H, et al. Neutralizing anti-4-1BBL treatment improves cardiac function in viral myocarditis. Lab Invest. 2007 Jul. 87(7):651-61. [Medline].
Dagan R, Jenista JA, Menegus MA. Association of clinical presentation, laboratory findings, and virus serotypes with the presence of meningitis in hospitalized infants with enterovirus infection. J Pediatr. 1988 Dec. 113(6):975-8. [Medline].
Dagan R, Menegus MA. A combination of four cell types for rapid detection of enteroviruses in clinical specimens. J Med Virol. 1986 Jul. 19(3):219-28. [Medline].
Dulbecco R, Ginsberg H. Virology. 2nd ed. 1988. 207-209.
Enterovirus surveillance--United States, 2002-2004. MMWR Morb Mortal Wkly Rep. 2006 Feb 17. 55(6):153-6. [Medline].
Jaïdane H, Hober D. Role of coxsackievirus B4 in the pathogenesis of type 1 diabetes. Diabetes Metab. 2008 Dec. 34(6 Pt 1):537-48. [Medline].
Jenista JA, Powell KR, Menegus MA. Epidemiology of neonatal enterovirus infection. J Pediatr. 1984 May. 104(5):685-90. [Medline].
Levinson W, Jawetz E. Medical Microbiology & Immunology: Examination & Board Review. 6th ed. New York, NY: McGraw Hill Text; 2000. 238-239.
Mao Q, Wang Y, Yao X, Bian L, Wu X, Xu M, et al. Coxsackievirus A16: epidemiology, diagnosis, and vaccine. Hum Vaccin Immunother. 2014 Feb. 10(2):360-7. [Medline].
Modlin JF. Coxsackieviruses, Echoviruses, Newer Enteroviruses, and Parechoviruses. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 7th ed. Philadelphia, Pa: Churchill-Livingstone; 2009. 2353-2365.
Moore M. Centers for Disease Control. Enteroviral disease in the United States, 1970-1979. J Infect Dis. 1982 Jul. 146(1):103-8. [Medline].
Morens DM, Pallansch MA. Epidemiology. Human Enterovirus Infections. 1995. 1:
Morgan NG, Richardson SJ. Enteroviruses as causative agents in type 1 diabetes: loose ends or lost cause?. Trends Endocrinol Metab. 2014 Aug 28. [Medline].
Pallansch MA, Anderson LJ. Coxsackievirus, echovirus, and other enteroviruses. Gorbach SL, ed. Infectious Diseases. 2nd ed. Philadelphia, Pa: WB Saunders Co; 1998. 2164-2170.
Piqueur MA, Verstrepen WA, Bruynseels P, Mertens AH. Improvement of a real-time RT-PCR assay for the detection of enterovirus RNA. Virol J. 2009 Jul 7. 6:95. [Medline]. [Full Text].
Rantala H, Uhari M. Occurrence of childhood encephalitis: a population-based study. Pediatr Infect Dis J. 1989 Jul. 8(7):426-30. [Medline].
Richer MJ, Horwitz MS. Coxsackievirus infection as an environmental factor in the etiology of type 1 diabetes. Autoimmun Rev. 2009 Jun. 8(7):611-5. [Medline].
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 Aug. 92(2):206-11. [Medline].
Rotbart HA. Pleconaril therapy of potentially life-threatening enterovirus infections. 36th Annual Meeting of the Infectious Disease Society of America. 1998.
Rotbart HA. Pleconaril treatment of enterovirus and rhinovirus infections. Infect Med. 2000. 17:488.
Rotbart HA. Treatment of picornavirus infections. Antiviral Res. 2002 Feb. 53(2):83-98. [Medline].
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 Apr. 16(4):409-11. [Medline].
Rotbart HA, McCracken GH Jr, Whitley RJ, et al. Clinical significance of enteroviruses in serious summer febrile illnesses of children. Pediatr Infect Dis J. 1999 Oct. 18(10):869-74. [Medline].
Rotbart HA, Webster AD. Treatment of potentially life-threatening enterovirus infections with pleconaril. Clin Infect Dis. 2001 Jan 15. 32(2):228-35. [Medline].
Sauter P, Hober D. Mechanisms and results of the antibody-dependent enhancement of viral infections and role in the pathogenesis of coxsackievirus B-induced diseases. Microbes Infect. 2009 Apr. 11(4):443-51. [Medline].
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 Mar. 13(3):177-82. [Medline].
Tebruegge M, Curtis N. Enterovirus infections in neonates. Semin Fetal Neonatal Med. 2009 Aug. 14(4):222-7. [Medline].
Voroshilova MK, Chumakov MP. Poliomyelitis-like properties of AB-IV Coxsackie A7 group of viruses. Prog Med Virol. 1959. 2:106.
Weller TH, Enders JF, Buckingham M, et al. The etiology of epidemic pleurodynia: a study of two viruses isolated from a typical outbreak. J Immunol. 1950 Sep. 65(3):337-46. [Medline].
Yeung WC, Rawlinson WD, Craig ME. Enterovirus infection and type 1 diabetes mellitus: systematic review and meta-analysis of observational molecular studies. BMJ. 3 February 2011. 342:1-9. [Medline]. [Full Text].