The anti-cyclic citrullinated peptide response in tuberculosis patients is not citrulline-dependent and sensitive to treatment

Introduction  

Patients with tuberculosis (TB) frequently produce anti-citrullinated protein antibodies (ACPA). The objective of this study is to characterize the citrulline-dependence of the ACPA reactivity in sera of patients with mycobacterium infections.     

<Emphasis Type="Italic">Mycobacterium tuberculosis</Emphasis> interactome analysis unravels potential pathways to drug resistance

Background  

Emergence of drug resistant varieties of tuberculosis is posing a major threat to global tuberculosis eradication programmes. Although several approaches have been explored to counter resistance, there has been limited success due to a lack of understanding of how resistance emerges in bacteria upon drug treatment. A systems level analysis of the proteins involved is essential to gain insights into the routes required for emergence of drug resistance.     

Lysis of tubercle bacilli in fresh and stored sputum specimens: implications for diagnosing tuberculosis in stored and paucibacillary specimens by PCR

Background  

Nucleic acid amplification techniques are being used increasingly in diagnosing tuberculosis. In developing countries clinical samples are often stored for subsequent analysis since molecular tests are conducted at only a limited number of laboratories. This study was conducted to assess the speed at which mycobacteria undergo autolysis and free DNA is detected in the supernatant during low-temperature storage.     

Antituberculosis drug resistance patterns in two regions of Turkey: a retrospective analysis

Backround  

The emergence of Mycobacterium tuberculosis strains resistant to antituberculosis agents has recently received increased attention owing largely to the dramatic outbreaks of multi drug resistance tuberculosis (MDR-TB).     

Biochemical and physiological characterization of the GTP-binding protein Obg of Mycobacterium tuberculosis

Background  

Obg is a highly conserved GTP-binding protein that has homologues in bacteria, archaea and eukaryotes. In bacteria, Obg proteins are essential for growth, and they participate in spore formation, stress adaptation, ribosome assembly and chromosomal partitioning. This study was undertaken to investigate the biochemical and physiological characteristics of Obg in Mycobacterium tuberculosis, which causes tuberculosis in humans.     

Investigating the metabolic capabilities of Mycobacterium tuberculosis H37Rv using the in silico strain iNJ661 and proposing alternative drug targets

Background:  

Mycobacterium tuberculosis continues to be a major pathogen in the third world, killing almost 2 million people a year by the most recent estimates. Even in industrialized countries, the emergence of multi-drug resistant (MDR) strains of tuberculosis hails the need to develop additional medications for treatment. Many of the drugs used for treatment of tuberculosis target metabolic enzymes. Genome-scale models can be used for analysis, discovery, and as hypothesis generating tools, which will hopefully assist the rational drug development process. These models need to be able to assimilate data from large datasets and analyze them.     

Analysis of stress- and host cell-induced expression of the Mycobacterium tuberculosis inorganic pyrophosphatase

Background  

The gene encoding the inorganic pyrophosphatase (PPase) of the intracellular pathogen Legionella pneumophila is induced during intracellular infection, but is constitutively expressed in Eschericia coli. The causative agent of tuberculosis, Mycobacterium tuberculosis, contains a well conserved copy of PPase. We sought to determine if expression of the M. tuberculosis PPase is regulated by the intracellular environment.     

Role of <Emphasis Type="Italic">Mycobacterium tuberculosis pknD</Emphasis> in the Pathogenesis of central nervous system tuberculosis

Background  

Central nervous system disease is the most serious form of tuberculosis, and is associated with high mortality and severe neurological sequelae. Though recent clinical reports suggest an association of distinct Mycobacterium tuberculosis strains with central nervous system disease, the microbial virulence factors required have not been described previously.     

Association between Diabetes Mellitus and Tuberculosis in United States-Born and Foreign-Born Populations in San Francisco

Setting

The impact of diabetes on tuberculosis in United States and foreign-born populations in San Francisco has not been studied.

Objective

To determine the characteristics, prevalence and temporal trends of diabetes in US and foreign-born persons attending the San Francisco Tuberculosis Clinic.

Design

We analyzed data from individuals seeking medical attention at the San Francisco Tuberculosis Clinic. We included patients with diagnosis of tuberculosis, latent infection, or not infected with Mycobacterium tuberculosis. We assessed the temporal trend and the characteristics of individuals with and without diabetes.

Result

Between 2005 and 2012, there were 4371 (19.0%) individuals without evidence of tuberculosis infection, 17,856 (77.6%) with latent tuberculosis, and 791 (3.4%) with tuberculosis. 66% were born in the United States, China, Mexico, and the Philippines. The prevalence of diabetes was the highest among individuals with tuberculosis and increased during the study period. Patients with tuberculosis and diabetes were more likely to be male, older than 45 years and born in the Philippines. There was a disproportionate association of TB and DM relative to LTBI and DM among Filipinos in individuals older than 45 years old.

Conclusions

Our data suggest that Filipinos older than 45 years old are more likely to have tuberculosis probably due to a higher prevalence of diabetes. In San Francisco, tuberculosis-screening programs in individuals with diabetes and latent tuberculosis may be beneficial in patients older than 45 years old especially from the Philippines.     

Tuberculosis: evidence review for newly arriving immigrants and refugees

Background:

The foreign-born population bears a disproportionate health burden from tuberculosis, with a rate of active tuberculosis 20 times that of the non-Aboriginal Canadian-born population, and could therefore benefit from tuberculosis screening programs. We reviewed evidence to determine the burden of tuberculosis in immigrant populations, to assess the effectiveness of screening and treatment programs for latent tuberculosis infection, and to identify potential interventions to improve effectiveness.

Methods:

We performed a systematic search for evidence of the burden of tuberculosis in immigrant populations and the benefits and harms, applicability, clinical considerations, and implementation issues of screening and treatment programs for latent tuberculosis infection in the general and immigrant populations. The quality of this evidence was assessed and ranked using the GRADE approach (Grading of Recommendations Assessment, Development and Evaluation).

Results:

Chemoprophylaxis with isoniazid is highly efficacious in decreasing the development of active tuberculosis in people with latent tuberculosis infection who adhere to treatment. Monitoring for hepatotoxicity is required at all ages, but close monitoring is required in those 50 years of age and older. Adherence to screening and treatment for latent tuberculosis infection is poor, but it can be increased if care is delivered in a culturally sensitive manner.

Interpretation:

Immigrant populations have high rates of active tuberculosis that could be decreased by screening for and treating latent tuberculosis infection. Several patient, provider and infrastructure barriers, poor diagnostic tests, and the long treatment course, however, limit effectiveness of current programs. Novel approaches that educate and engage patients, their communities and primary care practitioners might improve the effectiveness of these programs.     

Évaluation de la TEP au 18F-FDG dans la tuberculose extrapulmonaire : premiers résultats d’une étude pilote observationnelle

Aim

Extrapulmonary tuberculosis treatment is difficult to assess and there is a need for new tools. The aim of this observational pilot study is to evaluate the potential role of 18F-FDG PET/CT in the initial staging and treatment evaluation of extrapulmonary tuberculosis.

Methods

Twenty-eight patients were included between January 2009 and 2010. Twenty-three had a 18F-FDG PET/CT before treatment and/or during and/or after treatment. All patients will be followed for 18 months after the end of treatment. A control group of five patients with previous history of tuberculosis was also included and PET/CT was performed.

Results

Three cases of differential diagnosis were excluded of the study. The initial PET for staging showed additional lesions in 8/10 patients compared to conventional imaging. At the end of treatment, 6/11 patients had a negative PET, and 5/11 patients had a positive PET. PET had a significant clinical impact for 3/10 patients at initial staging (guiding biopsy or increase of planned treatment duration), and for 3/16 during follow up (extend or early interruption of the treatment). All PET scans in the control group were negative.

Conclusion

18F-FDG PET has an excellent sensitivity for the detection of extrapulmonary tuberculosis lesion and excellent negative predictive values. The impact of initial PET staging seems significant. The interest of 18F-FDG PET for the evaluation of response to treatment remains to be assessed and will be correlated with patients’ follow up in a second phase of this study.     

Genotyping of <Emphasis Type="Italic">Mycobacterium tuberculosis</Emphasis> clinical isolates in two cities of Turkey: Description of a new family of genotypes that is phylogeographically specific for Asia Minor

Background  

Population-based bacterial genetics using repeated DNA loci is an efficient approach to study the biodiversity and phylogeographical structure of human pathogens, such as Mycobacterium tuberculosis, the agent of tuberculosis. Indeed large genetic diversity databases are available for this pathogen and are regularly updated. No population-based polymorphism data were yet available for M. tuberculosis in Turkey, at the crossroads of Eurasia.     

Attitudes about Tuberculosis Prevention in the Elimination Phase: A Survey among Physicians in Germany

Background

Targeted and stringent measures of tuberculosis prevention are necessary to achieve the goal of tuberculosis elimination in countries of low tuberculosis incidence.

Methods

We ascertained the knowledge about tuberculosis risk factors and stringency of tuberculosis prevention measures by a standardized questionnaire among physicians in Germany involved in the care of individuals from classical risk groups for tuberculosis.

Results

510 physicians responded to the online survey. Among 16 risk factors immunosuppressive therapy, HIV-infection and treatment with TNF-antagonist were thought to be the most important risk factors for the development of tuberculosis in Germany. Exposure to a patient with tuberculosis ranked on the 10^th position. In the event of a positive tuberculin-skin-test or interferon-γ release assay only 50%, 40%, 36% and 25% of physicians found that preventive chemotherapy was indicated for individuals undergoing tumor necrosis factor-antagonist therapy, close contacts of tuberculosis patients, HIV-infected individuals and migrants, respectively.

Conclusions

A remarkably low proportion of individuals with latent infection with Mycobacterium tuberculosis belonging to classical risk groups for tuberculosis are considered candidates for preventive chemotherapy in Germany. Better knowledge about the risk for tuberculosis in different groups and more stringent and targeted preventive interventions will probably be necessary to achieve tuberculosis elimination in Germany.     

Identification of two Mycobacterium tuberculosis H37Rv ORFs involved in resistance to killing by human macrophages

Background  

The ability of Mycobacterium tuberculosis to survive and replicate in macrophages is crucial for the mycobacterium's ability to infect the host and cause tuberculosis. To identify Mycobacterium tuberculosis genes involved in survival in macrophages, a library of non-pathogenic Mycobacterium smegmatis bacteria, each carrying an individual integrated cosmid containing M. tuberculosis H37Rv genomic DNA, was passed through THP-1 human macrophages three times.     

Infection control and the significance of sputum and other respiratory secretions from adult patients with cystic fibrosis

Background

Although various hematologic abnormalities are seen in tuberculosis, immune thrombocytopenic purpura is a rare event.

Case Presentation

We report a case of a 29 year-old male who was presented with immune thrombocytopenia-induced hemoptysis, macroscopic hematuria and generalized petechiae. The patient was found to have clinical, microbiological and radiological evidence of active pulmonary tuberculosis. The immune thrombocytopenic purpura was successfully treated with anti-tuberculous drugs combined with corticosteroids and high dose immune globulin therapy.

Conclusion

Immune thrombocytopenic purpura can be one of the hematological manifestations of tuberculosis which has a global prevalence with increasing incidence secondary to HIV infection.     

Natural history of tuberculosis: duration and fatality of untreated pulmonary tuberculosis in HIV negative patients: a systematic review

Background

The prognosis, specifically the case fatality and duration, of untreated tuberculosis is important as many patients are not correctly diagnosed and therefore receive inadequate or no treatment. Furthermore, duration and case fatality of tuberculosis are key parameters in interpreting epidemiological data.

Methodology and Principal Findings

To estimate the duration and case fatality of untreated pulmonary tuberculosis in HIV negative patients we reviewed studies from the pre-chemotherapy era. Untreated smear-positive tuberculosis among HIV negative individuals has a 10-year case fatality variously reported between 53% and 86%, with a weighted mean of 70%. Ten-year case fatality of culture-positive smear-negative tuberculosis was nowhere reported directly but can be indirectly estimated to be approximately 20%. The duration of tuberculosis from onset to cure or death is approximately 3 years and appears to be similar for smear-positive and smear-negative tuberculosis.

Conclusions

Current models of untreated tuberculosis that assume a total duration of 2 years until self-cure or death underestimate the duration of disease by about one year, but their case fatality estimates of 70% for smear-positive and 20% for culture-positive smear-negative tuberculosis appear to be satisfactory.     

Isolation and characterization of Mycobacterium bovis strains from indigenous Zambian cattle using Spacer oligonucleotide typing technique

Background  

Bovine tuberculosis (BTB), caused by Mycobacterium bovis, has remained a major source of concern to public health officials in Zambia. Previous investigations have used traditional epidemiological methods that are unable to identify the causative agent and from which dynamics of disease dispersion is difficult to discern. The objective of this study was to isolate, characterize and determine the genetic diversity and relatedness of M. bovis from major cattle rearing districts in Zambia by spoligotyping. A total of 695 carcasses were examined and 98 tissues had gross post-mortem lesions compatible with BTB.     

Clinical and Radiographic Factors Do Not Accurately Diagnose Smear-Negative Tuberculosis in HIV-infected Inpatients in Uganda: A Cross-Sectional Study

Background

Although World Health Organization guidelines recommend clinical judgment and chest radiography for diagnosing tuberculosis in HIV-infected adults with unexplained cough and negative sputum smears for acid-fast bacilli, the diagnostic performance of this approach is unknown. Therefore, we sought to assess the accuracy of symptoms, physical signs, and radiographic findings for diagnosing tuberculosis in this population in a low-income country with a high incidence of tuberculosis.

Methodology

We performed a cross-sectional study enrolling consecutive HIV-infected inpatients with unexplained cough and negative sputum smears for acid-fast bacilli at Mulago Hospital in Kampala, Uganda. Trained medical officers prospectively collected data on standard symptoms and signs of systemic respiratory illness, and two radiologists interpreted chest radiographs in a standardized fashion. We calculated positive- and negative-likelihood ratios of these factors for diagnosing pulmonary tuberculosis (defined when mycobacterial cultures of sputum or bronchoalveolar lavage fluid were positive). We used both conventional and novel regression techniques to develop multivariable prediction models for pulmonary tuberculosis.

Principal Findings

Among 202 enrolled HIV-infected adults with negative sputum smears for acid-fast bacilli, 72 (36%) had culture-positive pulmonary tuberculosis. No single factor, including respiratory symptoms, physical findings, CD4+ T-cell count, or chest radiographic abnormalities, substantially increased or decreased the likelihood of pulmonary tuberculosis. After exhaustive testing, we were also unable to identify any combination of factors which reliably predicted bacteriologically confirmed tuberculosis.

Conclusions and Significance

Clinical and radiographic criteria did not help diagnose smear-negative pulmonary tuberculosis among HIV-infected patients with unexplained cough in a low-income setting. Enhanced diagnostic methods for smear-negative tuberculosis are urgently needed.