nontuberculous mycobacteriosis
Introduction
Introduction to nontuberculous mycobacterial disease In recent years, the detection rate of nontuberculous mycobacteria (NTM) has gradually increased, and the corresponding knowledge of various diseases caused by it has gradually increased. Non-tuberculous mycobacteria refers to mycobacteria. In addition to Mycobacterium tuberculosis complex (human, bovine, African and zebra M. tuberculosis) and mycobacteria other than M. leprae. Most of them are spoilage parasites with low virulence and are conditional pathogens. Previously named as Mycobacterium tuberculosis, pseudotuberculosis, Mycobacterium, unclassified mycobacteria, Mycobacterium wildotype, opportunistic mycobacteria, atypical acid-fast bacilli, etc., the most common name is currently non- Mycobacterium tuberculosis (NTM), a disease caused by NTM, is called diseasecaused by NTM. NTM has been found to date with more than 100 species, of which 37 have been reported for pathogenic cases. According to the Bergysmanualofsystematicbacteriology, NTM is divided into two categories: fast-growing and slow-growing, of which 42 are approved by the International Bacterial Nomenclature Committee. basic knowledge The proportion of illness: 0.025% Susceptible people: no special people Mode of infection: fecal-mouth transmission Complications: osteomyelitis septic arthritis
Cause
The cause of nontuberculous mycobacterial disease
NTM is widely distributed in natural soil, dust, running water and raw milk. The morphology of NTM under microscope is similar to that of Mycobacterium tuberculosis. The acid-fast staining is red, but in culture, the biochemical characteristics are different from those of Mycobacterium tuberculosis, which can be based on NTM on solid medium. The growth rate and the effect of light on its pigmentation, the Runyon classification rules divide it into the following four groups:
Group I photosynthetic bacteria (20%):
Group I is photochromogen. There are Mycobacterium kansii, Mycobacterium marinum, Mycobacterium phlei and Mycobacterium asiatica. The first two are pathogenic bacteria, and the bacteria in this group need light color. The colonies are creamy in the dark. After exposure for 1 hour, they are cultivated into orange, which grows slowly and the colonies are smooth. These bacteria are easy to cause lung infection, but the condition is mild, and the clinical symptoms are similar to those of tuberculosis.
Group II dark chromogenic bacteria (20%):
Group II is scotochromogen, Mycobacterium sputum, Mycobacterium sulcata, Mycobacterium gordonii, Mycobacterium phlei, this group of bacteria facultative color, colonies in either light or no light It can produce color under the condition, produce yellow in the dark, produce orange in the light, grow slowly at 37 °C, and the colony is smooth. These bacteria can cause cervical lymphadenitis in children, lung or extrapulmonary infection and bruise. Sexual abscesses, etc.
Group III non-chromogenic bacteria (20%):
Group III is achromatic mycobaterium. M. avium complex (MAC), intracellular mycobacteria, Mycobacterium ulcerosa, Mycobacterium marinum, Mycobacterium haemophilus (M.hemophilum), Mycobacterium phlei, this group of bacteria does not produce pigment in light or dark, slow growth, cultured on modified Roche medium at 37 ° C for 7 days or longer, visible smooth colorless colonies, These bacteria can cause lung infections, lymphadenitis, arthritis and meningitis.
Group IV fast growing bacteria (20%):
The IV group is a rapid grower. There are Mycobacterium fortuitum, Mycobacterium sinensis, Mycobacterium abscessus, Mycobacterium smegmatis, etc. This group of bacteria grows at 25-45 ° C, grows fast, and cultures 5-7 Colonies can be seen in the day, the colonies are rough, and some can also produce color. The first three are pathogenic to humans, which can cause lung diseases and skin infections. Although Mycobacterium smegmatis does not cause disease, it is often present in the genital sebum. Attention should be paid to the identification. In 1982, Wayne classified tuberculosis and nontuberculous mycobacteria into six complex groups according to their pathogenicity and biological characteristics:
1 Mycobacterium tuberculosis complex: human, cattle, Africa, voles type Mycobacterium tuberculosis
2 bird-M. avium-intracellulae complex (MAIC): bird, intracellular, sputum, M. tuberculosis, etc., is a common conditional pathogen
3 Gordon Mycobacterium complex: Gordon, Asia, Mycobacterium sulcata, etc.
4 Kansas Mycobacterium complex: Kansas, Mycobacterium tuberculosis, etc.
5 Mycobacterium group complex: land, no color, secondary mycobacteria, etc.
6 Occulted Mycobacterium complexes: accidental, turtle, mycobacteria, etc. According to recent literature reports, six important NTMs that can cause lung diseases clinically, their culture characteristics (including growth temperature, light/dark pigmentation, Aerobic and hydrolyzed Tween 80, etc.) may have similar or different points (Table 2)
Whether NTM has pathogenicity can be identified by anti-boiling test. Non-pathogenic strains lose acid resistance when boiled for 1 min, while pathogenic strains can withstand 10 min, even autoclaving does not lose acid resistance, M. tuberculosis and non-tuberculous fractions. Identification of Mycobacterium, in addition to the thermo-contact enzyme test, the lawn can be ground on a slide containing saline droplets, the former is not easy to emulsify and the latter is easy to emulsify, NTM is resistant to most anti-tuberculosis drugs, and its resistance mechanism In terms of genetic variation of the drug target site of bacteria: INH resistance is mainly related to the production of a kat G gene mutation encoding a peroxidase-catalase, and a small part of the ahp gene encoding an alkyl peroxidase and coding IV. - The acetyltransferase is involved in a mutation in the Nat gene. The resistance to RFP is related to the mutation of 507-533 of the rpo B gene encoding the RNA polymerase subunit. The resistance to SM and the rps L gene encoding the ribosomal protein S12 are mutated to make 16S rRNA. Structurally related, EMB resistance is associated with mutation of the emb B gene encoding arabinose transferase, and pyrazinamide-resistant (PZA) is associated with mutations in the pnc A gene encoding pyrazinamide, fluoroquinolones and The gyr A and lfrA genes of the A subunit in the DNA gyrase are involved in mutations.
Pathogenesis
The pathological changes of NTM disease are similar to those of tuberculosis. Because NTM is weak in pathogenicity, the pathological changes are relatively light, but there may be some differences in the pathological changes of NTM disease in different types and different hosts. NTM lung disease is very common. Multiple manifestations of multiple or multi-atrial thin-walled cavities, the pleura is rarely involved, pathological changes are often non-specific inflammation, but there are a large number of NTM pathogens, skin soft tissue NTM disease if it is caused by Mycobacterium abscessus, it shows granulomatous lesions And non-specific suppurative inflammation, according to a pathological examination of 114 surgically resected specimens of a hospital infection of a mycobacteria in a hospital in Shenzhen, the granuloma has three forms:
1 suppurative tuberculosis, accounting for 70%
2 atypical tuberculous granuloma, accounting for 28%
3 typical "tuberculosis" granuloma, accounting for 59.7%, disseminated NTM disease can be seen in many bones mainly caused by neutrophils, including more acid-fast bacilli, occasionally a large number of bacteria in the bone marrow Other organs see atrophic granuloma and a few acid-fast bacilli
Prevention
Non-tuberculous mycobacterial disease prevention
People with HTV infection should be alert to concurrent NTM. When peripheral blood CD4+ cells are <0.1×109/L, azithromycin or rifabutin can be used alone or in combination to reduce the infection rate of MAIC. It is necessary to prevent hospital NTM infection. The key is Disinfection and sterilization, for invasive operation, surgery should be carried out in strict accordance with the rules and regulations, disinfectant preparation is strictly in accordance with the requirements, hospitals with conditions should strengthen the inspection of NTM.
Complication
Non-tuberculous mycobacterial complications Complications osteomyelitis septic arthritis
Often can be complicated by synovitis, osteomyelitis, septic arthritis and endocarditis, pericarditis.
Symptom
Symptoms of non-tuberculous mycobacterial diseases Common symptoms Low heat liver splenomegaly, difficulty breathing, fatigue, hydronephrosis
NTM can invade many organs and tissues throughout the body, with the lungs being the most common. Extrapulmonary lesions include lymph nodes, skin, soft tissues, and bones.
Chronic lung disease
Common pathogens are MAIC, Mycobacterium kansii, Mycobacterium fortuitum, Mycobacterium abscessus and Mycobacterium phlei. The lung diseases caused by the above bacteria are very similar to those of tuberculosis. Patients often have chronic obstructive pulmonary disease and tuberculosis. Silicosis, lung abscess, bronchiectasis, cystic fibrosis, diabetes, ulcer disease and application of hormones, history of immunosuppressants, more men than women, symptoms of cough, cough, hemoptysis, chest pain, difficulty breathing, low fever, weight loss, Weak, but lack of specificity, slow progression, X-ray chest X-ray lesions are more common in the right upper lung, showing infiltration, cavities, nodules, fiber cheese and extensive fiber contraction and other lesions, the incidence of cavitation is as high as 80%, a single Or multiple, the cavity caused by intracellular mycobacteria is mostly located under the pleura, the wall is thin, and there is less oozing around. Mycobacterium phlei causes pulmonary lesions in children, which is similar to the original tuberculosis. MAIC infection can be diffuse. Sexually disseminated lesions, in the case of NTM infection, often take 2 to 4 years from the initial stage of the lesion to the formation of cavities. In addition, pleural effusion is rare.
2. Lymphadenitis
Lymphadenitis caused by NTM is much more common than lymphadenopathy. Pathogenic bacteria are more common in birds, intracellular mycobacteria, mycobacteria and mycobacteria, and are more common in children under 12 years old, 2 to 4 years old. Children are predominant, 91% of children aged 0-5 years, the incidence rate is 10 times that of tuberculous lymphadenitis, children have fun playing with soil, pond water habits, lesions located in the neck, submandibular, groin, upper iliac crest, Axillary fossa, swollen lymph nodes, no pain, but can have tenderness, slow progress, sinus formation after lymph node rupture, repeated deterioration and improvement, and finally fibrosis and calcification outcome.
3. Meningitis
Common in AIDS, back trauma and neurosurgery, patients with Mycobacterium avium, Occa M., Mycobacterium phlei and Mycobacterium kansii are more common, and their clinical manifestations are similar to tuberculous meningitis, but The mortality rate is high.
4. Skin and soft tissue infections
Infected by Mycobacterium marinum, more common in swimming pools, or swimmers in the sea, such as elbows, knees, sputum, finger (toe) skin, starting with reddish brown papules, small nodules or plaques, followed by Softening and ulceration becomes a superficial ulcer, which can often be delayed for several months or even several years, but it does not form a fistula. Occasionally, the lesion develops centripetally along the lymphatic vessels. The lesions are self-limiting, and the occasional mycobacterial complex can be localized. Skin wound invasion forms a localized abscess, focal cellulitis, mostly iatrogenic infection, ulcerative mycobacteria often cause painless subcutaneous nodules in the calf and forearm, which in turn form blisters, rupture leading to necrotizing ulcers, surface Covering yellow necrosis, surrounding skin bulging, pigmentation, known as Baimsdal ulcer (called Searl disease in Australia; Buruli ulcer in Uganda), post-mechanization of scar formation can cause malformation, mycobacteria can also cause skin granuloma Sexual nodules, rupture with fistula formation, accompanied by lymphadenopathy, Kansas mycobacterial infection can often cause warts or granulomatous papules and necrotizing papuloid pustules, occasionally breast augmentation Breast infections caused by NTM.
5. Skeletal system lesions
Pathogenic bacteria are more common in Mycobacterium Kansas, Avian Mycobacterium, Mycobacterium phlei and Mycobacterium, and often infected by wounds in contact with soil and water, causing bones, joints, tendon sheaths, bursae and Bone marrow infection, secondary mycobacteria can cause septic arthritis.
6. Blood-borne disseminated mycobacterial disease
Found in severe cellular immunosuppressive drugs, such as hematological malignancies or concurrent treatment with adrenal glucocorticoids and AIDS patients, the pathogens are mostly avian-intracellular mycobacteria, followed by Kansas and mycobacteria, Its clinical features are long and undulating, involving various system organs, anti-tuberculosis drug resistance, poor prognosis, high mortality, pulmonary lesions showing inflammatory changes, 1/4 of which are miliary changes, can also occur Hepatosplenomegaly, Mycobacterium phlei and Avian Mycobacterium can cause systemic lymphadenopathy, his histology resembles sarcoidosis, and these two bacteria can cause extensive multiple bone lesions, manifested as Chronic osteomyelitis and sinus formation, prolonged unhealed, or repeated attacks, bird-cell intracellular mycobacteria can also cause extensive intra-abdominal infections, including mesenteric, retroperitoneal lymph nodes and visceral diffuse miliary lesions.
7. Other parts of the infection
There are still MAC-induced urinary and reproductive system infections; occasional mycobacteria cause eye and tooth infections; M. linda causes gastrointestinal infections; Mycobacterium tuberculosis and Mycobacterium tuberculosis (Mycobacterium tuberculosis) M.wood pigeon) is associated with Crohn's disease.
8. Nosocomial infection
In recent years, NTM has attracted the attention of hospital infections. There have been reports of 26 outbreaks of NTM infection in the world. The common pathogens are caused by the rapid growth of Mycobacterium marinum, caused by Mycobacterium abscessus, mainly due to surgical contamination. Invasive treatment of pollution, intubation pollution, artificial dialysis pollution and cardiac extracorporeal circulation pollution caused by infection, in 1998, a hospital in Shenzhen, China, due to disinfectant mismatch caused by 168 patients after surgery, M. abscess The outbreak of infection, the incidence rate of patients after surgery is 57.53% (168/292), which is characterized by a large number of cases, high incidence, long incubation period, is a rare hospital infection.
Examine
Non-tuberculous mycobacterial disease examination
1. Bacteriological examination: For patients suspected of NTM lung disease, sputum smear can be taken for acid-fast staining, sputum culture, and bronchial lavage specimen culture, such as acid-fast staining, should be identified after culture, such as 2 to 3 times. The same NTM can be used to diagnose cerebrospinal fluid, blood or bone marrow in patients with NTM meningitis and blood-borne disseminated NTM.
2. Pathological examination: NTM infection of skin soft tissue, NTM lymphadenitis can be performed by biopsy. The pathological features of NTM lymphadenitis are granulomatous inflammation, while tuberculous nodules formed by epithelial cells and Langhans giant cells are rare. Without central cheese-like necrosis.
3. Molecular biological examination: PCR-restriction fragment length polymorphism (PCR-RFLP) analysis of 16S-23:SrDNA gene spacer sequence (IGS) of NTM was used as NTM strain Identification, more accurate than the morphology, biochemical routine methods, rapid and simple.
4. Mantoux skin test: Mycobacterium tuberculosis and NTM have a common antigen. Although the PPD skin test can produce cross-reaction, there are still differences. PPD-T of Mycobacterium tuberculosis and PPD-NTM of NTM are used simultaneously. In the test, the diameter of the PPD-T induration in NTM patients is generally less than 15 mm. If the diameter of the induration of the PPD-NTM skin test is 5 mm or more than the PPD-T skin test, it can be considered as NTM infection.
X-ray chest X-ray lesions are more common in the right upper lung, showing infiltration, cavities, nodules, fiber cheese and extensive fiber contraction and other lesions, the incidence of cavitation is as high as 80%, single or multiple.
Diagnosis
Diagnosis and identification of nontuberculous mycobacterial diseases
Diagnostic criteria
The diagnosis of non-tuberculous mycobacterial disease depends on clinical, X-ray and bacterial culture and strain identification, especially the latter is the main basis for diagnosis, according to the 2000 National Atypical Mycobacterial Symposium The opinions on the diagnosis and treatment of mycobacterial diseases are described as follows:
1. NTM infection can be diagnosed as NTM infection if it has the following two conditions:
1PPD-NTM skin test is positive,
2 lack of tissue, organs are based on M. tuberculosis infection.
2. NTM Suspects One of the following conditions is a suspected NTM disease and requires an NTM check:
1 tuberculosis patients who are not treated with conventional anti-tuberculosis treatment or specimens with smear acid-staining are still positive,
2 specimen smear positive for acid-fast bacilli and clinical manifestations are not consistent with tuberculosis,
3 specimens were positive for mycobacterial culture, but the colony status and growth were different from the Mycobacterium tuberculosis complex.
4 microscopic examination of abnormal mycobacteria,
5 The first isolated mycobacteria of tuberculosis patients were resistant to tuberculosis drugs,
6 have immunodeficiency, leukemia, tumor and long-term use of immunosuppressive agents, diabetes and other lung infections that have ruled out tuberculosis,
7 iatrogenic or non-iatrogenic soft tissue injury, the wound can not be found for a long time after the operation.
3. NTM lung disease has respiratory symptoms or systemic symptoms. There are lung lesions on chest X-ray. Other diseases have been ruled out. Under the condition that the specimen is non-polluting, one of the following conditions can be diagnosed as NTM lung disease:
1NTM cultured 3 times are all the same NTM bacteria,
2NTM was cultured twice for the same NTM bacteria, and the sputum smear was positive for acid-fast staining once.
3 bronchial lavage fluid NTM culture positive,
4 Bronchopulmonary biopsy NTM culture was positive, 5 lung biopsy showed granuloma similar to NTM lesion, and NTM culture was positive once.
4. Extrapulmonary NTM disease has local or systemic symptoms. After examination, there are extrapulmonary tissues and organ lesions. Other diseases have been ruled out. Under the condition that the specimens are non-polluted, the NTM culture of the lesions is positive, and the diagnosis can be made. NTM lymphadenitis It should be differentiated from other bacteria-induced suppurative lymphadenitis, tuberculous lymphadenitis, cat scratching, infectious mononucleosis, etc. PPD-NTM skin test has different value.
Differential diagnosis
NTM lung disease should be differentiated from tuberculosis, bronchiectasis, mycoplasmal pneumonia, cystic fibrosis, Legionnaires' disease, pulmonary mycosis and Pneumocystis carinii. It depends on PPD-NTM skin test and pathogen examination, disseminated NTM disease should be differentiated from sepsis, typhoid fever, disseminated mycosis, and whole body miliary tuberculosis, mainly relying on PPD-NTM skin test and pathogen examination.
