Reactivation Of Tuberculosis Research Articles

TNF-α blockade impairs in vitro tuberculous granuloma formation and down modulate Th1, Th17 and Treg cytokines.

Tuberculosis (TB) is a granulomatous disease that has affected humanity for thousands of years. The production of cytokines, such as IFN-γ and TNF-α, is fundamental in the formation and maintenance of granulomas and in the control of the disease. Recently, the introduction of TNF-α-blocking monoclonal antibodies, such as Infliximab, has brought improvements in the treatment of patients with chronic inflammatory diseases, but this treatment also increases the risk of reactivation of latent tuberculosis. Our objective was to analyze, in an in vitro model, the influence of Infliximab on the granulomatous reactions and on the production of antigen-specific cytokines (TNF-α, IFN-γ, IL-12p40, IL-10 and IL-17) from beads sensitized with soluble Bacillus Calmette-Guérin (BCG) antigens cultured in the presence of peripheral blood mononuclear cells (PBMC) from TB patients. We evaluated 76 individuals, with tuberculosis active, treated and subjects with positive PPD. Granuloma formation was induced in the presence or absence of Infliximab for up to 10 days. The use of Infliximab in cultures significantly blocked TNF-α production (p <0.05), and led to significant changes in granuloma structure, in vitro, only in the treated TB group. On the other hand, there was a significant reduction in the levels of IFN-γ, IL-12p40, IL-10 and IL-17 after TNF-α blockade in the three experimental groups (p <0.05). Taken together, our results demonstrate that TNF-α blockade by Infliximab directly influenced the structure of granuloma only in the treated TB group, but negatively modulated the production of Th1, Th17 and regulatory T cytokines in the three groups analyzed.

ОТДАЛЕННЫЕ РЕЗУЛЬТАТЫ ЛЕЧЕНИЯ БОЛЬНЫХ ТУБЕРКУЛЕЗОМ ЛЕГКИХ, ПЕРЕНЕСШИХ РАДИКАЛЬНУЮ РЕЗЕКЦИЮ ЛЕГКИХ

The objective of the study: to investigate the efficiency of surgical treatment in pulmonary tuberculosis patients and to define main risk factors of tuberculosis re-activation in those who had surgery Methods The postponed surgery results (in 6-7 years) were investigated in 273 patients, who were operated in 2010-2011 Two groups were formed: Group 1 included patients taken off the register due to recovery, Group 2 included patients who had relapse or exacerbation of the disease after the surgery Those taken off the register due to some other reasons were not included in the comparative analysis Results. It was proved that postponed treatment efficiency exceeded 90% Tuberculosis re-activated in 77% of cases, in those with multiple and extensive drug resistance (533%), lung tissue destruction (62%), fibrous-cavernous tuberculosis (333%), concurrent conditions (524%) and complications in the early post-operative period (95%) The re-activation occurred more often after large surgeries including consecutive corrective thoracoplasty Should there be indications for surgery, it is sensible to decide about the surgery within the 1st year of follow-up.

Demographic predictors of active tuberculosis in people migrating to British Columbia, Canada: a retrospective cohort study.

Canadian tuberculosis (TB) guidelines recommend targeting postlanding screening for and treatment of latent tuberculosis infection (LTBI) in people migrating to Canada who are at increased risk for TB reactivation. Our objectives were to calculate robust longitudinal estimates of TB incidence in a cohort of people migrating to British Columbia, Canada, over a 29-year period, and to identify groups at highest risk of developing TB based on demographic characteristics at time of landing. We included all individuals (n = 1 080 908) who became permanent residents of Canada between Jan. 1, 1985, and Dec. 31, 2012, and were resident in BC at any time between 1985 and 2013. Multiple administrative databases were linked to the provincial TB registry. We used recursive partitioning models to identify populations with high TB yield. Active TB was diagnosed in 2814 individuals (incidence rate 24.2/100 000 person-years). Demographic factors (live-in caregiver, family, refugee immigration classes; higher TB incidence in country of birth; and older age) were strong predictors of TB incidence in BC, with elevated rates continuing many years after entry into the cohort. Recursive partitioning identified refugees 18-64 years of age from countries with a TB incidence greater than 224/100 000 population as a high-yield group, with 1% developing TB within the first 10 years. These findings support recommendations in Canadian guidelines to target postlanding screening for and treatment of LTBI in adult refugees from high-incidence countries. Because high-yield populations can be identified at entry via demographic data, screening at this point may be practical and high-impact, particularly if the LTBI care cascade can be optimized.

Low Indeterminate Rates Associated With Use of the QuantiFERON-TB Gold In-Tube Test in Children With Inflammatory Bowel Disease on Long-term Infliximab.

Tumor necrosis factor alpha (TNF-α) inhibitors are linked with increased risk of reactivation of active tuberculosis. The QuantiFERON-TB Gold In-Tube test is approved for screening latent tuberculosis infection in children and adults. There are limited data on the test performance in children on long-term treatment with TNF-α inhibitors. The objective of this study was to assess the proportion of indeterminate results for the QuantiFERON-TB Gold In-Tube in children with inflammatory bowel disease (IBD) on long-term infliximab treatment and to evaluate the range of interferon-γ responses to mitogen. A single-center prospective study of children 5 to 19 years of age with IBD on long-term infliximab treatment (>3 months). Each child was assessed for tuberculosis exposure risk and had blood drawn for the QuantiFERON-TB Gold In-Tube. Data on the range of interferon-γ responses and final QuantiFERON-TB Gold In-Tube test results were collected. Ninety-three children were included, with a median age of 16 years. The median total duration of infliximab therapy was 34 months (range, 3-119 months). The QuantiFERON-TB Gold In-Tube was indeterminate in 1 patient (1.1%), positive in 2 patients, and negative in 90 patients. The maximum interferon-γ response to mitogen (10 IU/mL) was observed in 82 patients (88%), with only 1 patient having an inadequate response. The proportion of indeterminate results was significantly lower than the prospectively hypothesized rate of 8%, based on prior studies in nonimmunosuppressed patients (P = 0.004). Pediatric patients with IBD on long-term treatment with infliximab had an adequate interferon-γ response to mitogen and a low indeterminate rate when assessed with the QuantiFERON-TB Gold In-Tube test. This study demonstrates a robust interferon gamma response to phytohemagglutinin stimulation in a pediatric population on long-term therapy with infliximab. The QuantiFERON-TB Gold In-Tube test may therefore be useful as a periodic screening tactic for latent TB in children on long-term infliximab therapy.

Interferon Alpha-2a for the Treatment of Post-Infectious Uveitis Secondary to Presumed Intraocular Tuberculosis

ABSTRACTPurpose: To assess the efficacy and tolerability of interferon (IFN) alpha-2a in post-infectious uveitis secondary to presumed intraocular tuberculosis (IOTB).Methods: Patients with chronic uveitis secondary to presumed IOTB who, after completing an antitubercular treatment, showed poor response to treatments or recurred after tapering oral corticosteroids to ≤7.5 mg/day were enrolled. All patients were treated with IFN alpha-2a subcutaneous injections. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), and inflammatory signs were compared between baseline and follow-up visits up to six months.Results: Twelve eyes (six patients) were enrolled. Mean BCVA improved from 0.64 ± 0.55 logMAR at baseline to 0.32 ± 0.31 logMAR at 6 months (p = 0.03). Mean CRT decreased from 372 ± 132.2 μm to 274.66 ± 34.9 μm at six months (p = 0.01). Inflammatory signs (vitritis, vasculitis) also decreased overtime. No major complications or tuberculosis reactivations were recorded.Conclusions: IFN alpha-2a was efficacious and safe in treating chronic post-infectious uveitis secondary to presumed IOTB.

High Turnover of Tissue Macrophages Contributes to Tuberculosis Reactivation in Simian Immunodeficiency Virus-Infected Rhesus Macaques.

Tuberculosis (TB) and human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) profoundly affect the immune system and synergistically accelerate disease progression. It is believed that CD4+ T-cell depletion by HIV is the major cause of immunodeficiency and reactivation of latent TB. Previous studies demonstrated that blood monocyte turnover concurrent with tissue macrophage death from virus infection better predicted AIDS onset than CD4+ T-cell depletion in macaques infected with simian immunodeficiency virus (SIV). In this study, we describe the contribution of macrophages to the pathogenesis of Mycobacterium tuberculosis (Mtb)/SIV coinfection in a rhesus macaque model using in vivo BrdU labeling, immunostaining, flow cytometry, and confocal microscopy. We found that increased monocyte and macrophage turnover and levels of SIV-infected lung macrophages correlated with TB reactivation. All Mtb/SIV-coinfected monkeys exhibited declines in CD4+ T cells regardless of reactivation or latency outcomes, negating lower CD4+ T-cell levels as a primary cause of Mtb reactivation. Results suggest that SIV-related damage to macrophages contributes to Mtb reactivation during coinfection. This also supports strategies to target lung macrophages for the treatment of TB.

Pathogenesis and Animal Models of Post-Primary (Bronchogenic) Tuberculosis, A Review.

Primary and post-primary tuberculosis (TB) are different diseases caused by the same organism. Primary TB produces systemic immunity. Post-primary TB produces cavities to support massive proliferation of organisms for transmission of infection to new hosts from a person with sufficient immunity to prevent systemic infection. Post-primary, also known as bronchogenic, TB begins in humans as asymptomatic bronchial spread of obstructive lobular pneumonia, not as expanding granulomas. Most lesions regress spontaneously. However, some undergo caseation necrosis that is coughed out through the necrotic bronchi to form cavities. Caseous pneumonia that is not expelled through the bronchi is retained to become the focus of fibrocaseous disease. No animal reproduces this entire process. However, it appears that many mammals utilize similar mechanisms, but fail to coordinate them as do humans. Understanding this makes it possible to use human tuberculous lung sections to guide manipulation of animals to produce models of particular human lesions. For example, slowly progressive and reactivation TB in mice resemble developing human bronchogenic TB. Similarly, bronchogenic TB and cavities resembling those in humans can be induced by bronchial infection of sensitized rabbits. Granulomas in guinea pigs have characteristics of both primary and post primary TB. Mice can be induced to produce a spectrum of human like caseating granulomas. There is evidence that primates can develop bronchogenic TB. We are optimistic that such models developed by coordinated study of human and animal tissues can be used with modern technologies to finally address long-standing questions about host/parasite relationships in TB, and support development of targeted therapeutics and vaccines.

Cost-effectiveness analysis of strategies using new immunological diagnostic tests of latent tuberculosis infection before TNF-blockers therapy

To evaluate the cost-effectiveness of different interferon-gamma release assays based strategies used to screen LTB before tumour necrosis factor (TNF) blockers initiation. Consecutive patients with rheumatoid arthritis, spondyloarthritis or Crohn's disease for whom TNF-blockers were considered, were recruited in 15 tertiary care centres. All were screened for LTB with tuberculin skin test (TST), QuantiFERON TB Gold® in tube (QFT) and T-SPOT.TB® (TSpot) on the same day. Cost-minimization and cost-effectiveness analysis, testing 8 screening test combinations, were conducted. Effectiveness was defined as the percentage of LTB treatment avoided and compared with TST alone. Cost were elicited in the payer perspective, included all the costs related to the screening procedure. No tuberculosis reactivation was observed after TNF-blocker initiation. TST followed by QFT if TST was positive was found as the best screening strategy, i.e. the less costly (-54€ compared to reference) and most effective (effectiveness 0.93), resulting in an incremental cost-effectiveness ratio of -192€ per treatment avoided. A probabilistic sensitivity analysis confirmed this result in 72.3% of simulations. TST followed by QFT if TST was positive is the most cost-effective strategy in screening for LTB in patients before starting anti-TNF therapy. NCT00811343.

Immunologic response to antiretroviral therapy by age among treatment-naive patients in Sub-Saharan Africa

To estimate the association between age at antiretroviral therapy (ART) initiation and immunologic response over time by stratum of baseline CD4 cell counts. Retrospective cohort analysis of data pooled from four President's Emergency Plan for AIDS Relief funded countries in Sub-Saharan Africa. General linear models were used to estimate the mean CD4 cell count by age group within groups defined by baseline CD4 cell count. Kaplan-Meier methods were used to estimate time to achieving a CD4 cell count of at least 500 cells/μl by age group and stratified by baseline CD4 cell count. A total of 126 672 previously treatment-naive patients provided 466 482 repeated CD4 cell count measurements over 4 years of ART. The median baseline CD4 cell count for all age groups was less than 200 cells/μl. Patients aged 30-39, 40-49, 50-59, and 60 and older at ART initiation had significantly lower mean CD4 cell counts in most strata and at most time points than those 20-29 years old. Compared with those 20-29, all older age groups had a significantly longer time to, and lower rate of, achieving a CD4 cell count of 500 cells. Age is associated with the magnitude of CD4 cell gain and the amount of time it takes to gain cells at different levels of baseline CD4 cell count. The delay in achieving a robust immune response could have significant implications for the risk of tuberculosis reactivation as well as comorbidities associated with age in the management of older HIV-infected patients.

Efficacy and safety of the adalimumab biosimilar Exemptia as induction therapy in moderate-to-severe ulcerative colitis.

Background/AimsData on the efficacy and safety of the adalimumab biosimilar Exemptia are limited.MethodsPatients with moderate-to-severe active steroid-refractory ulcerative colitis (UC) treated at Dayanand Medical College and Hospital, India were offered cyclosporine A, biologicals or biosimilars, or surgery. A retrospective analysis was conducted on patients who were treated with the adalimumab biosimilar, Exemptia. These patients were administered an induction dosing schedule of 160 mg Exemptia at week 0, 80 mg at week 2, and then 40 mg every other week from week 4 to 8. The clinical response and remission were assessed at week 8 using Mayo score.ResultsA total of 29 patients (62.1% male; mean age, 34.9 ± 9.7 years) with moderate-to-severe steroid-refractory active UC (mean disease duration, 6.3±5.1 years; pancolitis in 9 patients [31.1%]; left-sided colitis in 20 patients [68.9%]) were treated with the Exemptia induction dosing schedule. The mean Mayo score at presentation was 8.2±1.4. At week 8, clinical response was observed in 7 patients (24.1%), whereas clinical remission was observed only in 1 patient (3.5%). Among the non-responders (n=21), 4 patients required colectomy, 1 died, 1 was lost to follow-up, 10 were offered fecal microbiota transplant, 3 were administered infliximab, and 2 patients were administered cyclosporine and tacrolimus, respectively. Four patients (13.8%) developed extrapulmonary tuberculosis.ConclusionsThe adalimumab biosimilar Exemptia has limited efficacy for the attainment of clinical response and remission in moderate-to-severe steroid-refractory UC, with a significant risk of acquisition or reactivation of tuberculosis in developing countries such as India.

Reactivation and Dissemination of Tuberculosis to Extrapulmonary Sites in Patients With Hematologic Malignancies

Abstract The increased utilization of immunosuppressive, antineoplastic agents in patients with hematologic malignancies and hematopoietic stem cell transplant recipients impairs humoral and cellular immunity. As a result, susceptibility to infectious diseases, including reactivation/development of tuberculosis and its dissemination to extrapulmonary sites, is a serious concern. Tuberculosis dissemination to extrapulmonary sites can mimic both clinical and radiological presentations of other etiologic agents. Thus, early diagnosis is often challenging. We present 3 cases of tuberculosis infection, of which 2 disseminated to extrapulmonary sites in patients with hematologic malignancies, along with literature review, clinical presentation, diagnostic evaluation, and differential diagnosis.

Tuberculosis and interleukin blocking monoclonal antibodies: Is there risk?

Several new monoclonal antibodies that interfere with interleukin (IL) cascades have come to market in recent years. They follow a generation of drugs that block tumor necrosis factor (TNF). It has been well established that TNF is important in the containment of Mycobacterium tuberculosis (Mtb) and that blocking this cytokine increases the risk of tuberculosis (TB) infection. Thus, judicious screening for Mtb of patients taking TNF blocking drugs has been the standard of care. It remains unclear if the newer monoclonal, interleukin blocking drugs, which affect IL-12, IL-23, and IL-17 pathways are associated with risk of Mtb reactivation. Herein we discuss what is known about the immunologic response to Mtb and discuss the data that is currently available for the new interleukin monoclonal antibody blocking medications regarding the risk of latent TB reactivation or active TB infection.

P203 VEDOLIZUMAB IS SAFE AFTER ANTI-TNF-ASSOCIATED PULMONARY TUBERCULOSIS IN CROHN'S DISEASE: CASE REPORT

Anti-TNFα agents increase risk of infections due to systemic immunosuppression. Vedolizumab (VDZ) inhibits adhesions of gut-specific lymphocytes and thus may carry a lower risk. However, its safety in patients with prior tuberculosis (TB) infection is not known. We report a patient who developed TB while on anti-TNFα and was later safely maintained on VDZ. A 55-year-old Bosnian female with prior BCG vaccination was diagnosed with ileocolonic Crohn’s disease (CD) in 2008. It was poorly controlled despite infliximab & later adalimumab treatment. She developed Azathioprine-related pancreatitis and remained on prednisone from diagnosis until ileocecectomy in 2012. Shortly thereafter, she developed a cavitary lung lesion due to tuberculosis (TB). Anti-TNF α was discontinued. She completed 6 months of TB therapy. She remained in remission off IBD specific therapies for 18 months. However, she then developed recurrent abscesses and enteroenteric/enterocutaneous fistulas with intermittent courses of prednisone therapy. She underwent enterocutaneous fistula takedown, ileocolic anastomosis resection & diverting loop ileostomy. VDZ and oral methotrexate were started 3 months later with symptom resolution and inflammatory marker normalization. Colonoscopy/ileoscopy 12 months later confirmed mucosal and histological healing. Surveillance with low-dose CT for lung cancer (continued tobacco use) and TB screening a year later was non-revealing. She remains asymptomatic from a Crohn’s and TB perspective at 15 months. TB infection/reactivation is a known complication of anti-TNFα therapy. In post marketing analysis, in 66,390 patient-years of VDZ therapy, 5 patients developed TB, 2 of whom received anti-TNFα previously. Our patient is unique in that she developed active pulmonary TB after anti-TNFα therapy despite being BCG-vaccinated. She was actively followed for TB reactivation while on VDZ and responded to VDZ therapy without symptoms of TB or Crohns after 12 month follow up.

Why Has the Management of Latent Tuberculosis Been Relegated in High Burden Countries? An Ounce of Prevention is Worth A Pound of Cure

Latent tuberculosis infection (LTBI) is defined as the persistent immune response to stimulation by Mycobacterium tuberculosis antigens without evidence of clinically manifest active tuberculosis (TB). The lifetime risk of reactivation TB for an immunocompetent person with documented LTBI is estimated to be 5-15%. The most recent estimates of global latent tuberculosis infection (LTBI) is that approximately 1.7 billion people are infected worldwide, of which 10% are infected with an isoniazid-resistant strain. Prevention of new infections of Mycobacterium tuberculosis and their progression to active disease is critical to reduce the burden of disease and death caused by TB. Several high-risk groups, including individuals living with HIV and household contacts regardless of their age will benefit with treatment of LTBI. Unfortunately, according to the literature, globally, the proportion of LTBI subjects initiating treatment ranges from 24% to 98%, while the proportion of people completing LTBI treatment varies from 19% to 90%. Treatment of LTBI, as part of an integral approach to TB control, will facilitate the achievement of the targets of the WHO End TB strategy and eventually contribute to the elimination of TB.

Ustekinumab to treat Crohn's disease

Ustekinumab is a monoclonal antibody directed against the p40 subunit, which is part of interleukins IL-12 and IL-23. The efficacy of ustekinumab versus placebo in terms of clinical response and remission of induction has been shown in phase3 clinical trials. When used as subcutaneous maintenance therapy, the therapeutic benefit of ustekinumab over placebo has been confirmed in both clinical response and remission in patients who have responded clinically to induction therapy. In addition, ustekinumab has demonstrated an improvement in mucosal healing parameters. The safety profile of the drug has been good, with low infection rates (without reactivation of tuberculosis) and absence of tumour reporting. The development of drug immunogenicity appears to be rare. In summary, ustekinumab is a promising treatment option in patients with Crohn's disease, as an alternative to anti-TNFα drugs.

PM2·5 concentration and elderly tuberculosis: analysis of spatial and temporal associations

BackgroundChina periodically has severe ambient particulate matter (PM) pollution, which could cause compromised pulmonary immunity in the population and result in high cardio-respiratory morbidity and mortality. Acknowledging the highly prevalent latent tuberculosis in elderly people, we hypothesise that they are more prone to tuberculosis reactivation in the presence of air pollution. MethodsWe examined the spatial and temporal association between PM2·5 concentration and the number of reported cases of tuberculosis in elderly people aged 65 years and older in Hong Kong. Tuberculosis notification data in 2005–07 were collected from the Chinese Government's TB and Chest Service. Monthly and annual PM2·5 concentration by geographical subdistrict (DCCA) for the corresponding years were derived from satellite images. Age–gender standardised notification rate (SNR) of tuberculosis cases in elderly people was calculated per DCCA/time. Their temporal association with PM2·5 was examined by dynamic linear regression in R, and spatial association by spatial regression in GeoDa. FindingsAmong 17 294 new cases of tuberculosis reported in 2005–07, 6879 (40%) cases were in elderly people (2·69 men for every woman). The mean monthly SNR for elderly men was 35·4 per 100 000 persons (range 25·2–45·3), and the mean of mean PM2·5 in DCCA was 30·5 μg/m3 (16·1–47·1). Temporally, the SNR for elderly men was associated with PM2·5 in lag 0, lag −1 (ie, moving PM2·5 1 month earlier), and lag −4 to −6 months, with the most significant positive association at lag −6 months. However, no temporal association between the SNR for elderly women and PM2·5 was observed. Spatially, the SNR was associated with PM2·5 for elderly men in all 3 years but only for women in 2005. InterpretationWe detected spatial and temporal associations between cases of tuberculosis in elderly men and PM2·5. Tuberculosis reactivation might have occurred after exposure to high PM2·5 in the environment, as inferred from the lag interval of 6 months revealed in our results. The discrepancy between sexes and the effects of potential confounders such as sunshine duration, income level, and locality would need to be further investigated. FundingResearch Grants Council under Theme-based Research Scheme (T32-102/14N).

Mycobacterium tuberculosis Latent Antigen Rv2029c from the Multistage DNA Vaccine A39 Drives TH1 Responses via TLR-mediated Macrophage Activation.

Targeting of Mycobacterium tuberculosis (MTB) latent antigens comprises a crucial strategy for the development of alternative tuberculosis (TB) vaccine(s) that protects against TB reactivation. Here, we generated a multistage DNA vaccine, A39, containing the early antigens Ag85A and Rv3425 as well as the latency-associated protein Rv2029c, which conferred protective immunity in a pre-exposure mouse model. Moreover, administration of the A39 vaccination after MTB exposure inhibited reactivation and resulted in significantly lower bacterial loads in the lungs and spleen of mice, compared to those in the control population. Subsequently, we investigated the effect of Rv2029c on innate immunity and characterized the molecular details of the interaction of this protein with the host via iTRAQ proteomic and biochemical assay analyses. Rv2029c activated macrophages, triggered the production of pro-inflammatory cytokines, and promoted toll-like receptor/mitogen-activated protein kinase (TLR/MAPK)-dependent macrophage apoptosis. Furthermore, Rv2029c treatment enhanced the ability of Mycobacterium bovis Bacillus Calmette-Guérin (BCG)-infected macrophages to present antigens to CD4+ T cells in vitro, which correlated with an increase in MHC-II expression. Lastly, Rv2029c-treated macrophages activated T cells, effectively polarized CD4+ and CD8+ T cells to secrete IFN-γ and IL-2, and specifically expanded a population of CD44highCD62LlowCD4+/CD8+ effector/memory cells, indicating that Rv2029c, as a specific recall antigen, contributes to Th1 polarization in T cell immunity. These results suggest that Rv2029c and A39 comprise promising targets for the development of next-generation clinical TB therapeutic vaccines.

Sub-minimum inhibitory concentration of rifampin: a potential risk factor for resuscitation of Mycobacterium tuberculosis

BackgroundMycobacterium tuberculosis possesses five resuscitation-promoting factors, Rpf A to E, which are required for the resuscitation of dormancy in mycobacteria. This study explores the transcriptional profile of all five rpfs of M. tuberculosis, in response to sub-MIC concentration of rifampin, in multidrug and mono-rifampin resistant clinical isolates.MethodsThirteen multidrug and two rifampin mono resistant clinical isolates were analyzed. Drug susceptibility testing and determination of MIC were performed. The relative expression of rpfs was measured, by real-time quantitative PCR.ResultsA significant upregulation of relative expression (p < 0.05) was observed, as follows: 7/15(46.66%); 5/15(33.33%); 9/15(60%); 10/15(66.66%) and 9/15(60%) in rpfA, rpfB, rpfC, rpfD and rpfE, respectively.ConclusionOur results showed that the rpfs could be overexpressed in some extent in the presence of sub-MIC concentration of rifampin in multidrug and mono drug resistant M. tuberculosis. These results highlight the potential risk of sub-MIC rifampin concentrations, as a risk factor for tuberculosis reactivation.

Self-Administered Treatment of Latent TB

Reactivation of latent tuberculosis (TB) accounts for about 86% of active TB cases in the U.S. One anti-TB regimen that effectively prevents

Le risque infectieux au cours de la polyarthrite rhumatoïde et sa prévention

Patients with rheumatoid arthritis (RA) have a higher risk of infections compared to healthy subjects. Viral and bacterial pneumonia are the most frequent infections observed in RA. Moreover, drugs used to treat RA and especially biologic and synthetic targeted disease modifying antirheumatic drugs (DMARDs) increase this risk of infection and expose RA patients to opportunistic infections such as tuberculosis reactivation. In order, to limit the risk of infection, the benefit and risk ratio has to be evaluated for each patient according to characteristics and comorbidites. To prevent infections, an initial pretreatment work up has to be performed especially before initiation of biological and synthetic targeted DMARDs. Vaccinations update has to be checked and recommended vaccines for patients with autoimmune diseases and treated with immuno-suppressors, bDMARDs and/or steroids should be done. Information and education of patients are very important. During specific workshop, they learn how to manage drugs in situations at risk and they learn symptoms that require drug discontinuation.