History
Polio
Disease due to wild-type poliovirus infection no longer occurs in the Western Hemisphere, and a World Health Organization (WHO) international eradication program is making significant progress in the rest of the world. [36]
Patients with abortive polio present with symptoms similar to those of other viral infections, including fever, headache, sore throat, loss of appetite, vomiting, and abdominal pain. Neurologic symptoms are typically not reported.
The symptoms of nonparalytic polio are similar to those of abortive polio but are more intense. Patients report stiffness of the posterior muscles of the neck, trunk, and limbs.
Paralytic polio
Paralytic polio presents similarly to nonparalytic polio. It is an acute febrile illness characterized by aseptic meningitis and weakness or paralysis of one or more extremities, along with weakness of one or more muscle groups. Exercise increases the severity of paralytic polio, especially during the first 3 days of the major illness. Intramuscular injections or skeletal muscle injury predisposes to localization of polio to that extremity (termed provocation poliomyelitis).
Spinal: Patients have a prolonged prodrome, with features of aseptic meningitis followed in 1-2 days by weakness and, eventually, paralysis.
Bulbar: Cranial nerves are involved, most commonly IX, X, and XII. Tonsillectomy increases the risk of bulbar polio. Patients are unable to swallow smoothly. They accumulate pharyngeal secretions, have a nasal twang to the voice, and develop paralysis of vocal cords, causing hoarseness, aphonia, and, eventually, asphyxia.
Polioencephalitis: This form is principally reported in children. Unlike in other forms of polio, seizures are common and paralysis may be spastic.
Nonpolio viruses
More than 90% of infections caused by the nonpolio enterovirus are asymptomatic or result only in an undifferentiated febrile illness. [2]
Pleurodynia
Group B coxsackieviruses, particularly B3 and B5, are the most important causes of epidemic pleurodynia. Multiple family members may be affected. [40, 41]
Pleurodynia manifestations include a sudden onset of fever accompanied by muscular pain in the chest and abdomen. [42] The pain is spasmodic in nature, with spasms lasting 15-30 minutes and worsening during inspiration or coughing. This paroxysmal pain is characteristically associated with fever, peaking within 1 hour after onset of each paroxysm and subsiding with the subsequent paroxysm. Headache, nausea, and vomiting are also frequently reported.
Myopericarditis
Enteroviruses appear to be the most common viral cause of myopericarditis and account for at least half of all cases of acute myopericarditis.
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.
The typical presentation in adolescents and adults is shortness of breath, chest pain, and fever 1-2 weeks following an upper respiratory tract infection. Chest pain may be dull or sharp; it is worsened by inspiration and may improve with sitting and leaning forward. It can be differentiated from angina by lack of response to nitroglycerin.
Enteroviral myocarditis can present as acute myocardial infarction associated with arrhythmias and heart failure. Some patients with myocardial infarction who have normal findings on coronary angiographic studies have been shown to have myocarditis by radiolabeled antimyosin antibody cardiac scanning. [43]
Acute hemorrhagic conjunctivitis
This highly contagious ocular infection can cause large-scale epidemics. AHC was first described in 1969. Enterovirus 70 is the most common etiology in epidemics. Coxsackievirus A24 causes a similar disease. AHC was initially recognized in Ghana and Indonesia and is now epidemic in India and the Far East. [44]
The first reported outbreak of AHC in United States was Key West, Florida, in 1981; subsequently, 2,500 cases were reported in Miami. Since then, with the exception of few imported cases, AHC activity has not been reported in the United States. [45]
The mode of transmission is from finger or fomite to eye. AHC is highly contagious, and crowding and unsanitary conditions favor spread. Reuse of water for bathing and sharing of towels have been implicated as factors contributing to the spread of infection. [46, 16]
Onset is abrupt, and the most common symptoms include ocular pain and burning, swelling of the eyelids, and the sensation of a foreign body in the eye. Patients may also experience photophobia and watery discharge. The other eye becomes involved within hours of the first eye.
Nonspecific symptoms such as fever, malaise, and headache may be present. The symptoms typically improve by the second or third day of infection, and recovery is complete within 7-10 days.
Nonspecific febrile illness
This is the most common presentation of enterovirus infection.
More than 90% present with a nonspecific febrile illness that manifests as sudden fever (temperature, 101-104°F). The fever may last for as long as a week and may show a biphasic pattern. [2]
Patients may also report myalgia, headache, sore throat, nausea, vomiting, mild abdominal discomfort, and diarrhea.
Human enterovirus 68 infection in children may produce a respiratory outbreak characterized by pneumonia and wheezing. [47]
Aseptic meningitis
Enteroviral infections (group B coxsackievirus and echovirus) account for 90% of cases of aseptic meningitis in patients younger than one year and 50% of cases in older children and adults. [48, 49]
The clinical presentations of aseptic meningitis vary greatly. Prodromal symptoms include fever, chills, headache, photophobia, and nuchal rigidity. Rash and upper respiratory tract symptoms may also occur. In infants, fever and irritability are the most common symptoms. [7]
Fever and meningeal signs subside within 2-7 days.
Enterovirus 71, which causes HFMD, has also been associated with a particularly more aggressive and, in some instances, fatal CNS infection in children. It manifests as flaccid motor paralysis and brain stem encephalitis. Large outbreaks were reported in the late 1990s in Eastern Europe, Russia, Thailand, and Taiwan. [50]
Most of the enterovirus-positive 758 children in a Korean outbreak experienced fever, headache, vomiting, and neck stiffness, although some also showed cold symptoms, sore throat, altered mental status, and seizures. [37] More than 80% of these had either echovirus types 6 or 30. The majority recovered uneventfully.
Herpangina
Coxsackie A virus is the main etiologic agent of herpangina, described as a vesicular enanthem of the tonsillar fauces and soft palate that principally affects children aged 3-10 years. [51] Other serotypes have been isolated including enterovirus 71 (EV71), which has cause recent outbreaks and epidemics in South-East Asia. [52]
Symptoms include sudden onset of fever, sore throat, and difficulty swallowing, followed a day later by a painful vesicular eruption of the oral mucosa. The posterior pharynx and tonsils may also be involved. Most disease occurs in the summer.
Patients may report anorexia, malaise, irritability, headache, backache, and diarrhea. Symptoms resolve in 3-4 days.
Hand-foot-and-mouth disease
This is mainly a disease of children; most patients are younger than 10 years. Epidemics of HFMD occur approximately every 3 years. It is a common and potentially but infrequently fatal in children under 5 years of age. [53] Seasonal trends and climatic factors may be evident and have been delineated in Guangzhou (Canton) China.
Coxsackievirus A16 is the most common etiologic agent, although enterovirus 71 and numerous other coxsackievirus serotypes may also cause the disease. [3]
Following an incubation period of 3-6 days, patients experience prodromal symptoms such as fever, cough, sore throat, malaise, and anorexia. The prodrome lasts from 12-36 hours; afterward, vesicular eruptions of the hands, feet, and oral cavity develop. This may cause decreased oral intake in young children. The lesions self-resolve within 5-7 days.
Infection with enterovirus 71 may be accompanied by severe neurologic disease including encephalitis, meningitis, and poliolike paralysis. [52]
Coxsackievirus A6 may have become the commonest enterovirus in seasonal outbreaks of hand-foot-and-mouth disease in children in France and Finland. [54]
Encephalitis
Frank encephalitis is an unusual manifestation of enterovirus infection. [55]
Echovirus 9 is the most common etiologic agent.
Clinical manifestations have ranged from lethargy, drowsiness, and personality change to seizures, paresis, and coma. Children with focal encephalitis present with partial motor seizures, hemichorea, and acute cerebellar ataxia; this may mimic herpes simplex encephalitis. [56, 57]
Nonpoliovirus paralytic disease
Enterovirus 71 and coxsackievirus A7 have been associated with large outbreaks of poliomyelitislike disease in Russia, Eastern Europe, Thailand, and Taiwan. [50] Some cases have manifested as brainstem encephalitis or noncardiogenic pulmonary edema, with some having a fatal course.
Paralytic disease caused by nonpolioviruses other than enterovirus 71 is usually less severe and is associated with paralysis. It manifests as muscle weakness and complete unilateral oculomotor palsy.
Guillain-Barré syndrome and transverse myelitis has been reported in a small number of patients infected with coxsackievirus serotypes A2, A5, A9, and B4 and with echovirus serotypes 5, 6, and 22. [58]
Neonatal infections
Refer to Medscape Reference article Pediatric Enteroviral Infections.
Physical
Physical examination findings in enteroviral disease vary greatly depending on the type of illness and etiologic agent, as follows:
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Nonspecific febrile illness: Physical findings are those of general viral illness; mild pharyngeal erythema or conjunctivitis may be present.
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Pleurodynia: Paroxysmal chest pain is characteristic, has no prodrome, and begins with an abrupt onset of spasmodic pain, typically over the lower part of the rib cage or the upper abdominal region. Fever often occurs within one hour of the onset of pain and subsides as the pain recedes. During paroxysms, respirations are rapid and shallow. The pain is reproducible, and patients appear healthy between paroxysms of pain. Auscultation may reveal a pleural friction rub.
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Myopericarditis: The most common symptoms are dyspnea, chest pain, fever, and malaise. [4] Pain in the precordial area maybe sharp or dull and is often exacerbated by the recumbency position. A pericardial friction rub is transient, if present. Signs of congestive heart failure are present in 20% of cases. [5]
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AHC: The hallmark physical findings include ocular erythema and subconjunctival hemorrhage, which seems to be more profuse in young patients. [6] Palpebral edema, chemosis, and ocular discharge may also be noted. Preauricular lymphadenopathy is an associated finding in AHC.
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Aseptic meningitis: Meningeal signs (nuchal rigidity, bulging fontanelles in infants) may be present, along with a positive Kernig and/or Brudzinski sign. Some patients develop a rash. Adults may experience a more prolonged period of headache and fever than children. [59] Approximately 5%-10% of infants with aseptic meningitis experience complications such as febrile seizures, complex seizures, lethargy, coma, and movement disorders early in the course. [7]
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Encephalitis: Manifestations range from lethargy, drowsiness, and personality change to seizures, paresis, coma, motor seizures, hemichorea, and acute cerebellar ataxia. [8]
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Herpangina: Examination of the oral mucosa reveals punctate macular lesions that evolve into vesicles and eventually ulcerate. The most common site of involvement is the anterior tonsillar pillar and soft palate (mimics pharyngitis or tonsillitis). The lesions are tender and subside within one week.
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HFMD: Vesicular lesions develop on the hands and feet and in the oral cavity. Hands are involved more commonly than feet. The skin lesions consist of mixed papules. Clear vesicles appear gray and are surrounded by erythematous rings. Lesions are tender and resemble those of herpes simplex or varicella zoster infection. They resolve in approximately 1 week.
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The coxsackievirus A6 (CVA6)–associated North American enterovirus outbreak of 2011-2012 was evaluated. [60] Atypical HFMD was noted as a vesiculobullous and erosive eruption, with 61% of patients having the rash involving more than 10% body surface area in a perioral, extremity, and truncal distribution in addition to palms, soles, and buttocks. In half the patients, there was an accentuation in areas of eczematous dermatitis. Other morphologic patterns included those of Gianotti-Crosti disease in 37% and petechial/purpuric eruptions in 17%.
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Poliomyelitis
Nonparalytic polio: Signs of meningeal irritation are present, and patients may have positive Kernig and Brudzinski signs. In infants, the head drop sign can be elicited.
Paralytic polio: In early-stage disease, reflexes are normally active. A change in the character of reflexes precedes paralysis by 12-24 hours. Superficial reflexes are the first to decrease, followed in 8-24 hours by loss of deep tendon reflexes. The resultant paralysis is flaccid and characteristically asymmetric in distribution. Proximal limb muscles are involved more than distal muscles. The lower extremities are affected more commonly than the upper extremities.
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Orchitis: In some remote cases, the presentation of coxsackievirus B infection clinically resembles mumps orchitis.
Causes
The most common mode of transmission of enteroviruses is via the fecal-oral route. Poor sanitation, low socioeconomic status, and crowded living conditions all facilitate the spread of infection. Direct contact with feces occurs with activities such as diaper changing. Indirect transmission due to poor sanitary conditions may occur via numerous routes, including via contaminated water, food, fingers, fomites, or contaminated ophthalmological instruments (eg, AHC).
Respiratory-oral spread may also be the mode of transmission for coxsackievirus A21 and other coxsackievirus serotypes.
Transmission of enteroviruses has been described among travelers swimming in sewage-contaminated seawater. [61]
