106 ENTEROVIRAL INFECTIONS
Harrison’s Manual of Medicine
Coxsackievirus, Echovirus, and Other Enteroviral Infections
Enteroviruses belong to the family of small, nonenveloped viruses with single- stranded RNA called picornaviruses. Their stability allows these viruses to survive in the presence of acid and standard disinfectants and to persist for days at room temperature. Enteroviruses include polioviruses, coxsackieviruses, echoviruses, and recently discovered agents so far designated simply as enteroviruses. Nearly 70 serotypes are known to infect humans via intestinal tract epithelium and lymphoid tissue. Although enteroviruses are shed in stool, the clinical syndromes they cause are not gastrointestinal.
EPIDEMIOLOGY Enteroviruses are distributed worldwide and commonly cause asymptomatic infection. In temperate climates, most infections occur in the late summer and fall. The common mode of transmission is via direct or indirect fecal-oral spread. Enterovirus infection is more common in areas of crowding and with poor hygiene. Incubation periods can be 2–14 d long but generally last for <1 week. More is known about poliovirus than about other enteroviruses. Poliovirus can persist in the oropharynx for up to 3 weeks after infection and can be shed in stool for up to 8 weeks; shedding by immunocompromised pts can persist for much longer.
PATHOGENESIS After ingestion, poliovirus is thought to infect epithelial cells in the mucosa of the GI tract and then to spread to submucosal lymphoid tissue. After spread to regional lymph nodes, the first (minor) viremic phase occurs, with replication in organs of the reticuloendothelial system. In some cases a secondary (major) viremic phase occurs. Virus enters the CNS either during viremia or via peripheral nerves.
CLINICAL MANIFESTATIONS Most poliovirus infections are mild or asymptomatic. Disease falls into three classes: (1) abortive poliomyelitis, a nonspecific febrile illness of 2–3 days’ duration with no signs of CNS localization; (2) nonparalytic poliomyelitis, aseptic meningitis with complete recovery in a few days (~1% of pts); and (3) paralytic poliomyelitis, the least common presentation. In paralytic poliomyelitis, signs of aseptic meningitis are followed after one or several days by severe back, neck, and muscle pain and by the development of motor weakness. In some cases the disease appears to be biphasic, with a period of apparent recovery following the aseptic meningitis. Weakness is generally asymmetric and may involve the legs, the arms, or the abdominal, thoracic, or bulbar muscles. Paralytic disease is more common among older individuals, pregnant women, and persons with muscle trauma (including that incurred by strenuous exercise) at the time of CNS symptoms. Paralysis develops during the febrile phase of the illness, and many pts recover some or all function. Findings include weakness, fasciculations, and absent or decreased deep-tendon reflexes; sensation is intact. Postpolio syndrome consists of progressive muscle weakness beginning 20–40 years after the original infection and is thought not to involve persistent or reactivated infection.
COXSACKIEVIRUS, ECHOVIRUS, AND OTHER ENTEROVIRAL INFECTIONS
Between 5 and 10 million symptomatic enteroviral infections occur in the U.S. each year, with different serotypes accounting for different types of disease.
CLINICAL MANIFESTATIONS Nonspecific Febrile Illness In contrast to other respiratory viral infections, enteroviral febrile illness generally occurs in the summer. After an incubation period of 3–6 d, pts present with an acute onset of fever, malaise, and headache, often accompanied by upper respiratory symptoms and sometimes by nausea and vomiting. Symptoms generally persist for 3–4 d; most resolve within a week.
Aseptic Meningitis Enteroviruses cause up to 90% of the cases of aseptic meningitis in children and young adults in which an etiology is identified. Pts present with fever, headache, photophobia, and stiff neck and may have signs of meningeal irritation and drowsiness or irritability but no localizing neurologic findings. CSF analysis shows pleocytosis, with an early predominance of PMNs sometimes making it difficult to exclude a diagnosis of bacterial meningitis (particularly if the infection has been partially treated). In enteroviral meningitis, a shift to lymphocyte predominance occurs within 24 h of presentation, and the total WBC count is generally <1000/µL. The CSF glucose level is usually normal, and the CSF protein concentration is normal or only slightly elevated. Symptoms generally resolve within a week, but CSF abnormalities may persist for several weeks. Enteroviral encephalitis occurs less commonly and generally carries a good prognosis except in immunocompromised pts, who may develop chronic meningitis or encephalitis.
Acute Myocarditis/Pericarditis Enteroviruses, most commonly coxsackievirus B, cause an estimated one-third of cases of acute myocarditis/pericarditis.
Generalized Disease of the Newborn Enteroviral infection of the heart, liver, adrenals, brain, and other organs may resemble bacterial sepsis and is highly lethal. Most disease occurs during the first week of life, although cases may occur up to 3 months of age.
Herpangina Usually caused by coxsackievirus A serotypes, herpangina involves mucous membranes and is characterized by the acute onset of fever and sore throat and the appearance of small white papules or vesicles over the posterior half of the palate.
Pleurodynia (Bornholm Disease) An acute onset of fever and intense lower thoracic or abdominal pain aggravated by breathing or movement characterizes this syndrome, which is usually caused by coxsackievirus B.
Hand-Foot-and-Mouth Disease This illness, often caused by coxsackievirus A16 or enterovirus 71, is characterized by fever, anorexia, and malaise followed by the development of vesicular lesions in the oral cavity and on the dorsum or palm of the hands. The disease is highly infectious, with attack rates close to 100% among young children. The lesions usually resolve in 1 week.
Other Illnesses Enteroviruses commonly cause exanthems in children in summer and early fall. A sudden onset of severe eye pain, blurred vision, photophobia, and watery discharge from the eye characterizes acute hemorrhagic enteroviral conjunctivitis, which is often caused by enterovirus 70 and coxsackievirus A24. Enteroviruses are uncommon causes of childhood pneumonia and the common cold.
DIAGNOSIS Enteroviral infections are most often diagnosed by isolation of virus from throat swabs, stool, or rectal swabs. However, isolation of virus from these sites does not prove an association with disease since many pts with subclinical infections are colonized. Isolation of virus from normally sterile body fluids (CSF, pleural or pericardial fluid) or from tissues is less common but diagnostic. PCR of CSF is highly sensitive and specific and is more rapid than culture. Serologic testing is usually reserved for epidemiologic studies since the large number of serotypes makes it expensive and cumbersome and the result has little clinical utility.
TREATMENT AND PREVENTION Treatment is supportive and directed at symptoms. Use of IV immunoglobulin remains controversial. Glucocorticoids are contraindicated. For polio, prevention is key. Two vaccines are licensed in the U.S.: inactivated (IPV) and live, oral, attenuated (OPV). OPV offers several advantages, including ease of administration, low cost, high efficacy, and induction of intestinal immunity. However, vaccine-associated paralytic poliomyelitis occurs at a rate of about 1 case per 2.6 million doses of OPV (a figure accounting for all cases of paralytic polio in the U.S.), and OPV must be avoided in immunosuppressed pts, including those infected with HIV and their family members. As of January 2000, the Advisory Committee for Immunization Practices suggested that children receive IPV for all four doses to further reduce the risk of vaccine-associated polio. OPV is to be used only in special circumstances (e.g., mass immunization campaigns).
For a more detailed discussion, see Cohen JI: Enteroviruses and Reoviruses, Chap. 193, p. 1138, in HPIM-15.