I. Changes related to the body after CMV infection
A variety of antibodies can appear in the organism after infection with CMV. Specific antibodies, including neutralizing antibodies, appear in milk, cervical secretions and saliva despite the presence of CMV. However, CMV can still be detected, indicating that antibodies do not prevent the spread of the virus. Antibodies passively acquired by the fetus from the mother do not block infection transmitted intrauterine, through the birth canal or through breast milk. It was demonstrated that 0.2 ml of high potency anti-CMV globulin injected intraperitoneally or intravenously into mice before lethal CMV attack completely protected the animals from death. 1 month after a second attack with CMV and others, the animals all still survived, indicating that antibodies have the effect of reducing the virulence of CMV.
After the initial infection, CMV will exist indefinitely in the host cells into a latent state. A variety of tissues and organs may be involved, and necropsy suggests that the lungs, liver, pancreas, salivary glands, central nervous system and intestine may also be sites of viral latency. The severity of congenital infection is related to the lack of ability to produce precipitating antibodies and the T-cell response to CMV.
After CMV infection in children and adults, activated T lymphocytes with a suppressive cytotoxic phenotype appear in the peripheral blood, and if the host’s T cell function is impaired, the latent virus may resurface and cause a variety of syndromes. The chronic stimulation that occurs after tissue transplantation provides the conditions for CMV activation and the induction of disease. Certain strong immunosuppressive agents that target T cells, such as anti-thymocyte globulin, are associated with a high incidence of clinical CMV syndromes. In addition, CMV can function as a cofactor to activate latently infected HIV.
CMV infection can cause a decrease in the immune function of the organism, especially cellular immunity.CMV infection has a significant effect on thymus development and the function of splenocytes, mononuclear phagocytes, NK cells and CTL cells.
(a) Effects on thymus and spleen
In neonatal guinea pigs with acute CMV infection in the laboratory, thymus development was suppressed and the number of T cells was reduced. In adult rats infected with CMV, CMV was detectable in 88% of the thymus.
The splenic function was affected by CMV infection, the proliferation of splenic lymphocytes in response to conA stimulation was decreased, and IL-2 production by splenocytes was significantly reduced.
(ii) Effects on immune cells
The immunosuppression caused by CMV infection is related to the intracellular replication of the virus. CMV can replicate in mononuclear phagocytes, T cells, B cells and some as yet unidentified monocytes, among which mononuclear phagocytes are most susceptible to CMV infection. lymphocytes have important regulatory and effector functions in the immune response. CMV infection can cause impairment of various immune functions of lymphocytes.
CMV infection mostly manifests as acute mononucleosis. Peripheral blood lymphocytes have a diminished proliferative response to mitogens, CMV antigens, and HSV antigens, inducing a decrease in interferon levels, a decrease in the CD4/CD8 ratio from 1.7±0.7 to 0.2+0.2, and a decrease in T-cell activity. Some of these changes can last for a long time, and 10 months after the disease, the ratio of T-cell subsets has not fully returned to normal in most patients.
The immunosuppressive effect of CMV infection is mainly due to the abnormal function of large monocytes and CD8 cells infected by the virus. Mononuclear phagocytes play a pivotal role in anti-CMV immunity, not only directly engulfing and killing the virus, but more importantly, processing and presenting antigens, secreting cytokines, and regulating and amplifying the immune response.
After CMV infection, the function of mononuclear phagocytes is affected, and CMV infection of macrophages causes a decrease in their phagocytic function, a decrease in intracellular oxygen radical production, and changes in the expression of FC receptors and complement receptors, as well as a decrease in their antigen-presentation function, a decrease in IL-1 production, and a decrease in the response to IL-1 and IL-2. The decrease in IL-1 production can cause an imbalance in the TH/TS cell ratio.
NK cells have an antagonistic effect on the spread of CMV. nK cells are actively involved in the whole process of anti-CMV infection, but the presence of high NK activity is not necessarily a protective response, but evidence of active infection. nK cells cannot prevent the emergence of primary CMV infection, but once infection is present, nK cells can emerge early in CMV infection and have a role in limiting the spread and confining the infection.
NK cells and CTL cells are important effector cells against CMV. They can lyse infected cells early in CMV replication, before infectious virosomes are produced, and abort the spread of virus between cells. In mouse models, the antiviral effect is mediated by NK cells when the virus has acted for 3-5 days, and NK cell activity can be enhanced by IFN. 6-21 days, killing activity of CTL cells is present in spleen and peripheral blood.
The level of NK cell and CTL cell activity determines the susceptibility of the organism to CMV infection and the ease of recovery from infection. However, NK cell and CTL cell activities are also severely affected by CMV infection. In addition, specific cellular immunity has a role in preventing the re-emergence of CMV infection. The T-cell response of 20 renal transplant recipients with CMV infection was examined and 14 had a cytotoxic response to CMV, whereas 6 who did not have a cytotoxic response had serious clinical consequences. Thus, the presence of specific T cells has a role in preventing the recurrence of CMV infection.
II. Clinical manifestations
Clinical manifestations vary depending on the route of infection. Twenty percent of people with congenital cytomegalovirus infection are asymptomatic at birth, but some develop lethargy, respiratory distress, and convulsions shortly after birth and die within a few days or weeks. Other symptoms include impaired consciousness and movement, mental retardation, hepatosplenomegaly, deafness, and central nervous system symptoms.
The vast majority of infants infected perinatally are asymptomatic, with only a few developing intermittent fever, pneumonia, and mononucleosis in the first 3 months of life. Cytomegalovirus mononucleosis is more common in adults than in children and manifests mainly as fever and fatigue. After 1-2 weeks of fever, there is an increase in the absolute value of lymphocytes in the blood with anisocytic changes, splenomegaly and lymphadenitis.
Cytomegalovirus mononucleosis due to blood transfusion mostly occurs 3-4 weeks after transfusion and has the same symptoms as general cytomegalovirus mononucleosis. Occasionally, interstitial pneumonia, hepatitis, meningitis, myocarditis, hemolytic anemia and thrombocytopenia may occur. Cytomegalovirus infection occurs in almost all renal transplant patients within 2 months after surgery, with 50-60% asymptomatic and 40%-50% of patients presenting with a self-limiting, non-specific syndrome. Patients with AIDS almost always have cytomegalovirus infection with extensive visceral damage.
III. Prevention :
Cytomegalovirus is very harmful to humans, so we should actively prevent its occurrence.
1. Conscious physical exercise. To improve the immune function and resistance to disease, especially for women of childbearing age, in order to reduce the serious harm of cytomegalovirus to the fetus.
2. Pay attention to the protection of pregnant women or patients with chronic wasting diseases and low immunity to keep them away from infectious sources.
3.Pay attention to environmental hygiene and dietary hygiene.
4.People who are cytomegalovirus positive in breast milk should not breastfeed.
5.Immunization control. Still under research and exploration.
IV. Laboratory tests for cytomegalovirus infection:
(a), virus isolation
It is best to use saliva, urine, genital tract secretions, breast milk and leukocytes, inoculated into human fibroblasts to multiply and isolate, cytopathic effects (CPE) appear after 1 day or several weeks, after fixation and HE staining can be observed in giant cells, nuclear inclusions, perinuclear halo and eosinophilic intracytoplasmic inclusions, much like “owl′s eye “(owl′s eye) can also be examined by fluorescent staining with monoclonal or polyclonal antibodies.
(B), serum antibody detection
The most commonly used are complement binding test (CF), indirect immunofluorescence test (IIF), immunoenzymatic assay (EIA), indirect hemagglutination test (IHA) and radioimmunoassay (RIA) to detect CMV-IgG and IgM antibodies. When a single serum specimen has identified previous CMV infection, serum specimens should be retained immediately, as well as at intervals of 2 weeks, 4 weeks, and 8 weeks, combined with virus isolation can be used for the diagnosis of primary infection.
(iii) DNA probes
It has been widely used to detect CMV, among which 32P-labeled probes are the most sensitive. For some specimens, hybridization methods may be more sensitive than virus isolation.
(iv), polymerase chain reaction (PCR)
1, cytomegalovirus infection is divided into congenital infection (intrauterine infection) and acquired infection; two to three weeks after birth of a newborn ) cytomegalovirus infection is divided into congenital infection (intrauterine infection) and acquired infection; two to three weeks after birth of a newborn Positive, generally judged as intrauterine infection. A positive serum cytomegalovirus IgM and DNA test is generally considered an intrauterine infection. Intrauterine infections can mainly affect the baby’s hearing. Intrauterine infections tend to be problematic, while acquired infections are usually asymptomatic. Hearing. Intrauterine infections tend to be problematic, while acquired infections are usually asymptomatic. Viral infections are very common Sometimes it is difficult to distinguish between an intrauterine infection or an infection at birth.
2. Cytomegalovirus infections are very common Sometimes it is difficult to distinguish between an intrauterine infection or an infection at birth. The most common cytomegalovirus infection is sometimes difficult to distinguish between an intrauterine infection and an infection at birth. The main danger is that it affects hearing.
3, cytomegalovirus infection will always be in the body. Most people in our country have this virus in their bodies. Cytomegalovirus infection will always be in the body. Most people in our country have this virus in their bodies. Positive.
4. Breastfeeding is not a contraindication to cytomegalovirus infection. Many people in our country have positive cytomegalovirus DNA in their breast milk. Breastfeeding is not a contraindication to cytomegalovirus infection, as long as the child is full-term, normal immune function, you can breastfeed. As long as the child is full-term, normal immune function, you can breastfeed.
5. Cytomegalovirus treatment drugs can have side effects, so treatment is limited to symptomatic infections and restricted to those with cytomegalovirus disease. Cytomegalovirus treatment medications can have side effects, so treatment is limited to symptomatic infections, limited to those with toxic active replication. An indicator of active replication is positive CMV-DNA in the blood. Positive. If hearing is normal, negative, the virus is actively replicating. If hearing is normal and blood is negative for CMV-DNA, no treatment is needed. No treatment is needed. There are many causes of
6. There are many causes of high aminotransferases and jaundice, not necessarily giant cell infection.) There are many causes of high transaminases and jaundice It is not necessarily a giant cell infection.
(7) Giant cell infection is mainly a primary infection will cause problems that
V. Treatment
Cytomegalovirus infections in normal children and adults usually have only mild symptoms and do not require treatment. Usually only patients with immune system deficiencies require treatment. Antiviral drugs such as adenosine, acyclovir and interferon, which are effective against herpes simplex and herpes zoster, are not effective against this disease. It has been reported that prophylactic application of high-dose acyclovir can reduce the incidence of cytomegalovirus infection in bone marrow transplant and renal transplant patients, but it is not recognized.
1. Ganciclovir: Ganciclovir is l0-100 times more active than acyclovir against herpes simplex virus and cytomegalovirus in vitro, and is licensed for cytomegalovirus retinitis in AIDS patients, and for the prevention of cytomegalovirus infection in organ transplant patients.
Ganciclovir for cytomegalovirus retinitis is administered at a dose of 5 mg/kg body weight, twice a day, for 14 to 21 days, and then continued at 5 to 6 mg/kg body weight daily for 6 to 7 days to slow the progression of retinitis.
If cytomegalovirus infection is diagnosed in infants, they can be treated with ganciclovir at 5 mg/kg twice a day and liver function (GPT, jaundice index, etc.) can be rechecked after two weeks, with physical examination for changes in liver size. Most of the children have a good prognosis. Breastfeeding can be continued. Parents do not need to be rechecked.
Note: Ganciclovir for cytomegalovirus, although blood and urine cultures turn negative 1 to 4 weeks after initiation of treatment, 2 to 5 weeks after discontinuation of the drug, clinical symptoms return and virological tests turn positive again in all patients, so a maintenance dose of 5 mg/kg body weight per day, 5 days per week, must be applied for a long time, but treatment often has to be discontinued because leukopenia occurs.
The effect of ganciclovir on other types of cytomegalovirus infections is variable. Early treatment may be effective, but, as in retinitis, treatment is often discontinued and relapses.
The efficacy of ganciclovir alone in the treatment of cytomegalovirus pneumonia is poor, but when combined with cytomegalovirus immunoglobulin, the clinical efficiency can be significantly improved.
2. Sodium phosphonate: It can inhibit the DNA polymerase of herpes virus and the reverse transcriptase of HIV-l. Recently, it has been approved for use in AIDS patients with cytomegalovirus retinitis at a dose of 60 mg/kg body weight 3 times a day, followed by 90 mg daily maintenance dose after 3 weeks, which can delay the progression of retinitis and prolong survival time, probably related to its anti-human immunodeficiency virus effect.
Phosphonates are effective in cytomegalovirus infections tolerant to ganciclovir, but are not easily tolerated by patients because of side effects such as nephrotoxicity, electrolyte imbalance, convulsions, and nausea.
Mild CMV infections usually resolve on their own without treatment, and antiviral therapy with ganciclovir or phosphonate is required when the infection threatens a person’s life or vision.