Coxsackie virus infection
Introduction
Introduction to Coxsackie Virus Infection Coxsackie virus infection is a viral infectious disease caused by Coxsackie virus. The clinical manifestations are complex and diverse. There are aseptic meningitis, encephalitis, myocarditis, pericarditis, epidemic chest pain, herpes angina, etc. Some conditions are similar to polio. Coxsackie virus is a kind of enterovirus, which is divided into two types, A and B. It is usually spread or scattered in summer and autumn. The transmission route is through the digestive tract and respiratory tract, and can also be transmitted to the fetus through the placenta through blood. The virus begins to replicate in the intestinal and upper respiratory tract endothelial cells and lymphoid tissues, and is transmitted through the blood. Its tropic target organs are the central nervous system, heart, vascular endothelial cells, liver, pancreas, lung, reproductive organs, skeletal muscle, Skin mucosa, etc. basic knowledge The proportion of illness: 0.025% Susceptible people: no specific population Mode of infection: digestive tract transmission, respiratory tract transmission Complications: Myocarditis Meningitis
Cause
Coxsackie virus infection etiology
(1) Causes of the disease
Coxsackie virus belongs to the genus of enteroviruses of the picornavirus family. The virus particles are spherical or ovoid, 22 to 30 nm in diameter, and are round granular. The viral genome is single stranded linear RNA with a total length of about 6000. ~8500 bp, constitutes the core of the virus, the outer shell is a icosahedron, stereo symmetry, consisting of 32 shell particles, each shell contains four shell proteins VP1 ~ VP4 encoded by viral nucleic acid, and a viral gene protein Vpg is bound at the 5' end. After Vpg followed by a non-coding region of about 740 bp in length, Coxsackie virus was divided into A and B groups according to the lesions in the suckling mice. The original 24 serotypes in group A, of which type 23 was later There are 23 serotypes in the Echovirus type 9, and these serotypes can be distinguished by the neutralization test and the complement-binding test. The group A virus does not have a common antigen, but has cross-immunity between the types, such as There may be a cross-sero-reaction between A3 and A8, A11 and A15, A13 and A18; conversely, between the serotypes of 6 B viruses and A9, there is a common group antigen, except for a few strains, Koza Odd virus does not produce red blood cell agglutinin, so blood coagulation cannot be used Experimentation identified.
Coxsackie virus is highly pathogenic to newborn mice. Group A virus causes musculoskeletal myositis and flaccid paralysis and dies within 1 week. Group B virus can cause focal distribution of myositis and can cause Adipose tissue inflammation, encephalitis, myocarditis, pancreatitis, hepatitis and endocarditis, body tremors, spasms and tonic spasm often appear in suckling rats.
Older mice can tolerate group B virus infection, but pancreatitis can be induced by the use of adrenocortical hormone, which can cause serious disease in adult mice, including in the heart, spleen, liver, and brain. Persistent infection, lymphoid tissue atrophy, lymphocytes of immunocompetent mice are transferred to malnourished mice, which can protect the mice against B3 virus and prevent serious consequences.
A7, A9 and A16 viruses can also be grown in monkey kidney cell culture. Some group A strains can grow in human amnion cells, Hela cells or RD cell lines, but A1, A19 and A22 viruses fail to be in any cells. Propagation in culture, transient appearance in the blood, and excretion through feces for 2 to 5 weeks, A14 virus causes polio-like lesions in adult mice and monkeys, and A7 virus causes severe central nervous system lesions and paralysis in monkeys.
In cell culture, group B virus can cause cytopathic changes, the infected cells become rounded, shrinkage, nucleus pyknosis, reflection, and finally degenerate and fall off, and group A virus does not produce cytopathic effects.
(two) pathogenesis
After the virus enters the human body through the intestines or respiratory tract, it propagates and replicates in the small intestine, epithelial cells of the pharynx and nearby lymphoid tissues. After reaching a certain level, it invades the blood circulation and forms the first (secondary) viremia. At this time, the patient may appear. Mild discomfort or no symptoms, the virus enters various target tissues with blood flow, and continues to multiply in it, causing damage to the tissue cells; at the same time, it invades the blood circulation again (2nd or major viremia), making various target tissues Once again, it is attacked by viruses. Clinical symptoms usually occur after the occurrence of tissue damage and the second viremia.
In the latter stage of the incubation period or the prodromal period, and about 1 week thereafter, the virus can be isolated from the pharyngeal solution or throat swab, and the period of isolation of the virus from the stool or anal swab is longer, up to 2 A week later, a few cases were still positive even after 70 days of illness; the positive rate was the highest in the first week after the disease, and then gradually decreased, the virus can also be from the patient's cerebrospinal fluid, blister, blood, urine, Pleural effusion, pericardial fluid, bone marrow, etc. are detected, and viruses can be isolated in various organs such as heart, brain, liver, spleen, kidney, testis, muscle, etc. of the deceased.
The continuous reproduction and reproduction of the virus in the body produces an interferon that inhibits viral replication. When interferon and specific neutralizing antibodies appear in the blood, the virus disappears from the blood circulation, and secretion in saliva and intestinal secretions. Type IgA is the earliest of various immunoglobulins. It has the effect of suppressing the invasion of the virus from the digestive tract, and then IgM appears in the blood. It rises rapidly from the first week of the disease and falls within 3 to 4 weeks. When disappeared, the IgG-type neutralizing antibody appeared 7 to 14 days after infection, reached a peak within 3 to 4 weeks, and could be maintained for many years. The complement-binding antibody and the neutralizing antibody appeared simultaneously, but only for 2 to 3 months.
Some Coxsackie virus enters the human body through the respiratory tract and causes only upper respiratory tract infection without viremia. The virus is confined to the respiratory mucosal surface and is discharged along with respiratory secretions. There is no virus in the feces.
Tissue damage mainly produces inhibitory factors by intracellular replication of the virus, inhibits the synthesis of ribonucleic acid and protein, and causes cell destruction. However, in some enteroviruses, tissue damage caused by immune response may be the cause of disease prolongation, such as Early myocardial damage in myocarditis may be caused by viral replication, and later lesions are associated with immune responses.
The central nervous system lesions caused by Coxsackie and Echovirus are similar to those caused by poliovirus, but Coxsackie B virus can cause gray matter and white matter lesions. In infants, brain stems are often involved. .
Myocarditis caused by Coxsackie B virus is interstitial mononuclear cell infiltration with a certain degree of edema and myocardial fiber necrosis, left ventricular dilatation and hypertrophy, and some cases have pericarditis, which can cause endocarditis. Pericarditis is usually fibrinous, but it is also exudative. The endocardium can be seen in the heart of the heart, the heart valve is free, the edges are sacral, and the dense fibrous tissue and chronic inflammatory cells infiltrate under the microscope.
In addition, hepatitis (focal cell infiltration) and pancreatitis can be observed.
Prevention
Coxsackie virus infection prevention
Due to the excessive serotype of enterovirus (nearly 70 types), it is not possible to make an effective and feasible vaccine, and the preventive measures are far less effective than polio.
1. Manage the source of infection
Patients should be quarantined for 2 weeks. The focus of management of infectious sources should be placed in child care institutions and delivery rooms; pregnant women with intestinal viral diseases have a great threat to newborns and should be isolated.
2. Cut off the route of transmission
Strengthen food management and personal hygiene, do not eat food contaminated by dirty water or flies, avoid swimming in sewage, tap water should be boiled, drink, because the patient may discharge the virus in the oropharynx, wear masks when exposed to these patients, popular During the period, reduce the group activities, the patient's feces need to add 20% quicklime and chlorine-containing lime suspension, and then mix for 2h before they can be discharged into the sewer.
3. Protect susceptible people
Infants and young children who are exposed to the patient can be intramuscularly injected with 3 to 6 ml of gamma globulin to prevent infection. It is not necessary for older children and young people. Oral polio vaccine OPV can also be tried, using its interference in the intestine. It is possible to control the prevalence of meningitis. The use of Coxsackie B vaccines in high-risk populations may prevent the prevalence of infant myocarditis.
Complication
Coxsackie virus infection complications Complications Myocarditis meningitis
Severe cases can be combined with myocarditis, encephalitis, meningitis, secondary bacterial infection.
Symptom
Coxsackie virus infection symptoms common symptoms fatigue fatigue gastrointestinal symptoms sore throat rash nausea rash anorexia dyspnea
Because asymptomatic infections of enteroviruses are common, and viruses are often isolated only in feces and cannot be detected from the lesion, or only by serological examination, so in a few cases it can be determined that the clinical manifestation is In addition to the type of enterovirus, most cases can only be considered to be related to a certain enterovirus, and there are many different clinical manifestations:
1. herpetic angina (herpangina)
It is mainly caused by Coxsackie group A virus (A1A6, A8, A10, A22). Other group A viruses, B1B5 viruses are rare, and are common in children aged 1-7 years, which occur in summer and autumn. Sporadic morbidity or epidemic outbreaks, the same patient may repeat the disease caused by different types of viruses.
The incubation period is 3 to 6 days, with an average of about 4 days. It usually begins with sudden high fever (up to 40 °C), with severe sore throat, difficulty swallowing, increased salivation, decreased appetite, fatigue, etc. About 1/4 of the children have Vomiting and abdominal pain, sometimes headache, but the whole body muscle pain is not significant, in addition to sore throat, other respiratory symptoms such as rhinitis, cough, etc. are rare, occasionally horrified.
At the beginning of the pharynx congestion, visible scattered and more typical oral lesions, showing grayish white papules or macules, about 1 ~ 2mm in diameter, surrounded by blush, this mucosal rash is more common in the anterior column of the pharynx, soft palate, The sag (hanging sag), the tonsils, etc., but not in the gums, buccal mucosa and tongue surface, so it is significantly different from the herpes simplex virus caused by the number of rashes, from 1 to 2 to 10 to 20 The average is about 5, after 2 to 3 days, the surrounding redness expands, the color deepens, the blisters become larger and become gray or yellow ulcers with a diameter of no more than 5mm. In some cases, new herpes appears in batches, so both herpes can be seen at the same time. Ulcers, cervical lymph nodes are not swollen or mildly enlarged, individual female children with the same herpes in the vaginal mucosa, complications are rare, occasionally mumps, meningitis and so on.
The heat course of the disease is 1 to 4 days, with an average of 2 days. After the fever, the systemic and local symptoms are obviously improved. Most of the patients recover completely after 4 to 6 days, even or extended to 2 weeks.
Differential diagnosis: it should be differentiated from herpes simplex sputum sputum, which can occur in any part of the mouth. Coxsackie virus infection is seasonal, often caused by epidemics, and its herpes distribution area is also special (not seen in the gums). , buccal mucosa, etc., herpes simplex virus infection is generally sporadic and no seasonal.
2. Aseptic meningitis
Enterovirus is the most common pathogen of aseptic meningitis, accounting for more than 90% of all cases. In temperate zone, meningitis caused by enterovirus occurs in summer; in tropical, it is endemic and is endemic. More common in adolescents and children, especially in infants under 1 year old, 80% of Coxsackie virus can cause this disease, common serotypes are B2 ~ B5, A7 and A9, the latency of each type is different, such as A9 is 2 ~ 12 Days, B5 is 3 to 5 days, but the clinical manifestations of each type are not specific.
Typical cases start suddenly, or there are several hours of chills, high fever, then severe forehead and post-ocular pain, irregular heat, can have biphasic heat, fatigue, lethargy, myalgia, nausea and vomiting, often pharyngitis and upper Respiratory tract infections, less common symptoms are fear of light, tinnitus, dizziness, chest and abdominal pain and paresthesia. Some cases have rash at the same time. Meningeal irritation often becomes obvious after 1 to 3 days of onset, but farther than purulent meninges. Inflammation is mild, some cases have 2 to 6 days of prodromal symptoms (fever, myalgia, etc.), followed by short-term (1 to several days) symptom improvement and heat loss, followed by fever and meningeal irritation, biphasic The heat type is equivalent to the development stage of two viremias. The general condition of the patients is good, the mind is mostly clear, the cone system sign, the Kelniig sign, the Bruzinski sign are rarely strong positive, the deep reflection is normal or Slightly active, the irritation of meningitis in infants under 1 year old is mostly absent, or only the neck, the back is slightly stiff, but in 5% to 10% of cases, convulsions, stupor, coma, sensation or movement disorder may occur.
Examine
Coxsackie virus infection check
Peripheral blood
The total number of white blood cells is normal or slightly increased.
2. Virus separation
It is the main method of diagnosis, with the advantages of saving, fast and accurate, while avoiding the difficulties of the serotype encountered by serological methods.
The positive rate of virus isolation from feces is the highest, and it can still be positive within 10 days after onset. The virus can be isolated from the blood 36 hours before the onset of illness and during fever, and the virus can be isolated from the throat swab or sputum. The positive rate of isolated virus in cerebrospinal fluid is low, but the diagnosis is significant. Other specimens including pleural effusion, pericardial effusion, urine, muscle biopsy tissue and autopsy nerve tissue can be sent for examination. Fecal specimens can be stored at 4 °C for many days. Other specimens should be kept below -7 °C.
The isolation of viruses from the feces and respiratory tract is only of reference, as it may be a co-infection, and the isolation of viruses from blood, cerebrospinal fluid and pericardial effusion is diagnostic, so specimens should be collected from multiple sources to increase The reliability of the results.
Coxsackie A virus can be isolated from the A9 and A16 serotypes by cell culture. The other serotypes need to be inoculated into the mice by various routes (subcutaneous, intraperitoneal, intracerebral, etc.) to isolate the virus. Then, it was confirmed by a specific antiserum as a neutralization test. Recently, RD cells (human rhabdomyosarcoma cells) strains were used to isolate and culture other group A viruses other than Coxsackie A1, A19, and A22 viruses.
Tissue culture is the first choice for the isolation of Coxsackie B virus. Common cell lines include monkey kidney, human embryonic kidney and Hela cells. The African green monkey kidney (BGM) cell line and RD cell line are better, 2 to 5 days later. Observing the cytopathic effect for initial diagnosis, and then using specific antiserum for neutralization test to identify, the whole process takes about 1 to 3 weeks, but as a clinical diagnosis, you do not have to wait for the serotype identification results.
3. Serological examination
Due to the large number of serotypes, it only applies if:
1 The virus has been isolated as a serotype;
2 has been found to have characteristic clinical manifestations such as epidemic chest pain, which clearly indicates when certain antibodies (such as group B viruses) are used to detect antibodies; or when hands, feet, and oral diseases are usually caused by Coxsackie A16 virus;
3 is occurring when a single serotype virus causes epidemics;
4 for sero-epidemiological investigation of a particular serotype.
In the serological test method, the neutralization test is the most specific method for identifying the isolated serotype of the virus, but as an antibody for detecting enterovirus infection, the neutralization test is not sensitive enough, and the operation is complicated and expensive, and the patient is in the course of the disease. Neutralizing antibodies began to appear at 2 weeks, peaked after 2 to 3 weeks, and remained for 3 to 6 years. The specificity of the complement-binding assay was lower, and the rate of heterotypic antibody was higher, but the complement-binding antibody appeared simultaneously with the neutralizing antibody. It can be used as a basis for recent infections for 2 to 3 months. The hemagglutination inhibition test is not useful, because only 1/3 of the enterovirus produces erythropoietin, and even some strains can be produced in the same serotype. The strain does not produce erythrocyte lectin. Recently, it has been reported to detect IgM enterovirus antibody by immunoblotting. The positive rate is 60%, most of which are group specific (22/31), a few are type specific, and have been reported to be heat treated. The virus is the antigen and the IgG antibody is detected by ELISA as the antigen. The sensitivity (by virus isolation as control) is 0.67 and 0.62, respectively, which is higher than the complement binding test. In 56 patients, paired serum titer IgG-ELISA method were significantly increased 13 and 19, respectively, applicable to clinical diagnosis.
In recent years, it has been reported that the detection of enterovirus RNA in serum by PCR has high sensitivity and specificity, and the positive rate is significantly higher than that of cell culture.
The same virus was isolated from the patient's throat swab.
Diagnosis
Diagnosis and identification of Coxsackie virus infection
1. Epidemiological data
It is popular in summer and autumn, and there are many children. The incidence of many people in the family has reference significance. The data popular in the region in the near future is especially valuable in diagnosis.
2. Clinical features
Some characteristic clinical manifestations, such as oral herpes, chest pain or myalgia, myocarditis, meningitis, special rash, etc. are valuable for assisting diagnosis, the total number of white blood cells is normal, and bimodal fever has certain reference significance.
When the newborn has any serious episodes of serious epidemics, and sudden neonatal cardiopulmonary dysfunction, the possibility of coxsackie virus infection should be considered. In the summer and autumn, unexplained fever and/or rash may occur, especially when the patient For infants and young children, Coxsackie virus infection should also be suspected.
3. Basis for diagnosis
Because there are often such viruses in the intestines of healthy people, if the Coxsackie virus is isolated only in the stool or anal swab of the patient, the conclusion cannot be made on this basis. The following points should be used as the basis for diagnosis:
1 from the patient's various body fluids or secretions such as cerebrospinal fluid, blood, blister, pleural effusion, etc., or autopsy organs such as heart, brain, liver, spleen and other viruses;
2 using double serum for neutralization test (or other serological tests), antibody titer increased by more than 4 times;
3 The virus isolation rate in patients is much higher than that in normal controls without contact patients;
4 No other known pathogens can cause such syndromes, but the same virus can be repeatedly separated from the patient's pharyngeal lotion, throat swab, feces, anal swab, etc., and the same is detected from the surrounding contacts. virus.
