Pediatric Adenovirus Pneumonia

　　First, Etiology

　　The pathogen is adenovirus. It is known that there are 41 serotypes of adenovirus, many of which are closely related to human upper and lower respiratory tract infections. The adenovirus pneumonia prevalent in China is mostly caused by type 3 and 7, but types 11, 5, 9, 10, and 21 have also been reported. Clinically, type 7 is more severe than type 3. Observations of pathogenic organisms from inpatients in various parts of northern and southern China (Changchun Institute of Biological Products, 1962; Baqianren Medical University, 1962; Institute of Pediatrics, Chinese Academy of Medical Sciences and Institute of Virology, 1962-1967, 1974-1977; Shanghai First Medical College, 1962-1964; Guangzhou People's Hospital, 1973-1983; Hubei Medical College, 1973-1980, etc.) all prove that type 3 and 7 adenovirus are the main pathogens of adenovirus pneumonia. The virus can be isolated from throat swabs, feces, or post-mortem lung tissue. The antibody titer in convalescent serum rises more than 4 times higher than that in the early stage (5-10 days after onset or earlier). In some severe cases of measles complicated with pneumonia, the same pathogenic examination results were obtained. Beijing and other places also found that type 11 adenovirus is also a relatively common pathogen for pneumonia and upper respiratory tract infections (Pediatric Research Institute, 1964-1966). In addition, types 21, 14, and 1, 2, 5, 6 are also gradually appearing on the mainland of China, while Taiwan is mainly type 1, 2, 5, 6. Baqianren Medical University analyzed the genotypes of type 3 and 7 adenoviruses isolated from 1976 to 1988, proving that type 7 often leads to severe pneumonia.

　　Second, Pathogenesis

　　Adenovirus is a DNA virus, mainly reproduces in the nucleus of cells, with strong resistance to temperature, acid, and liposolvents. In addition to the pharynx, conjunctiva, and lymphatic tissue, it also reproduces in the intestines. It can be divided into 3 groups according to its agglutinating ability to special animal red blood cells. Group 3, 7, 11, 14, 21, which are easy to cause pediatric pneumonia, can all agglutinate monkey red blood cells. The pathological changes of adenovirus pneumonia are extensive, manifested as focal or confluent, necrotic lung infiltration and bronchitis. Both lungs can have large areas of consolidation and necrosis, mainly in the lower two lobes. The lung tissue outside the consolidation can have significant emphysema. The bronchi, bronchioles, and alveoli have infiltration of monocytes and lymphocytes, epithelial cell damage, necrosis and hemorrhage in the wall, significant hyperplasia of alveolar epithelial cells, inclusion bodies in the nuclei of cells.

　　1, Around 10 days after onset, the condition does not improve, or it improves temporarily and then worsens again.

　　2, Phlegm turns yellow or milky rice water color.

　　3. There are purulent foci in other parts of the body.

　　4. Empyema occurs.

　　5. New shadows appear on X-ray examination.

　　6. Increased white blood cell count and increased proportion of neutrophils or left shift of the nucleus.

　　7. Alkaline phosphatase or azo blue staining values of neutrophils increased. In the acute phase of severe adenovirus pneumonia (from the 6th to 15th day of illness), a few cases may have disseminated intravascular coagulation (DIC), especially when there is secondary bacterial infection. Before the occurrence of DIC, there is dysfunction of the microcirculation, which is initially limited to minor bleeding in the respiratory tract and gastrointestinal tract. Later, there may be widespread bleeding in the lungs, gastrointestinal tract, and skin. This condition can be diagnosed by preliminary screening tests, screening tests, and confirmatory tests. Changchun Baosheng Medical University found that severe cases or those with concurrent 7th or 3rd type adenovirus myocarditis are characterized by acute onset and rapid recovery. It is generally seen in the early stage of the 2nd week of the disease course. With the elimination of myocardial hypoxia and edema, recovery is relatively fast. However, due to the occurrence of heart failure, myocarditis may be missed. Therefore, attention should be paid to sudden onset of pallor, sweating, vomiting, abdominal pain, enlargement of the cardiac border, and changes in heart rate, as well as liver enlargement. Routine electrocardiogram and myocardial enzyme tests should be performed to confirm the diagnosis. Severe pneumonia may also be complicated with pulmonary fibrosis, chronic pneumonia, atelectasis, and bronchiectasis, etc.

　　1. General Manifestations

　　The incubation period is 3 to 8 days, and the onset is usually acute with fever. The fever pattern of adenovirus pneumonia is inconsistent, often with high fever above 39℃ from the 1st to 2nd day, with most cases maintaining a fever of 39℃ to 40℃ or higher. Secondly, there is irregular fever, and remittent fever is less common. More than 3/5 of the cases have a maximum body temperature exceeding 40℃. Mild cases usually have a rapid drop in body temperature between 7 to 11 days, with other symptoms also disappearing quickly. Infants and young children tend to have more severe conditions, with fever subsiding between the 10th to 15th day. Half of the cases have a sudden drop in fever, while the other half have a gradual decline. Sometimes there may be a residual fever wave after a sudden drop, which then decreases to normal after 1 to 2 days. In cases with complications, the fever may persist.

　　2. Respiratory System Symptoms and Signs

　　Most children have coughing from the onset of the disease, often表现为 frequent or paroxysmal coughing, accompanied by pharyngeal congestion. Nasal catarrhal symptoms are not prominent, and dyspnea and cyanosis often begin on the 3rd to 6th day, gradually worsening. Severe cases may show flaring of the nostrils, tracheal depression, and dyspnea (obstructive respiratory difficulty with wheezing and stridor), as well as cyanosis of the lips and nail beds. Auscultation may reveal dull sounds; the area with dull sounds is associated with reduced respiratory sounds, and sometimes tubular breathing sounds may be heard. In the early stage, auscultation usually reveals粗糙 or dry rales, and wet rales appear as signs of emphysema 3 to 4 days after onset. Severe cases may have pleural reactions or pleural effusion (more common in the second week), with transudative fluid being straw-colored and not turbid. In cases with secondary infection, the fluid is turbid, and the white blood cell count is often over 10×10^9/L.

　　3. Neurological Symptoms

　　After 3 to 4 days of onset, drowsiness and malaise may appear, sometimes alternating with irritability and malaise. In the late stage of severe cases, semi-comatose and convulsive states may occur. Some children may tilt their heads back and have stiff necks. In addition to toxic encephalopathy, there is also encephalitis caused by adenovirus, so lumbar puncture may be needed for differentiation at times.

　　4. Circulatory system symptoms

　　Pale complexion is common, with a gray complexion in severe cases. Heart rate increases, with mild cases generally not exceeding 160 times/min, severe cases often between 160 to 180 times/min, and sometimes above 200 times/min. 35.8% of severe cases may develop heart failure between the 6th to 14th day of onset, with the liver gradually enlarging to 3 to 6 cm below the ribs, with a relatively hard texture. Some may also have spleen enlargement.

　　5. Digestive system symptoms

　　More than half of the patients have mild diarrhea and vomiting, and severe cases often have abdominal distension. Diarrhea may be related to the reproduction of adenovirus in the intestines, but in some cases, it may also be due to severe illness and high fever, which affects the digestive function.

　　6. Other symptoms

　　Catarrhal conjunctivitis, red macules, maculopapular rash, scarlet fever-like rash, and the appearance of calcareous white spots on the tonsils are not very common but are relatively special signs in the early stage of the disease.

　　7. Course of the disease

　　This condition is divided into mild and severe cases based on respiratory and poisoning symptoms. Mild cases usually see a drop in body temperature between 7 to 14 days, and other symptoms also begin to improve. However, the lung shadows need 2 to 6 weeks to completely absorb. In severe cases after the 5th to 6th day, there is often marked drowsiness, pale and gray complexion, significant liver enlargement, obvious shortness of breath, and large areas of lung consolidation. Some children may experience heart failure, seizures, semi-comatose states, and the recovery period of lung lesions is longer, lasting from 1 to 4 months. After 3 to 4 months, if there is still no absorption, it is often pulmonary atresia, and it may develop into bronchiectasis in the future. We have followed up on 3 and 7 types of adenovirus pneumonia for 1 to 5 years, with 30.1% suffering from chronic pneumonia, pulmonary atresia, and individual cases of bronchiectasis. Later, we followed up on 109 cases of 3, 7, and 11 types of adenovirus pneumonia for 10 years, and X-ray films showed that 45.3% had pulmonary interstitial thickening, fibrosis, and chronic bronchitis. Chronic pneumonia combined with bronchiectasis accounted for 3.8%, while bronchiectasis and chronic pneumonia each accounted for 4.7%. Adenovirus pneumonia in preschool and school-age children is generally mild, often with persistent high fever, but respiratory and neurological symptoms are not severe. When measles is complicated with or follows adenovirus pneumonia, all symptoms are more severe, and the condition often suddenly worsens. We have observed the clinical manifestations of 34 cases (1964-1980) of 11 type adenovirus pneumonia and found that there is no significant difference in symptoms compared to 3 and 7 type adenovirus pneumonia, but severe cases and deaths are similar to type 3 and significantly fewer than type 7. We have observed 38 cases of adenovirus pneumonia in infants aged 1 to 5 months (20 cases of type 3, 12 cases of type 7, 6 cases of type 11, 1981-1983), with 8 cases of bronchiolitis and 30 cases of pneumonia. The clinical characteristics are: more mild or moderate fever, short duration of fever, no signs of lung consolidation, chest X-rays showing mainly small shadow areas, weakness, drowsiness, and other neurological symptoms occur less frequently and are milder than in infants over 6 months. Clinically, it is impossible to distinguish from respiratory syncytial virus or parainfluenza virus pneumonia, resulting in none of the cases in this group being diagnosed as adenovirus pneumonia before the etiological report.

　　The attenuated live vaccine for adenovirus types 3, 4, and 7 has been proven to have a preventive effect through small-scale application abroad, but it has not been produced or used on a large scale. During the epidemic period, especially in the ward, isolation should be done as much as possible to prevent cross-infection; more home treatment for infant upper respiratory tract infections should be done in local area work, and in nurseries and kindergartens, early isolation and avoiding nurseries with cold symptoms should be paid special attention to in order to reduce the chance of transmission. It is reported that the incidence of adenovirus cross-infection reaches 60% to 85%. It can cause disease within 20 minutes for those with short contact time, and the incubation period is 4-6 days. Therefore, children with adenovirus infection should not be in the same room as other children to avoid cross-infection.

　　1. Total white blood cell count in blood count

　　In the early stage (1-5 days), most of the white blood cell count is reduced or normal, about 62% of the cases are below 10×10^9/L, 36% are between (10-15)×10^9/L. The classification shows no special changes. In the late stage, the white blood cell count is similar to the early stage, only when secondary bacterial infection occurs will it increase. Blood smear examination, alkaline phosphatase in neutrophils and nitrotetrazolium blue staining are generally lower than those in normal children or children with bacterial pneumonia. Although the total white blood cell count may reach 15×10^9/L, the alkaline phosphatase index of white blood cells is still significantly reduced.

　　2. Pathogenetic examination

　　Diagnosis should be based on virus isolation from nasopharyngeal lavage fluid, double serum antibody determination, and some children's serum cold agglutination test may be positive. Currently, immunofluorescence method (indirect method is more applicable than direct method) is used, along with enzyme-linked immunosorbent assay and specific IgM determination. Immunoenzyme technique for rapid diagnosis helps in timely diagnosis, but cannot type adenoviruses. Routine throat swab virus isolation and double serum antibody tests are only suitable for laboratory retrospective diagnosis.

　　3. Urinalysis

　　During the fever period, some cases have a small amount of protein in the urine.

　　4. Cerebrospinal fluid examination

　　In children with symptoms of meningeal irritation, the cerebrospinal fluid examination is generally normal.

　　5. X-ray examination

　　The X-ray pattern is closely related to the condition and the course of the disease. The thickening and blurring of the pulmonary vessels are early manifestations of adenovirus pneumonia. Pulmonary lesions usually appear on the 3rd to 5th day of onset, with areas of varying sizes or confluent lesions, most commonly in the lower lung fields and the upper right lung. By the 6th to 11th day after onset, the density of the lesions increases with the progression of the disease, and the number of lesions also increases, spreading more widely, merging with each other. Unlike lobar pneumonia, the lesions of this disease are not limited to a specific lobe of the lung. Most of the lesions absorb after the 8th to 14th day. If the lesions continue to increase at this time, the condition may worsen, suggesting a mixed infection. Pneumatocele is quite common, and there is no obvious difference between the early and extreme stages. It is bilateral diffuse pulmonary emphysema or peripheral pulmonary emphysema around the lesions. In 1/6 cases, there may be pleural changes, which usually appear during the extreme stage, with pleural reaction or pleural effusion.

　　6. Ultrasound

　　Abdominal ultrasound shows enlargement of the liver and spleen; chest ultrasound shows pleural effusion.

　　7. Electrocardiogram

　　Patients with myocardial damage generally show sinus tachycardia on electrocardiogram, severe cases have increased right heart load, changes in T waves, ST segments, and low voltage. Some have 1°-2° atrioventricular block, and occasionally, pulmonary-type P waves may appear.

　　Eat more fresh vegetables and fruits rich in vitamin C (the B-carotene contained can be converted into vitamin A in the body) or take some multivitamin preparations or colostrum, which can also effectively enhance the child's immunity. Ensure adequate sleep, which is also an important aspect of strengthening the physique. Physical exercise is an effective measure to enhance physical fitness..

　　1. Treatment

　　General treatment for bronchopneumonia can be referred to. At present, there is no specific antiviral drug for adenovirus infection, and ribavirin (Virazole), interferon, polymyxin B injection, levamisole, human blood gamma globulin, and other drugs can be considered. Ribavirin (Virazole): 10-15mg/(kg·d), taken orally, by intravenous injection or intravenous infusion. Interferon: 1 million U/time, once a day, intramuscular injection. Polymyxin B: neonates 0.05-0.075mg/time, 1-month-old infants 0.075-0.1mg/time, infants aged 3-6 months 0.1-0.3mg/time, 1-year-old 0.2-0.4mg/time, 2-4 years old 0.25-0.6mg/time, 5-8 years old 0.25-0.8mg/time, 9 years and above 0.5-1.5mg/time, every other day, intramuscular injection. Levamisole: 1-1.5mg/(kg·d), taken orally in 2-3 doses. For severe viral infections, human blood gamma globulin can be considered, 400mg/(kg·d), for 3-5 consecutive days. The following will focus on the experiences gained from clinical practice in recent years:

　　1. Antiviral drugs are still under intensive research. Ribavirin (triazine nucleoside) is used to treat adenovirus pneumonia, with little effect through nasal drops; when changed to intravenous and/or intramuscular injection, it is superior to the control group in early cases, but has no significant effect in late cases (Beijing Children's Hospital and Institute of Medical Sciences, 1978-1980); research on nebulized inhalation therapy is pending.

　　2. Prevention and treatment of secondary infections: Pay attention to the prevention and treatment of secondary bacterial infections. If secondary infection is initially diagnosed, active treatment should be carried out, for example, Staphylococcus aureus infection is treated with novel penicillin, ceftriaxone, and others; Escherichia coli is treated with ampicillin (aminopenicillin) and others.

　　3. Sedatives, anticonvulsants, and antitussives: Chlorpromazine, promethazine, and others are used.

　　4. Cardiotonic drugs: Digitalis is used.

　　5. Supportive therapy: The use of human blood gamma globulin may have a supportive effect.

　　6. Oxygen therapy and intravenous fluid therapy: Correct oxygen therapy and intravenous fluid therapy can help the child through the critical period if handled properly.

　　7. Adrenal cortical hormones have been tried in early patients, but no efficacy has been observed; however, in cases with obvious respiratory obstruction or severe toxic symptoms (convulsions, coma, shock, persistent fever above 40℃), short-term intravenous hormone therapy is recommended.

　　8. Physical therapy: During the recovery period, if the pulmonary signs disappear slowly, physical therapy should be performed.

　　II. Prognosis

　　Adenovirus pneumonia is severe in northern China. During the first major outbreak in 1958, the mortality rate of inpatients reached 25%. After the combined treatment of traditional Chinese and Western medicine, the mortality rate dropped to 5% to 10%. In the past 10 years, there has been no significant outbreak, the condition has improved, and the mortality rate is below 5%. Most deaths occur during the 10th to 15th day of the disease course, and the main factors affecting the prognosis are:

　　1. Age: Young children lack specific antibodies, and most deaths occur in children aged 6 to 18 months, with almost no deaths in those over 2 years old.

　　2. Secondary infections, such as those concurrent or secondary to measles, general pneumonia, or other severe diseases, have a high mortality rate. The prognosis is also serious when secondary infections such as Staphylococcus aureus or Escherichia coli occur.

　　3. Compared with 3A and 11A adenoviruses, 7A adenovirus pneumonia has more severe cases and deaths.