Pediatric human parvovirus B19 infection

Introduction to Pediatric Human Parvovirus B19 Infection The typical disease caused by human parvovirus B19 (hereinafter referred to as B19) is infectious erythema and acute joint disease, but the virus can cause aplastic crisis in some blood diseases and immunocompromised patients, and can cause fetal edema in pregnant women. Even the stillbirth. basic knowledge Sickness ratio: 0.0001% Susceptible people: children Mode of infection: respiratory transmission Complications: anemia

Pediatric human parvovirus B19 infection etiology

(1) Causes of the disease

In 1980, B19 was confirmed to be pathogenic to humans. In recent years, HPV B19 virus infection has been found to be an important infectious disease. B19 is the smallest and simple structure of DNA virus. Its DNA is single-stranded, linear. B19 in its name comes from the specimen number of the virus originally found. The diameter of the virus particle is 20-25 nm. It is a icosahedral stereosymmetry and has no capsule. The nucleocapsid of this virus is composed of two structural proteins, and the individual virus particles. The DNA contained is positive or negative strand DNA. The virus is stable and maintains its infectivity after incubation at 60 ° C for 16 h. This virus cannot grow in conventional cell lines and animal models, but can be derived from humans in vitro. Replication in the erythroid progenitor cells of the bone marrow, umbilical cord, peripheral blood or embryonic liver.

(two) pathogenesis

Two studies of adult volunteers provided the basis for understanding the pathogenesis of B19.

1. The pathogenesis of the disease caused by the virus is divided into two phases.

(1) Phase 1: The first phase is characterized by viremia in about 6 days after nasal inoculation to susceptible individuals (in the serum lacking antibodies against this virus), viremia lasts for about 1 week; virus IgM antibodies against this virus appeared several days after being cleared. This antibody persisted for several months. After several days, IgG antibodies appeared and lasted for a long time. In the early stage of viremia, non-specific systemic symptoms appeared, lasting 2 to 3 These symptoms include headache, discomfort, myalgia, fever, chills, and itching; these symptoms are accompanied by a decrease in reticulocytes and the discharge of the virus from the respiratory tract. A few days after the onset of symptoms, an insignificant decrease in hemoglobin concentration occurs; For 7 to 10 days, bone marrow examination revealed a significant reduction in erythroid progenitor cells, as well as transient lymphopenia, neutropenia, and platelet count reduction.

(2) Phase 2: The second phase of the disease begins 17 to 18 days after the virus inoculation (after the viremia is removed, the discharge of the virus in the pharyngeal secretion is terminated, and the reticulocyte reduction is eliminated). The disease is similar to infectious erythema in adults. There are small porcine rashes lasting 2 to 3 days, accompanied by joint pain and arthritis. There is another 1-2 days. This period is when the serum B19 antibody titer is rising. The situation occurs.

2. It is an immune complex disease. The above studies have shown that in people without other diseases, B19 disease manifests itself as a self-limiting infectious erythema and/or joint disease, which is almost certain to be an immune complex disease. A concept is supported by the fact that injecting immunoglobulin into patients with chronic viremia can trigger infectious erythema. Conversely, in immunocompromised (such as chronic hemolytic disease or immunodeficiency syndrome) hosts, the disease caused by this virus is often Seriously, the erythrocyte lineage precursor cells are destroyed by B19. The normal host can tolerate erythrocyte production stoppage for 7-10 days. However, patients with hemolytic disease need to increase erythropoiesis, and patients are difficult to tolerate erythroid progenitor cells. Destruction, so there is usually a serious temporary aplastic crisis. Patients with immunodeficiency may not be able to clear B19 viremia. As a result, the red blood cell system is continuously infected and chronic severe anemia occurs. Embryos need higher levels than adults. Red blood cell production, and its immune system is immature; both of these factors can explain fetal edema caused by B19.

It was confirmed by follow-up of 53 patients with acute B19 infection for 26 to 85 months that the occurrence of chronic arthritis after B19 infection is related to the anti-B19 non-structural protein 1 (NS1) antibody produced in vivo, and B19 specifically binds to cells. On the erythrocyte P antigen, this specific binding can explain the philophilicity of B19 on erythroid progenitor cells, especially the pro-tropical erythrocytes and young red blood cells. A few people lack P antigen and they are not affected by B19. infection.

Pediatric human parvovirus B19 infection prevention

1. Patients with acute HPV B19 virus infection should be taken by respiratory tract isolation measures. Respiratory isolation measures should be taken in a timely manner. In particular, control should be taken to control outbreaks in children's collective institutions, families and wards.

2. Perform HPV B19 virus antibody monitoring

(1) Childbearing age, pregnant women: women of childbearing age should try to monitor HPV B19 virus antibody, and those who are negative should avoid contact with HPV B19 virus infected patients, and should be protected during pregnancy.

(2) Patients with low immune function and anemia:

1 to protect: for patients with low immune function, chronic anemia patients should be protected, reduce transmission.

2 use of immunoglobulin: for patients with chronic hemolysis or immunodeficiency and pregnant women, consider using immunoglobulin to prevent B19 infection, whether it is possible to prevent infection before or after exposure, it is not clear.

3 Wash hands frequently: For these people, in a community known to have B19 infection, washing hands after eating with the respiratory tract or other secretions before eating can reduce the risk of B19 infection.

(3) People who are at risk of iatrogenic transmission: patients with temporary aplastic crisis or chronic B19 infection (rather than patients with infectious erythema or joint disease) have a risk of iatrogenic transmission. Patients should be hospitalized in separate wards and treated for respiratory tract isolation.

3. Vaccines There are currently no vaccines available for B19. However, an insect cell line infected with baculovirus and capable of expressing non-infectious but immunogenic B19 capsid protein was evaluated as a candidate vaccine.

Pediatric human parvovirus B19 infection complications Complications anemia

Inducing a crisis of aplastic disorders can cause life-threatening anemia.

Pediatric human parvovirus B19 infection symptoms common symptoms myalgia low fever erythrocytosis plaque rash whole blood cell reduction protein urinary sore throat drowsiness pruritus herpes

1. Infectious erythema is the most common manifestation of B19 infection and is mainly found in children. This disease is also known as No. 5 because it was classified as a child's 6 rash diseases in the late 19th century. The fifth type, in general, infectious erythema is a mild disease, the typical manifestation is a rash on the face, a "scratched cheek" appearance, pale mouth; previously may have a slight fever, rash It can appear rapidly in the arms and legs, and usually has a lace-like erythema, with less trunk, palms and ankles. The rash occasionally manifests as maculopapular, measles-like, herpes-like, purpuric or itchy. A typical rash subsides in about a week, but it can also occur intermittently for weeks, especially when tension, exercise, exposure to sunlight, bathing or changes in environmental humidity are common in children, joint pain and arthritis. Common in adults, but the latter rash is absent or non-specific, lacking characteristic facial erythema.

2. Arthritis can be seen in adults and older children with acute joint pain and arthritis, may be associated with rash, typical arthritis is symmetrical, most often involving the wrist, hand and knee joints, arthritis usually subsides in about 3 weeks, no Destructive, however, in a small number of patients, arthritis can last for months or even years.

Some case reports indicate that B19 infection may be associated with idiopathic thrombocytopenic purpura, and similar reports have been reported in pediatrics in China, but whether it is relevant or not, more studies are needed to confirm that B19 may also be associated with virus-associated hemophagocytic syndrome. Complete blood cell reduction, Lyme disease-like arthritis, recurrent paresthesia, fibromyalgia, systemic lupus erythematosus and vasculitis (including nodular polyarteritis, Wegener's granulomatosis and Kawasaki disease), but It remains to be confirmed that B19 DNA has been detected from the serum of some children with fulminant hepatitis with unknown etiology; these cases are mostly under 5 years of age, liver function recovery is faster, and the prognosis is better.

3. Temporary aplastic crisis In most cases, B19 is the causative of a transient aplastic crisis that occurs suddenly in patients with chronic hemolytic disease, almost all hemolytic diseases, including sickle cells. Sexual diseases, erythrocyte enzyme deficiency, hereditary spherocytosis, thalassemia, paroxysmal nocturnal hemoglobinuria and autoimmune hemolysis can all be affected by B19 infection. B19-induced aplastic crisis can also occur in acute In patients with blood loss, the patient presented with weakness, lethargy, paleness and severe anemia. This syndrome often had non-specific symptoms lasting for several days. The patient had significant reticulocyte reduction for 7 to 10 days, and there was no red blood cells in the bone marrow. Precursor cells, although the granulocyte system is normal, transient aplastic crisis can cause life-threatening anemia and require urgent blood transfusion therapy.

4. Patients with immunodeficiency in chronic anemia in immunocompromised patients may not be able to eliminate B19 infection, most likely because they are unable to produce sufficient levels of virus-specific IgG antibodies, resulting in persistent infection with red blood cells in the bone marrow Destruction of systemic precursor cells and chronic anemia that depends on blood transfusion, which has been associated with immunodeficiency patients associated with human immunodeficiency virus infection, congenital immunodeficiency, maintenance of chemotherapy for acute lymphocytic leukemia, and patients undergoing bone marrow transplantation In addition, some idiopathic pure red cell aplasia is likely to be caused by persistent infection of B19. B19-induced chronic anemia may be an immunodeficiency that has not been identified from other aspects, the degree of chronic anemia. It may fluctuate and may be cured or controlled by immunoglobulin therapy. The type of immunodeficiency disease induced by B19 infection and the frequency of this correlation are yet to be determined.

5. Embryo and congenital infections Mothers' B19 infection usually does not adversely affect the fetus. In fact, the fetus is often uninfected. Therefore, when pregnant women are infected with B19, they should be informed that the risk of fetal infection is low. It is estimated that less than 10% of B19-infected mothers may have fetal death, usually because the fetus has severe anemia and congestive heart failure, causing non-immune fetal edema, B19 can be detected in fetal tissues, and mainly infected. Young red blood cells, pregnant women who are known to be exposed to B19 should be monitored for elevated levels of serum B19 IgM antibodies and alpha-fetoprotein; ultrasound should also be performed on fetal edema, and certain fetuses with fetal edema can survive. Down, and looks normal during childbirth, occasionally fetal infection and edema caused by anemia and hypogammaglobulinemia, and no response to immunoglobulin therapy, domestic studies confirmed that a small number of late pregnancy women and newborns There is B19 infection, but it seems to be unrelated to the occurrence of premature birth or small gestational age. However, foreign studies have shown that intrauterine B19 infection can be It causes fetal brain tissue infection, the infection is mainly in white matter, and multinucleated giant cells can appear, and the DNA and antigen of the virus can be detected locally in the infection.

6. Others In addition to the above-mentioned more common clinical findings, HPV B19 virus infection may have other clinical manifestations.

(1) Respiratory tract disease: Acute respiratory tract inflammation is seen in the early stage of acute HPV B19 virus infection, which shows flu-like symptoms. HPV B19 virus infection is associated with acute asthma attacks and acute obstructive bronchiolitis in some infants.

(2) Acute myocarditis or myocardial pericarditis: Infants and children with HPV B19 virus infection can occasionally develop severe myocarditis.

(3) various vascular inflammatory syndrome: HPV B19 virus infection may also play an important role in capillary vasculitis, leukocyte fragmentation vasculitis and necrotizing vasculitis.

(4) chronic fatigue syndrome (chronic fatigue syndrome): pathogenesis and immune regulation dysfunction, genetic factors, viral infections, etc., low fever, general weakness, joint muscle pain, sore throat, etc., the pathogenesis of HPV B19, Enterovirus, EBV, human herpesvirus type 6 (HHV-6) and other infections are involved.

Pediatric human parvovirus B19 infection check

The HPV B19 virus pathogen test is the basis for the diagnosis of HPV B19 virus infection. Currently used in clinical practice:

1. HPV B19 virus antibody detection is a routine method for clinical diagnosis and epidemiological investigation of HPV19 virus infection.

(1) Serum HPV B19 antibody: detection of specific IgM, IgG using enzyme-linked immunosorbent assay, fluorescence immunoassay or radioimmunoassay, capture blood adhesion test (MACHAT), within 3 days after the onset of HPV B19 acute infection symptoms, 90% of HPV B19 virus IgM antibodies can be detected until 2 to 3 months after the disease, serum HPV B19 virus IgG antibody is detected in the second week after the disease, lasting for several years or even life, HPV B19 virus in immunodeficient patients Chronic persistent infection, HPV B19 virus antibody is difficult to detect, early diagnosis of fetal HPV B19 infection can detect serum specific IgM in pregnant women, cord blood-specific IgM can be measured after delivery.

(2) Saliva antibody: In patients with acute HPV B19 virus infection, the detection rate of HPV B19-IgM in saliva is 55% to 83%.

2. HPV B19 virus DNA detection In the viremia phase of HPV B19 virus infection, it is easier to detect viral DNA from patient serum by molecular hybridization technique. The sensitivity of polymerase chain reaction (PCR) technology is higher, and the positive rate is 94. %, but there may be false positives, specimens can also be respiratory secretions, cord blood, bone marrow, amniotic fluid, fetal tissue, in situ PCR technology can be used for tissue intracellular localization analysis of HPV B19 to study its pathogenesis.

3. HPV B19 antigen detection ELISA method can directly detect viral capsid protein VP1 and VP2 from the serum of acute patients, its sensitivity is lower than PCR, but fast, cheap, reliable, suitable for routine examination.

4. Electron microscopy can directly observe the virus inclusion bodies and particles in the nucleus of the infected cells under electron microscope.

Should do X-ray, B-ultrasound, ECG examination, if necessary, do brain CT examination.

Diagnosis and diagnosis of human parvovirus B19 infection in children

The diagnosis of B19 infection mainly depends on the determination of specific IgM and IgG antibodies. These antibodies can be detected by commercially available immunoassay kits. In some patients infected with this virus, the virus itself can also be detected from serum or tissue, viral DNA or Its antigen, for acute infection, if there is a corresponding symptom with specific IgM antibody or B19 virus, it can be diagnosed; IgG antibody generally indicates past infection, unless double serum test confirms that the antibody titer in the second serum has 4 times or more, individuals with infectious erythema and acute joint disease, usually have IgM antibodies in the serum, but can not detect the virus, people with transient aplastic crisis can have IgM antibodies, and in the serum in the typical case There are also high titers of viruses and their DNA; in these patients, there are characteristic large pro-young red blood cells and erythrocyte system hyperplasia, and patients with immunodeficiency and anemia are often not easy to detect antibodies, but can be detected in serum. Viral particles and DNA, which can be identified by fetal infection, can be identified by fetal edema or by the presence of B19 DNA in the amniotic fluid or fetal blood in combination with B19 IgM antibodies in maternal blood.

According to the clinical manifestations and laboratory test positive results for diagnosis, during the epidemic erythema epidemic, it is not difficult to diagnose the typical skin manifestations. Infectious erythema has the characteristics of cheek flushing and pale perioral, which needs to be differentiated from scarlet fever. Typical infectious erythema should be distinguished from light measles, rubella, other viral rashes and drug rashes.

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