A group of novel serum diagnostic biomarkers for multidrug‐resistant tuberculosis by iTRAQ‐2D LC‐MS/MS and Solexa sequencing
Chong WangChangming LiuLiliang WeiLiying ShiZhifen PanLian‐Gen MaoXiaochen WanZepeng PingTingting JiangZhong‐Liang ChenZhongjie LiJi‐Cheng Li
1
Citation
0
Reference
10
Related Paper
Citation Trend
Abstract:
The epidemic of pulmonary tuberculosis (TB), especially multidrug‐resistance tuberculosis (MDR‐TB) presented a major challenge for TB treatment today. We performed iTRAQ labeling coupled with two‐dimensional liquid chromatography‐tandem mass spectrometry (2D LC‐MS/MS) and Solexa sequencing among MDR‐TB patients, drug‐sensitive tuberculosis (DS‐TB) patients, and healthy controls. A total of 50 differentially expressed proteins and 43 differentially expressed miRNAs (fold change >1.50 or <0.60, P <0.05) were identified in the MDR‐TB patients compared to both DS‐TB patients and healthy controls. We found that 22.00% of differentially expressed proteins and 32.56% of differentially expressed miRNAs were related, and could construct a network mainly in complement and coagulation cascades. Significant differences in CD44 antigen (CD44), coagulation factor XI (F11), kininogen‐1 (KNG1), miR‐4433b‐5p, miR‐424‐5p, and miR‐199b‐5p were found among MDR‐TB patients, DS‐TB patients and healthy controls ( P <0.05) by enzyme‐linked immunosorbent assay (ELISA) and SYBR green qRT‐PCR validation. A strong negative correlation, consistent with the target gene prediction, was found between KNG1 and miR‐199b‐5p (r=−0.232, P =0.017). Moreover, we established a diagnostic model for MDR‐TB patients and healthy controls with a sensitivity of 100.00% and a specificity of 88.33% (overall accuracy 93.14%), and also established a diagnostic model for MDR‐TB patients and DS‐TB patients with a sensitivity of 83.33% and a specificity of 88.33% (overall accuracy 86.27%). Our study proposes potential biomarkers for MDR‐TB diagnosis, and also provides a new experimental basis to understand the pathogenesis of MDR‐TB. Support or Funding Information This work was supported by grants from the National Natural Science Foundation of China (No.81573709, No.81273882), the National Basic Research Program of China (No.2014CB543002) and the National Special Sci‐Tech Projects (No.2012ZX10005001‐006).Keywords:
Fold change
Multidrug-resistant (MDR) tuberculosis has increased among migrants in Canada. The cause(s) of this increase is unknown.We performed a retrospective cohort study in a Canadian province with substantially increased immigration between 1982-2001 and 2002-2019. The proportion of MDR tuberculosis among migrants arriving from high MDR (HMDR) tuberculosis burden countries during these 2 periods was used to estimate the proportion of cases due to immigration versus change in proportion in the country of birth. Epidemiologic, spatiotemporal, and drug resistance pattern data were used to confirm local transmission.Fifty-two of 3514 (1.48%) foreign-born culture-positive tuberculosis patients had MDR tuberculosis: 8 (0.6%) in 1982-2001 and 44 (2.0%) in 2002-2019. Between time periods, the proportion of MDR tuberculosis among migrants with tuberculosis from HMDR tuberculosis countries increased from 1.11% to 3.62%, P = .003; 31.6% attributable to recent immigration and 68.4% to a higher proportion of MDR tuberculosis in cases arrived from HMDR tuberculosis countries. No cases of MDR tuberculosis were attributable to local transmission.In stark contrast to HMDR tuberculosis countries, local transmission plays no important role in the occurrence of MDR tuberculosis in Canada. Improved tuberculosis programming in HMDR tuberculosis countries is urgently needed.
Cite
Citations (2)
The structure of tuberculosis patients with HIV infection who died from any causes, other than tuberculosis, in the Sverdlovsk Region in 2000-2006 did not differ from that of patients with concurrent pathology who died from tuberculosis. The general health care facilities had revealed tuberculosis during life in most patients who died from terminal-stage HIV infection; at death these patients had endstage HIV infection which tuberculosis joined to 4 years or more after HIV infection registration. A fatal outcome in 88.1% of the patients died from the terminal stage of HIV infection was observed within the first year after tuberculosis detection, in half the cases the background disease being generalized tuberculosis at autopsy; every two patients discharged microorganisms during life, drug resistance in the causative agent of tuberculosis was found in every three patients. Half the patients who died from other causes, other than HIV infection and tuberculosis lost their life within the first year after registration of the tuberculous process. Lifetime bacterial discharge was recorded in half the patients; drug resistance of Mycobacterium tuberculosis has developed a third of the patients with comorbidity who died from other causes, other than tuberculosis and HIV infection. The volume of lifetime specialized care for HIV infection to deceased patients with comorbidity had been inadequate. The importance of the problem of notification of cases, when the autopsy background disease was tuberculosis in comorbidity patients not included into the regional tuberculosis morbidity and mortality statistics, will increase with further development of the epidemics of tuberculosis and HIV infection to the Svedlovsk Region.
Cite
Citations (1)
Primary Mycobacterium tuberculosis transmission is an important driver of the global epidemic of resistance to tuberculosis drugs. A few studies have compared tuberculosis infection in contacts of index cases with different drug-resistant profiles, suggesting that contacts of multidrug-resistant (MDR) tuberculosis cases are at higher risk. Repeated tuberculosis exposure in contacts of MDR tuberculosis patients through recurrent tuberculosis may modify this relationship. We compared tuberculosis infection in household contacts of MDR and drug-susceptible (DS) tuberculosis patients from six cities in southeastern China and investigated whether repeated tuberculosis exposure was a mediating factor. Tuberculosis infection was defined as a tuberculin skin test induration ≥ 10 mm. In all, 111 (28.0%) of 397 household contacts of MDR tuberculosis patients and 165 (24.7%) of 667 contacts of DS tuberculosis index cases were infected with tuberculosis. In a multivariate model not including the previous tuberculosis exposure, contacts of MDR tuberculosis patients had a higher likelihood of tuberculosis infection (adjusted odds ratio [AOR] = 1.37; 95% confidence interval [CI] = 1.01-1.84; P = 0.041). In a separate multivariate model adjusted for the previous tuberculosis exposure, the odds ratio of tuberculosis infection flipped and contacts of MDR cases were now at lower risk for tuberculosis infection (AOR = 0.55; 95% CI = 0.38-0.81; P = 0.003). These findings suggest prior tuberculosis exposure in contacts strongly mediates the relationship between tuberculosis infection and the index drug resistance profile. Prior studies showing lower risk of developing tuberculosis among contacts of MDR tuberculosis patients may be partially explained by a lower rate of tuberculosis infection at baseline.
Cite
Citations (6)
A retrospective investigation was made to compare the occupational risk of tuberculosis in personnel assisting human immunodeficiency virus (HIV)-infected and uninfected subjects with active tuberculosis.We retrospectively reviewed 6 years of hospital activity in 3 units where HIV-infected patients with tuberculosis are hospitalized and in 2 units where non-HIV-infected tuberculosis patients are hospitalized. The risk of occupational tuberculosis in healthcare workers who assisted HIV-infected and non-HIV-infected patients with tuberculosis was investigated.The risk of occupational tuberculosis in healthcare workers was studied by considering the numbers of potential source cases (hospitalized patients with tuberculosis) in the two conditions investigated (HIV-positive and HIV-negative). Both potential source cases and cases of tuberculosis in healthcare workers had to be microbiologically proven in order to be considered.Seven cases of tuberculosis occurred in persons who cared for 85 HIV-infected subjects with tuberculosis, while only 2 cases occurred in staff members who took care of 1,079 HIV-negative tuberculosis patients over the same period (relative risk = 44.4; 95% confidence interval = 8.5-438).Tuberculosis seems no longer to be a neglectable risk in healthcare workers assisting patients with HIV infection. Further study is urgently needed to see whether such unexpectedly high dissemination of tuberculosis also is demonstrable in the community.
Healthcare worker
Cite
Citations (43)
The effectiveness of the Diaskintest for detecting tuberculosis in 61 children and young people in the Children's Hospital of Samara city was studied. The most frequent forms of tuberculosis were intrathoracic lymph node tuberculosis (39, 3%) and infiltrative tuberculosis (27,9%).
The Diaskintest® has shown its high diagnostic importance when dealing with local forms of active tuberculosis (88,5%). The negative test result by Diaskintest® does not exclude presence of tuberculosis. The Mantoux test remains important diagnostic test for detecting tuberculosis.
Mantoux test
Active tuberculosis
Tuberculosis diagnosis
Cite
Citations (0)
The risk and timing of tuberculosis among recently exposed close contacts of patients with infectious tuberculosis are not well established.
Cite
Citations (83)
Tuberculosis remains a global health problem with an enormous burden of disease, estimated at 10.4 million new cases in 2015. To stop the tuberculosis epidemic, it is critical that we interrupt tuberculosis transmission. Further, the interventions required to interrupt tuberculosis transmission must be targeted to high-risk groups and settings. A simple cascade for tuberculosis transmission has been proposed in which (1) a source case of tuberculosis (2) generates infectious particles (3) that survive in the air and (4) are inhaled by a susceptible individual (5) who may become infected and (6) then has the potential to develop tuberculosis. Interventions that target these events will interrupt tuberculosis transmission and accelerate the decline in tuberculosis incidence and mortality. The purpose of this article is to provide a high-level overview of what is known about tuberculosis transmission, using the tuberculosis transmission cascade as a framework, and to set the scene for the articles in this series, which address specific aspects of tuberculosis transmission.
Global Health
Cite
Citations (280)
History of tuberculosis
Tuberculosis diagnosis
Cite
Citations (17)
There are many pros and cons with the protocols used to diagnose patient with TB, particularly because research isn't able to correlate findings with the virulence of the tuberculosis pathogen. This has resulted in further experiments to try optimise protocols for better evaluation of susceptible and resistant tuberculosis strains. This indicates the need for more health-care facilities to treat patients with tuberculosis, or co-tuberculosis infections, more precisely. This article presents some advantages and disadvantages of tuberculosis treatment protocols, with emphasis on drugs, tuberculosis data sets and the administration of plant compounds. This paper also highlights some points on the mechanism of drug action with tuberculosis. Controversies and the present status of tuberculosis studies are also commented on. This is the first (generalised) paper to highlight laboratory as well as non-laboratory points pertaining to tuberculosis and tuberculosis protocols.
cons
Cite
Citations (0)
Tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis, which threats the health of children worldwide.Accompany with the increase of drug-resistance tuberculosis, great challenging has arose in the prevention and treatment of tuberculosis.Nowadays, the diagnosis and treatment of drug-resistance tuberculosis is still difficult in pediatric patients.Based on molecular diagnosis, fast detect as well as reliable treatment of drug-resistance tuberculosis become available.Currently, the principle of drug-resistant tuberculosis treatment in children is essentially similar to adults.In this review, the mechanism, diagnosis and treatment of pediatric drug resistance tuberculosis were discussed.
Key words:
Child; Drug-resistance tuberculosis; Prevalence; Mechanisms of drug-resistance; Diagnosis; Treatment
Cite
Citations (0)