Pediatric human herpesvirus 6, 7, 8 infectious disease

Introduction to pediatric human herpesvirus type 6,7,8 infectious diseases Human herpesvirus (HHV) 6,7,8 is a herpes virus found in the past decade and has a wide range of clinical pathogenesis. HHV-6,7 is an important cause of acute rash and febrile seizures in children. HHV-8 is a causative agent of Kaposi's sarcoma and is directly related to the occurrence of AIDS-related lymphoid tumors. HHV-6,7 Type 8 is a new virus that poses a serious threat to human health. basic knowledge The proportion of illness: 32.5% Susceptible people: children Mode of transmission: saliva transmission Complications: epilepsy, convulsions in children, meningitis, interstitial pneumonia

Pediatric human herpesvirus type 6,7,8 infectious disease etiology

HHV-6 (25%):

Salahuddin of the United States was equivalent to the isolation of a new virus from peripheral blood mononuclear cells (PBMCs) in 6 patients with various lymphoproliferative disorders in 1986. Subsequent studies have shown that its genetic configuration and human herpesvirus, especially with CMV, are 66. % homology, belonging to the -herpesvirus family, was named HHV-6 in 1987.

HHV-6 has the morphological characteristics of a typical herpesvirus family. The virus particles are round, consisting of 162 shells composed of a icosahedral symmetrical nucleocapsid with a diameter of 90-110 nm. The outer layer is composed of a cortex and a cortical layer. ~40nm; the outermost layer is covered with a lipid membrane, the surface has irregular glycoprotein protrusions, the core is linear double-stranded DNA entangled around a core protein to form axon; the mature released virus particles are 180-200nm in diameter, HHV-6 The genome is 163-170 kb and encodes more than 70 products, including the early immediate proteins IE-A and IE-B.

HHV-6 cannot be distinguished from other herpesviruses by electron microscopy, but can be distinguished from other herpes viruses by DNA hybridization, PCR or HHV-6 specific polyclonal or monoclonal antibodies by immunofluorescence antibody method. HHV- 6 Although it is closest to the cytomegalovirus in the herpesvirus genus, there is no antibody cross-reactivity between the two viruses.

HHV-7 (25%):

Frenkel first isolated HHV-7 from a healthy adult peripheral blood T lymphocyte in 1990, and then isolated the virus from a patient with chronic fatigue syndrome. The virus particle diameter is about 200 nm, and HHV-7 has a capsule. It belongs to the -Herpesviridae family with HHV-6 and CMV. Genetic studies show that HHV-7 has high homology with HHV-6 and HCMV DNA. HHV-7 can be used in cord blood mononuclear cells and normal human peripheral blood. Cultured in lymphocytes, the method is similar to HHV-6, and this virus is also often found in the saliva of healthy adults.

HHV-8 (28%):

Chang et al. found HHV-8 DNA in the sarcoma of patients with Kaposi's sarcoma (KS) AIDS by PCR in 1994. At the time, this virus with high homology to certain herpesviruses was named KS-associated herpesvirus ( KSHV), later renamed HHV-8.

HHV-8 has the same morphological characteristics as other herpes viruses and is the largest herpesvirus with a DNA of 270 kb.

Pathogenesis

Their common feature is the affinity for lymphocytes.

HHV-6 has two variants, variants A and B. The homology of the two variants at the nucleotide level is 95% to 99% in the most conserved genes, and 75 in the most differentially different regions. %, it has been suggested that these two variants of HHV-6 should be included in two different genera. Different variants may have different eosinophilic effects in infecting children or adults. Similar to other herpes viruses, HHV-6 is caused in humans. The primary infection, and after the infection has subsided, the genome of the virus can be latently stored in the host cell. The virus has several glycoproteins, and the gH glycoprotein may start from the virus entering the cell to cause infection and fusion of the infected cells. main role.

HHV-7 has a strong affinity for T lymphocytes.

Genetic analysis indicated that HHV-8 is a new member of the genus -2 herpesvirus and is the only virus in the genus that can infect humans. If HHV-8 is detected from B lymphocytes of AIDS patients, it indicates that patients may occur. KS, HHV-8 infection can occur in all types of KS patients, in addition to infection with B lymphocytes, the virus can also infect stromal cells of KS sarcoma, spindle cells and so on.

Pediatric human herpesvirus 6,7,8 infectious disease prevention

According to the prevention method of respiratory virus infectious diseases, many viral infectious diseases are self-limiting and have a good prognosis. For serious viral diseases and chronic migratory viral diseases, preventive measures should be strengthened, such as doing various passive immune prevention. Inoculation, application of immunoglobulins, etc.

Pediatric human herpesvirus 6,7,8 infectious disease complications Complications, epilepsy, convulsions, meningitis, interstitial pneumonia

Can cause convulsions, epilepsy, meningitis or encephalitis, necrotizing lymphadenitis and other diseases, infection after organ transplantation, can cause interstitial pneumonia and encephalitis; trigger rejection of transplanted organs.

Pediatric human herpesvirus type 6,7,8 infectious disease symptoms common symptoms herpes rash rash high fever fatigue sore throat tonsil congestion eyelid edema chills myalgia cervical lymphadenopathy

1. HHV-6 infection caused by HHV-6 primary infection, its nucleic acid can lurk in the body for a long time, HHV-6 nucleic acid is mainly lurking in peripheral blood mononuclear cells, salivary glands, kidney and bronchial glands, in Under certain conditions, HHV-6 can be activated and cause reinfection. The mechanism of HHV-6 activation is still unclear. Studies have shown that HHV-6 can be activated in the presence of HIV, Epstein-Barr virus, measles virus, and cytomegalovirus infection.

(1) Children's acute rash (exanthema subitum, ES): Children's acute rash is a common disease in infants and young children characterized by high fever and rash. It occurs mostly in spring and autumn, and there is no gender difference. The typical clinical manifestations are:

1 fever 1 to 5 days, body temperature as much as 39 ° C or higher.

2 rash after hot retreat, rash is red maculopapular rash, distributed in the face and trunk, can last for 3-4 days, some children with soft palate can appear characteristic erythema (Nagayamas spots).

3 other symptoms: including eyelid edema, anterior hernia, cough, diarrhea, convulsions and so on.

Typical signs include cervical lymphadenopathy in some children except rash.

In 1988, HHV-6 was isolated from peripheral blood polymorphonuclear leukocytes of ES patients for the first time, and then isolated from ES patients with CD4, CD8, CD3, monocytes/macrophages to HHV-6, and the neutralization test was used to determine ES disease. The positive rate of HHV-6 antibody in the stage is 18%-100%. It is confirmed that HHV-6 infection is the cause of ES. Most of the ES is caused by HHV-6 B infection, and rarely infected by group A. cause.

(2) febrile seizures and neurological complications: only 40% of children with primary or reactivated HHV-6 infection show ES, 60% do not have typical ES symptoms, but only fever is clinical manifestation, The etiological examination of the performance of emergency children found that 39.6% were caused by HHV-6 infection. Studies have confirmed that febrile seizures caused by HHV-6 infection account for 30% to 70% of the cause of febrile seizures. It has been observed that Of the 243 children under 2 years of age who were admitted to the emergency room with acute fever, 34 (14%) had evidence of primary HHV-6 infection, and evidence of infection included HHV detected in cerebrospinal fluid from children with febrile seizures. -6 DNA, HHV-6 IgG antibody titer recovery period 4 times higher than the acute phase, HHV-6 IgM antibody positive, etc., some children with hyperthermia convulsions can appear brain hippocampus sclerosis, and then cause seizures.

In addition to causing febrile seizures, HHV-6 primary infection can cause other serious central nervous system diseases such as meningitis or encephalitis. HHV-6 DNA and antibodies can be detected from cerebrospinal fluid in patients with encephalitis. HHV-6 infection causes The pathogenesis of central nervous system symptoms may be that HHV-6 persists in cerebrospinal fluid and peripheral blood lymphocytes in latent form after acute HHV-6 infection. Some patients are only present in cerebrospinal fluid, and HHV-6 may cause reactivation after HHV-6 reactivation. Febrile seizures or encephalitis, studies have examined 13 healthy adult brain tissues, and HHV-6 DNA was detected in 11 of the anterior extracortex and basal ganglia specimens, confirming latent infection.

(3) Nonheterophile-negative infectious mononucleosis: Infectious mononucleosis (IM) is a self-limiting lymphoproliferative caused by primary infection with EBV (EBV). Disease, HHV-6 infection can also cause IM, and the patient's age is similar to that of typical EBV IM.

1 clinical manifestations include:

A. Fever, the course of disease is longer than EBV IM, and some patients can be more than 30 days.

B. There is angina, tonsil congestion, swelling, covering the pseudomembrane.

C. Hepatosplenomegaly.

D. Retroperitoneal lymphadenopathy.

E. Blurred vision.

2 laboratory tests differ from EBV-like IM in:

A. The heterophilic agglutination test was negative.

B. Blood, the atypical lymphocytes in the peripheral blood are significantly increased, and the number of CD38 cells is increased.

C. Etiology examination, HHV-6 IgM antibody can be detected in the acute phase, and the IgG antibody is increased by 4 times during the recovery period.

Since HHV-6 can be activated by HSV, CMV, EBV, or double infection with these viruses, it is determined that the cause of HHV-6 infection is IM after the exclusion of other viral infections.

(4) Kikuchi-Fujimoto (KF) disease: This disease is a necrotizing lymphadenitis disease first discovered by the Japanese. It is currently reported in the United States, Europe and some parts of Asia, and more women than men (2) 1: 1 ~ 4: 1), the age of good hair is 10 to 60 years old, especially 10 to 40 years old, the clinical manifestations of rapid progression of cervical lymph node pain or painless swelling is typical symptoms, with sore throat , chills, myalgia and other symptoms, in addition to cervical lymphadenopathy, supraclavicular, armpit, arm lymph nodes can also be affected, hepatosplenomegaly is rare, lymphadenopathy can last for several months, occasionally fibrosis, pathology The change is characterized by the enlargement of the paracortical area and the activation of lymphoid follicles. The paracortical area can also disappear. The changes of enlargement and disappearance can be seen in the same lymph node. The focal necrosis is also characteristic, but it is not its inherent characteristics. The infiltrating cells are polymorphonuclear cells, but mainly macrophages, which surround the single or focal necrotic lymphocytes.

HHV-6 IgM antibody was detected in the acute phase of KF disease, and HHV-6 IgG antibody was increased 4-fold during recovery. In addition, HHV-6 DNA and antigen were detected from a large number of KF lymphoid tissues, indicating that HHV-6 is causing KF. The cause.

(5) Infection after organ transplantation: Some patients receiving heart, kidney, liver and bone marrow transplantation may have a significant increase in HHV-6 IgG antibody after transplantation for a period of time. In addition, the researchers have transplanted organs from transplanted patients, lymphocytes, giants. HHV-6 virus was isolated from phagocytes/monocytes, bone marrow, and lung tissue. It has been confirmed that more than 50% of HHV-6 infections after transplantation are reactivated, and the reactivation time is 80% after transplantation. Days, ranging from 39 to 102 days, when HHV-6 is reactivated, fever and leukopenia can occur clinically. After bone marrow transplantation, HHV-6 reactivation can cause interstitial pneumonia and encephalitis. HHV-6 infection after transplantation Reactivation can cause rejection of transplanted organs. Therefore, the relevant items should be closely monitored after transplantation. HHV-6 IgM and IgG antibody levels should be closely monitored after bone marrow transplantation. If necessary, antiviral drugs should be considered for HHV-6 infection to avoid Complications and rejection occur.

There have been many studies showing that some diseases or syndromes may be associated with HHV-6 infection, but the causal relationship has not been completely determined. These diseases include chronic fatigue syndrome (CFS) and Sjögren syndrome (dry). Syndrome), systemic lupus erythematosus (SLE), atypical lymphocytosis, myelodysplasia, chronic bone marrow and extramedullary proliferative disease, lymphocytic leukemia, idiopathic lymphopenic purpura, thrombocytopenia Aster (Chinese scholars reported that HHV-6 DNA was detected from 41% of a group of thrombocytopenic purpura cases), hemophagocytic syndrome, Kawasaki disease, etc., during the occurrence and development of these diseases, HHV exists. -6 evidence of active infection, but its causal relationship is not completely determined, and further research is needed to confirm it.

2. Diseases caused by HHV-7 infection Although epidemiological studies have confirmed that HHV-7 infection is widespread, so far, children's acute rash is the only disease that has a causal relationship with HHV-7 infection, HHV-7 infection. The range of other diseases caused is still under investigation.

(1) Childhood acute rash (ES): Recent studies have confirmed that HHV-7 infection is another pathogen causing acute rash in children, which accounts for 10% of the cause of acute rash in children. In patients with seroconversion of HHV-7, The detection rate of ES was 47%, ES caused by HHV-7 infection, about 30% had a history of previous ES, and two episodes were separated by several months. The cause of the first ES was caused by HHV-6 infection. HHV-7 is similar to the clinical manifestations of ES caused by HHV-6 infection. Etiological examination can detect HHV-7 IgM antibody, HHV-7 DNA and HHV-7 IgG antibody recovery period is 4 times higher, from some patients It can be separated into HHV-7.

(2) febrile seizures and neurological complications: Torigoe has reported 2 children with ES caused by HHV-7 infection, in addition to ES performance, accompanied by febrile seizures and hemiplegia symptoms, from patients peripheral blood mononuclear cells and saliva The virus isolated from the virus was confirmed to be HHV-7 virus by immunofluorescence, PCR and endonuclease analysis. The HHV-7 antibody titer in the recovery period of the two patients was increased by 4 fold, while the HHV-6 antibody was unchanged. The HHV-7 antibody titer in the cerebrospinal fluid of patients also increased, suggesting that HHV-7 infection is the cause of convulsions and hemiplegia in these two children, so when patients have neurological symptoms associated with acute rash in children, In addition to HHV-6 infection, the possibility of HHV-7 infection should also be considered.

(3) Other diseases: In addition to the above diseases, infant hepatitis syndrome, mononucleosis-like disease, chronic fatigue syndrome and post-transplant infection may also be related to HHV-7 infection, but only a case report is needed, further the study.

3. Disease caused by HHV-8 infection After the initial infection of HHV-8, the virus gene exists in the lymphocyte in an integrated state, and the gene is not expressed, showing a latent infection. Under certain conditions, the virus is activated, but its activation mechanism It is unclear that HHV-8, as a new DNA tumor virus, can cause the proliferation and transformation of epithelial cells, endothelial cells and lymphocytes, eventually leading to the formation of tumors. This virus may play a carcinogenic role through two mechanisms, first The viral proto-oncogene directly stimulates cell proliferation by causing DNA mutations in the host cell. Second, cells infected with HHV-8 stimulate tumor cell growth by releasing growth factors. It is now clear that HHV-8 infection is closely related to the following diseases. Related.

(1) Kaposis sarcoma (KS): KS is a proliferative malignant tumor of endothelial cells. Histopathologically, there may be unique manifestations of new blood vessels, such as skin, lymph nodes and internal organs. KS can be divided into 4 Type:

Type 1I: typical sporadic KS, also known as special-type skin pleomorphic pigmented sarcoma, more common in older men, prevalent population of Italian and Eastern European Jewish species, 1/3 of secondary lymphoid malignancies, prognosis Mostly good.

Type 2 II: African-type KS, popular in central Africa, mainly for children and young males, involving the visceral lymphatic system and lymph nodes, with poor prognosis.

Type 3III: iatrogenic or post-transplant KS, its occurrence is related to long-term use of immunosuppressive agents after transplantation, clinical manifestations are close to type II, and the incidence is not high.

Type 4IV: Epidemic or AIDS-related KS, 40% of AIDS patients can be combined with KS, 95% of which are homosexual or heterosexual, AIDS-related: KS is the cause of death in 12% of AIDS patients.

So far, studies have confirmed that HHV-8 infection is closely related to the occurrence of various types of KS. From the samples of various types of KS patients, the detection rate of HHV-8 is more than 60%, especially type IV, HHV-8. The detection rate of DNA is 100%, and the cause of HHV-8 infection as KS has been clarified.

(2) Lymphatic diseases:

1 body cavity based lymphoma (BCBL): BCBL is a lymphocyte cancer found in the body cavity of AIDS patients after 1989. There is no solid tumor tissue. The normal immune system can also suffer from BCBL. However, it is rare that the diagnosis of BCBL needs to consider epidemiology, pathology, genetics and clinical aspects. The prognosis is poor, and the survival time is 2 to 6 months. In Europe and North America, HHV-8 infection It can occur in all AIDS-related BCBL patients. A large number of HHV-8 DNA can be detected in BCBL cells by semi-quantitative PCR and Sounthen blotting, which can indirectly confirm that HHV-8 is the cause of BCBL.

2 multiple Castleman's disease (MCD): MCD, also known as multiple vascular follicular lymphoproliferative disease, is atypical polyplymphoid hyperplasia involving multiple lymphoid organs, manifesting severe multisystem involvement, MCD and KS disease Close, especially in AIDS patients, KS is more closely related to MCD, and the incidence of HHV-8 infection in AIDS-related MCD patients can reach 100%. These patients may or may not be combined with KS in immunocompetent MCD patients. The detection rate of HHV-8 was 40%. These results suggest that HHV-8 infection is the causative factor of MCD.

(3) Skin disorders: Some researchers have detected HHV-8 DNA from the pathological tissues of proliferative and non-proliferative skin diseases. The former includes acanthosis cell carcinoma (SCC), ultraviolet keratosis (AK), and Bowen's disease ( BD), Paget's disease (PD), etc., the latter include: chronic dermatitis, localized scleroderma, epidermal pustules, etc. The detection rates of HHV-8 from BD and SCC are 71.4% and 50%, respectively, and AK is 33.3. %, PD was 16.7%, and the total detection rate of non-proliferative skin disorders was 16.7%. These results indicate that HHV-8 infection is associated with partial proliferative and non-proliferative skin diseases.

Examination of pediatric human herpesvirus type 6,7,8 infectious diseases

1. Virus isolation Virus isolation is a diagnostic method for HHV-6,7,8 infection. HHV-6,7,8 can be propagated in fresh cord blood mononuclear cells or adult peripheral blood mononuclear cells, but it needs to be cultured. The plant contains hemagglutinin (PHA), IL-2, dexamethasone and other substances. The infected cells appear lesions in about 7 days. The cells are pleomorphic, nuclear pyknosis, and multinucleated cells appear. It can continue to survive for 7 days, and uninfected cells die within 7 days of culture. Because the virus isolation and culture takes time, it is not suitable for early diagnosis, and is generally only used for laboratory research.

2. Detection of viral antigens The detection of viral antigens is suitable for early diagnosis, but the maintenance time of viremia is short, and it is difficult to take specimens in time. Immunohistochemical methods are widely used to detect viral antigens in cells and tissues. Antigen positive results can be used as The basis for the diagnosis.

3. Determination of viral antibodies ELISA and indirect immunofluorescence methods for the determination of HHV-6,7,8 IgG, IgM antibodies, is currently the most common and simple method, IgM antibody positive, high titer IgG and recovery IgG The 4-fold increase of antibody can indicate the presence of HHV-6,7,8 infection. When IgM antibody or IgG antibody is detected from cerebrospinal fluid, it indicates the presence of central nervous system infection. IgM antibody is generally produced 5 days after infection. For 2 to 3 weeks, IgG antibodies are produced 7 days after infection and reach a peak after 4 weeks, which can last for a long time. However, due to the presence of certain antigenic crossover between herpes viruses, other herpesvirus infections can also cause antibodies to increase, and anti-complement immunity can be used. Fluorescence test to identify.

4. Detection of viral nucleic acid HHV-6,7,8 DNA can be detected by nucleic acid hybridization method and PCR method. Due to the latent infection of HHV-6,7,8, the DNA of the virus is sometimes detected and cannot be determined to be in a latent state. Or activation status, quantitative, semi-quantitative PCR can be used to determine the amount of DNA to determine the presence of active infection, high concentrations of viral DNA suggest the existence of active infection.

5. Blood picture examination ES patients have significantly reduced white blood cell count, lymphocytes increased, up to 90%, lymphocytes including atypical lymphocytes.

X-ray chest X-ray, electrocardiogram and B-ultrasound for routine examination, if necessary, do brain CT examination.

Diagnosis and diagnosis of infectious diseases of human herpesvirus 6,7,8

The diagnosis of HHV-6,7,8 infection should be combined with clinical manifestations and multiple etiological examination results to make a comprehensive judgment. According to clinical manifestations and laboratory tests, other infectious diseases such as bacteria can be diagnosed.

ES differential diagnosis should be considered in combination with pneumococcal sepsis, rubella, adenovirus, enterovirus infection, sexually transmitted diseases and other rash diseases, and meningitis, encephalitis should be noted with other bacteria Identification of intracranial infections caused by infection, KF disease should be differentiated from Hodgkin's disease and non-Hodgkin's lymphoma.

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