Summary Since 1958, it has been proved in all parts of China that adenovirus can cause pneumonia in children besides upper respiratory tract infection, and it is most common in infants aged 6 months to 2 years, especially in northern provinces, with more severe patients than in the south. In the winter of 1958 and 1963, there was a large-scale epidemic of adenovirus pneumonia in North China, Northeast China and Northwest China, and the condition was extremely serious.
The diagnosis should be based on the epidemic situation and combined with clinical diagnosis. The differences between typical infantile adenovirus pneumonia and general bacterial pneumonia in the early stage are as follows: ① Most cases have persistent high fever at the onset or shortly after onset, which is ineffective after antibiotic treatment; ② Nervous symptoms such as drowsiness and fatigue appeared on the 3rd to 6th day after onset. Sometimes sleepiness and irritability appear alternately, with pale face and obvious hepatomegaly, which is prone to complications such as heart failure and convulsions in the future. The above symptoms suggest that adenovirus pneumonia not only involves respiratory tract, but also other systems. ③ The lung signs appeared late, generally after the 3rd to 5th day of onset, the lesion area gradually increased, and it was easy to produce voiced sound and decreased breathing sound, and wheezing became more and more serious in the 2nd week of onset. ④ The total number of white blood cells is low, most of the children do not exceed12×109/L (12000/mm3), and the neutrophils do not exceed 70%. The alkaline phosphatase and tetrazolium blue staining values of neutrophils were significantly lower than those of pyogenic bacterial infection, but they increased again if pyogenic bacterial infection was combined. ⑤ The X-ray examination of lung may have a large flaky shadow, especially at the lower left. In short, in the epidemic season of this disease, when the baby has severe pneumonia and the X-ray and blood picture are consistent, a preliminary diagnosis can be made. Conditional units can carry out rapid virus diagnosis. At present, immunofluorescence technique (indirect method is more suitable than direct method), enzyme-linked immunosorbent assay and specific IgM determination can be carried out, but these three methods can not classify adenovirus, which is its deficiency. However, routine throat swab virus isolation and double serum antibody examination are only suitable for laboratory as retrospective diagnosis.
4 treatment measures for general treatment, please refer to the treatment chapter of bronchopneumonia. The following focuses on the experience gained in clinical practice in recent years. ① Antiviral drugs have yet to be vigorously studied. The effect of ribavirin on adenovirus pneumonia is not obvious. Intravenous and/or intramuscular injection in early cases is better than that in control group, but the effect in late cases is not obvious (Beijing Children's Hospital and Institute of Pharmacology, Academy of Medical Sciences,1978 ~1980); The research of atomization inhalation therapy needs to be carried out urgently. ② Pay attention to the prevention and treatment of secondary bacterial infection. If there is a secondary infection, it should be actively treated, such as new penicillin and cephalosporin for Staphylococcus aureus infection; Escherichia coli was treated with aminobenzylpenicillin, etc. ③ Chlorpromazine and promethazine were used for sedation, spasmolysis and asthma. ④ Use digitalis to control heart failure. ⑤ Blood transfusion, plasma transfusion or application of gamma globulin may play an auxiliary role. ⑥ Proper oxygen delivery and infusion, if handled properly, can help sick children get through the critical period. ⑦ Early patients tried adrenocortical hormone, but no curative effect was found; However, when there are obvious symptoms of respiratory obstruction and severe poisoning (convulsion, coma, shock, persistent high fever above 40.6℃, etc.). ), short-term hormone therapy should be applied intravenously. ⑧ Specific horse serum treatment. 196 1 ~ 1964 to observe the clinical efficacy of horse serum against adenovirus types 3 and 7, and the conclusions are different. 1973, the process of the serum was improved and the titer was increased. It has been applied in Jilin, Heilongjiang and other provinces, and it is considered that it has the functions of rapid cooling, early disappearance of symptoms and less afterlife, and has achieved good curative effect (Pediatrics of Bethune Medical University, Changchun Institute of Biological Products, etc. ). However, products after 1976 are more likely to cause serum sickness. Pet-name ruby in the recovery period, such as lung signs slowly disappear, appropriate physical therapy.
Chinese medicine therapy? The treatment of adenovirus pneumonia mainly focuses on dispersing lung, clearing heat and detoxicating in the early stage, and resolving phlegm in the middle stage, so as to strengthen the body resistance and strengthen the foundation and save the adverse events in severe stage. According to the experience of Pu Fuzhou, an old doctor in the Institute of Traditional Chinese Medicine, pneumonia is an exogenous disease, not limited to the category of febrile diseases, including wind, cold, summer and dampness. The focus of pneumonia is always in the lung, and in severe cases, it can involve other organs. Treatment is divided into active treatment and adverse event rescue. The principle of treatment is to spread the lung and eliminate the evil in real time, and to save adverse events, we need to use the methods of nourishing yin and restoring yang, supplementing qi and replenishing fluid, that is, the active treatment is mainly to spread the lung and penetrate the exterior, and the treatment of adverse events is mainly based on syndrome differentiation. Specifically, it can be summarized as one of the eight methods of conditioning after illness. (1) solution: add and subtract Sangju decoction with onion and black bean soup for wind-heat invading the lungs, and add and subtract Yinqiao powder for too hot; Cold attacks the lungs, using Su Xing powder and onion drum soup; Summer evil, add and subtract and drink with fragrance. (2) Exterior-interior double solution: exterior cold and interior heat are treated with Maxingshi dry soup; External cold and internal heat, I used Xiaoqinglong plus gypsum soup. If the internal drink is not heavy, there is phlegm in the throat, watery chicken crow, pale or reddish tongue and floating pulse, I used Shegan Mahuang decoction to treat it. It is suggested that Guizhi Houpu Almond Decoction be used to treat exterior depression and internal cold. Epistasis is heated with Gegen Qinlian decoction; Treatment of facial depression and chest obstruction with Xiaoxian decoction and Gualou Xiebai decoction. (3) strengthening yang and promoting diuresis: dampness evil is flavored with Qianjin Weijing decoction; If damp heat closes the lungs, the body is faint, and the body is white, it is treated with coix seed and bamboo leaf powder. (4) Method of clearing heat and nourishing yin: 3g of American ginseng and 5g of bezoar powder were taken evenly for five times; If you enter the camp in vain, you should use the agent of clearing the camp and detoxifying, supplemented by an announcement; The residual heat is not exhausted, and the bamboo leaf gypsum soup is added or reduced; Summer heat injures lung qi, imitating Yvonne Wang's method of regulating qi in summer heat. (5) Method of reducing qi and resolving phlegm: Asthma due to unfavorable qi, Perilla Jiangqi Decoction should be modified; Liver-qi goes up and down, so it is advisable to replace the ochre decoction. (6) The method of opening and closing the body can not heal after a long illness, and the lung qi is already deficient, and the pathogenic factors are still very close. Polygonatum odoratum, polygala tenuifolia, japonica rice, jujube and terminalia chebula should be used to tonify lung qi in order to strengthen the body resistance and consolidate the foundation; If the lungs are very closed, you can make up a little bit of burnt ephedra, almond, gypsum, platycodon grandiflorum, scallion and the like, and attack and mend the opening and closing. (7) The method of consolidating yin and descending adverse flow: the fire goes against the wind, so it is advisable to add or subtract Maimendong decoction; Both gas and liquid injuries should be seasoned with raw wheat flour; Yin fluid is exhausted, and it is advisable to use Sanjia Fumai Decoction; Long-term illness hurts yin, so it is advisable to add or subtract wind beads. (8) The method of restoring yang to save the inverse: Drink Shenfu decoction or Fu Jiang decoction frequently. In addition, conditioning after illness: spleen and stomach are not adjusted, and Erchen decoction is used to add flavor; People with spleen and stomach deficiency and cold are treated with Magnolia Officinalis, Ginger, Pinellia ternata, Glycyrrhiza uralensis and ginseng soup; Deficiency and annoyance after illness were treated with gardenia black bean soup; Deficiency of middle qi, use Buzhong Yiqi decoction to add and subtract.
DIC has been observed in severe adenovirus pneumonia since 1970s. The addition of drugs for promoting blood circulation and removing blood stasis in Beijing Friendship Hospital has certain effect on the prevention and treatment of DIC. Chinese angelica, red peony root, Ligusticum wallichii, Spatholobus suberectus, leech, tabanus, astragalus root, etc.
The etiology of adenovirus is known to be 4 1 serotype, many of which are closely related to human upper and lower respiratory tract infections. From the etiological observation of hospitalized children in northern and southern China, it is proved that adenovirus types 3 and 7 are the main pathogens of adenovirus pneumonia. The virus can be isolated from throat swabs, feces or postmortem lung tissues, and the serum antibody titer in recovery period is more than 4 times higher than that in early period (5 ~ 10 days or earlier). The same result was obtained in some severe cases of measles complicated with pneumonia. Adenovirus 1 1 was also found to be a common pathogen of pneumonia and upper respiratory tract infection in Beijing and other places (Institute of Pediatrics, 1964 ~ 1966). In addition, types 2 1, 14 and 1, 2, 5 and 6 are gradually appearing in Chinese mainland, while types 1, 2, 5 and 6 are the main types in Taiwan Province province. Recently, Bethune Medical University analyzed the genome types of adenovirus types 3 and 7 isolated from 1976 ~ 1988, which proved that 7b caused severe pneumonia.
Adenovirus is a kind of DNA virus, which mainly reproduces in the nucleus. It has strong resistance to temperature, acid and fat solvents, and it breeds in the intestine besides pharynx, connective tissue and lymphatic tissue. It can be divided into three groups according to its agglutination ability to red blood cells of special animals. Groups 3, 7, 1 1, 14, 2 1 which are easy to cause pneumonia in infants can agglutinate monkey red blood cells.
Pathological changes Focal or fused necrotizing lung infiltration and bronchitis are the main pathological changes of this disease. Pneumonia consolidation can occupy the whole lung lobe, especially the lower left lobe. On the lung section, tubes composed of yellowish-white necrosis can be extruded from the consolidation area, and there are many obvious emphysema in the lung tissue other than consolidation. Microscopically, the lesions are mainly bronchitis and inflammation around bronchi, which often progresses to necrosis and exudate fills the whole lumen. There is also exudate in the alveolar cavity around the bronchus, mostly lymph, monocytes, serous fluid and cellulose, sometimes accompanied by bleeding, while neutrophils are few, and the alveolar wall is also common necrosis. Bronchial or alveolar epithelial hyperplasia can be seen at the edge of the inflammatory area. Intranuclear inclusions are common in proliferating and swollen epithelial nuclei, similar in size to normal red blood cells, with clear boundaries, eosinophilic or bichromatic staining and a transparent circle around them. The nuclear membrane is clear, and a small amount of chromatin accumulates on the inner surface of the nuclear membrane; However, there are no inclusion bodies in the cytoplasm and no multinucleated giant cells are formed. Therefore, it can be morphologically distinguished from measles virus pneumonia and giant cell inclusion disease of lung. In addition, there are interstitial inflammation and proliferation of small blood vessel wall cells in various organs of the whole body, such as the central nervous system and the heart.
Epidemic gonadal virus is generally transmitted through respiratory tract. In collective children's institutions, adenovirus upper respiratory tract infection and pneumonia often occur at the same time. Population serological studies show that adenovirus-specific antibodies from the mother often remain in the first few months after birth, and then the antibodies are lacking until the age of 2, and gradually increase after the age of 2. This is completely consistent with the clinical observation that 80% of adenovirus pneumonia occurs in infants aged 7-24 months. It is worth noting that the more susceptible people of all ages, the more people with adenovirus respiratory infection, and the greater the chance of infants suffering from adenovirus pneumonia. Adenovirus pneumonia is more common in winter and spring in northern China, only occasionally in summer and autumn, and more common in Guangzhou in autumn. This kind of pneumonia accounts for about 20% ~ 30% of Beijing viral pneumonia.
8 clinical manifestations? According to 1959- 1963, the clinical characteristics of 245 cases of adenovirus pneumonia of type 3 and 7 diagnosed by virology in Beijing can be summarized as follows.
1. Symptoms
(1) onset: the incubation period is 3-8 days. Generally, sudden fever usually occurs with high fever above 39℃ on 1 ~ 2 days, and late or irregular high fever on 3 ~ 4 days; More than 3/5 patients have a maximum body temperature of over 40℃.
(2) Respiratory symptoms: Most children have coughs since the onset, often manifested as frequent cough or mild paroxysmal cough, and congestion in the pharynx can be seen at the same time, but the symptoms of nasal mucositis are not obvious. Dyspnea and cyanosis mostly started from the 3rd to 6th day, and gradually increased. Severe cases include alar flap, depression sign, wheezing (obstructive dyspnea with wheezing and breath holding) and cyanosis of labial nail. Percussion is easy to get voiced; The voiced part is accompanied by the weakening of breathing sounds, and sometimes tubular breathing sounds can be heard. The initial auscultation is mostly rough or dry rales, and after 3 ~ 4 days of onset, wet rales appear, which get worse day by day, often showing signs of emphysema. Severe children may have pleural reaction or pleural effusion (more common in the second week), and the exudate without secondary infection is grass yellow and not turbid; When there is secondary infection, it is turbid liquid, and its white blood cell count is greater than10×109/L.
(3) Symptoms of nervous system: Generally, drowsiness and discomfort appear 3-4 days after onset, and sometimes irritability and discomfort appear alternately. In severe cases, semi-coma and convulsion occurred in the middle and late stage. Some sick children have their heads tilted back and their necks stiff. In addition to toxic encephalopathy, there are encephalitis caused by adenovirus, and sometimes lumbar puncture is needed to identify it.
(4) Symptoms of circulatory system: pallor is more common, and in severe cases, the complexion is gloomy. The heart rhythm increases rapidly, with mild symptoms generally not exceeding 160 beats per minute, and severe symptoms mostly between 160 ~ 180 beats, sometimes reaching more than 200 beats. Electrocardiogram usually shows sinus tachycardia. In severe cases, the right heart load increases, T wave and ST segment change, and the voltage is low. Some cases have 1 ~ 2 degree atrioventricular block, and occasionally have pulmonary P wave. 35.8% of severe cases developed heart failure on the 6th-14th day. The liver is gradually enlarged, reaching 3 ~ 6 cm under the ribs, with hard texture and a few splenomegaly.
(5) Symptoms of digestive system: More than half of them have mild diarrhea and vomiting, and severe cases often have abdominal distension. Diarrhea may be related to adenovirus propagation in intestine, but in some cases, it may also affect digestive function due to serious illness and high fever.
(6) Other symptoms: catarrhal conjunctivitis, red papules, maculopapules, scarlet fever-like rash, and low incidence of calcareous white spots on tonsils, which are also special signs in the early stage of this disease.
2. X-ray inspection
X-ray morphology is closely related to the condition and stage of the disease. Thickening and blurring of lung texture is the early manifestation of adenovirus pneumonia. Lung consolidation usually begins on the 3rd to 5th day after onset, and there may be patchy or fused lesions of different sizes, especially in the lower field of both lungs and the upper lobe of the right lung. 6 ~ 1 1 day after onset, the density of lesions increased with the development of the disease, and the lesions also increased, distributed widely and merged with each other. Different from lobar pneumonia, the pathological changes of this disease are not limited to a certain lobe. Most lesions were absorbed after 8 ~ 14 days. Sometimes mixed infection should be suspected if the lesion continues to increase and the condition worsens. Emphysema is common, and there is no obvious difference between early stage and extreme stage. It is bilateral diffuse emphysema or peripheral emphysema (figure 1). 1/6 cases may have pleural changes, and most of them have pleural reaction or effusion in the extreme stage.
Figure 1 adenovirus pneumonia, emphysema
3-year-old girl. After 8 days of high fever and cough, adenovirus type ⅶ was isolated from throat swab. X-ray chest film shows that the right hilum is dense, the bilateral pulmonary veins are getting thicker and thicker, and the right lung has a patchy shadow. The transparency of both lungs was significantly improved. The diaphragm is located at the level of 10 posterior rib, and the radian of diaphragm surface is flattened, which is a serious manifestation of emphysema.
3. Course of disease
According to the respiratory system and poisoning symptoms, the disease is divided into mild and severe. The heat type is inconsistent, mostly staying above 39 ~ 40℃, followed by irregular heat and rare relaxation heat. Mild symptoms generally include a sudden drop in body temperature from 7 to 1 1, and other symptoms disappear quickly, but it takes 2 to 6 weeks for lung shadow to be completely absorbed. In severe cases, obvious drowsiness appeared on the 5th to 6th day, with pale and gray face, obvious hepatomegaly, obvious wheezing, large consolidation of the lungs, and heart failure, convulsion and semi-coma in some cases. The fever of the recovered patients decreased from 10 to 15, half of them suddenly retreated, half gradually retreated, and sometimes suddenly retreated with afterglow of fever, and returned to normal after 1 ~ 2 days. The recovery period of lung disease is long, which takes 1 ~ 4 months. Those who do not absorb after 3 ~ 4 months often have atelectasis, which may develop into bronchiectasis in the future. We followed up adenovirus pneumonia types 3 and 7 for 1 ~ 5 years, and 30. 1% had chronic pneumonia, atelectasis and individual bronchiectasis. Later 109 adenovirus pneumonia type 3, 7, 1 109 follow-up 10 years. Plain film showed that 45.3% had pulmonary interstitial thickening, fibrosis and chronic bronchitis. Chronic pneumonia complicated with bronchiectasis accounted for 3.8%; Bronchiectasis and chronic pneumonia accounted for 4.7% respectively.
Adenovirus pneumonia in preschool and school-age children is generally mild and persistent with high fever, but the symptoms of respiratory tract and nervous system are not serious. When measles is complicated with or secondary to adenovirus pneumonia, all symptoms are serious, and the condition is often prone to sudden deterioration.
We observed the clinical manifestations of 34 cases (1964 ~ 1980) of adenovirus pneumonia 1 1. There was no obvious difference between the symptoms of adenovirus pneumonia types 3 and 7, but the severity and death were similar to those of adenovirus pneumonia type 3, but less than those of adenovirus pneumonia type 7.
Clinical features of adenovirus pneumonia in infants aged 1 ~ 5 months: We observed 38 cases (20 cases of type 3, 7 cases of type 12, 1 1 case,1981~1988). The incidence of neurological symptoms, such as discomfort and drowsiness, is less and lighter than that of infants over 6 months old, which can not be distinguished from respiratory syncytial virus or parainfluenza virus pneumonia in clinic, resulting in no 1 case of adenovirus pneumonia in this group before the etiological report.
9 Complications During the course of adenovirus pneumonia, staphylococcus aureus, Escherichia coli, pneumococcus, pneumobacillus, Pseudomonas aeruginosa and other infections may be complicated, making the condition worse. In the late stage of adenovirus pneumonia, the following points often suggest the existence of secondary bacterial infection: ① The condition has not improved about 10 days after onset, or it has been aggravated after once remission; (2) The sputum turns yellow or washed with rice; ③ suppurative lesions in other parts of the body; ④ Empyema; ⑤ New shadows appear in X-ray examination; ⑥ The white blood cell count increases, the proportion of neutrophils increases or the nucleus moves to the left; ⑦ The staining value of neutrophil alkaline phosphatase or tetrazolium blue increased.
In the extreme stage of severe adenovirus pneumonia (day 6 ~ 15), a few cases may be complicated with disseminated intravascular coagulation (DIC), especially when there is secondary bacterial infection. There was microcirculation dysfunction before DIC, which was initially limited to a small amount of bleeding in respiratory tract and gastrointestinal tract. There may be massive bleeding in the lungs, gastrointestinal tract and skin in the future. The diagnosis of the disease is determined by primary screening test, primary screening test and final test. Positive fecal occult blood test and decreased platelet count are important indicators of the primary screening test. The positive diagnosis is based on two abnormalities in thrombocytopenia, fibrinogen decrease and prolongation of prothrombin time or one abnormality in protamine paracoagulation test (triple P test), ethanol gel test and euglobulin lysis time test.
Changchun Bethune Medical University found severe cases or patients complicated with adenovirus type 7 or 3 myocarditis, with acute onset and quick recovery. It is usually seen in the early second week of the course of the disease and quickly recovers with the elimination of myocardial hypoxia and edema. However, due to heart failure, myocarditis is often missed; Attention should be paid to sudden pallor, hyperhidrosis, vomiting, abdominal pain, enlarged heart, accelerated or slowed heart rate, hepatomegaly, etc. Routine electrocardiogram and myocardial enzyme examination should be performed to confirm the diagnosis.
The total white blood cell count of 10 was mostly decreased or normal at the early stage (day 1 ~ 5), about 62% of cases were lower than10×109/l (10000/mm3), and 36% were (. Blood smear, neutrophil alkaline phosphatase and tetrazolium blue staining are generally lower than those of normal children or children with bacterial pneumonia. Although the total number of white blood cells is as high as 15000, the index of alkaline phosphatase of white blood cells is still significantly reduced. Some sick children can be positive for serum concentration test. During the period of fever, some cases have a small amount of protein in urine. Cerebrospinal fluid examination in children with meningeal symptoms is generally normal.
1 1 Special attention should be paid to preschool and school-age children in differential diagnosis. The clinical manifestations of adenovirus and mycoplasma pneumonia are almost the same, with symptoms such as high fever, dyspnea and lethargy, which are not obvious. However, there are signs in general adenovirus pneumonia. Some mycoplasma pneumonia only has X-ray shadow without rales or other signs, which can help to differentiate. Many cases can only rely on laboratory-specific diagnosis.
The clinical manifestations of adenovirus pneumonia in infants under 5 months old are obviously lighter than those in infants, so it can not be distinguished from pneumonia caused by respiratory syncytial virus and parainfluenza virus, and can only rely on rapid diagnosis or etiological diagnosis.
12 oral attenuated live vaccine against adenovirus types 3, 4 and 7 has been proved to have preventive effect by small-scale application abroad, but it has not been produced and applied on a large scale. During the epidemic, especially in the ward, it is necessary to isolate as much as possible to prevent cross-infection; Do more home treatment areas for infant influenza, and pay special attention to the nurses who isolate and avoid colds at an early stage to continue their nursing work in kindergartens, so as to reduce the chance of transmission.
13 has a serious prognosis in northern China. 1958 during the first epidemic, the mortality rate of hospitalized patients was as high as 25%. After the treatment of integrated traditional Chinese and western medicine, the mortality rate dropped to 5% ~ 10%. In recent years 10, there was no obvious epidemic situation, and sometimes the number of cases in the north even dropped to the second place (RSV pneumonia was the first), and the illness was alleviated, with the mortality rate below 5%. During the epidemic period, most deaths occurred on the first 10 ~ 15 days of the disease course. The main factors affecting the prognosis are: ① lack of specific antibodies in young age, most of the deaths occurred in children aged 6 ~ 18 months, and almost no deaths occurred in children over 2 years old; ② If measles, systemic pneumonia or other severe diseases are complicated or secondary, the mortality rate is high, and the prognosis is also serious when infected with Staphylococcus aureus or Escherichia coli. ③ Compared with pneumonia caused by adenovirus type 7 and adenovirus type 3, 1 1, there are more severe cases and deaths.
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