EVF
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Associations

Diseases and Conditions

This section provides an overview of recent research on the diseases and conditions associated with enteroviruses. Diseases associated with enteroviruses can be acute or chronic. Acute infections are of the "hit and run" type and are generally cleared rapidly by the immune system, although there are a percentage that can be very severe and life threatening.

We have provided information on specific diseases associated with enteroviruses and at least one reference to assist in finding more information. Some of these diseases are caused by enteroviruses; others have been linked and more research is required to determine the role of enterovirus with the disease.

Acute Hemorrhagic Conjuctivitis (AHC)

AHC is a highly contagious, occular infection characterized by pain and burning, swelling of the eyelids, the sensation of a foreign body in the eye, and subconjuctival hemorrhages . Fever, malaise, and headache may also be present. It is self-limiting, with symptoms typically improving in two or three days, and recovery within 7 to 10 days.

AHC can cause large-scale epidemics, with crowding and unsanitary conditions contributing to its spread. AHC was initially recognized in Ghana and Indonesia and is epidemic in India and the Far East. AHC can be caused by EV-70 and coxsackie A24.

For more information:
Pal, SR, Szucs, Gy, Melnick JL;(1983) "Rapid Immunofluorescence Diagnosis of Acute Hemorrhagic Conjunctivitis Caused by Enterovirus 70." Intervirology; 20:19-22 (DOI: 10.1159/000149369)

Arthritis, Seronegative

Seronegative arthritis is a classification given to the group of joint conditions with similar features to rheumatoid arthritis, but affecting different joints and lacking the specific autoantibodies used to identify rheumatoid arthritis. While not common, there have been associations made between this type of arthritis and enteroviruses.

For more information:
Hurst, NP, et at.; (1983) "Coxsackie B infections and arthritis" British Medical Journal, Vol 286, Feb 19, 1983. http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1546875&blobtype=pdf

Attention Deficit Hyperactivity Disorder (ADHD)

Attention Deficit Hyperactivity Disorder (ADHD) is a neurobehavioral developmental disorder characterized by a persistent pattern of impulsiveness and inattention, with or without a component of hyperactivity.

A clinical report in 2008 states that "children who had had an enterovirus 71 infection involving the central nervous system were significantly more likely to have symptoms of attention-deficit/hyperactivity disorder than were matched controls in a prospective study that evaluated children at 3-7 years after the infection."

For more information:
Mechcatie, E;( 2008) "ADHD symptoms linked to enteroviral infection, Pediatric News, Vol. Sep. http://findarticles.com/p/articles/mi_hb4384/is_9_42/ai_n29481482

Birth Defects and Problems During Pregnancy

Enteroviral infections during pregnancy have been associated with spontaneous abortion, stillbirth, and congenital anomalies. Defects of the cardiovascular, urogenital, and digestive systems have been associated with coxsackie B2, B3, B4 and A9, and cocksackie B viral antibodies have been found in infants with severe anatomic defects of the central nervous system.

For more information:
Palmer, AL, et al; (1997) "Adverse Effects of Maternal Enteroviral infection on the Fetus and Placenta" JID 1997;176 (December.) http://www.journals.uchicago.edu/doi/pdf/10.1086/514139

Cardiac Arrhythmia (also known as Dysrhythmia)

Cardiac arrhythmia is any of a large and heterogeneous group of conditions in which there is abnormal electrical activity in the heart. The heartbeat may be too fast or too slow, and may be regular or irregular. This is usually associated with Cocksackie B and EV-71.

For more information:
Pauschinger, M, et al; (1999) “Enteroviral RNA Replication in the Myocardium of Patients With Left Ventricular Dysfunction and Clinically Suspected Myocarditis,” Circulation. 1999;99: 889-895. http://www.circ.ahajournals.org/cgi/content/full/99/7/889

Chronic Fatigue Syndrome (CFS) - also known as Chronic Fatigue and Immune Dysfunction Syndrome (CFIDS) and Myalgic Encephalomyelitis (ME)

Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is a complex and debilitating illness that affects the brain and multiple body systems. Symptoms include widespread muscle and joint pain, cognitive difficulties, chronic, often severe mental and physical exhaustion and other characteristic symptoms in a previously healthy and active person.

A recent study found VP1, RNA and non-cytopathic viruses in the stomach biopsy specimens of CFS/ME patients with chronic abdominal complaints. A significant subset of CFS/ME patients may have a chronic, disseminated, non-cytolytic form of enteroviral infection, which could be diagnosed by stomach biopsy.

For more information:
Chia, JKS, Chia, AY;(2008), "Chronic fatigue syndrome is associated with chronic enteroviral infection of the stomach," Journal of Clinical Pathology 2008;61:43-48.

Coronary Heart Disease (CHD)

Coronary heart disease (CHD) is a narrowing of the small blood vessels that supply blood and oxygen to the heart. This restricts blood flow to the heart, starving it of the oxygen and vital nutrients it needs to work properly. Research suggests that enteroviral infection may increase the risk of CHD and myocardial infarction in those with normal cholesterol levels. CHD is associated with cocksackievirus group B.

For more information:
Roivainen, M, et al.;(2000) "Infections, inflammation, and the risk of coronary heart disease," Circulation. 2000 Jan 25;101(3):252-7. http://circ.ahajournals.org/cgi/content/full/101/3/252

Dermatomyositis (DM), Juvenile

Dermatomyositis is an autoimmune disease that damages the skin and muscles resulting in muscle weakness, pain, and fatigue. The affected person develops a distinctive patchy, reddish rash on the eyelids, cheeks, bridge of the nose, back or upper chest, elbows, knees, and knuckles. There may also be hardened, tender bumps under the skin. DM can occur at any age and is more common in females than males. This is usually related with coxsackie B.

For more information: Sontheimer, RD, et al., (2000),"Skin Disease In Dermatomyositis - What Patients And Their Families Should Know," Sept 2, 2000. http://tray.dermatology.uiowa.edu/dermatomyositis.htm

>Diabetes Mellitus Type 1 (Type I Diabetes, T1D, T1DM, IDDM, Juvenile Diabetes)

In type 1 diabetes the body does not produce insulin, a hormone needed to convert sugar, starches, and other food into energy needed for daily life. Type 1 diabetes is usually found in children and young adults.

Many studies have evaluated the role of enteroviral infections as environmental triggers of Type 1 diabetes. Although a causal association has not been established, enteroviral infection may increase susceptibility or hasten the onset of type 1 diabetes in children with impaired immunity or autoimmunity to pancreatic beta cells. The association is typically with coxsackieviruses B4 and B5.

For more information:
Drescher, KM, Tracy, S; (2008), "The CVB and Etiology of Type 1 Diabetes" Current Topics in Microbiology and Immunology Vol 323, pp259-274.

Dilated Cardiomyopathy (DCM)

Dilated cardiomyopathy is a condition where the main pumping chamber of the heart is enlarged and weakened, decreasing the ability to pump blood. Symptoms include chest pain, shortness of breath, fatigue, swelling of the lower extremities, weight gain, fainting, heart palpitations and dizziness or lightheadedness, and blood clots. The chances are even between improvement/maintenance of the disease or the need for heart transplantation to avoid death.

There are other triggers and causes of this disease besides enteroviruses. However, when related with enteroviral infections, DCM is usually associated with cocksackie B.

For more information:
Why, HJ, et al, (2001)"Clinical and prognostic significance of detection of enteroviral RNA in the myocardium of patients with myocarditis or dilated cardiomyopathy," Circulation 89: 2582-2589. http://www.circ.ahajournals.org/cgi/content/abstract/89/6/2582

Chapman, NM, et al., (2008) "terminal deletions in the genome of a coxsackievirus B2 strain occurred naturally in human heart," Virology. 2008 Jun 5;375(2):480-91.

Encephalitis

Encephalitis is an acute inflammation of the brain. While this is an uncommon manifestation of enteroviral infection, echovirus 9 is the most common etiologic agent. Echovirus 6, coxsackie A9, coxsackie B2, coxsackie B5, and poliovirus have also been implicated.

For more information:
Romero JR, (2008), :Pediatric group B coxsackievirus infections,” Current Topics in Microbiology and Immunology Vol 323, 223-240.

Exanthems, Viral

An exanthem is a widespread rash usually occurring in children. Exanthems are a frequent cause of emergency department visits and manifest as rubelliform or roseola-like rashes that occur in the summer months. These exanthems occur in children younger than 5 years and have a benign 3- to 5-day course. The responsible agents are usually echoviruses; however, group B coxsackieviruses have also been implicated.

For more information: Scott, LA, Stone, MS; (2003)," Viral exanthems," Dermatology Online Journal 9 (3): 4 http://dermatology.cdlib.org/93/reviews/viral/scott.html

Guillain-Barre Syndrome

Guillain-Barre Syndrome is an acute inflammatory demyelinating polyneuropathy (AIDP). It is an autoimmune disease affecting the peripheral nervous system usually triggered by an acute infectious process. Coxsackie and enteroviruses in general have been associated with this condition.

For more information:
Clement, O,et al.;(2000),"Enterovirus determination in cases with a diagnosis of the Guillain-Barr" syndrome by using the acid-concentration technic," Gac Med Mex 2000 Mar-Apr;136(2):93-7. http://www.ncbi.nlm.nih.gov/pubmed/10815319?dopt=Abstract

Hand, Foot, and Mouth Disease (HFMD)

Hand, foot, and mouth disease is a common viral illness of infants and children. The disease causes fever and blister-like eruptions in the mouth and/or a skin rash. Following an incubation period of 3-6 days, patients experience prodromal symptoms such as fever, cough, sore throat, malaise, and anorexia. After 12 to 36 hours, patients report vesicular eruptions of the hands, feet, and oral cavity. The lesions typically self-resolve within 5-7 days; however, this disease can be fatal. In 2008, 32 children died during a hand, foot, and mouth disease outbreak in China caused by EV-71.

Coxsackievirus A16 is the most common etiologic agent, although enterovirus 71 and numerous other coxsackievirus serotypes may also cause the disease.

For more information: "Hand foot and mouth disease," US Centers for Disease Control and Prevention, Division of Viral Diseases, http://www.cdc.gov/ncidod/dvrd/revb/enterovirus/hfhf.htm

Hepatitis

Hepatitis means "inflammation of the liver." Enteroviral hepatitis infections can range in severity from a mild illness lasting a few weeks to a severe illness lasting several months. This is associated with many enteroviruses.

For more information:
"Viral Hepitits," US Centers for Disease Control and Prevention, Division of Viral Diseases, http://www.cdc.gov/hepatitis/index.htm

Herpangina

Herpangina are painful vesicles on the posterior pharynx and tonsils usually in children ages 3 to 10. Symptoms include sudden onset of fever, sore throat, and difficulty swallowing, followed one day later by a painful vesicular eruption of the oral mucosa. This ulceration of tissue can occur in vaginal tissue as well. Patients may report anorexia, malaise, irritability, headache, backache, and diarrhea. Symptoms usually resolve in 3-4 days, but they can reoccur. Herpangina is typically associated with coxsackie A, coxsackie B, and echoviruses.

For more information:
Kramer, M,(2008) "Nonpolio Enteroviruses," Sribd. (Web site)http://www.scribd.com/doc/6624944/Non-Polio-Enteroviruses

Meningitis, Viral, also called Aseptic Meningitis

Meningitis is inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges. The clinical presentation of aseptic meningitis varies greatly among patients. Prodromal symptoms include fever, chills, headache, photophobia, and nuchal rigidity. Rash and upper respiratory symptoms are also common. Viral meningitis is not as dangerous as bacterial menegitis; the fever and meningeal signs subside within 2-7 days. Ninety percent of viral meningitis cases are due to enteroviral infections. Coxsackievirus B and echoviruses are the most common causes of viral meningitis; however, EV-71 causes a particularly aggressive central nervous system infection.

For more information:
"Viral Meningitis," Directors of Health Promotion and Education (Web site) http://www.dhpe.org/infect/vmenin.html

Myelitis

Myelitis is a disease involving inflammation of the spinal cord which disrupts central nervous system functions linking the brain and limbs. Symptoms vary by region of the CNS affected, and include fever, headaches, tingling, pain or loss of feeling, and may extend to central or peripheral paresis and loss of bladder control. Meningeal signs may develop. (Wikipedia, Myelitis, 2009) When related with enteroviruses, it is typically caused by poliovirus and EV-71.

For more information:
Kramer, Michael, MD, "Nonpolio Enteroviruses" http://www.scribd.com/doc/6624944/Non-Polio-Enteroviruses

Myocarditas, Viral

Myocarditis is the inflammation of the heart muscle. It can be a very serious or deadly disease, especially in neonates, young children, or strenuously exercising athletes. Myocarditis has been associated with coxsackievirus B4, coxsackievirus B5, and echoviruses.

For more information:
Why, HJ, et al, (2001) "Clinical and prognostic significance of detection of enteroviral RNA in the myocardium of patients with myocarditis or dilated cardiomyopathy," Circulation 89: 2582-2589. http://www.circ.ahajournals.org/cgi/content/abstract/89/6/2582

Kim K, Hofling K, Carson, SD, Chapman NM, Tracy S; (2003) “The Primary Viruses of Myocarditis,” Myocarditis from Bench to Bedside, LT Cooper, ed. (Humana Press) pp23-54.

Myopericarditis

Patients with myocarditis or pericarditis report chest pain, fatigue, and dyspnea on exertion. These symptoms can progress to dysrhythmia and heart failure. This disease can cause sudden death in otherwise healthy individuals.

The most common cause of cardiac involvement is coxsackievirus group B5 infection, but echoviruses are also etiologies of infection. Neonatal infections typically develop within the first week of life, and involvement is predominantly myocardial. In contrast, older children and adults usually present with symptoms of pericarditis.

This has been associated with coxsackie B, coxsackie A, echoviruses, and polioviruses.

For more information:
Kramer, M; "Nonpolio Enteroviruses," Scribd (Web site) http://www.scribd.com/doc/6624944/Non-Polio-Enteroviruses

Neonatal infections and sepsis

Neonates with nonpolio enteroviral infections are at a high risk of developing a sepsis-like condition, including meningoencephalitis, myocarditis, and hepatitis. Presenting symptoms include poor feeding, lethargy, fever, irritability, hypoperfusion, and jaundice. Differentiating these infections from bacterial sepsis is impossible. Infants younger than 10 days may be unable to mount a significant immune response and are at a higher risk of a serious infection from echoviruses and coxsackie group B viruses. Breast milk contains antibodies that can protect newborns.

For more information:
Abzug, MJ, Levin, MJ, Rotbart, HA; (1993) "Profile of enterovirus disease in the first two weeks of life," Pediatr Infect Dis J. 1993;12:820-824.

Nonspecific Febrile Illness

A nonspecific febrile illness is an illness with sudden fever (101 - 104 F) that may last a week. Additional symptoms may be myalgia, headache, sore throat, nausea, vomiting, mild abdominal discomfort, and diarrhea. This is the most common presentation of enteroviral infection.

For more information:
McCarthy, PL, Klig, JE, Kennedy, WP, Kahn, JS; (2000) "Fever without apparent source on clinical examination, lower respiratory infections in children, and enteroviral infections." Curr Opin Pediatr. 2000 Feb;12(1):77-95.

Pancreatitis

Pancreatitis is inflammation of the pancreas. This can be associated with any coxsackievirus B.

For more information:
"Our interest in acute and chronic pancreatitis," Enterovirus Research Laboratory at the University of Nebraska, (Web site) http://www.unmc.edu/dept/pathology/enteroviruslab/index.cfm?L1_ID=6&CONREF=6

De Palma, A, et al., (2008) "Increased gelatinase B/matrix metalloproteinase 9 (MMP-9) activity in a murine model of acute coxsackievirus B4-induced pancreatitis," Virology, Aug 27, 2008. http://www.unmc.edu/dept/pathology/Enteroviruslab/

Pleuodynia - also Bornholm disease, Devil Grippe

Pleuodynia is an acute illness characterized by fever and spasms of the chest and abdominal muscles. Multiple family members may be affected. Pleurodynia manifests with a sudden onset of fever accompanied by muscular pain in the chest and abdomen. The attacks are unpredictable and strike "out of the blue" with a feeling like an iron grip around the rib cage. The illness lasts about a week and is rarely fatal. Major epidemics reported at infrequent intervals, often 10 - 20 years.

Group B coxsackieviruses, particularly B3 and B5, are the most important causes of epidemic pleurodynia.

For more information:
Ikeda, RM, Kondracki, SF, Drabkin, PD, Birkhead, GS, Morse, DL.(1993) "Pleurodynia among football players at a high school. An outbreak associated with coxsackievirus B1." JAMA. 1993 Nov 10;270(18):2205-6.

Polio

Polio enteroviruses cause poliomyelitis, also called polio or infantile paralysis. This highly infectious viral disease may attack the central nervous system and is characterized by symptoms that range from a mild nonparalytic infection to total paralysis in a matter of hours. There is no cure for polio; however, it can be prevented. The polio vaccine, given multiple times, can protect a child for life. For more information: "Poliomyelitis," Wikipedia, Feb 4, 2009. http://en.wikipedia.org/wiki/Poliomyelitis

Rhombencephalitis

Rhombencephalitis is inflammation of the brain stem and has been associated with EV-71. Rhombencephalitis occurs during outbreaks of hand, foot, and mouth disease in the eastern hemisphere, particularly Taiwan, Japan, Malaysia, and Australia. Fatality rates have been as high as 14%.

For more information:
Fu ,YC, et al; (2004) "Cardiac complications of enterovirus rhombencephalitis." Arch Dis Child. 2004 Apr;89(4):368-73. http://adc.bmj.com/cgi/content/full/89/4/368