Pediatric tuberculosis

　　1. Morphology of Mycobacterium tuberculosis

　　Mycobacterium tuberculosis is slender, slightly curved, with blunt ends, often arranged in a branched shape. It is about 2 to 4 μm long and 0.2 to 0.5 μm wide; under an electron microscope, the outermost layer of the bacterial body can be seen to be the cell membrane, inside is the cytoplasmic membrane, which contains cytoplasm and many particles, which may be mitochondria-like substances. After being stained with aniline, Mycobacterium tuberculosis is not easily decolorized by acidic decolorizing agents, hence the name acid-fast bacillus.

　　2. Characteristics of the growth of Mycobacterium tuberculosis

　　Mycobacterium tuberculosis grows slowly, with a division and reproduction cycle of about 14 to 22 hours. Its main nutritional requirements are glycerol, aspartic acid or glutamic acid, as well as inorganic salts such as phosphorus, potassium, sulfur, magnesium, and a small amount of iron. It is an aerobic bacterium, and the most suitable growth environment is pH 7.4, PO2 13.3 to 18.7 kPa (100 to 140 mmHg). When the pH is not suitable and the PO2 is low, such as in closed lesions and within macrophages, the metabolism of Mycobacterium tuberculosis is inactive, growth and reproduction slow down or stop, but at the same time, it is not easily killed by antituberculosis drugs and becomes the source of recurrence in the future.

　　3. Typing of Mycobacterium tuberculosis

　　Mycobacterium tuberculosis can be divided into 4 types: human, bovine, avian, and murine. The type that is pathogenic to humans is mainly human, followed by bovine, with very few infected with avian, and no reports have been made in China. Bovine tuberculosis infection is mainly due to poor management and disinfection of milk and the consumption of milk products from sick cows, which is now rare. According to a report from the Beijing Tuberculosis Research Institute, among 50 isolated strains of mycobacterium tuberculosis, 3 were identified as bovine mycobacterium tuberculosis (accounting for 6%). In 1979, Beijing Children's Hospital conducted a strain identification on the mycobacterium isolated from the cerebrospinal fluid of 16 children with tuberculous meningitis, and found 1 strain was bovine mycobacterium tuberculosis, and the other 15 were human mycobacterium tuberculosis, indicating that although bovine infection is rare, it can also cause tuberculous meningitis, which deserves attention.

　　4. Resistance of Mycobacterium tuberculosis

　　Mycobacterium tuberculosis has a strong resistance to the environment, and it can survive for half a year in dark and humid indoor conditions. The bacterium dies within 2 hours when directly exposed to sunlight and within 10 to 20 minutes under ultraviolet light. When using ultraviolet light, attention should be paid to the size of the照射范围 and the distance of the照射 to determine the照射 time, such as when the distance is 1m and the area is 1m2, the照射 time should be 20 minutes to kill the bacterium. Mycobacterium tuberculosis has strong resistance to acids, bases, and alcohols, and hot and humid conditions have a strong bactericidal effect. It can be killed by boiling for 1 minute at 65℃ for 30 minutes, 70℃ for 10 minutes, 80℃ for 5 minutes, or boiling for 1 minute. It takes more than 20 minutes to kill it at dry heat of 100℃, so the temperature should be high and the time long during dry heat sterilization. Generally speaking, the disinfection time of mycobacterium tuberculosis in sputum should be long, as the sputum mucus forms a protective layer around the bacterial body, making it difficult for rays and disinfectants to penetrate. Therefore, 5% carbolic acid or 20% bleaching powder should be used to disinfect sputum, and the disinfection should be processed for 24 hours to be relatively safe. Contacting with 5% to 12% Lysol for 2 to 12 hours or 70% alcohol for 2 minutes can kill the bacterium.

　　5. Drug Resistance of Mycobacterium tuberculosis

　　Antituberculosis drugs require long-term use, and drug resistance strains are prone to occur when used irregularly or when a single drug is used alone or the dose is insufficient. Experimental and clinical practice have proven that the use of combined drugs can delay or reduce the occurrence of drug resistance. In recent years, there has been increasing attention to tuberculosis infections caused by primary drug-resistant strains. The incidence varies from place to place, with primary resistance to isoniazid accounting for about 1% to 18%, primary resistance to streptomycin about 2% to 14%, and primary resistance to para-aminosalicylic acid about 1% to 13%. Abroad, Steiner (1974) reported that in 79 cases of pediatric tuberculosis, more than one-third had primary drug resistance to one or more antituberculosis drugs. From 1963 to 1967 and 1973 to 1977, Beijing Children's Hospital observed the primary resistance rate of pediatric tuberculous meningitis, and the resistance rate in the latter stage was twice that of the former stage (40.8% vs. 19.7%). Isoniazid-resistant strains generally have reduced virulence, and clinical observations have shown that there is still efficacy if isoniazid is continued to be used for treatment.

　　1. Hemoptysis

　　Hemoptysis is the most common complication of pulmonary tuberculosis, with an incidence rate of 20% to 90%. The amount of hemoptysis can vary, and patients with massive hemoptysis often have complications such as aspiration pneumonia, atelectasis, tuberculosis bronchial dissemination, hemorrhagic shock, and even asphyxia. Tuberculosis hemoptysis is often due to the presence of exudative or cavitated lesions, or bronchial tuberculosis and local tuberculosis lesions causing bronchial deformation, tortuosity, and dilation.

　　[Treatment] In most cases, hemoptysis indicates active and progressive tuberculosis lesions, so tuberculosis patients with hemoptysis should seek medical attention at a hospital for regular anti-tuberculosis treatment. For patients with moderate or large amounts of hemoptysis, it is necessary to actively control bleeding, maintain airway patency, and prevent asphyxia and hemorrhagic shock.

　　2. Spontaneous pneumothorax

　　The incidence of spontaneous pneumothorax in pulmonary tuberculosis patients is about 1.4%, and patients often have sudden chest pain, cough, dyspnea, and cyanosis. Pneumothorax is common in the following situations: subpleural lesions or cavities break into the pleural cavity; fibrosis or scarring of tuberculosis lesions leads to pulmonary emphysema or pulmonary bullae rupture; millet-like pulmonary tuberculosis causes interstitial emphysematous pulmonary bullae rupture.

　　[Treatment] For simple pneumothorax with no obvious clinical symptoms, conservative treatments such as bed rest and high-flow oxygen therapy can be adopted. For tension pneumothorax, communicating pneumothorax, and simple pneumothorax that has not healed for more than 2 weeks, chest tube insertion is often required. If the puncture site does not heal after more than a week of continuous chest tube drainage or if there is pleural effusion or empyema, intermittent negative pressure aspiration or continuous constant negative pressure aspiration should be used.

　　3. Chronic pulmonary heart disease

　　Severe pulmonary tuberculosis patients, due to extensive destruction of lung tissue, lead to dysfunction of pulmonary ventilation and gas exchange, and in the late stage, can be complicated by pulmonary hypertension and pulmonary heart disease. Patients often present with cyanosis, palpitations, dyspnea, and edema of both lower extremities.

　　[Treatment] Due to the difficulty in treating chronic pulmonary heart disease, it is necessary to actively control the changes of pulmonary tuberculosis to prevent further deterioration of the condition and delay heart involvement. For patients with pulmonary tuberculosis who have complications of pulmonary heart disease, timely hospitalization for treatment is essential.

　　4. Secondary pulmonary infection

　　Pulmonary tuberculosis cavities (especially fibrous cavities), pleural thickening, and tuberculosis fibrotic changes causing bronchial dilation, atelectasis, and bronchial tuberculosis leading to airway obstruction are the pathological basis for secondary bacterial infections in pulmonary tuberculosis. The most common pathogenic bacteria are G-bacilli, and due to the long-term use of antibiotics, fungal infections can occur secondarily, often presenting as mixed infections.

　　[Treatment] When secondary infection occurs, it is necessary to target different pathogenic bacteria and use corresponding antibiotics or antifungal drugs for treatment.

　　1. Fever: Children will present with irregular high fever at the early stage of the disease. After 1-2 weeks, the fever gradually shifts to low-grade fever. It is usually low-grade fever in the afternoon, with body temperature below 38 degrees Celsius, and daily fluctuations of more than 1 degree Celsius.

　　2, night sweats: often occur simultaneously with fever. It is manifested as sweating before waking up at midnight or in the early morning. It often occurs in the chest, head, or armpits.

　　3, the child may appear fatigue, lack of spirit, love to cry and闹, abnormal temperament, unexplained loss of appetite, and weight loss, and other systemic symptoms.

　　4, the child may repeatedly appear herpetic conjunctivitis, accompanied by systemic symptoms, along with symptoms of damage at the site of the lesion, such as headache, cough, abdominal pain, diarrhea, and so on.

　　One, strengthen primary healthcare

　　Reliance on the power of the primary healthcare network in urban and rural areas, giving full play to the role of doctors at all levels, including rural doctors. Clinical evidence shows that the onset of tuberculosis is closely related to the health status and living environment of children, and attention should be paid to reasonable nutrition, good hygiene habits, and preventive measures such as the prevention of measles and pertussis.

　　Two, detect cases and prevent and treat early

　　Early detection is a prerequisite for early treatment of children. Regular physical examinations should be conducted to detect diseases early. Children who come into contact with active pulmonary tuberculosis patients have significantly higher infection rates, incidence rates, and prevalence rates than general children. According to a survey by Beijing Children's Hospital from 1962 to 1965, the prevalence rate of children in contact with patients was 6.5%, while the prevalence rate of collective children at the same time was 0.15%. Also, according to an average of 13 years of follow-up observation of children in contact with active pulmonary tuberculosis, the cumulative prevalence rate was 6%. Therefore, checking children for tuberculosis infection or disease through contacts is an important way to detect tuberculosis early. Secondly, special attention should be paid to early detection work among children with strong positive OT reactions. Although tuberculosis is a chronic and extremely tenacious infectious disease, it can be completely cured if it is treated early and followed up carefully.

　　Three, education and isolation

　　Conduct extensive health education work to ensure that the masses have a correct understanding of tuberculosis. Carry out disinfection and isolation work in the families of tuberculosis patients to protect children from infection. In collective institutions such as nurseries, kindergartens, and primary school teachers and caregivers, regular checks should be conducted for tuberculosis, and once active patients are found, they should leave their jobs and receive thorough and active treatment. For household employees or tutors, a chest X-ray should be performed first to ensure there is no tuberculosis. In addition, attention should be paid to other preventive measures, such as the management of dairy cows, milk sterilization, premarital examination, prenatal examination, and propaganda against spitting on the ground.

　　Four, BCG (Bacillus Calmette-Guérin) Vaccination

　　In 1908, Callmette and Guérin used bovine tuberculosis bacilli, cultivated on a 5% glycerol bile potato medium, through 230 generations of repeated cultivation over 13 years, the pathogenicity of the bacteria was lost, and then the vaccine (BCG, Bacillus Calmette-Guérin) was prepared and administered to humans to induce immunity against tuberculosis. It is reported that the effective protection rate of BCG is 14% to 80%. BCG has been used since 1921 and has been used for over 70 years. Experience has shown that BCG vaccination can reduce the incidence and mortality rate of tuberculosis. BCG vaccination was widely implemented in China after liberation, with remarkable effects. The following are three types of vaccination methods described below.

　　1. Intradermal method

　　For those with negative tuberculin test results, 0.1 ml of BCG (containing 0.05 to 0.075 mg of bacteria) is injected intradermally at the lower end of the outer edge of the deltoid muscle of the left arm (never subcutaneous injection). Newborns without a history of tuberculosis exposure within 2 months can be exempted from the tuberculin test. It is recommended to avoid children from contacting tuberculosis patients within 6 weeks after vaccination to prevent the risk of infection before immunity is established. Three to four weeks after BCG vaccination, a firm red papule may occur at the vaccination site, which gradually forms into a small pustule or small ulcer, dries up and scabs over, and can heal in 1 to 2 months. In severe papules, the center may have necrosis, and local lymph nodes may develop cold abscesses, which may break down to form deeper ulcers, healing more slowly.

　　2. Scratch method

　　A drop of BCG containing 50 to 75 mg of bacteria per 1 ml is dropped on the lower end of the outer edge of the deltoid muscle of the left arm, and a "well" mark 1 to 1.5 cm long is drawn on the skin, aiming for a red mark without bleeding. After drawing, gently spread the vaccine on the scratch. Wait for the vaccine to dry (about 10 minutes) before putting on the sleeve. This method is simple to operate, easy to popularize, has mild local reactions, and fewer lymph node reactions.

　　3. Oral method

　　It is limited to infants within 2 months of birth. Kastner first invented BCG, using the neonatal oral method because the neonatal intestinal mucosal tissue has not fully developed, and BCG is easy to pass through and enter the mesenteric lymphatic system to induce immunity. The BCG oral method is now rarely used.

　　4. Revaccination

　　The immunity after BCG vaccination can last for several years, and it is recommended to revaccinate once every 3 to 4 years after the initial vaccination (when the tuberculin test turns negative). There is a trend to extend the interval to once every 6 to 7 years. Generally, it is not necessary to revaccinate after adulthood.

　　V. Chemical prophylaxis

　　That is, taking isoniazid for tuberculosis prevention, the following situations can be considered:

　　1. Infants who have been in contact with parents with open pulmonary tuberculosis;

　　2. Children with a recent change from negative to positive tuberculin reactions due to natural infection;

　　3. Young children and preschool children with strong positive tuberculin reactions;

　　4. Children with positive tuberculin reactions and early symptoms of tuberculosis intoxication, but whose chest X-ray is still normal;

　　5. Children with positive tuberculin reactions and those who need to be treated with adrenal cortical hormones for other diseases at the same time;

　　6. Children with positive tuberculin reactions may develop measles and pertussis after them.

　　Tuberculin test:

　　It is a diagnostic tool for tuberculosis. It is one of the two main tuberculin skin tests in the world and has largely replaced various puncture tests, such as the Tinetest.

　　1. Provide sufficient high-protein and enough calories, with the child's protein intake at 2.5 to 4 grams per kilogram of body weight. The calorie intake should be 100 to 120 kcal (per kilogram of body weight per day) to supplement the consumption.

　　2. Fat intake should not be too high, 1 to 2 grams per kilogram of body weight, with appropriate mixing of meat and vegetables, not too greasy, in order to avoid affecting digestion.

　　3. Diet should be rich in inorganic salts and vitamins. It is conducive to the calcification of lesions and the recovery of the patient.

　　4. For children with hemoptysis, iron intake should be increased.

　　5. For children with long-term low fever, they can eat more milk, eggs, lean meat, fish, tofu, etc., to supplement the consumption of protein metabolism.

　　Early treatment
　　Early lesions bacteria are in a state of growth and reproduction, with active metabolism, and drugs are most effective. Early lesions are also easier to repair.
　　Appropriate dosage
　　It can exert the maximum bactericidal or antibacterial effect while the patient can tolerate it with minimal toxic reactions. If the dose is insufficient, not only will the treatment be ineffective, but it is also easy to produce drug resistance.
　　Combination therapy
　　This is because: ① Different bacteria in the flora have different sensitivity to drugs, and there are different proportions of naturally resistant variant bacteria. Combination therapy can prevent the occurrence of drug resistance. ② Combination therapy can target bacteria in various metabolic states, select drugs for the flora inside and outside the cells, to achieve the synergistic effect of enhancing the therapeutic effect. Combination therapy should select drugs with synergistic effects for co-administration, such as INH combined with RFP or PAS, and RFP combined with EB. However, in the following situations, some drugs are better not to be co-administered: ① Drugs with the same side effects; ② Drugs with cross-resistance; ③ Drugs with antagonistic effects; ④ Drugs with equally weak efficacy.
　　Regular medication
　　Medication cannot be arbitrarily interrupted, otherwise it is easy to produce drug-resistant strains. As for intermittent therapy, there are specific requirements for dosage and interval, and there is also a certain regularity in use, which does not belong to arbitrary interruption.
　　Persist throughout the course
　　To eliminate persisting bacteria and prevent recurrence, chemotherapy should support the entire course. Short-term chemotherapy has emerged in the past decade, regardless of whether it is as short as 9 months or 6 months, it is still necessary to persist throughout the course.
　　Segmented treatment
　　Whether it is the traditional long-term therapy or the newly emerged short-term chemotherapy, stage-by-stage treatment is required, namely: ① Intensive phase. Use strong drugs in combination therapy to quickly eliminate sensitive bacteria and bacteria with active growth and division, and make the possible drug-resistant bacteria effectively resist during the intensive phase of traditional chemotherapy, which is generally half a year, while for short-term chemotherapy, it is 2 to 3 months. This is the key stage of chemotherapy. ② Consolidation (continuous) phase. The purpose is to eliminate persisting bacteria, consolidate the therapeutic effect, and prevent recurrence. Traditional chemotherapy is generally half a year, even 4 months.
　　Short-term chemotherapy is a new scheme that has emerged in the past decade. Its effectiveness depends on two factors: the drug's inhibitory effect on the rapid growth and metabolism of Mycobacterium tuberculosis, preventing the occurrence of drug-resistant bacteria; and the drug's sterilizing effect on Mycobacterium tuberculosis with low growth and metabolism (persisting bacteria), which can prevent recurrence. Therefore, the selection principle for short-term chemotherapy is: ① For bacteria with active division and metabolism, strong bactericidal drugs should be used, such as SM, INH, and RFP; ② Consider using sterilizing drugs effective against persisting tuberculosis bacteria to prevent recurrence, such as PZA, RFP, and INH; ③ Antibiotics such as EMB, PAS, ETH, and TB1 are not suitable for short-term chemotherapy.
　　When selecting drugs for pediatric short-term chemotherapy, the following points should be considered: ① Pediatric tuberculosis is mostly newly infected, especially blood-borne dissemination, so preventing and treating meningeal invasion is most important. First, drugs that are easy to penetrate the meninges into the cerebrospinal fluid, such as INH, RFP, and ETH, should be selected, and EB should not be used. ② The best choice during acute blood-borne dissemination is drugs that can kill growing sensitive bacteria, such as SM. ③ When treating tuberculous meningitis, consider using injectable anti-tuberculosis drugs, such as SM. ④ Primary tuberculosis infections that are resistant to INH and SM are more common in children than in adults. In addition to selecting drugs based on the source of infection, it is necessary to choose potentially sensitive杀菌 drugs, such as RFP and PZA or ETH and EB. ⑤ During acute tuberculosis infection, monocytes are often affected, so it is important to use杀菌 drugs that can enter cells (such as PZA). ⑥ The reproductive cycle of Mycobacterium tuberculosis is 14-22 hours, so it can be administered once a day. It has been proven that the peak concentration of INH taken in a single dose is more important than the constant concentration of the conventional method of taking multiple doses a day. Therefore, taking the full daily dose in a single dose can both improve efficacy and ensure adherence to medication.
　　Type of drug
　　Anti-tuberculosis drugs are divided into three classes: A, B, and C according to their quality and quantity:
　　Class A drugs include isoniazid and rifampicin.
　　Class B drugs include streptomycin, pyrazinamide, ethambutol, kanamycin, ethionamide, cysostatin, purpuric acid, and talcycin.
　　Class C drugs: include sodium aminosalicylate and amithiourea.
　　Clinical experience has proven that the efficacy of chemotherapy for pediatric tuberculosis is good. The evaluation of anti-tuberculosis drugs according to the efficacy and toxicity of the drugs is as follows: ① First-class: isoniazid and rifampicin; second-class: streptomycin, pyrazinamide, ethionamide, and ethambutol. ② Second-class: sodium aminosalicylate, kanamycin, talcycin, purpuric acid, and cysostatin. ③ Third-class: amithiourea.