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Enterovirus are small non-enveloped isometric viruses that multiply in gastrointestinal tract (gut mucosa) and are transmitted from person to person by the faecal-oral route. They are spread throughout the body by the blood stream. Most infections occur during childhood(5-12) and they are usually transient but produce lifelong immunity. Clinical syndromes are generally mild, but occasional infections may cause serious disease e.g. paralytic poliomyelitis, meningitis, or myocarditis. There is a high degree of serological cross reactivity between the 72 members. (Dalldorf et al,1955)
Viruses belong to the family Picornaviridae (pico=SMALL - RNA viruses)
Polio 1, 2, 3
Coxsackie A 1-24
Coxsackie B 1-6
Entero 72 (Hepatitis A)
Rhino viruses: > 120 serotypes
Coxsackie virus: (also written as coxsackievirus) is a member of the Picornaviridae family of viruses in the genus termed Enterovirus. Coxsackie viruses are subtype members of Enterovirus that have a single strand of ribonucleic acid (RNA) for its genetic material.
Coxsackie is a collection of closely related viruses classified among the enteroviruses. The coxsackie viruses were named after the town Coxsackie inNew York. A strain of this virus was discovered there during the investigation of an epidemic that occurred in 1949 together with a polio epidemic (polio being another enterovirus).
The first isolates of what are now termed coxsackieviruses were made from the feces of two boys suffering from paralytic poliomyelitis who lived in the village of Coxsackie, New York (Dalldorf and Sickles 1948). These two isolates were not neutralized by antisera against polioviruses and provided the first evidence of the existence of a large number of human enteric viruses, many of which caused no apparent disease and so were called "enteric cytopathic human orphan" or choviruses. However, the coxsackieviruses had in common the property of being highly pathogenic on injection into newborn mice and hamsters, and within 1 year following their discovery it was found that some isolates of coxsackievirus induced more severe pathological changes, such as generalized skeletal muscle destruction, than others (Gifford and Dalldorf 1951). On this basis, the viruses were divided into two groups termed A and B, with group B viruses causing the more severe symptoms.
As further coxsackieviruses were isolated, they were assigned to one of the two
groups and given sequential numbers (Dalldorf 1955).
In 1958, coxsackieviruses of group B were found to have caused epidemic myocarditis in newborn infants in South Africa (Gear and Measroch 1958), and it was
realized that these viruses had a worldwide distribution. Coxsackie B viruses were found to be responsible for cases of pleurodynia in South Africa (Patz et al. 1953) including a laboratory accident in which a worker infected with coxsackie B2 virus
developed pleurodynia and aseptic meningitis (Curnen 1950). Pleurodynia is also called epidemic myalgia, devil's grippe, or Bornholm's disease, named after anepidemic on the Danish island of Bornholm, and an outbreak of this disease in Oxford, England was shown to be due to coxsackie B3 virus (Warin et al. 1953).
Despite the subsequent discovery of more than 100 human enteroviruses, 23 of which are classified as serotypes of coxsackievirus A, only six serotypes of coxsackievirus B have been recognized. One of these serotypes, B5, is now believed to be virtually identical to the porcine enterovirus, swine vesicular disease virus, based on genome sequence analysis, and is now classified as a subspecies of Coxsackievirus B5, which is itself regarded as a strain of Human enterovirus B. Coxsackievirus B5 was first identified in 1952 in the feces of a patient with mild paralytic disease, and vesicular disease was first recognized in pigs in Italy in 1966 and subsequently shown to be caused by an enterovirus and named swine vesicular disease (Nardelli et al. 1968). The importance of swine vesicular disease virus (SVDV) is that, although it causes only low morbidity and mortality in pigs, it is highly contagious and induces lesions that are clinically indistinguishable from those seen in pigs infected with the economically important foot-and-mouth disease virus. Attempts have been made to induce clinical lesions in pigs with human coxsackie B5 virus, with little success, and the molecular basis for the differences in pathogenesis between the viruses is not presently understood (Seechurn et al. 1990; Zhang et al. 1993).
Man is the only natural host for human enteroviruses. The virus replicates in the upper and lower alimentary tract and is excreted from these sites. Enteroviruses spread mainly by the faecal-oral route, and during the acute stage also by the respiratory route. They have a worldwide distribution. In the temperate zones spread takes place in the summer and autumn months, in tropical and subtropical zones throughout the year. Children are infected more frequently than adults, and males somewhat more frequently than females. Poor sanitary conditions will favour spread of these viruses. (Haaheim et al,2002)
Enteroviruses spread from person to person mainly by the faecal-oral route, and to a lesser degree by the respiratory route. Some types associated with conjunctivitis spread by direct contact. The incubation period is 5-14 (2-25) days. Enterovirus conjunctivitis has an incubation period of 12-24 hours. (Pattison et al 2002)
2.6.SYMPTOMS AND SIGNS:
The coxsackieviruses multiply primarily in lymphoid tissue in the pharynx and the small intestine. In about 5% of cases virus may spread to other target organs, the main ones being the meninges, the brain and spinal cord, myocardium and pericardium, striated muscles and skin.Infection leads to lasting type-specific immunity. Fever of short duration and sometimes a rash or mild upper respiratory symptoms are the most frequent clinical diseases. A few cases progress to one of the following syndromes:
2.6.1Aseptic meningitis. In typical cases a biphasic course is seen.After an interval of
1-2 days with few or no symptoms, the temperature rises again to 38-39.8C, accompanied by headache, neck stiffness and vomiting. A non-specific maculopapular rash, sometimes with petechial elements, may be seen. The illness may last for 2-10 days, sometimes followed by a convalescent phase of rather long duration. The prognosis is good as most patients recover completely.
2.6.2 Meningoencephalitis or encephalitis may occur in some cases. (Oram et al,2000)
2.7.1.Epidemic myalgia/pleurodynia (Bornholm disease): This is a painful inflammation of the muscles, most pronounced in the intercostal muscles or abdominal muscles, accompanied by pain that may be severe (devil's grip) and resemble ischaemic heart disease or 'acute abdomen'. The pain is often intermittent for periods of 2-10 hours, combined with rise in temperature. The illness lasts for 4-6 days, but relapses in the following weeks are not infrequent. Complete recovery is the rule. Myocarditis/pericarditis: This is observed in 5% of patients with coxsackie B virus infections. Typical features are fever, chest pain and dyspnoea. Other signs are pericardial rub, heart dilatation and arrhythmias. Heart failure may occur. The illness usually lasts for 1-2 weeks. Relapse may occur during the following weeks and months in 20% of patients. The most important differential diagnoses are cardiac ischaemia, infarction and myopericarditis of other aetiology. Neonatal myocarditis. Some enteroviruses, mostly coxsackie B3 and 4, may cause a severe, often fatal disease in infants characterized by sudden onset, lethargy, tachycardia, dyspnoea and cyanosis. It is a systemic infection as many organs (heart, brain, liver, pancreas) are involved. The virus is transmitted from mother to child just before or at birth. (Pattison et al 2002)
2.7.2.Herpangina: The illness is seen mainly in children. Some 8-10 vesicles or small ulcers, 1-3mm in diameter, are seen on the posterior pharyngeal wall. There is pain on swallowing and usually slight fever of a few days' duration. Differential diagnoses are herpes simplex, varicella, aphthous stomatitis.
2.7.3.Hand, foot and mouth disease: This occurs most often in children. Moderate fever of 38-398C may be seen. Vesicles up to 5mm in diameter are localized on the buccal mucosa and tongue as well as on the hands and feet.
2.7.4.Rashes: Maculopapular rashes ('rubelliform' or non-specific) are seen quite frequently in coxsackie A and echovirus infections, accompanied by pharyngitis and fever. A rash is sometimes seen in the course of meningitis.
Differential diagnoses are erythema infectiosum, rubella, measles and rashes seen in meningococcal disease. (Pattison et al 2002)
2.7.5.Acute haemorrhagic conjunctivitis: This eye disease is characterized by pain, swelling of the eyelids and subconjunctival haemorrhages of a few days' duration, usually healing spontaneously in less than a week. It is highly contagious, with an incubation time of 12-24 hours, and spreads by direct contact. Extensive epidemics have been observed in the Far East (caused by coxsackie A type 24) and in Africa, Japan and India (enterovirus type 70). Spread is favoured by poor hygienic conditions as in refugee camps. Associated neurological disease (radiculomyelopathy, cranial nerve involvement) occurs rarely and may lead to residual paralysis. .(Kimberlin et al,2001)
- Isolation of virus from stools, rectal swabs, nasopharynx samples, CSF, vesicular fluid and eye secretions has until recently been the most reliable method for laboratory diagnosis of an enterovirus infection. Several types of cell cultures may be used for isolation. Appearance of cytopathic effect (CPE) is observed after a few days, and neutralization tests are used for virus identification. Inoculation of coxsackie viruses into newborn mice will lead to disease and death. During the last years molecular virological methods such as PCR for the detection of enterovirus nucleic acid (RNA or DNA) have been developed, and nested PCR is considered to be more sensitive than virus isolation, particularly since some enterovirus strains do not grow or fail to show CPE in cell culture. Samples should be taken in the early phase of the disease since patients will usually excrete virus in the faeces for about 1 week (several weeks for children). Presence of virus is a strong indication of a causal relationship to disease. As virus shedding may be intermittent during the later phases of illness, a negative result does not exclude recent infection.
- Antibody investigations: A test for specific IgM is used in some laboratories and is considered to be the method of choice for coxsackievirus B infections. The CFT is easy to perform, but because of the occurrence of cross-reactions the CFT is of limited value for enterovirus diagnosis. (Davis, 1994)
It has long been recognised that picornavirus infection in cell culture could be inhibited by agents which bind stably to the virion, preventing cellular attachment, uncoating and intracellular delivery of the viral genome. Although a series of such compounds has been developed, to date only one agent, pleconaril, has sufficiently low toxicity to be a promising therapeutic agent (Romero, 2001). Pleconaril (3-[3,5-dimethyl-4[[3- (3-methyl-5-isoxazolyl)propyl]oly]phenyl]-5-(trifluoromethyl)-1,2,4-oxadiazole; Picovir) reduces viral replication and morbidity in animal models of enterovirus disease and in a Phase II clinical trial, reduced the duration and severity of picornavirus-related respiratory infections. Pleconaril is also effective in children and adults with enteroviral meningitis, although no benefit was observable in a study of infants under 1 year with meningitis. (Pattison et al 2002)
Prevention of Coxsackie virus infections is complicated process but possible. With children, keeping harsh hygienic safety measures is almost impossible, but good practice such as hand washing after diaper changing or touching infected skin may reduce viral transmission to other family members. Attempts to regularly clean items that children contact, especially toys, pacifiers, and any items they may place in their mouths, may also reduce viral transmission. Hand washing, in general, is the best prevention technique to avoid Coxsackie virus infections.
Currently, there is no vaccine available.