Primary pulmonary tuberculosis in children

Introduction to children with primary tuberculosis Primary pulmonary tuberculosis is the most common type of primary tuberculosis. It is the primary infection of tuberculosis after initial invasion into the lungs. It is the main type of tuberculosis in children, accounting for 85.3% of the total number of tuberculosis in children. Primary tuberculosis includes primary syndrome and bronchial lymph node tuberculosis. The former consists of primary lung lesions, local lymph node lesions, and lymphangiitis connected to the two. The latter is mainly caused by enlarged lymph nodes in the thoracic cavity, and the primary lesions of the lungs are either small or covered by mediastinal images. X-ray films cannot be detected, or the primary lesions have been absorbed, leaving only local enlargement. The lymph nodes are clinically diagnosed as bronchial lymph node tuberculosis. The two are the same type, that is, the original type of tuberculosis. basic knowledge The proportion of sickness: 0.0031% Susceptible people: children Mode of transmission: respiratory transmission mother-infant vertical transmission Complications: emphysema, atelectasis, tuberculous pleurisy, tuberculous meningitis

Causes of primary pulmonary tuberculosis in children

(1) Causes of the disease

Primary tuberculosis is a disease caused by Mycobacterium tuberculosis invading the body for the first time. There are 4 types of Mycobacterium tuberculosis: human, bovine, bird and mouse, while human pathogenic bacteria are human tuberculosis and tuberculosis. Most of the pediatric tuberculosis in China is caused by human tuberculosis. The tuberculosis has strong resistance. In addition to acid, alkali and alcohol resistance, it is strong for cold, heat, dryness, light and chemicals. Tolerance, damp heat has strong bactericidal power against tuberculosis, it can be killed at 65 ° C for 30 min, 70 ° C for 10 min, 80 ° C for 5 min to kill, dry heat sterilization is poor, dry heat 100 ° C takes more than 20 min to kill, Therefore, dry heat sterilization, the temperature needs to be high, the time needs to be long, the tuberculosis bacteria in the sputum is killed within 2 hours under direct sunlight, and the ultraviolet ray only takes 10 minutes, instead it can survive for several months in the dark, in the sputum If tuberculosis is disinfected with 5% carbolic acid (phenol) or 20% bleaching solution, it takes 24 hours to take effect.

(two) pathogenesis

1. Infection route

(1) Respiratory tract infection: also known as droplet infection, is the most common form of infection, mainly by inhaling the droplets of tuberculosis or floating in the air with tuberculosis dust into the lungs, producing the lungs Lesion.

(2) Digestive tract infections: Mung tuberculosis can enter the digestive tract and cause pharynx or intestines by drinking milk from unsterilized tuberculosis cattle or eating food contaminated with tubercle bacilli or sharing utensils with tuberculosis patients. The original stove, at present, the fresh milk in China has been disinfected, so the infection of Bovine Mycobacterium tuberculosis is rare.

(3) transplacental and skin mucosal infection: transplacental infection can cause intrauterine infection of tuberculosis, mostly found in postpartum, the mother has active tuberculosis or miliary tuberculosis before birth, although congenital tuberculosis is very rare, but we used to Two cases of hematogenous disseminated tuberculosis were found at birth, one patient had cavities in the prenatal period, and one had miliary tuberculosis.

2. Pathogenesis

Mycobacterium tuberculosis reaches the lungs through the respiratory tract, grows in the bronchioles and alveoli, causes tuberculous bronchiolitis, and then forms nodules or tuberculous pneumonia. The primary tumor can occur in any part of the lung, but mostly in the upper lobe of the lung. Or the middle, lower part of the lower lobe, more common in the right lung, often close to the pleura, during the primary infection process, tuberculosis through the lymphatics to the local lymph nodes, causing paratracheal or parabronchial lymphitis, when the paratracheal or parabronchial lymph nodes The lesion continues to develop, even piercing the tracheobronchial wall to form intratracheal tuberculosis, erosion, oppression, if the lymph node cheese material breaks into the trachea, it can cause disseminated lesions in the lung.

3. Immunity mechanism and disease

Whether children develop tuberculosis after first contact with tuberculosis, mainly related to the immunity of the body, the virulence and quantity of bacteria, and the children with negative tuberculin test. After contact with tuberculosis for the first time, when tuberculosis invades the body, it activates. T lymphocytes cause a large number of proliferation. After 2 to 10 weeks, the body develops a delayed type of allergic reaction to tuberculosis and its metabolites. At this time, the tuberculin test can be turned positive, and the body also produces immunity. When T cells in the body are sensitized and then contact with the corresponding antigen or contact with macrophages that have swallowed tuberculosis, various lymphokines, such as macrophage migration inhibitory factor and macrophage activating factor, can be released. The cells accumulate around the tuberculosis, and the macrophage activating factor enhances its ability to phagocytose and kill tuberculosis. Lymphoxins can also kill tuberculosis, and with the participation of other immune mechanisms, the lesions are limited. In the process of tuberculosis infection, cellular immunity is involved, so after the infection of tuberculosis, the body has both an allergic reaction and a certain immunity. In particular, infants and young children, due to poor immunity, such as multiple exposure to a large number of virulence tuberculosis can directly develop into the original tuberculosis, or even miliary tuberculosis, most children after the initial infection, the body obtained Specific immunity, generally not easy to onset, but because children are generally susceptible to tuberculosis, in order to improve the body's specific immunity against Mycobacterium tuberculosis, a more effective measure is to inoculate BCG.

4. Characteristics of primary tuberculosis in children

(1) The high sensitivity of tissue organs to Mycobacterium tuberculosis, that is, the various tissues and organs of the whole body are highly sensitive to Mycobacterium tuberculosis, as follows:

1 extensive inflammation around the lesions in the lungs.

2 skin and mucous membranes are non-specific, such as herpetic conjunctivitis, calf nodular erythema, sputum capacity.

3 joints can be transient arthritis, also known as tuberculous rheumatic fever.

4 serosal exudative lesions, manifested as multiple serositis.

5 tuberculin test showed a strong positive reaction, the above performance often precedes the appearance of tuberculosis lesions, should be identified in time.

(2) The lymphatic system is widely affected by the lymph nodes of the whole body, which can form adhesions, hardening of the meat or tendency of cheese necrosis. It becomes one of the causes of chronic tuberculosis poisoning and dissemination. Lymph node puncture or biopsy can detect tuberculosis and tuberculosis. Bacterial, thoracic lymph nodes can be swollen, X-ray examination can be found in the paratracheal and parabronchial lymph nodes, for the common type of primary pulmonary tuberculosis in children, mesenteric lymph nodes can also affect the lesions.

(3) There is a tendency to spread throughout the body: lymphatic and bloody dissemination are prone to occur, so blood-borne disseminated tuberculosis, tuberculous meningitis, etc. are more common in young children, and early skin can be seen with miliary rash. Not uncommon.

(4) Healing method: end with calcification.

Primary child tuberculosis prevention

1. Control the source of infection and reduce the chance of infection

Tuberculosis smear-positive patients are the main source of tuberculosis in children. Early detection and rational treatment of smear-positive tuberculosis patients is a fundamental measure to prevent tuberculosis in children. Infants and young children suffer from active tuberculosis, and their family members should be examined in detail. , PPD, etc.), regular physical examinations for primary and child care institutions, timely detection and isolation of infectious sources, can effectively reduce the chance of tuberculosis infection in children.

2. Popularization of BCG vaccination

Practice has proved that vaccination with BCG is an effective measure to prevent tuberculosis in children. BCG was invented by French physicians Calmette and Guerin in 1921, so it is also called BCG. China has vaccinated BCG in the neonatal period and inoculated BCG in the upper left arm of the left upper arm. Intradermal injection, the dose is 0.05mg / time, the scratch method is rarely used, the Ministry of Health notified in 1997 to cancel the 7-year-old and 12-year-old BCG re-integration plan, but if necessary, the child with negative age test Multiple cropping can be given, and BCG vaccine can be injected in the same day as the hepatitis B vaccine.

Contraindications to vaccination with BCG: positive lignin response; patients with eczema or skin disease; recovery period of acute infectious disease (1 month); congenital thymic dysplasia or severe combined immunodeficiency disease.

3. Prophylactic chemotherapy

Mainly used for the following objects:

(1) Infants under the age of 3 have not been vaccinated with BCG and have a positive test.

(2) Close contact with patients with open tuberculosis (multiple family members).

(3) The sputum test has recently changed from negative to positive.

(4) The sputum test is a strong positive responder.

(5) Children with positive serotonin test need to use adrenocortical hormone or other immunosuppressive agents for a longer period of time.

The drug used for chemopreventive drugs is mainly isoniazid, the dose is 10mg/(kg·d), the course of treatment is 6-9 months, the newborns of the newly born tuberculosis parents under the age of 6 and the newborns born to the tuberculosis women, regardless of the knot If the results of the test are all the same, the isoniazid should be given. The dose is the same as above. After 3 months of administration, the test is performed. If it is positive, the isoniazid is continued for 9 months; if the test is negative (<5mm) ), then stop the isoniazid.

Anti-HIV-positive children with a history of tuberculosis should receive isoniazid for 12 months regardless of the outcome of the nodule test.

If the tuberculosis patient with children is resistant to isoniazid, the chemotherapy drug should be changed to rifampicin, 15mg/(kg·d), 6-9 months. If it is resistant to isoniazid and resistant to rifampicin, it is recommended to give pyrazinamide plus ofloxacin for 6 to 9 months, or pyrazinamide plus ethambutol for 6 to 9 months.

Pediatric original pulmonary tuberculosis complications Complications emphysema atelectasis tuberculous pleurisy tuberculous meningitis

There may be local emphysema or poor gas, even atelectasis; lymphatic tracheal fistula may occur; lymph node enlargement obviously compresses the trachea, there may be gas shortage oxygen performance.

Progress

Young, recurrent infections, large numbers of bacteria invading or low immunity, the disease can progress and deteriorate, causing a series of consequences:

(1) Tuberculous pleurisy.

(2) The primary lesion is enlarged, resulting in cavities and caseous pneumonia.

(3) inflammation around the bronchial lymph nodes, formation of lymph node bronchospasm, endobronchial tuberculosis, segmental lesions or caseous pneumonia.

(4) bronchial lymphadenopathy, resulting in obstructive atelectasis or emphysema.

Deterioration

Bacteria are spread by blood, leading to miliary tuberculosis, tuberculous meningitis or other organ miliary tuberculosis.

Symptoms of primary tuberculosis in children Common symptoms Hemoptysis with jaundice, fatigue, night sweats, shortness of sweat, poor appetite, atelectasis, hoarseness, tracheal pressure, low breath sound

Symptom

The severity of the onset is mild, the mild can be asymptomatic, often found in the chest X-ray examination during physical examination, or mild symptoms of tuberculosis, such as low fever, light cough, anorexia, weight loss, night sweats, fatigue, etc. It is acute, has high fever, cough, resembles flu, pneumonia, or skin mucosal allergy. In young children, when the swollen lymph nodes compress the trachea, compression symptoms may occur, and if the recurrent laryngeal nerve is pressed, it may cause hoarseness. A pertussis-like cough can occur at the intersection of the oppressed trachea. If the bronchial pressure is present, incomplete obstruction or complete obstruction may occur, resulting in local emphysema or poor gas, and even atelectasis. Compression of the vein can cause angulation on one or both sides of the chest surface. Irritating cough can also occur when swollen lymph nodes press the esophagus to cause lymphatic fistula.

2. Physical examination

When the lymph node enlargement is not obvious, there may be no special signs. However, when the lymph node enlargement obviously compresses the trachea, there may be a shortage of oxygen in the gas; if the total bronchi is compressed, the lungs may be percussed with dullness, low breath sounds or audible bronchial breath sounds.

Examination of primary pulmonary tuberculosis in children

Laboratory inspection

1. Smear and culture

The detection of acid-fast bacilli from sputum, gastric juice, cerebrospinal fluid and serosal fluid is an important means of diagnosing tuberculosis, but the positive rate is low, only 20% to 30%. For infants and young children, gastric juice can be pumped on an empty stomach in the morning, using thick slices. The positive rate of tubercle bacillus can be higher than that of the general method by method or fluorescent staining. In addition, the above specimens can be inoculated into guinea pigs for tuberculosis culture, tuberculosis grows slowly, and typical pathological changes appear after 4 to 6 weeks. Bactec460 rapid culture identification system, using 7H12 mycobacterial medium with radioactive nutrients (14C palmitic acid) as substrate, tuberculosis growth period can be shortened to 1-3 weeks, tuberculosis test for 9 days, can identify Mycobacterium tuberculosis With non-tuberculous mycobacteria, the drug sensitivity test takes another 3 to 5 days. In 1991, the tuberculosis was quickly isolated using the dual-phase culture technique Rocheseptichek-AFB system, which can be reported in 2 to 4 weeks. The acid-fast bacteria L-type bacteria are cells. And a variation of colony morphology, difficult to culture by conventional methods, acid-fast staining is not easy to find, domestically applied modified pancreatic soy protein agar medium (TSA-L), fast protein agar bovine serum culture , Sheep blood separation medium for culturing Mycobacterium L, reported in 1998 at 260 retreated, refractory pulmonary tuberculosis cultured in L-type Mycobacterium tuberculosis, the positive rate of 29.6%.

2. Mycobacterium tuberculosis antibody detection

In the past, antibodies such as natural antigen PPD (PPD-IgG, PPD-IgM) were used, and the sensitivity and specificity were poor. For more than ten years, the purified or semi-purified antigen of Mycobacterium tuberculosis was prepared to make Mycobacterium tuberculosis specific antibody. The detection has made significant progress. The commonly used antigens are semi-purified Mycobacterium tuberculosis antigen 5, antigen 6, AOO antigen; semi-purified glycolipid antigens such as glycolipids SAGA1, B1 and C, phenol glycolipid (PGL-Tb1), lipid Arabinose (LAM) antigen, thiolipid (SL-I, SL-IV), TB-C-1 antigen, lipopolysaccharide (LPS), etc.; purified antigen has tuberculosis protein antigen (38kDa, 30/31kDa, 71kDa, 45kDa, 14kDa, 19kD3a Mycobacterium tuberculosis antigen), recombinant 38kDa tuberculosis protein.

(1) Enzyme-linked immunosorbent assay (ELISA): used to detect anti-tuberculosis antibodies in serum, cerebrospinal fluid and serosal fluid of tuberculosis patients, which can be used as an auxiliary diagnostic index. The sensitivity of ELISA for semi-purified antigen is 65%~ 85%, sensitivity to sputum smear-negative tuberculosis is 53% to 62%, sensitivity to extrapulmonary tuberculosis is 34% to 40%, specificity is 95%, ELISA detection antibody using 38kDa purified antigen, sensitivity is 73 %, sensitivity to tuberculosis-negative tuberculosis was 70%, specificity was 98%. ELISA was used to detect specific antibodies in cerebrospinal fluid of patients with tuberculous meningitis with sensitivity of 70% and specificity of 100%.

(2) Enzyme-linked immunosorbent electrophoresis (ELIEP): an immunological technique that combines ELISA with electrophoresis and is a serological method for the diagnosis of various tuberculosis.

3. Mycobacterium tuberculosis antigen detection

Detection of Mycobacterium tuberculosis antigen in body fluid by ELISA, latex agglutination test, reverse passive hemagglutination test, etc., such as detection of Mycobacterium tuberculosis 34kDa cytoplasmic protein (antigen 5) in cerebrospinal fluid by ELISA for diagnosis of tuberculous meningitis, sensitivity 80%, specificity 100%, double antibody sandwich ELISA method for detection of cerebrospinal fluid, peritoneal effusion, Mycobacterium tuberculosis 43kDa immunodominant antigen in pleural effusion, sensitivity 100%, specificity 96%, determination of lipid arabinose by synergistic agglutination test Glycan antigen, sensitivity 85%90%, specificity 93%, detection of Mycobacterium tuberculosis antigen by Western blotting, sensitivity 89.7%, specificity 95.7%, extrapulmonary tuberculosis, sputum smear negative tuberculosis The disease is diagnostic.

4. Determination of structural components of tubercle bacilli

Gas chromatography-mass spectrometry was used to detect the bacterial structural components of Mycobacterium tuberculosis in serum and cerebrospinal fluid, namely tuberculosis stearic acid (10-methyloctadecanoic acid), which has high specificity and sensitivity. The carboxylic acid of Mycobacterium tuberculosis in cerebrospinal fluid was determined by pulsed electron capture gas chromatography with sensitivity of 95% and specificity of 91%, but the equipment and technology required were complicated and expensive.

5. Molecular biology examination

(1) DNA probe molecular hybridization: DNA probe method is not sensitive to the detection of clinical specimens. The number of bacteria in the specimen is 10,000/ml, and the gene probe technology labeled with acridinium ester and The chemiluminescence measurement system replaces the enzyme standard color development system, can improve sensitivity, can identify a variety of mycobacteria, rapidly detect Mycobacterium tuberculosis, and use bacterial luciferase to detect hybridization signals, which can improve sensitivity by 100 times.

(2) Polymerase chain reaction (PCR): selectively amplifying a gene fragment encoding the MPB64 protein specific for Mycobacterium tuberculosis complex, capable of amplifying this extremely small amount of DNA sample by several hundred thousand times or more for several hours The results are fast, sensitive and specific, but they are more likely to produce false positive and false negative results. PCR amplification of Mycobacterium tuberculosis specific insertion sequence IS6110, detection of sputum specimens, positive rate of 93%, false positive rate of 2.9%, Domestic horses use nested PCR to determine pathological specimens, sputum specimens and other Mycobacterium tuberculosis DNA, no false positives. Some people used nested PCR to detect the specific repeat insertion sequence IS6110 of Mycobacterium tuberculosis in peripheral blood mononuclear cells of tuberculosis patients, the positive rate was 64%. , 32% higher than sputum smear and 35% higher than sputum culture.

(3) DNA fingerprinting technique: A specific band spectrum of a restriction endonuclease fragment of a bacterial chromosome, such as the DNA insertion sequence IS6110, was analyzed to identify a strain for epidemiological studies.

(4) Detection of drug resistance genes in Mycobacterium tuberculosis: PCR-SSCP analysis, PCR-restriction fragment length polymorphism (PCR-RFLP) analysis, PCR-DNA sequencing, and tuberculosis Bacillus resistance gene.

(5) Gene chip technology: Many DNA probes are fixed on a solid phase carrier in a certain order and arrangement to form a probe matrix, which hybridizes with the DNA to be tested, and simultaneously obtains a large amount of genetic information. A 16SrRNA gene chip for the determination of mycobacterial interspecies polymorphism was developed to identify Mycobacterium tuberculosis and other non-tuberculous mycobacteria, and the other was a gene chip for analyzing the genotype of drug-resistant tuberculosis strain rpoB for analysis of rpoB gene. mutation.

6. ESR

The erythrocyte sedimentation rate during the active period of tuberculosis can be accelerated. After the anti-tuberculosis treatment, the erythrocyte sedimentation rate gradually decreases. It means that there is active disease, and the erythrocyte sedimentation rate is not specific. The erythrocyte sedimentation rate cannot exclude active tuberculosis.

7. Do the following checks through fiberoptic bronchoscopy

The lower respiratory secretions or lavage specimens can be collected for bacteriological examination, and the histopathological examination of bronchial and intrapulmonary lesions can be performed. Fine needle aspiration biopsy can be performed under B-mode ultrasound, X-ray or CT guidance. Fiberoptic bronchoscopy itself has an "irritation" effect, and continuous detection of sputum within 3 to 4 days after surgery can improve the detection rate of bacteria in sputum smear.

Primary features in the lung can be seen in the lungs of the primary lesions and trachea, para-bronchial lymph nodes, lymphangiitis between them is often not obvious, sometimes visible inter-leaf pleural reaction, see Figure 1, the primary can be round Shape or flaky shadow, can occupy a lung segment or even a lung lobes, the density is uneven, sometimes the primary tumor and the lung are not coincident, when the lymph nodes in the trachea or bronchi are sharp and the edges are evenly dense and clumped. It is called tumor type. If it has inflammatory infiltrates around it, it is called infiltrating or inflammatory type. When trache tuberculosis occurs, it can cause atelectasis or local compensatory emphysema.

Film degree exam

X-ray inspection

X-ray radiographs of the chest and lateral radiographs were performed, and the lateral radiographs were important for finding enlarged lymph nodes or lesions near the hilar.

(1) Primary compound syndrome: typical manifested as primary lesion in the lung, hilar lymph node enlargement, connecting the linear shadow of lymphangitis between the former two, forming a dumbbell-shaped bipolar shadow, the size of the primary lesion in the lung Invariably, the local inflammatory lymph nodes are relatively large and the primary lung lesions are small. It is a characteristic of primary pulmonary tuberculosis. The lung lesions of infants and young children can be wide, occupying a lung segment or even a lung lobe; The lesions are small in scope, mostly in small pieces or small round shadows. In some cases, local pleural lesions can be seen. Many children have less inflammation due to lung lesions, and the range is small. X-ray films cannot be detected or treated. At the time, the lung lesions have been absorbed, leaving only the hilar lymph nodes. Therefore, it is rare for children with primary tuberculosis to appear as a typical dumbbell-shaped bipolar image on X-ray films.

(2) bronchial lymph node tuberculosis: is the most common manifestation of pediatric primary tuberculosis on X-ray films, divided into 3 types of performance:

1 Inflammatory type: also known as infiltrative type, exudative inflammatory infiltration of lung tissue around the lymph nodes, high-density shadows extending from the hilar to the chest X-ray, blurred edges, which is hilar lymphadenopathy shadow.

2 nodular type: also known as tumor type, mass type, lung tissue around the lymph node has less exudative inflammation or has been absorbed, on the chest X-ray, the lung area is round or oval dense shadow, the edge is clear From the lungs to the lungs.

3 micro-small: it is easy to ignore, should pay attention to the type, manifested as small nodules around the hilar and small flaky shadows, hilar shadow and lung texture disorder, should be combined with medical history, clinical manifestations, combined with bacteriocin test Comprehensive analysis and judgment.

2. Fiberoptic bronchoscopy

Tuberculosis lesions spread to the bronchial tuberculosis, and the following lesions were seen by fiberoptic bronchoscopy:

(1) The enlarged lymph nodes compress the bronchial stenosis, or adhere to the bronchial wall, so that the activity is limited.

(2) mucosal congestion, edema, inflammatory infiltration, ulceration or granuloma formation.

(3) In the early stage of lymph node perforation, a mass that protrudes into the bronchial lumen can be seen.

(4) Lymph node perforation forms lymph node bronchospasm, the perforation mouth is volcanic-like protrusion, the color is red and the cheese-like substance is discharged.

Diagnosis and diagnosis of primary pulmonary tuberculosis in children

diagnosis

1. History of exposure to tuberculosis: a history of close exposure to tuberculosis.

2. X-ray performance, especially when the lungs are large lesions and the signs are not obvious, that is, the signs and X-rays are different. This is the characteristic of this disease.

3. The tuberculin test or PPD test is strongly positive.

4. Find the pathogen: sputum or gastric juice to find or cultivate tuberculosis, help diagnose.

5. Fiber bronchoscopy: fiber bronchoscopy or lymph node biopsy can help diagnose.

Differential diagnosis

Before X-ray examination, it should be differentiated from upper respiratory tract infection, influenza, bronchitis, typhoid fever, rheumatic fever, etc. Invasive tracheal lymph node tuberculosis should be differentiated from tracheobronchial inflammation and various pneumonia after X-ray examination. Tumor-type tracheal tuberculosis should be differentiated from lung, tracheal, bronchial and bronchial cysts, intestinal cysts, teratoma, pulmonary hamartoma, Hodgkin's disease, lymphosarcoma, etc., except for past medical history, current clinical manifestations, In addition to the tuberculin test, positive, lateral X-ray and mediastinal tomography are helpful for identification; the shadow of the mass is located in the anterior and posterior mediastinum, and the bronchial lymph node tuberculosis is located in the mediastinum; the common mediastinum in the mediastinum is Hodgkin Disease, lymphosarcoma or lymphocytic leukemia, however, they all have their own special clinical manifestations, in addition to bronchoscopy and chest CT, the examination is also very helpful, there are reports of primary tuberculosis, CT diagnosis accuracy rate 90%.

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