COXSACKIEVIRUSES
المؤلف:
Stefan Riedel, Jeffery A. Hobden, Steve Miller, Stephen A. Morse, Timothy A. Mietzner, Barbara Detrick, Thomas G. Mitchell, Judy A. Sakanari, Peter Hotez, Rojelio Mejia
المصدر:
Jawetz, Melnick, & Adelberg’s Medical Microbiology
الجزء والصفحة:
28e , p537-540
2025-12-08
65
Coxsackieviruses, a large subgroup of the enteroviruses, were divided into two groups, A and B, having different pathogenic potentials for mice. They are now classified into HEV groups A, B, and C. They produce a variety of illnesses in humans, including aseptic meningitis and respiratory and undifferentiated febrile illnesses. Herpangina (vesicular pharyngitis), hand-foot-and-mouth disease, and acute hemorrhagic conjunctivitis are caused by certain coxsackievirus group A serotypes; pleurodynia (epidemic myalgia), myocarditis, pericarditis, and severe generalized disease of infants are caused by some group B coxsackieviruses. In addition to these, a number of group A and B serotypes can give rise to meningoencephalitis and paralysis. Generally, paralysis produced by nonpolio enteroviruses is incomplete and reversible. Coxsackie B viruses are the most commonly identified causative agents of viral heart disease in humans (Table 1). The coxsackieviruses tend to be more pathogenic than the echoviruses. Some of the more recent isolates of enteroviruses exhibit properties similar to the coxsackieviruses.
Table1. Human Enteroviruses and Parechoviruses and Commonly Associated Clinical Syndromes a
Properties of the Virus
Coxsackieviruses are highly infective for newborn mice, in contrast to most other human enteroviruses. Certain strains (B1–6, A7, 9, 16, and 24) also grow in monkey kidney cell culture. Some group A strains grow in human amnion and human embryonic lung fibroblast cells. Type A14 produces poliomyelitis-like lesions in adult mice and in monkeys but only myositis in suckling mice. Type A7 strains produce paralysis and severe CNS lesions in monkeys. Group A viruses produce widespread myositis in the skeletal muscles of newborn mice, resulting in flaccid paralysis without other observable lesions. The genetic makeup of inbred strains of mice deter mines their susceptibility to coxsackie B viruses.
Pathogenesis and Pathology
Virus has been recovered from the blood in the early stages of natural infection in humans. Virus is also found in the throat for a few days early in the infection and in the stools for up to 5–6 weeks. Virus distribution is similar to that of the other enteroviruses.
Clinical Findings
The incubation period of coxsackievirus infection ranges from 2 to 9 days. The clinical manifestations of infection with various coxsackieviruses are diverse and may present as dis tinct disease entities. They range from mild febrile illness to CNS, skin, cardiac, and respiratory diseases. The examples shown are not all-inclusive; different serotypes may be associated with a particular outbreak.
Aseptic meningitis is caused by all types of group B coxsackieviruses and by many group A coxsackieviruses, most commonly A7 and A9. Fever, malaise, headache, nausea, and abdominal pain are common early symptoms. The disease sometimes progresses to mild muscle weakness suggestive of paralytic poliomyelitis. Patients almost always recover completely from nonpoliovirus paresis.
Herpangina is a severe febrile pharyngitis that is caused by certain group A viruses. Despite its name, it has nothing to do with herpesviruses. There is an abrupt onset of fever and sore throat with discrete vesicles on the posterior half of the palate, pharynx, tonsils, or tongue. The illness is self-limited and most frequent in small children.
Hand-foot-and-mouth disease is characterized by oral and pharyngeal ulcerations and a vesicular rash of the palms and soles that may spread to the arms and legs. Vesicles heal without crusting, which clinically differentiates them from the vesicles of herpesviruses and poxviruses. This disease has been associated particularly with coxsackievirus A16 but also with B1 (and enterovirus 71). Coxsackievirus A6 has also emerged as a cause of severe hand-foot-and-mouth disease, sometimes followed by nail shedding. Virus may be recovered not only from the stool and pharyngeal secretions but also from vesicular fluid. It is not to be confused with foot and-mouth disease of cattle, which is caused by an unrelated picornavirus that does not normally infect humans.
Pleurodynia (also known as epidemic myalgia) is caused by group B viruses. Fever and stabbing chest pain are usually abrupt in onset but are sometimes preceded by malaise, headache, and anorexia. The chest pain may last from 2 days to 2 weeks. Abdominal pain occurs in approximately half of cases, and in children, this may be the chief complaint. The illness is self-limited and recovery is complete, although relapses are common.
Myocarditis is a serious disease. It is an acute inflammation of the heart or its covering membranes (pericarditis). Coxsackievirus B infections are a cause of primary myocardial disease in adults as well as children. About 5% of all symptomatic coxsackievirus infections induce heart disease. Infections may be fatal in neonates or may cause permanent heart damage at any age. Persistent viral infections of heart muscle may occur, sustaining chronic inflammation.
Enteroviruses are estimated to cause from 15% to 20% of respiratory tract infections, especially in the summer and fall. A number of coxsackieviruses have been associated with common colds and with undifferentiated febrile illnesses.
Generalized disease of infants is an extremely serious disease in which the infant is overwhelmed by simultaneous viral infections of multiple organs, including the heart, liver, and brain. The clinical course may be rapidly fatal, or the patient may recover completely. The disease is typically caused by group B coxsackieviruses. In severe cases, myocarditis or pericarditis can occur within the first 8 days of life; it may be preceded by a brief episode of diarrhea and anorexia. The disease may sometimes be acquired transplacentally.
Although the gastrointestinal tract is the primary site of replication for enteroviruses, they do not cause marked dis ease there. Certain group A coxsackieviruses have been associated with diarrhea in children, but causality is unproved.
Laboratory Diagnosis
A. Recovery of Virus
Virus can be isolated from throat washings during the first few days of illness and from stools during the first few weeks. In coxsackievirus A21 infections, the largest amount of virus is found in nasal secretions. In cases of aseptic meningitis, strains have been recovered from the cerebrospinal fluid as well as from the alimentary tract. In hemorrhagic conjunctivitis cases, A24 virus is isolated from conjunctival swabs, throat swabs, and feces.
Specimens can be inoculated into tissue cultures and suckling mice. In tissue culture, a cytopathic effect appears within 5–14 days. In suckling mice, signs of illness appear usually within 1–2 weeks. Because of the difficulty of the technique, virus isolation in suckling mice is rarely attempted.
B. Nucleic Acid Detection
Methods for the direct detection of enteroviruses provide rapid and sensitive assays useful for clinical samples. Reverse transcription PCR tests can be broadly reactive (detect many serotypes) or more specific. Such assays have advantages over cell culture methods because many enterovirus clinical iso lates have poor growth characteristics. Real-time PCR assays are comparable in sensitivity to conventional PCR assays but are less labor intensive to perform.
C. Serology
Neutralizing antibodies appear early during the course of infection, tend to be specific for the infecting virus, and persist for years. Serum antibodies can also be detected by other methods such as immunofluorescence. Serologic tests are difficult to evaluate (because of the multiplicity of virus types) unless the antigen used in the test has been isolated from a specific patient or during an epidemic outbreak.
Adults have antibodies against more types of coxsackie viruses than do children, indicating that multiple experiences with these viruses are common and increasingly so with age.
Epidemiology
Viruses of the coxsackie group have been encountered around the globe. Isolations have been made mainly from human feces, pharyngeal swabbings, and sewage. Antibodies to various coxsackieviruses are found in serum collected from per sons all over the world and in pooled immune globulin.
The most frequent types of coxsackieviruses recovered worldwide over an 8-year period (1967–1974) were types A9 and B2–B5. In the United States from 1970 to 2005, the most common coxsackievirus detections were types A9, B2, and B4 in endemic patterns and type B5 in an epidemic pattern. During 2006–2008, type B1 became the predominant enterovirus identified in the United States. However, in any given year or area, another type may predominate. Whereas an epi demic pattern is characterized by fluctuations in circulation levels, an endemic pattern shows stable, low-level circulation with few peaks.
Coxsackieviruses are recovered much more frequently in the summer and early fall. Children develop antibodies in the summer, indicating infection by coxsackieviruses during this period. Such children have much higher incidence rates for acute, febrile minor illnesses during the summer than children who fail to develop coxsackievirus antibodies.
Familial exposure is important in the acquisition of infections with coxsackieviruses. After the virus is introduced into a household, all susceptible persons usually become infected, although all do not develop clinically apparent disease.
The coxsackieviruses share many properties with other enteroviruses. Because of their epidemiologic similarities, various enteroviruses may occur together in nature even in the same human host or the same specimens of sewage.
Control
There are no vaccines or antiviral drugs currently available for prevention or treatment of diseases caused by coxsackieviruses; symptomatic treatment is given.
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