Activation Of Latent Tuberculosis Infection Research Articles

Expert consensus on diagnosis and treatment of latent tuberculosis infection in patients with rheumatic diseases

Rheumatic diseases, a typical kind of autoimmune disease, are often treated with glucocorticoids, immunosuppressants, biological agents, and small-molecule targeted drugs, which often leads to immune dysfunction in patients and increases the risk of activation of latent tuberculosis infection. To regulate the screening, diagnosis, and prophylactic treatment of latent tuberculosis infection in patients with rheumatic diseases, reduce the risk of developing active tuberculosis and improve the prognosis, Peking University Shenzhen Hospital, Shenzhen Third People's Hospital and Peking Union Medical College Hospital jointly organized domestic experts in the field of rheumatology and tuberculosis to establish the expert consensus on the diagnosis and treatment of latent tuberculosis infection in patients with rheumatic diseases. This consensus focuses on epidemiology, the importance of screening, screening methods, and prophylactic anti-tuberculosis treatment strategies for latent tuberculosis infection combined with rheumatic diseases.

Reactivation of latent tuberculosis through modulation of resuscitation promoting factors by diabetes

The evidence of an association between diabetes and latent tuberculosis infection (LTBI) remains limited and inconsistent. Thus, the study aims to delineate the role of diabetes in activation of latent tuberculosis infection. Murine model of latent tuberculosis and diabetes was developed, bacillary load and gene expression of resuscitation promoting factors (rpfA-E) along with histopathological changes in the lungs and spleen were studied. Treatment for LTBI [Rifampicin (RIF) + Isoniazid (INH)] was also given to latently infected mice with or without diabetes for 4 weeks. Diabetes was found to activate latent tuberculosis as the colony forming unit (CFU) counts were observed to be > 104 in lungs and spleen. The gene expression of hspX was downregulated and that of rpfB and rpfD was observed to be upregulated in latently infected mice with diabetes compared to those without diabetes. However, no significant reduction in the CFU counts was observed after 4 weeks of treatment with RIF and INH. Diabetes helps in the progression of LTBI to active disease mainly through altered expression of resuscitation promoting factors rpfB and rpfD, which can serve as important targets to reduce the shared burden of tuberculosis and diabetes.

Cost-effectiveness of the latent tuberculosis screening program for migrants in Stockholm Region

IntroductionThe majority of tuberculosis (TB) cases in Sweden occur among migrants from endemic countries through activation of latent tuberculosis infection (LTBI). Sweden has LTBI-screening policies for migrants that have not been previously evaluated. This study aimed to assess the cost-effectiveness of the current screening strategy in Stockholm.MethodsA Markov model was developed to predict the costs and effects of the current LTBI-screening program compared to a scenario of no LTBI screening over a 50-year time horizon. Epidemiological and cost data were obtained from local sources when available. The primary outcomes were incremental cost-effectiveness ratio (ICER) in terms of societal cost per quality-adjusted life year (QALY).ResultsScreening migrants in the age group 13–19 years had the lowest ICER, 300,082 Swedish Kronor (SEK)/QALY, which is considered cost-effective in Sweden. In the age group 20–34, ICER was 714,527 SEK/QALY (moderately cost-effectives) and in all age groups above 34 ICERs were above 1,000,000 SEK/QALY (not cost-effective). ICER decreased with increasing TB incidence in country of origin.ConclusionScreening is cost-effective for young cohorts, mainly between 13 and 19, while cost-effectiveness in age group 20–34 years could be enhanced by focusing on migrants from highest incidence countries and/or by increasing the LTBI treatment initiation rate. Screening is not cost-effective in older cohorts regardless of the country of origin.

Features of tuberculosis in a COVID-19 pandemic

Objective — to assess the prospects for the effects of the interaction between COVID-19 and tuberculosis and to strategize for the risks of tuberculosis infection in a coronavirus pandemic.Materials and methods. Test access to such full-text and abstract databases was used: single information base package EBSCO; the world’s largest single abstract database and scientometric platform Scopus; free search engine Google Scholar; MEDLINE with Full Text; MEDLINE Complete; Dyna Med Plus; EBSCO eBooks Clinical Collection; abstract scientometric database of scientific publications of the project Web of Know ledge companies Thomson Reuters —Web of Science Core Collection WoS (CC); (SCIE (Science Citation Index Expanded); SSCI (Social Science Citation Index); AHCI (Artand Humanities Citation Index).Results and discussion. An analysis of the available literature has shown that worldwide 3-month lockdown and long-term 10-month recovery could lead to an additional 6.3 million TB cases between 2020 and 2025 and another 1.4 million TB deaths during that period. time. On average, the detection of tuberculosis in Ukraine decreased by 27.4 %, and the incidence of tuberculosis among children decreased by 34.5 %. This is an alarming figure because we know very well that within six months the number of patients with tuberculosis has decreased, they simply stopped being detected. In addition, COVID-19 may accelerate the activation of latent tuberculosis infection and thus increase the number of active cases.Conclusions. The epidemiological indicators for tuberculosis control are expected to deteriorate for at least the next 5-8 years due to the COVID-19 pandemic.

Peculiarities of tuberculosis in the COVID‑19 pandemic

OBJECTIVE. The purpose of our comprehensive analysis is to assess the prospects for the effects of the interaction between coronavirus disease 2019 (COVID‑19) and tuberculosis (TB) and to strategize the risks of spreading TB infection in a coronavirus pandemic.
 MATERIALS AND METHODS. Test access to full-text and abstract databases was used.
 RESULTS AND DISCUSSION. An analysis of the available literature has shown that a 3-month lockdown and a long 10-month recovery worldwide could lead to an additional 6.3 million TB cases and another 1.4 million TB deaths between 2020 and 2025. On average, the detection of TB in Ukraine decreased by 27.4 %, and the incidence of TB among children decreased by 34.5 %. This is an alarming figure because we know very well that within 6 months the number of patients with TB has not decreased, they simply stopped being detected. In addition, COVID‑19 may accelerate the activation of latent TB infection and thus increase the number of active cases.
 CONCLUSIONS. The overall incidence of TB in 2021 will increase to the level that was last observed between 2013 and 2016. The epidemiological indicators of TB control are expected to deteriorate for at least 5-8 years due to the COVID‑19 pandemic. Long-term results can be strongly affected by the rate of short-term recovery. Priority should be given to all governments, during a pandemic, to ensure the continuity of basic health care, including the implementation of national TB programs.

Glucocorticoids in the treatment of patients with tuberculous meningitis — two sides of one medal (current trends, clinical case)

Corticosteroids have long been used as an adjunct to the treatment of tuberculous meningitis. In addition, glucocorticoid therapy is an integral aspect of the management of patients with systemic connective tissue diseases, which is due to the high effectiveness of these drugs in reducing disease activity. Immunological defects in systemic connective tissue diseases, a high total dose of corticosteroids in therapy cause the activation of latent tuberculosis infection and the rapid development of the disease when infected with mycobacterium tuberculosis.The results of presented clinical case have shown that doctors of different specialties should be tuned to the probability of developing tuberculous meningitis in patients with immunosuppression, even in the absence of meningeal symptoms (rigidity of the occipital muscles, the symptom of Kernig) against the background of the use of glucocorticoids in the treatment of other diseases. At the same time, corticosteroids should be prescribed to patients as an adjuvant for anti‑TB therapy (despite immunosuppressive effects), but the regimen should be developed for each patient according to the individual severity of the disease. A molecular genetic method G‑Xpert demonstrated considerable molecular diagnostic value for the diagnosis of tuberculous meningitis. The method allows not only detect Mycobacterium tuberculosis in the cerebrospinal fluid in 2 hours but also determine the presence of multiple drug resistance, which contributes to the immediate administration of adequate etiotropic therapy which prevents the development of severe neurological disorders and death. Neuroimaging is essential for the diagnosis and monitoring of tuberculous meningitis.In cases of differential diagnosis of tuberculous meningitis, physicians should refrain from using broad‑spectrum drugs from fluoroquinolones and aminoglycosides, as this may cause untimely detection of a correct diagnosis.

High risk of activation of latent tuberculosis infection in rheumatic disease patients

Objective: To evaluate the risk of activation of latent tuberculosis infection (LTBI) in Chinese patients with rheumatic diseases who have received glucocorticoid treatment.Methods: We conducted a 2-year study, enrolling 1788 patients with rheumatic diseases who were treated with glucocorticoid for at least 4 weeks at the Department of Immunology and Rheumatology, First Affiliated Hospital of Nanchang University. Interferon-release assays (IGRA) were performed with patient blood samples obtained at baseline. Patient data, including age, gender, body mass index (BMI), duration and dosage of glucocorticoid and disease-modifying antirheumatic drug (immunosuppressant) treatment and comorbidities (malignancies, diabetes, chronic renal failure, silicosis) were collected. Patients were followed for 2 years to detect the emergence of active tuberculosis (TB).Results: 21.8% (349/1600) of the patients tested positive in IGRA, indicating LTBI. 2-year follow-up showed that 18 (5.16%) patients with positive IGRA but only 4 (0.35%) patients with negative IGRA developed active TB (p < .05). SLE patients had the highest activation rate of 2.22 per 100 total recruitment cases/year. Univariate and multivariate analysis showed that low BMI(<18.5), administration of high dose glucocorticoids (>15 mg daily), and comorbidities that included interstitial lung disease and malignant cancers were significantly associated with LTBI activation.Conclusion: Our results suggest that screening and preventive therapy of LTBI may be advisable for Chinese rheumatic disease and particularly SLE patients undergoing glucocorticoid therapy with dosage above 15 mg prednisone equivalent daily for more than 4 weeks.

Management of Latent Tuberculosis Infection in Children from Developing Countries.

Tuberculosis (TB), once widely prevalent throughout the world, experienced falling incidence rates in early twentieth century in developed nations, even before the introduction of anti-TB drugs, attributed to improved hygiene and living conditions. Active TB may develop following fresh infection or activation of latent tuberculosis infection (LTBI). LTBI is a state of persistent bacterial viability, however, the host stays asymptomatic and there is no evidence of clinically active tuberculosis. Therefore, treatment of all LTBI is considered as one of the ways to control tuberculosis. Diagnosis of LTBI relies on presence of immune-reactivity to TB antigen and commonly used tests include tuberculin skin test and interferon gamma release assay (IGRA). At present there is no diagnostic test that can identify an individual with LTBI who will progress to develop active disease or remain asymptomatic. Therefore, it is unclear whom to treat. In the current scenario, treatment for LTBI is restricted to high risk groups which include under-5 y contacts of adults with pulmonary TB. Various regimens for treatment of LTBI are evolving and consist of isoniazid (INH) alone for 6-9 mo or combination of INH and rifampicin for 3-4 mo or once a week combination of rifapentin and INH for 3 mo. There is a need for research to identify LTBI, risk factors for progression of LTBI to active disease and a shorter regimen for treatment.

Hemoptoe by tuberculosis in near term pregnant woman: a case report

Tuberculosis (TB) is an important cause of morbidity and mortality in pregnancy because immunological changes in pregnancy make the activation of latent TB infection or de novo infection more likely than among non-pregnant women. The authors report the case of a pregnant woman referring for hemoptoe by TB infection. The patient showed a massive hemoptoe, because of it, the authors speculated that she was bleeding because of tubercular blood vessel erosion from bronchial or other systemic arteries supplying the lungs (high pressure system). Flexible or rigid bronchoscopy to identify the site of bleeding should be used. In the present case the authors preferred the flexible bronchoscopy because the cardiorespiratory status was stable and the bleeding was not ongoing. The flexible bronchoscopy permitted to make a diagnosis with microbiological exam on bronchial lavage.

Cigarette smoking and health-promoting behaviours among tuberculosis patients in rural areas.

To explore cigarette smoking and health-promoting behaviours among disadvantaged adults before their tuberculosis diagnosis and after their tuberculosis treatment. Although tuberculosis infection is associated with impaired immune function, healthy lifestyle habits can play a role in improving the immune system. However, limited research has explored the health-promoting behaviours and cigarette smoking habits among tuberculosis patients in Taiwan. A cross-sectional retrospective study with a convenience sample. This study was conducted between May 2013-June 2014 with 123 patients at a rural district hospital in Chiayi County, Taiwan. Statistical analyses included descriptive statistics, univariate analysis and stepwise regression analysis. Tuberculosis tended to be associated with less education, male sex, malnutrition, cigarette smoking and unhealthy lifestyle habits before the tuberculosis diagnosis. The percentage of smoking decreased from 46·9% before to 30·2% after the tuberculosis diagnosis. Body mass index and health-promoting behaviours also significantly improved after tuberculosis treatment. After controlling for potential confounding factors, multivariate analysis identified chronic disease and completed treatment as significant factors that were associated with current health-promoting behaviours. A high prevalence of cigarette smoking and low levels of health-promoting behaviours were observed before the diagnosis and during or after completing tuberculosis treatment. This study's findings indicate the importance of promoting healthy lifestyle changes among tuberculosis patients; aggressive measures should be implemented immediately after the first diagnosis of tuberculosis. Furthermore, health promotion and smoking cessation programmes should be initiated in the general population to prevent activation of latent tuberculosis infection, and these programmes should specifically target men and rural residents.

What Factors May Influence Epidemiological Situation of Tuberculosis in Poland and in the World?

The authors present the review of factors influencing epidemiological situation of tuberculosis in Poland and in the world. The groups of increased risk of tuberculosis, and clinical conditions predisposing to activation of latent tuberculosis infection (LTBI) such as HIV, uremia, diabetes mellitus, transplantation of organs, treatment with glucocorticosteroids and with antibodies to TNF and to its receptors, were presented. The higher prevalence and worse prognosis of tuberculosis in elderly people was emphasised. The methods of LTBI recognition, according to recent recommendations, with special consideration to patients in immunosupression, were shown. Methods of treatment to prevent LTBI activation, according to WHO experts, were also presented. All data were discussed in relation to the actual epidemiological situation of tuberculosis in Poland.

What factors may influence epidemiological situation of tuberculosis in Poland and in the world?

The authors present the review of factors influencing epidemiological situation of tuberculosis in Poland and in the world. The groups of increased risk of tuberculosis, and clinical conditions predisposing to activation of latent tuberculosis infection (LTBI) such as HIV, uremia, diabetes mellitus, transplantation of organs, treatment with glucocorticosteroids and with antibodies to TNF and to its receptors, were presented. The higher prevalence and worse prognosis of tuberculosis in elderly people was emphasised. The methods of LTBI recognition, according to recent recommendations, with special consideration to patients in immunosupression, were shown. Methods of treatment to prevent LTBI activation, according to WHO experts, were also presented. All data were discussed in relation to the actual epidemiological situation of tuberculosis in Poland.

Perspectives on tuberculosis in pregnancy

Tuberculosis (TB) has been recognized as an important cause of morbidity and mortality in pregnancy for nearly a century, but research and efforts to roll out comprehensive TB screening and treatment in high-risk populations such as those with a high prevalence of HIV or other diseases of poverty, have lagged behind similar efforts to address HIV infection in pregnancy and the prevention of mother-to-child-transmission. Immunological changes during pregnancy make the activation of latent TB infection or de novo infection more likely than among non-pregnant women. TB treatment in pregnancy poses several problems that have been under-researched, such as contraindications to anti-TB and anti-HIV drugs and potential risks to the neonate, which are particularly important with respect to second-line TB treatment. Whilst congenital TB is thought to be rare, data from high HIV burden settings suggest this is not the case. There is a need for more studies screening for TB in neonates and observing outcomes, and testing preventative or curative actions. National tuberculosis control programmes (NTPs) should work with antenatal and national HIV programmes in high-burden populations to provide screening at antenatal clinics, or to establish functioning systems whereby pregnant women at high risk can drop in to routine NTP screening stations.

Mo1066 Mercaptopurine Therapy in IBD Patients Modulates GTPase RAC1

Background: In any immunosuppressive therapy, the question always arises whether this therapy increases the risk of infectious complications. The most serious problem in modern medicine have severe infectious complications of anticytokine therapy in patients with inflammatory bowel disease (IBD), having acquired immune deficiency. Accumulated to date show that in spite of the pronounced effect on immunnosupressivny alloreaktivnye and mitogen-provoked reactions, mesenchymal stromal cells (MSC) did not inhibit the activity of immune cells directed against infectious agents. Objective: To compare the risk of infectious complications in patients treated with anticytokine therapy with infliximab (IFX) and cell therapy using culture MSC. Methods: 60 patients with ulcerative colitis (UC) and Crohn’s disease (CD) at the age of 19 to 58 years (Me-29), who received a comprehensive anti-inflammatory therapy with culture MSCs, which were introduced under the scheme 0 1-26. 59 patients with UC and CD in age from 20 to 62 years (Me-38) received induction IFX therapy 0 2-6 and maintenance therapy after 8 weeks for 12 months. The observation time for both groups of patients was 64 weeks. Results: Frequency of severe infection (SI) among patients treated with MSCs was 1.6% (1 case of pneumonia). Frequency of severe SI among patients receiving IFX was 15.6% (6 cases). For individual forms that look as follows: pneumonia 3 cases (5.7%), throat abscess 1 case (1.9%), lung abscess 1 case (1.9%), pleural effusion a case of (1.9%). The frequency of exacerbations of chronic inflammatory disease and mild SI was 10.0% and 33.9% respectively (p < 0.05). The risk of developing tuberculosis, and activation of latent tuberculosis infection was higher in patients who received IFX, than in patients receiving cell therapy 0.03 (95%CI 0.17 0.72), (p = 0.0007, x2 13.4). The relative risk of developing opportunistic infections and infectious complications in patients with IBD receiving biological therapy MSCs compared with anticytokine therapy was 0.3 (95%CI 0.13 0.68), OR-0, 22 (95%CI 0.07 0.64), (p = 0.003, x2 8.6). Conclusions: The frequency of infectious complications, acute exacerbations of chronic inflammatory diseases, the risks of opportunistic infection and activation of latent tuberculosis infection was higher in patients who received IFX, than in patients receiving therapy of MSC.

Mesenchymal Stromal Cells Did Not Increase The Risk of Infectious Complications in Patients With Inflammatory Bowel Disease

In any immunosuppressive therapy, the question always arises - whether this therapy increases the risk of infectious complications? The most serious problem in modern medicine have severe infectious complications of anticytokine therapy in patients with inflammatory bowel disease (IBD), having acquired immune deficiency. Accumulated to date show that in spite of the pronounced effect on immunosuppression, alloreactivity and mitogen-provoked reactions, mesenchymal stromal cells (MSC) did not inhibit the activity of immune cells directed against infectious agents. Objective: To compare the risk of infectious complications in patients treated with anticytokine therapy with infliximab (IFX) and cell therapy using culture MSC. Materials and Methods. 60 patients with ulcerative colitis (UC) and Crohn’s disease (CD) at the age of 19 to 58 years (M-29), who received a comprehensive anti-inflammatory therapy with culture MSCs, which were introduced under the scheme 0-1-26. 59 patients with UC and CD in age from 20 to 62 years (M-38) received induction IFX therapy 0-2-6 and maintenance therapy after 8 weeks for 12 months. The observation time for both groups of patients was 64 weeks. Frequency of severe infection (SI) among patients treated with MSCs was 1.6% (1 case of pneumonia). Frequency of severe SI among patients receiving IFX was 15.6% (6 cases). For individual forms that look as follows: pneumonia - 3 cases (5.7%), throat abscess - 1 case (1.9%), lung abscess - 1 case (1.9%), pleural effusion - a case of (1.9%). The frequency of exacerbations of chronic inflammatory disease and mild SI was 10.0% and 33.9% respectively (P < 0.05). The risk of developing tuberculosis, and activation of latent tuberculosis infection was higher in patients who received IFX, than in patients receiving cell therapy 0.03 (95% CI 0.17-0.72), (P = 0.0007, x2-13.4). The relative risk of developing opportunistic infections and infectious complications in patients with IBD receiving biological therapy MSCs compared with anticytokine therapy was 0.3 (95% CI 0.13-0.68), OR-0.22 (95% CI 0.07-0.64), (P = 0.003, x2-8.6). The frequency of infectious complications, acute exacerbations of chronic inflammatory diseases, the risks of opportunistic infection and activation of latent tuberculosis infection was higher in patients who received IFX, than in patients receiving biological therapy MSC.

Tuberculosis among Foreign-born Persons in the United States

In the United States, the number of annual reported cases of tuberculosis (TB) among U.S.-born persons declined by 62% from 1993 to 2004, but increased by 5% among foreign-born persons. Over half of all reported cases of TB in the United States occur among foreign-born persons, most of these due to activation of latent TB infection (LTBI). Current guidelines recommend targeting only foreign-born persons who entered the United States within the previous 5 yr for LTBI testing. We sought to assess the epidemiologic basis for this guideline. We calculated TB case rates among foreign-born persons, stratified by duration of United States residence and world region of origin. We determined the number of cases using 2004 U.S. TB surveillance data, and calculated case rates using population data from the 2004 American Community Survey. In 2004, a total of 14,517 cases of TB were reported; 3,444 (24%) of these were among foreign-born persons who had entered the United States more than 5 yr previously. The rate of TB disease among foreign-born persons was 21.5/100,000, compared with 2.7/100,000 for U.S.-born persons, and varied by duration of residence and world region of origin. Almost one-quarter of all TB cases in the United States occur among foreign-born persons who have resided in the United States for longer than 5 yr; case rates for such persons from selected regions of origin remain substantially elevated. To eliminate TB, we must address the burden of LTBI in this high-risk group.

Drug Abuse, HIV Infection, and Tuberculosis

<h3>To the Editor.—</h3> The recent article by Braun and colleagues¹and the accompanying editorial by Drs Snider and Hutton²are especially timely in focusing on the need for appropriate tuberculosis-control measures in correctional facilities. The relationship between drug abuse and tuberculosis was another finding of the study by Braun et al and confirms previous reports.^3,4The significance of the drug abuse— tuberculosis association is especially intriguing, given the recent trends of the concurrent rise of tuberculosis and acquired immunodeficiency syndrome case reporting in the United States. The increase in case reports of tuberculosis has been explained by most investigators as human immunodeficiency virus (HIV)—associated immunosuppression resulting in activation of latent tuberculosis infection.⁴ However, new infection has not been unequivocally dismissed as a possible contribution. More importantly, very little information is available about the efficacy of tuberculosis preventive or therapeutic regimens in persons with HIV infection or