Herpes simplex virus pneumonia

Introduction to herpes simplex virus pneumonia Herpes simplex virus (HSV) infection often occurs in the upper respiratory tract, and the lower respiratory tract is rare. Herpes simplex pneumonia is seen in immunocompromised patients, patients with alcoholism, burn patients, and most patients are adults; infants and young children can be a complication of herpes simplex virus infection. basic knowledge The proportion of illness: 0.005% Susceptible people: no specific people Mode of infection: non-infectious complication:

Herpes simplex virus pneumonia

(1) Causes of the disease

HSV-1 and HSV-2 belong to the subfamily of herpesvirus, and their signs are short replication cycle, cytolytic infection in tissue culture, latent state in ganglia, HSV-1 and HSV-2 have a 20 The core shell of the facet, the thickness of the core shell is about 100nm, consisting of 162 shells. The core shell envelops the core containing viral DNA. When the virion crosses the nuclear membrane, it obtains a virus-rich envelope. The nucleocapsid passes through the nucleus. Membrane budding is released to the cell surface and can be released to the outside of the cell or directly into adjacent cells for further replication. The intact virion is about 110-120 nm in diameter. HSV DNA is linear double-stranded, relatively GC-rich, and has a molecular weight of 96×106. Dalton, HSV-1 and HSV-2 have 50% homology to the genome, which is related to antigen cross-reactivity and some biological characteristics of the two serotypes; however, each type has unique biological characteristics. Can be distinguished by various techniques, herpes simplex virus replicates in the nucleus, producing histopathological features of herpesvirus replication, the so-called cytopathic effect (CPE), including cell swelling, rounding, and visible Giant cells and fused cells The lesion rapidly spreads to the entire cell layer, and the Cowdry A-type nuclear inclusion body can be seen. HSV can proliferate in many cells, commonly used human embryo lung, human embryo kidney, rabbit kidney, hamster kidney, monkey kidney, etc., host range of HSV It is very wide and can infect a variety of animals, such as mice, rabbits, guinea pigs, hamsters, cotton rats, chicken and chicken embryo chorioallantoic membranes.

HSV can be inactivated by a lipid solvent; the virus can be eliminated in an environment with a pH of less than 4 or a temperature of 56 ° C for more than 0.5 h.

HSV-1 may be a normal human oral parasitic virus strain, which can be isolated from normal human oral secretions. If there is no acute upper respiratory tract infection or immunosuppression, simply carrying the virus will not cause fatal respiratory failure, and few patients simply Herpes virus lung infection was admitted for the first cause.

(two) pathogenesis

The in vivo process of herpes simplex virus infection can be divided into five stages: primary skin mucosal infection, acute ganglion infection, latent infection, reactivation, repeated infection, in susceptible hosts, after inoculation of pathogenic viruses to the skin mucosa, The first infection occurs, the virus replication causes the progeny virus to spread to neighboring cells, and then spread to the skin mucosa dominating area of the sensory nerve. The virus reaches the nerve cell nucleus of the ganglion, causing latent infection, and the virus latency can be lifelong or The reactivation of the virus is terminated, resulting in clinical asymptomatic or obvious symptoms, and there is no evidence that the virus can be eliminated after the ganglion latent infection.

Normal skin acts as the first line of defense against herpes simplex virus infection. Mucosa, conjunctiva and skin damaged by eczema, burns, trauma or infection are more susceptible than normal skin. IgM, IgG and IgA antibodies are produced directly in patients infected with herpes simplex virus. The importance of antibodies against viral proteins is unclear. Specific antibodies do not prevent viral reactivation or neonatal infections. However, antibodies may play a role in changing the severity of infection.

Interferon also participates in the control of herpes simplex virus infection by inhibiting viral or immunoregulatory mechanisms. Genetic factors may also be involved in herpes virus infection. Cellular immunity is very important in controlling herpes simplex virus infection, congenital, acquired or iatrogenic. Patients with cellular immunodeficiency may have a more frequent, severe and long-term herpes virus infection. In patients with herpes simplex virus infection, there are maternal cell reactions, antibody-dependent or non-antibody-dependent cytotoxicity and natural killer cell activity, cellular immunity. It can limit infection, but it can't block latent infection and reactivation. Unlike cytomegalovirus, herpes virus can't replicate in human alveolar macrophages, which explains why herpes simplex virus is rarer than cytomegalovirus.

In addition to immunosuppressive factors, many factors can cause reactivation of latently infected viruses, including physiological, pathological, and psychiatric stimuli, which may depress the genes of latent viruses through cellular, humoral, or neuroendocrine pathways. Immunity monitoring mechanisms are dysfunctional, eventually leading to latent virus reactivation, such as fever, excessive sun exposure, menstrual cramps, taking corticosteroids, postpartum, trauma, alcoholism or any type of serious illness, HSV easily reactivated high-risk patients including the elderly, Hodgkin's disease, certain leukemias, acquired immunodeficiency syndrome (AIDS), acute respiratory distress syndrome (ARDS), organ transplants or tumor patients treated with immunosuppressive agents, T-lymphocyte function or number of these patients There are varying degrees of inhibition or reduction, so patients with impaired cellular immunity should closely observe signs of HSV infection.

Recently, herpes simplex virus may be an important cause of respiratory infection, especially in immunosuppressed patients. Herpes simplex pneumonia is caused by direct dissemination of upper and lower respiratory viruses, while diffuse herpes simplex pneumonia is derived from reproduction. Caused by a virus diffused from an organ or oral lesion (most likely blood-borne), viremia of HSV-1 and HSV-2 has been found, both of which are associated with diffuse infection, most of which are due to endogenous The activation of sexual viruses is partly caused by widespread dissemination of herpes simplex virus infection. Exogenous reinfection is rare. Herpes simplex virus infection in oral mucosa often precedes localized pneumonia, which is associated with herpes simplex bronchitis or esophagitis. However, herpes simplex virus pneumonia can also occur in patients without skin mucosal herpes virus infection. Tracheal injury secondary to endotracheal intubation or burn is likely to cause herpes simplex virus to spread directly to the lower respiratory tract, cytotoxic drug chemotherapy. And radiotherapy can also destroy the normal upper respiratory tract mucosa, affecting the regeneration of mucosal cells and promoting the spread of the virus.

Pathological changes: inflammatory infiltration of lung tissue, necrosis of lung parenchyma, hemorrhage, cell swelling and roundness, diffuse interstitial pneumonia, and most of the cell alteration characteristics associated with herpes virus infection, such as nuclear eosinophilic inclusions, may have Necrotizing herpes simplex virus bronchitis or herpes simplex esophagitis, herpes simplex bronchitis, manifested as mucosal erythema, edema, exudation and ulceration, the surface can be covered with fibrous purulent membrane-like secretions.

Herpes simplex virus pneumonia prevention

There is no special prevention method for HSV infection. Because HSV, especially HSV-2, is closely related to cervical cancer, it is generally not recommended to use conventional vaccine prevention. However, if the glycoprotein antigen on the viral envelope is isolated and purified as a vaccine, viral nucleic acid can be avoided. Potential cancer risk.

In patients who received bone marrow transplantation for the first 5 weeks after positive HSV antibody transplantation, 80% of patients had a chance of reactivation of the virus. HSV antibody-positive acute leukemia patients developed HSV infection 25% during induction chemotherapy. Some authors also found that: In 48% of patients with acute leukemia, HSV reactivation was initiated on average 17 days after induction of chemotherapy. Another study suggested that 66% of patients with HSV antibody-positive patients reactivated the virus, and patients with negative HSV antibodies were not infected, and immunocompromised cancer patients Repeated infections of HSV, especially hematological tumors, may be more common than patients with no immune damage, severe and long-lasting, such as no antiviral treatment, continuous spread of the virus, increased lesions, and bacterial and fungal infections. Increased risk.

The prevention of HSV infection in acyclovir is effective in patients with acute leukemia chemotherapy or in patients undergoing bone marrow transplantation. It is especially effective for intravenous administration. Other cancer patients with positive serum antibodies should not be given prophylactic medication unless it is determined during chemotherapy. In combination with HSV infection, once the drug is administered continuously throughout the chemotherapy period, or until the immune suppression state is restored, patients with acute leukemia induction chemotherapy should continue to use the drug during the consolidation and maintenance phase of leukopenia and chemotherapy. Lowive for at least 4 to 6 weeks, prophylactic intravenous acyclovir 250mg/m2 every 12 hours, 90% of patients can produce viral suppression, according to the pharmacokinetics of acyclovir, every 12 hours 75 ~ Intravenous application of 125mg/m2 may also be effective. Prophylactic oral acyclovir is also effective. 800mg orally, twice a day, can have obvious preventive effects. However, in cancer patients, intravenous and oral administration can be combined, especially when patients Prophylactic oral administration of acyclovir should be limited to people who may be infected when nausea, vomiting, or difficulty swallowing.

Herpes simplex virus pneumonia complications Complication

It can be accompanied by diffuse fungi, cytomegalovirus or bacterial infections.

Herpes simplex virus pneumonia symptoms common symptoms herpes respiratory failure

The clinical manifestations of herpes simplex pneumonia are similar to those of other lower respiratory tract infections: cough, shortness of breath, fever (>38.5 ° C), decreased white blood cells, lung vocalization, hypoxemia, respiratory insufficiency, azotemia, common The initial symptoms are shortness of breath and cough. HSV pneumonia may be associated with HSV damage of the skin and early stage of pneumonia. It may be accompanied by diffuse fungi, cytomegalovirus or bacterial infection. Herpes simplex viral tracheobronitis may be routine. Ineffective treatment of bronchospasm or stenosis, patients without chronic lung disease and no immunosuppressive diseases, sometimes can cause acute respiratory failure requiring mechanical ventilation.

The clinical manifestations and radiological manifestations of HSV pneumonia are non-specific. The diagnosis of herpes simplex pneumonia, in addition to the clinical manifestations of pneumonia, depends on the histological basis of HSV pulmonary infection and the isolation of lung viruses, directly isolated from the lower respiratory tract. The virus, preferably from the lung tissue, has a definitive diagnostic significance. Tracheoscopy combined with cytology and viral culture is diagnostic, although not required, but can provide tissue specimens, fiberoptic bronchoscopy showing tracheobronchial mucosal ulcers and (or Covered with a pseudomembrane that guides aspiration, bronchial flushing or biopsy, cytology and histology can provide specific evidence of HSV infection: multinucleated giant cells and intranuclear eosinophilic inclusions, and biopsy specimens for examination Sexual infiltration, substantial necrosis and hemorrhage.

In immunosuppressed patients, if there is a wide range of skin mucosal herpes simplex virus infection with limited or extensive pulmonary infiltration, especially in the presence of esophagitis or bronchitis or the discovery of herpes simplex virus spread to other organs should consider herpes Viral pneumonia, further, patients with oral mucosal herpes simplex virus infection should consider the possibility of secondary herpes simplex pneumonia when intubating the trachea. Virus biopsy tissue culture should be carried out, histological examination, by immunofluorescence Tissue examination of herpes simplex virus antigen.

Patients with acute bronchospasm who are not responding to conventional therapy should consider the possibility of herpes simplex virus lower respiratory tract infection.

Herpes simplex virus pneumonia check

HSV virus can be obtained from tracheobronchial secretions, bronchoalveolar lavage fluid, lung tissue, and specimens collected by fiberoptic bronchoscopy should be performed early. Percutaneous fine needle aspiration lung biopsy and open lung biopsy do not help much, skin mucosal damage The highest isolation rate of virus in vesicle fluid is 80%-98%. When the ulceration and healing separation rate is decreased (<25%), the collection and transportation of specimens are very important in the process of virus isolation. Specimens should be collected as soon as possible. Because the possibility of isolation of the virus after disease progression is reduced, timely inoculation after collection of specimens may have a higher rate of virus isolation. The conditions for transporting and storing specimens must be taken care of. Specimens should not be placed at -20 °C until formal testing. Freezing in the refrigerator; specimens can be stored at 4 ° C for 48 h during transport.

The laboratory diagnosis of HSV infection should be evaluated in two aspects: first, determine whether the patient is emitting the virus, whether there is a current infection of HSV for active antiviral therapy, and secondly, determine the patient's serum before the suspicious patient reactivates the clinical symptoms. Whether the antibody is positive to check for past HSV infection to determine whether prophylactic antiviral therapy is necessary before bone marrow transplantation, organ transplantation, and induction chemotherapy.

Cell culture

Tissue culture is the most sensitive and specific diagnostic method, and can also be used for virus typing. Positive results can be obtained within 24 to 48 hours of high titer of virus, and characteristic in 90% of medium can be produced within 72 hours after inoculation. The cytopathic effect; while in low-titer specimens, characteristic changes can be seen after 7 days. However, tissue culture does not always establish the presence of the virus because of the poor collection and delivery of specimens and the use of antiviral drugs. A false negative may occur.

2. Detection of viruses

(1) Papanicolaou (Pap) or Tzank test: It is a fast and inexpensive method for cell diagnosis. First, the staining of the scraping cells in the lesion site can show cell changes within 20 min, that is, multinucleated giant cell formation, cytoplasmic vacuolization. And inclusion bodies, positive smear results are reliable, but can not distinguish between varicella-zoster virus (VZV) and HSV-1 or HSV-2, negative smear can not rule out herpes virus infection, in an ideal situation Tzanck smears are approximately 50% positive, have low sensitivity and specificity, and rely on the experience of the tester; applications are limited due to many technical and practical reasons.

(2) Indirect immunofluorescence staining of monoclonal antibodies: for lesions, the sensitivity is 78% to 88%, false positives are rare, direct electron microscopy is very attractive, because it can be completed within 2h, but sensitivity It is versatile and low in specificity. The enzyme-linked immunosorbent assay is used for the detection of herpes simplex virus. The sensitivity is up to 95% and the specificity is high. However, if the specimens are not checked immediately after collection, the sensitivity is decreased, and radioimmunoassay is also used. Methods for the detection of herpes simplex virus, fluorescein-labeled antibody test, indirect immunoperoxidase test or enzyme immunoassay using monoclonal antibodies, etc. These methods are inexpensive, rapid, do not require cell culture techniques, and newly produced monoclonal antibodies The antibody is rapidly sensitive to the centrifugation technique of direct fluorescein-labeled antibody staining, but is more commonly used for the diagnosis of cytomegalovirus. The direct detection of HSV antigen by immunofluorescence has high specificity but poor sensitivity and depends on the quality of the specimen.

Enzyme immunoassay (EIA) measures HSV antigen, and has amplification technique and direct detection technology. The results show that HSV EIA is highly sensitive (93.7%) and highly specific (96.6%) to specimens of various origins; Good, rapid (4h), specimens affected by bacterial contamination, patients who have been cured or undergoing antiviral therapy are unreliable, virus culture of tracheobronchial specimens and lower respiratory secretions, positive results usually take 2 to 5 days However, a negative result takes 2 weeks to determine.

(3) Application of DNA probe technology: DNA probes are helpful for the diagnosis of HSV infection. DNA probes can be diagnosed when cell morphology is suspicious. Several factors can confuse morphological diagnosis:

The 1HSV inclusion bodies are similar to the inclusion bodies of cytomegalovirus (CMV) and adenovirus (adenovirus).

2 When HSV and CMV are infected,

3 In addition to HSV other respiratory viruses can also produce multinucleated cells, in situ hybridization allows specific viral genome sequences to be located, which is simpler and faster than traditional methods.

(4) Polymerase chain reaction (PCR): PCR can provide a conclusive basis for HSV infection. Even if there is a consistent viral pathological change in paraffin-embedded tissues, negative control tissue must be present for each examination, although The possibility of latent infection, but for control tissues without viral pathological changes, PCR test is still negative for HSV. If appropriate control is performed, the method is rapid (completed within 1 day), accurate and specific, sensitive, and can be stale or Complex specimens were processed, PCR and HSV culture results were similar, PCR did not have many technical and practical limitations of Tzanck smear and virus culture, and PCR showed superiority in immunosuppressed patients with rapid diagnosis of suspected HSV virus infection.

3. Serological examination

The greatest value of this method is to prove that the patient has been infected with HSV. The anti-HSV antibody in the blood circulation is a possible sign of repeated infection. The increase of antibody titer by 4 times or more indicates the recent infection of HSV. HSV antibody can be detected by many methods. Including complement binding assays, microneutralization assays and enzyme immunoassays, these methods are highly sensitive and reliable, but serological tests do not distinguish between endogenous viral infections and reinfections. Serological tests have no diagnostic significance and do not contribute to rapid diagnosis. Another problem is the cross-reactivity of HSV-1 and HSV, so the serotype of HSV acute infection cannot be determined. Serological tests can be used to diagnose primary HSV infection only when there is no HSV antibody in the acute phase serum. If the antibody in the serum of the recovery period appears, it can be called seroconversion. When the antibody titer is not increased in HSV pneumonia, the prognosis is often poor, and the virus is easily spread.

4. Virus typing

The three commonly used methods are herpes simplex virus typing. First, they are cut by restriction endonuclease and separated by agarose gel electrophoresis. The DNA types of HSV-1 and HSV-2 are different. Identification of HSV-1 and HSV-2, the second method for virus typing with fluorescein-labeled specific monoclonal antibodies, which has the advantage of rapid and direct detection of sections and media, the third method In order to use 5-bromovinyldeoxyuridine (BrdU), this substance can only block HSV-1 replication by maintaining an appropriate concentration in the cell culture medium. HSV serotyping is important for epidemiology, which is rarely needed by clinicians. Information, HSV genital tract infections and HSV encephalitis exceptions.

For non-fatal HSV infection, laboratory tests for virus culture can be performed because the infection is often clinically identifiable, virus confirmation can be obtained within a few days after the specimen is extracted, and immediate antiviral therapy is required for fatal HSV infection. Therefore, the diagnosis of HSV infection must be performed quickly and accurately. The best method is immunofluorescence staining. Patients with severe HSV infection have a good prognosis for early antiviral therapy, although they can be treated with antiviral therapy before diagnosis. The results of the examination can prompt doctors to start antiviral treatment as soon as possible. Patients with severe HSV infection in newborns may have only skin lesions as evidence of HSV infection. Rapid diagnosis is particularly important. If diagnosis and treatment are delayed, dissemination of other parts will soon occur. The prognosis will be significantly worse. In patients with asymptomatic HSV infection, the HSV rapid diagnostic test cannot be overemphasized.

X-ray films are more difficult to distinguish from other lung infections, showing localized, multiple or diffuse interstitial infiltration, with early typical hilar or diffuse interstitial density, thickening of the bronchial wall, with the condition Progress can be seen with patchy alveolar tamponade, herpes simplex viral tracheobronchitis chest radiographs can be normal.

Diagnosis and identification of herpes simplex virus pneumonia

Herpes simplex virus pneumonia can be identified by DNA probe, PCR technique and immunological examination with cytomegalovirus pneumonia, herpes zoster pneumonia, etc. Separation of virus-associated pneumonia from skin mucosal lesions cannot establish a diagnosis, upper respiratory tract and The isolation of HSV virus from the parotid gland has no diagnostic significance, and serological examination has no diagnostic significance.

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