Bath? Facial? Seafood? Never be too careful. –Knowledge of non-tuberculous mycobacteria (NTM)

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Relaxing by taking a bath but suffered from “hot tub lung disease”? Looking forward to a new look after a beauty treatment but didn’t expect to get a nightmare of purulent skin disease? Why a small cut by a shrimp but leads to amputation? Why did a common activity in life almost turn into a deadly disaster? How much do you know about the non-tuberculous mycobacteria (NTM)?

 

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Nontuberculous Mycobacteria (NTM) is a general term for a large group of mycobacteria other than Mycobacterium tuberculosis complex (MTBC) and Mycobacterium leprae, and it has a wide variety of species, with more than 190 species and 14 subspecies found so far. There are 14 subspecies. Most of them are parasitic bacteria, only a few of them are pathogenic to human and are conditional pathogens.

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Figure 1 Classification of Mycobacterium

According to the growth rate of NTM in the test tube and the relationship between pigment production and light reaction, they can be divided into two major groups and four minor groups, which are: slow-growing Mycobacterium (light color-producing bacteria, dark color-producing bacteria, non-color-producing bacteria) and fast-growing Mycobacterium (colonies visible to the naked eye within 3~5 days, most of them grow vigorously within 1 week). With the continuous development of genotyping technology, new NTM strains and subspecies will be discovered, and the classification of NTM strains will be more refined and perfected.

 

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NTM is widely found in the natural environment such as water and soil and can infect humans and some animals; NTM disease refers to the infection of human body with NTM, which causes lesions in related tissues and organs. The “hot tub lung disease” mentioned at the beginning of the article is due to the contamination of water by Mycobacterium avium complex (MAC), and the high frequency and longtime of bathing increases the possibility of aerosol formed by MAC aerosol being inhaled into the lungs; going to informal medical institutions for invasive medical aesthetic projects is likely to be infected with Mycobacterium abscessus complex (MABC), which leads to NTM disease. Cluster (MABC) thus leading to wound infection, septicemia and even necrosis; when the skin is cut while handling seafood such as fish and shrimp, it is possible to be infected with Mycobacterium marinum, and because the wound is small and the pain is not obvious, many people will ignore the symptoms leading to the delay of the disease and finally develop to the point of requiring amputation.

◆NTM lung disease is the most common form of NTM disease, which can occur at any age, and is more common in women and older people. Its clinical manifestations are like those of tuberculosis, but the systemic toxic symptoms are less severe than those of tuberculosis.

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Figure 2 Differences in clinical manifestations of patients with different NTM lung diseases

◆NTM can also involve lymph nodes, skin, bones and joints and cause inflammation. Immune-compromised patients may develop systemic disseminated NTM disease, with common symptoms such as fever, progressive weight loss, night sweats, abdominal pain and diarrhea.

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Figure 3 Pictures of NTM infection lesions (click after to view)

 

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 1. NTM disease is significantly on the rise nationwide

In China, epidemiological studies of NTM disease are more difficult because reporting of NTM disease is not mandatory and identifying NTM infection and onset is difficult. No large sample epidemiological survey has been conducted for NTM disease in China, and thus exact data on NTM disease are lacking. However, data from successive epidemiological surveys of tuberculosis in China show that NTM disease in China is significantly on the rise, with the NTM isolation rate rising fivefold from 4.2% in the 1980s to 22.9% in 2010.

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                                   Figure 4 NTM isolation rate in successive national epidemiological surveys of tuberculosis

2. Different NTM isolation rates in different regions

The China Non-tuberculous Mycobacteria Surveillance Study Group (CNTMS), organized by the Beijing TB Innovative Treatment Technology Consortium, used the MeltPro® Mycobacteria Identification Kit based on Multicolor Melting Curve Analysis (MMCA) technology to continuously In 2020, 6963 patients with suspected pulmonary tuberculosis attending hospitals were enrolled in the study, and mycobacterial testing and strain identification were performed along with the collection of demographic and sociological information. The statistical results of the study showed that the proportion of non-tuberculous mycobacterial pulmonary disease (NTM-PD) among suspected TB patients was significantly geographically diverse, showing a trend of increasing isolation rates from north to south and from west to east. And 10 Mycobacterium species were identified in NTM-PD patients, most commonly Mycobacterium intracellulare (52.6%), Mycobacterium abscessus complex (23.1%) and Mycobacterium avium complex (8.5%).

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Figure 5 NTM separation rate increases from north to south and west to east

Northwest (3.2%) Central (6.1%) South (9.2%)

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Figure 6 Distribution composition of NTM-PD-associated divergent bacilli species in China

In addition, the study suggested risk factors associated with NTM-PD: women and the elderly were more likely to develop NTM-PD, and patients with bronchiectasis, chronic obstructive pulmonary disease, and HIV were at higher risk of developing NTM-PD.

Reference: Tan Yaoju, et al., Nontuberculous mycobacterial pulmonary disease and associated risk factors in China: a prospective surveillance study. [J]. The Journal of infection, 2021, 83(1)

In addition, the study suggested risk factors associated with NTM-PD: women and the elderly were more likely to develop NTM-PD, and patients with bronchiectasis, chronic obstructive pulmonary disease, and HIV were at higher risk of developing NTM-PD.

Reference: Tan Yaoju, et al., Nontuberculous mycobacterial pulmonary disease and associated risk factors in China: a prospective surveillance study. [J]. The Journal of infection, 2021, 83(1)

 

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Diagnosis of NTM disease

7.6Smear microscopy: The positive rate is low, and smear microscopy alone cannot differentiate Mycobacterium tuberculosis from NTM.

7.7Isolation culture: Some NTM growth requires special medium and culture temperature, which is tedious and time-consuming.

7.8Strain identification: Since different strains have different susceptibility to drugs, strain identification can provide accurate diagnosis of NTM disease and is of great clinical value in formulating treatment plans.

Traditional biochemical methods: p-nitrobenzoic acid (PNB) selective medium method can distinguish NTM from MTBC, but it is only suitable for preliminary identification of strains and cannot identify NTM to species; MPB64 antigen detection method is used to detect one of the main secreted proteins of MTBC when growing in liquid medium – the The MPB64 antigen assay is used to discern the presence of MTBC and cannot detect the presence of both MTBC and NTM.

Based on the molecular biology method for strain identification, probes can be designed for single nucleotide polymorphic sites of specific homologous genes or sequences (e.g., 16sDNA, ITS, etc.), and the composition of DNA sequences can be judged by the binding of probes to the sequences to be tested, thus achieving the purpose of strain identification. This method has the advantages of easy operation, short time consumption and accurate identification, and is suitable for clinical laboratories to carry out.

The molecular biology methods commonly used for the identification of Mycobacterium are gene microarray, reverse hybridization, flight mass spectrometry and sequencing, but compared with the multicolor melting curve analysis, they are more cumbersome, time-consuming, cannot identify mixed infections, and require isolates for testing.

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Multi-color melting curve analysis (MMCA) for rapid strain identification and precise clinical treatment

● Single tube detects 51 species of Mycobacterium and identifies 19 of them.

It is suitable for a variety of specimen types, and both sputum and isolates can be used for testing.

● Differentiation of strains to avoid the use of ineffective drugs: Mycobacterium bovis is resistant to pyrazinamide and Mycobacterium abscessus complex is resistant to ethambutol.

● Detection of mixed mycobacterial infections is more useful in determining the treatment plan.

● The test is easy, fast, and accurate, which can buy valuable treatment time for patients.

 

                        

 

 


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