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The global trends of nontuberculous mycobacteria (NTM) infection and disease are both rising. Nontuberculous mycobacterial disease(NTMD) is a worldwide health burden associated with increasing morbidity, mortality, and economic costs. Antibiotic therapy is the mainstay of treatment for NTMD.Mycobacterial pathogens are intrinsically resistant to many available antibiotics, making treatment extremely challenging, especially in immunocompromised individuals and patients with underlying chronic lung conditions. Even with lengthy therapy and the use of a combination of antibiotics, only less than half NTMD patients can achieve clinical treatment success, so it is urgent to develop novel anti-NTM antibiotics. This article reviews the research progress on the medication of nontuberculous mycobacterial diseases.
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Drug-resistant tuberculosis (DR-TB) has been a serious global public health problem. There is an urgent need in new drug development for drug-resistant Mycobacterium tuberculosis (MTB). Bedaquiline (Bdq) is a new antituberculous drug belonging to the diarylquinoline class that efficiently inhibits the adenosine triphosphate synthase enzyme of MTB, now is one of the core drugs for the treatment of DR-TB. Bdq can significantly improve the negative rate of sputum culture and reduce the mortality with good safety and tolerance, and it can also shorten the course of treatment for patients with tuberculosis and save costs. This article reviews the efficacy, safety, tolerability and treatment-related issues of Bdq-containing regimens for DR-TB.
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Objective:To detect the inflammatory reaction of macrophages induced by lipoglycans of different genotypes of Mycobacterium tuberculosis ( Mtb) in vitro and to analyze the differences in lipoglycan virulence. Methods:Lipoglycans were extracted from Mtb of Beijing, T1 and MANU2 genotypes and H37Rv by Triton X-114 liquid phase method and the crude extracts of lipoglycans was used to stimulate RAW264.7 macrophages. Changes in cytokine and receptor expression and cell apoptosis were detected 24 h after stimulation. The virulence of lipoglycans from different genotypes of Mtb was analyzed and compared. One-way analysis of variance and Tukey′s multiple comparisons test were used to compare the differences in various indexes between groups. Results:The expression of IL-10 at mRNA level induced by lipoglycans from Mtb of Beijing, T1 and MANU2 genotypes and H37Rv was (0.94±0.24), (1.86±0.24), (1.90±0.24) and (2.55±0.75) times that of the control group. Moreover, IL-10 mRNA expression induced by lipoglycans from Mtb of Beijing genotype was significantly lower than that of H37Rv group ( P<0.05). After stimulating RAW264.7 cells with the crude extracts of lipoglycans, the proportions of living cells in H37Rv, Beijing genotype, T1 genotype and MANU2 genotype groups were (72.75±2.25)%, (60.99±0.13)%, (80.66±0.40)% and (79.06±1.19)%, and the total cell apoptosis ratios was (10.42±0.23)%, (8.30±0.03)%, (9.24±0.79)% and (8.04±0.48)%, respectively. The proportion of living cells in Beijing genotype group was the lowest ( P<0.05), and the proportions of living cells in T1 and MANU2 genotype groups were higher than that in H37Rv group ( P<0.05). There was no significant difference in cell apoptosis ratio among the groups ( P>0.05). Lipoglycan-induced cell death was increased in Beijing genotype group, and the lipoglycan from Beijing genotype Mtb was more virulent than those from Mtb of T1 and MANU2 genotypes. Conclusions:Lipoglycan from Mtb of Beijing genotype could induce a higher level of cell death in vitro. It was an antigen component with stronger virulence than those from Mtb of T1 and MANU2 genotypes.
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Tuberculous meningitis is the most common and serious type of central nervous system tuberculosis, with high mortality and disability rate, which has attracted extensive attention of global public health. The high mortality rate and disability rate of tuberculosis meningitis may be related to its lack of specific clinical and imaging characteristics, insufficient attention from clinicians, lack of early sensitive and specific diagnostic testing techniques, delay in treatment, and restricted penetration of anti-TB drugs into the blood-brain barrier or/and MDR-TB, etc. This article reviews the disease burden of TBM, chemotherapy drugs and regimens, anti-inflammatory agents, aspirin, interventional and surgical treatment to provide reference for clinical management of this disease.
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Tuberculosis is a kind of chronic infectious disease caused by Mycobacterium tuberculosis (MTB).Macrophages, as the main host cells against MTB ,play a crucial role in the natural and acquired immune response of the body.Under the stimulation of different inducing factors , macrophages can be polarized to M1-type macrophages and M2-type macrophages,which play different functions in the progression of tuberculosis.Further studies on the polarization signaling pathway of macrophages and dynamic balance between M1 and M2-type macrophages cells have provide a new way to explore the pathogenesis of tuberculosis.In addition, due to the importance of macrophage polarization in the development of MTB infection, the formation of tuberculous granuloma and prognosis of tuberculosis , the in-depth study on macrophages polarization will contribute to the development of new tuberculosis vaccines and immune agents , and lay an important theoretical foundation for the prevention and treatment of tuberculosis .
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Tuberculosis is a chronic infectious disease caused by Mycobacterium (M.)tuberculosis.Innate immunity plays an important role in the response to M.tuberculosis.Toll-like receptors (TLRs) are important pattern recognition receptors in innate immunity.TLRs serve as switches that play decisive roles in identifying pathogens-related components.Previous studies found that TLR1,TLR2,TLR4,TLR9 were essential to promote the development of innate immune responses.The SNPs of rs4833095,rs5743618,rs3923647 of TLR1,rs57473708,rs3804099 of TLR2 and rs352139,rs5743836 of TLR9 were closely related to the susceptibility of tuberculosis in some populations.And there appeared certain relationship between the polymorphisms of TLR3,TLR6,TLR7,TLR8,TLR10 and the susceptibility of tuberculosis.The normal function of TLRs ensures the body's normal immune response to M.tuberculosis.The diversity of TLRs genes allows different individuals to respond differently to the same pathogen.Studies targeting on the relationship between single nucleotide polymorphism in TLRs and susceptibility to tuberculosis can predict the susceptibility to tuberculosis in some populations,as well as discover new drugs targets.
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Tuberculosis is a chronic infectious disease caused by Mycobacterium (M.)tuberculosis.Innate immunity plays an important role in the response to M.tuberculosis.Toll-like receptors (TLRs) are important pattern recognition receptors in innate immunity.TLRs serve as switches that play decisive roles in identifying pathogens-related components.Previous studies found that TLR1,TLR2,TLR4,TLR9 were essential to promote the development of innate immune responses.The SNPs of rs4833095,rs5743618,rs3923647 of TLR1,rs57473708,rs3804099 of TLR2 and rs352139,rs5743836 of TLR9 were closely related to the susceptibility of tuberculosis in some populations.And there appeared certain relationship between the polymorphisms of TLR3,TLR6,TLR7,TLR8,TLR10 and the susceptibility of tuberculosis.The normal function of TLRs ensures the body's normal immune response to M.tuberculosis.The diversity of TLRs genes allows different individuals to respond differently to the same pathogen.Studies targeting on the relationship between single nucleotide polymorphism in TLRs and susceptibility to tuberculosis can predict the susceptibility to tuberculosis in some populations,as well as discover new drugs targets.
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The immune pathogenesis of tuberculosis,preparation of Mycobacterium tuberculosis vaccine,diagnosis of latent infection and active tuberculosis as well as the assessment of tuberculosis severity are still major challenges in the field of tuberculosis.In recent years,many studies have explored immune pathogenesis and new diagnostic and treatment targets of tuberculosis, and the high mobility group box-1 protein(HMGB1) receives wide attention for its unique pathophysiological mechanism.This article reviews the research progress on the correlation between HMGB1 and tuberculosis, which would be of help in diagnosis and treatment of tuberculosis.
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ObjectiveTo investigate the anti-tuberculosis treatment response and outcomes in treatment naive patients infected with multidrug-resistant tuberculosis (MDR-TB).MethodsA total of 408 patients who were diagnosed with MDR-TB in Shanghai Pulmonary Hospital from January 2006 to January 2009 were recruited in this study.These patients were divided into two groups based on their previous treatment history:treatment naive group and re treatment group. The treatment response,outcomes andadverse eventswere observed. The outcomes of thesetwo groupswere compared by cohort analysis and x2 test.ResultsThe sputum conversion rates,the lesions absorption rate and the cavity closing or shrinking rate of the treatment naive MDR TB group were significantly higher than those of the re treatment group,while the adverse events rate was not significantly different between two groups (x2 =0.434,P＞0.05).Among 89 treatment naive cases,66 cases (74.16％) were cured,8(8.99％) completed the full treatment course,7(7.87％) were treatment failure,3(3.37％) died,and 5(5.62％) were lost to follow-up.Among the 319 cases of re-treatment MDR TB group,134 (42.01％) were cured,31(9.72％) completed the full treatment course,116 (36.36％) were treatment failure,12(3.76％) died,26(8.15％) were lost to follow-up.The cure rate of the treatment naive MDR-TB group was significantly higher than that of re-treatment group (x2=28.783,P＜0.01).The factors influencing the treatment outcomes included the stage of the disease,the range of lesions and cavity, the patients'generalnutritional status, underlying complications,and the drug-resistant strains. Conclusions The anti-tuberculosis treatment outcomes are better in treatment naive patients with MDR-TB infection compared to the treatment experienced and retreated patients.Therefore,the status of the drug resistance should be closely monitored in order to detect MDR-TB as early as possible.With the early diagnosis,the treatmcnt regimen may be modified timely and as a result the treatment outcomes can be improved.
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Objective To analyze the risk factors of pulmonary non-tuberculous mycobacterial (NTM) infection in sputum acid-fast bacilli positive and/or mycobacteria culture positive patients.Methods One hundred and sixty-three patients with pulmonary NTM infection were recruited from Jan 2006 to Jun 2011 in Shanghai Pulmonary Hospital and 326 patients with sputum positive pulmonary tuberculosis who were selected by random systemic sampling method in the same period were recruited as control.The data were retrospectively analyzed.The related factors were compared between groups by chi-square test.The risk factors of pulmonary NTM infection were analyzed by binary Logistic regression model.Results There were statistically significant differences of age,history of smoking,chronic obstructive pulmonary disease (COPD),bronchiectasis,thin walled cavities focus,purified protein derivative (PPD) test between patients with pulmonary NTM infection and patients with pulmonary tuberculosis (all P＜0.05).Univariate analysis showed that age [45-60year (OR=2.637,95％CI:1.631-4.264; P＜0.001); ＞60 year (OR=4.194,95％CI:2.581-6,813 ; P＜0.001)],history of smoking [10-20 year (OR=1.842,95％CI:1.0843.070; P=0.024),＞20 year (OR=2.040,95％CI:1.167-3.567; P=0.012)],COPD (OR=2.698,95％CI:1.588-4.583; P＜0.001),bronchiectasis (OR=3.566,95％CI:2.343-5.427;P＜0.001),thin walled cavities focus (OR=2.592,95％CI:1.581-4.250; P＜0.001) and a weak-positive reaction of PPD test (OR=2.389,95％CI:1.276-4.472; P=0.006) were all risk factors of pulmonary NTM infection.Multivariate analysis showed that age＞60 year (OR=3.961,95％CI:2.183-7.189 ; P＜0.001),bronchiectasis (OR =3.880,95 ％ CI:2.342-6.487 ; P＜0.001),thin walled cavities focus (OR=2.898,95％CI:1.567-5.360; P＜0.001),COPD (OR=2.503,95％ CI:1.289-4.857; P=0.007),age45-60 year (OR=2.452,95％CI:1.391 4.325; P=0.002)anda weak-positive reaction of PPD test (OR=2.295,95％CI..1.132-4.652; P=0.021) were independent risk factors of pulmonary NTM infection.Conclusion In sputum acid-fast bacilli positive and/or mycobacteria culture positive patients,age≥ 45 year,COPD,bronchiectasis,thin walled cavities focus and a weak-positive reaction of PPD test are risk factors of pulmonary NTM infection.The clinicians should pay close attention to the results of species identification.
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Objective To investigate the resistant patterns of Mycobacterium tuberculosis (MTB) strains against first- and second-line anti-tuberculosis drugs. Methods Drug susceptibility tests of 518 MTB strains collected from January 2008 to March 2009 were performed using BactecMGIT 960. The data were analyzed by chi square test. ResultsIn 518 strains, 168 (32.44％) were all sensitive to all seven drugs, 350 (67.56％) were resistant to at least one drug. Among all strains, 72 (13.90％) were resistant to one drug, 24 (4.63％) were resistant to two drugs, 254 (49.03％) were resistant to three or more drugs. A total of 217 strains (41.89 ％) were classified as multi-drug resistant tuberculosis (MDR-TB)strains and 65(12.55％)were extensively drug resistant tuberculosis (XDR-TB) strains which accounted for 29.95 ％ of MDR-TB strains. The drug resistant rate of isoniazid which belonged to first-line drugs was 53.67％ (278 strains) and that of ofloxacin which belonged to second-line drugs was 39.77 ％ (206 strains). In 433 retreated patients, the drug resistant rate against any drugs, MDR rate and XDR rate were 72.05％, 46.42％ and 13.86％,respectively, which were all higher than those in treatment naive patients (44.70％, 18. 82％ and 5.88％, respectively; x2 = 24. 253, x2 ＝ 22. 229 and x2 ＝ 4. 117, respectively; all P ＜ 0.01).ConclusionsThe resistant rate of MTB is high in a tuberculosis specialized hospital in Shanghai, and MDR-TB also shares a high resistant rate as well as XDR-TB. Furthermore, drug resistance is more common in retreated patients.
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Objective To evaluate clinical application of phage amplified biologically assay (PhaB) in susceptibility test of Mycobacterium tuberculosis (MTB) in sputum. Methods The drug susceptibility of MTB was detected by PhaB in 143 patients with sputum-positive pulmonary tuberculosis (PTB),and the chemotherapy regimens were adjusted according to the results of susceptibility test.Independent samples t-tests were used for comparison of means.Count numbers were compared with Chisquare test.If there were count number of 0,Fisher probabilities should be used.ResultsThe total positive rate of PhaB was 94.4％ (135/143) with no differences between three types of PTB (x2 =1.886,P ＞ 0.05 ).The duration of testing for PhaB group was (6.6 ± 1.8) days,while for control was (29.4 ±8.7) days (t =29.01,P ＜ 0.01 ).Compared with control group,the 2-month negative-conversion rate (63.2％ vs.35.1％,x2 =3.989,P ＜ 0.05 ) and cure rate ( 100％ vs.78.4％,P ＜ 0.05 ) of PhaB group in type Ⅱ patients were significantly higher.But there were no differences between PhaB and control groups in type Ⅰ and Ⅲ PTB patients.ConclusionThe results of PhaB drug susceptibility test can be helpful for choosing effective chemotherapy regimen for PTB patients rapidly.
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Objective To evaluate the efficacy of low-dose levothyroxine sodium in treatment of severe pulmonary tuberculosis with euthyroid sick syndrome(ESS). Methods One hundred and twenty inpatients with severe pulmonary tuberculosis and ESS were randomly divided into treatment group and control group by gender, age, disease duration and severity. Both groups were given anti- tuberculosis, antiinfection treatment and nutritional support for 2 weeks; patients in treatment group were given low-dose levothyroxine sodium additionally. Thyroid function, clinical improvements, increase of albumin, reduction of acid-fast bacilli, improvements on images and the mortality rates were compared between the groups.Results After 2 weeks of treatment, symptoms including fever, cough and night sweats were improved in both groups. Marked improvements were observed in 19 patients(31.7%)of treatment group and 8 patients (13.3%)of control group(χ2 = 5. 73, P ＜ 0.05). Clearance rate of acid-fast bacilli in treatment group was 25.0%(15/60), but that in the control was only 6.7%(4/60)(χ2 = 7. 50, P ＜ 0.01). Serum albumin in the treatment group was increased to(34.2 ±0.4)g/L after the treatment, and that in the control group was(29.1 ±0.6)g/L(t =2.42, P＜0.05). T3 and FT3 were significantly increased in both groups, but more significant difference was observed in the treatment group(t = 59. 42 and 50. 66, P ＜ 0. 01). No empty closed after treatment in both groups, but the effective rate in treatment group was significantly higher than that in the control group(93.3% vs. 76.7%, χ2 =6. 54, P＜0.05). Two patients in control group died(2/60, 3. 3%), while no death was reported in treatment group. Conclusions Low-dose levothyroxine sodium treatment is effective for ESS in patients with severe pulmonary tuberculosis.Improvement on low T3 syndrome may be an important indicator for the overall improvement or recovery.
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Objective To investigate the characteristic and its clinical value of tumor necrosis factor (TNF)-α and its receptor, interleukin (IL)-1β and its receptor in serum and bronchoalveolar lavage fluid(BALF) in patients with pulmonary tuberculosis and to determine the role of them in the immunopathogenesis of tuberculosis. Methods The concentrations of TNF-α,soluble TNF receptor (sTNF-R) Ⅰ, IL-1β and IL-1 receptor were measured using sandwish ABC-enzyme-linked immunosorbent assay (ELISA) method in serum and BALF of 46 patients with active tuberculosis and 21 patients with inactive tuberculosis, and in the serum of 20 cases of healthy control. Meanwhile the above-mentioned cytokine levels in serum and BALF of 19 patients with active tuberculosis were followed up. Differences between groups were assessed for significance by t test. Results The TNF-α,sTNF-R Ⅰ, IL-1β and IL-1 receptor levels and TNF-α/sTNF-R Ⅰ ratios in BALF of active tuberculosis group were (286.2±96.3) pg/L,(2 431.5±1 124.6) pg/L,(58.6±3.2) pg/L,(162.4±17.1) pg/L and 0.06±0.01, respectively, which were all significantly higher than those with inactive tuberculosis group (t=3.36,3.25,2.95,2.27 and 3.12 respectively; P<0.05). The TNF-α,sTNF-R Ⅰ,IL-1β and IL-1 receptor levels and TNF-α/sTNF-R Ⅰ ratios in BALF of cavernous tuberculosis group were (381.4±106.4) pg/L,(2 824.7±1 318.5) pg/L,(66.4±4.6) pg/L,(176.4±18.7) pg/L and 0.07±0.01, respectively,which were all significantly higher than those of non-cavernous tuberculosis group (t= 3.46,2.37, 3.19, 2.99 and 3.22, respectively; P<0.05). After 2-month' antituberculosis treatments, among 19 cases, the TNF-α,sTNF-R Ⅰ,IL-1β and IL-1 receptor levels and TNF-α/sTNF-R Ⅰ ratios in BALF of 16 cases were significantly lower than those at the beginning of treatments (t= 3.26,3.17, 3.28, 2.92 and 3.12 respectively; P<0.01). Meanwhile, their clinical symptoms improved, sputum smear negative, lesions on chest X-ray resolved and the cavity shrinked or closed. Conclusions TNF-α, sTNF-R Ⅰ, IL-1β and IL-1 receptor are likely to be involved in the immunopathogenesis of tuberculosis. Detection of TNF-α, sTNF-R Ⅰ, IL-1β and IL-1 receptor levels in the serum and BALF is helpful to understand the activity of disease, determine the clinical pattern of disease,assess the prognosis of disease and monitor the therapeutic effect in patients with pulmonary tuberculosis.