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The Journal of Clinical Investigation Feb 2021Humans have been infected with Mycobacterium tuberculosis (Mtb) for thousands of years. While tuberculosis (TB), one of the deadliest infectious diseases, is caused by... (Review)
Review
Humans have been infected with Mycobacterium tuberculosis (Mtb) for thousands of years. While tuberculosis (TB), one of the deadliest infectious diseases, is caused by uncontrolled Mtb infection, over 90% of presumed infected individuals remain asymptomatic and contain Mtb in a latent TB infection (LTBI) without ever developing disease, and some may clear the infection. A small number of heavily Mtb-exposed individuals appear to resist developing traditional LTBI. Because Mtb has mechanisms for intracellular survival and immune evasion, successful control involves all of the arms of the immune system. Here, we focus on immune responses to Mtb in humans and nonhuman primates and discuss new concepts and outline major knowledge gaps in our understanding of LTBI, ranging from the earliest events of exposure and infection to success or failure of Mtb control.
Topics: Animals; Humans; Immune Evasion; Latent Tuberculosis; Mycobacterium tuberculosis
PubMed: 33529162
DOI: 10.1172/JCI136222 -
Revista Espanola de Quimioterapia :... Oct 2022Tuberculosis continues to be a major public health problem. A priority objective is the implementation of early diagnosis, contact investigation and latent tuberculosis... (Review)
Review
Tuberculosis continues to be a major public health problem. A priority objective is the implementation of early diagnosis, contact investigation and latent tuberculosis infection (LTBI) testing. World Health Organization (WHO) concludes that there is no gold standard for the diagnosis of LTBI; both the tuberculin test and IGRA (interferon gamma release assays) indirectly identify tuberculosis infection; both tests are considered acceptable but imperfect. WHO recommends that regimens that include rifamycins are equally effective but less toxic and more adherent than long regimens with isoniazid.
Topics: Humans; Latent Tuberculosis; Isoniazid; Interferon-gamma Release Tests; Tuberculosis; Rifamycins
PubMed: 36285867
DOI: 10.37201/req/s03.20.2022 -
American Journal of Respiratory and... Jul 2021
Topics: Antitubercular Agents; Female; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Latent Tuberculosis; Male; Mycobacterium tuberculosis; Practice Guidelines as Topic; United States
PubMed: 33761302
DOI: 10.1164/rccm.202011-4239PP -
International Journal of Infectious... Nov 2022The World Health Organization estimated that a quarter of the global population is infected by Mycobacterium tuberculosis (Mtb). A better control of tuberculosis (TB) is... (Review)
Review
The role of IGRA in the diagnosis of tuberculosis infection, differentiating from active tuberculosis, and decision making for initiating treatment or preventive therapy of tuberculosis infection.
OBJECTIVES
The World Health Organization estimated that a quarter of the global population is infected by Mycobacterium tuberculosis (Mtb). A better control of tuberculosis (TB) is based on the ability to detect Mtb infection, identifying the progressors to TB disease, undergoing to preventive therapy and implementing strategies to register the infections and treatment completion.
DESIGN
we reviewed the literature regarding the tests available for TB infection diagnosis, the preventive therapies options and the cascade of care for controlling TB at a public health level.
RESULTS
current tests for TB infection diagnosis as IFN-γ release assays or tuberculin skin tests are based on the detection of an immune response to Mtb in the absence of clinical disease. The main limit is their low accuracy to detect progressors to disease. New preventive treatments are available with short duration that are associated with better adherence. Options to register TB infections are presented.
CONCLUSIONS
Tests to diagnose TB infection are available but they lack accuracy to identify the progressors from infection to TB disease. Shorter preventive TB therapy are available but need to be implemented worldwide. A TB infection registry is crucial for improving the cascade of care leading to a better TB control.
Topics: Humans; Latent Tuberculosis; Tuberculosis; Tuberculin Test; Interferon-gamma Release Tests; Mycobacterium tuberculosis
PubMed: 35257904
DOI: 10.1016/j.ijid.2022.02.047 -
MMWR. Recommendations and Reports :... Feb 2020Comprehensive guidelines for treatment of latent tuberculosis infection (LTBI) among persons living in the United States were last published in 2000 (American Thoracic...
Comprehensive guidelines for treatment of latent tuberculosis infection (LTBI) among persons living in the United States were last published in 2000 (American Thoracic Society. CDC targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med 2000;161:S221-47). Since then, several new regimens have been evaluated in clinical trials. To update previous guidelines, the National Tuberculosis Controllers Association (NTCA) and CDC convened a committee to conduct a systematic literature review and make new recommendations for the most effective and least toxic regimens for treatment of LTBI among persons who live in the United States.The systematic literature review included clinical trials of regimens to treat LTBI. Quality of evidence (high, moderate, low, or very low) from clinical trial comparisons was appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. In addition, a network meta-analysis evaluated regimens that had not been compared directly in clinical trials. The effectiveness outcome was tuberculosis disease; the toxicity outcome was hepatotoxicity. Strong GRADE recommendations required at least moderate evidence of effectiveness and that the desirable consequences outweighed the undesirable consequences in the majority of patients. Conditional GRADE recommendations were made when determination of whether desirable consequences outweighed undesirable consequences was uncertain (e.g., with low-quality evidence).These updated 2020 LTBI treatment guidelines include the NTCA- and CDC-recommended treatment regimens that comprise three preferred rifamycin-based regimens and two alternative monotherapy regimens with daily isoniazid. All recommended treatment regimens are intended for persons infected with Mycobacterium tuberculosis that is presumed to be susceptible to isoniazid or rifampin. These updated guidelines do not apply when evidence is available that the infecting M. tuberculosis strain is resistant to both isoniazid and rifampin; recommendations for treating contacts exposed to multidrug-resistant tuberculosis were published in 2019 (Nahid P, Mase SR Migliori GB, et al. Treatment of drug-resistant tuberculosis. An official ATS/CDC/ERS/IDSA clinical practice guideline. Am J Respir Crit Care Med 2019;200:e93-e142). The three rifamycin-based preferred regimens are 3 months of once-weekly isoniazid plus rifapentine, 4 months of daily rifampin, or 3 months of daily isoniazid plus rifampin. Prescribing providers or pharmacists who are unfamiliar with rifampin and rifapentine might confuse the two drugs. They are not interchangeable, and caution should be taken to ensure that patients receive the correct medication for the intended regimen. Preference for these rifamycin-based regimens was made on the basis of effectiveness, safety, and high treatment completion rates. The two alternative treatment regimens are daily isoniazid for 6 or 9 months; isoniazid monotherapy is efficacious but has higher toxicity risk and lower treatment completion rates than shorter rifamycin-based regimens.In summary, short-course (3- to 4-month) rifamycin-based treatment regimens are preferred over longer-course (6-9 month) isoniazid monotherapy for treatment of LTBI. These updated guidelines can be used by clinicians, public health officials, policymakers, health care organizations, and other state and local stakeholders who might need to adapt them to fit individual clinical circumstances.
Topics: Centers for Disease Control and Prevention, U.S.; Humans; Latent Tuberculosis; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; United States
PubMed: 32053584
DOI: 10.15585/mmwr.rr6901a1 -
Obstetrics and Gynecology Jun 2020Tuberculosis (TB) in pregnancy poses a substantial risk of morbidity to both the pregnant woman and the fetus if not diagnosed and treated in a timely manner. Assessing... (Review)
Review
Tuberculosis (TB) in pregnancy poses a substantial risk of morbidity to both the pregnant woman and the fetus if not diagnosed and treated in a timely manner. Assessing the risk of having Mycobacterium tuberculosis infection is essential to determining when further evaluation should occur. Obstetrician-gynecologists are in a unique position to identify individuals with infection and facilitate further evaluation and follow up as needed. A TB evaluation consists of a TB risk assessment, medical history, physical examination, and a symptom screen; a TB test should be performed if indicated by the TB evaluation. If a pregnant woman has signs or symptoms of TB or if the test result for TB infection is positive, active TB disease must be ruled out before delivery, with a chest radiograph and other diagnostics as indicated. If active TB disease is diagnosed, it should be treated; providers must decide when treatment of latent TB infection is most beneficial. Most women will not require latent TB infection treatment while pregnant, but all require close follow up and monitoring. Treatment should be coordinated with the TB control program within the respective jurisdiction and initiated based on the woman's risk factors including social history, comorbidities (particularly human immunodeficiency virus [HIV] infection), and concomitant medications.
Topics: Antitubercular Agents; Female; HIV Infections; Humans; Latent Tuberculosis; Pregnancy; Pregnancy Complications, Infectious; Risk Factors; Tuberculosis
PubMed: 32459437
DOI: 10.1097/AOG.0000000000003890 -
La Medicina Del Lavoro Jun 2020Despite great efforts, tuberculosis (TB) is still a major public health threat worldwide. For decades, TB control programs have focused almost exclusively on infectious... (Review)
Review
INTRODUCTION
Despite great efforts, tuberculosis (TB) is still a major public health threat worldwide. For decades, TB control programs have focused almost exclusively on infectious TB active cases. However, it is evident that this strategy alone cannot achieve TB elimination. To achieve this objective a comprehensive strategy directed toward integrated latent tuberculosis infection (LTBI) management is needed. Recently it has been recognized that LTBI is not a stable condition but rather a spectrum of infections (e.g., intermittent, transient or progressive) which may lead to incipient, then subclinical, and finally active TB disease.
AIM
Provide an overview of current available LTBI diagnostic test including updates, future developments and perspectives.
RESULTS
There is currently no test for the direct identification of live MT infection in humans. The diagnosis of LTBI is indirect and relies on the detection of an immune response against MT antigens, assuming that the immune response has developed after a contact with the biological agent. Tuberculin skin test (TST) and interferon gamma release assays (IGRAs) are the main diagnostic tools for LTBI, however, both present strengths and limitations. The most ancient diagnostic test (TST) can be associated with several technical errors, has limited positive predictive value, is being influenced by BCG vaccination and several conditions can reduce the skin reactivity. Notwithstanding these limitations, prompt identification of TST conversion, should orientate indications for preventive therapy of LTBI. IGRAs have superior specificity, are not affected by M. bovis, BCG vaccination and other environmental mycobacteria. However, they present some logistical and organisational constraints and are more expensive. Currently, the WHO guidelines recommend that either a TST or an IGRA can be used to detect LTBI in high-income and upper middle-income countries with estimated TB incidences less than 100 per 100,000 population. Two skin tests (C-TB and Diaskintest), using only two specific M. tuberculosis antigens (ESAT-6 and CFP-10) instead of the tuberculin solution, have recently been developed but, to date, none of these tests is available on the European market.
CONCLUSION
Early identification and treatment of individuals with LTBI is an important priority for TB control in specific groups at risk within the population: this is of crucial meaning in recently infected cases both at the community level and in some occupational settings. Currently there is no gold standard test for LTBI: an improved understanding of the available tests is needed to develop better tools for diagnosing LTBI and predicting progression to clinical active disease.
Topics: Humans; Interferon-gamma; Latent Tuberculosis; Sensitivity and Specificity; Tuberculin Test; Tuberculosis
PubMed: 32624559
DOI: 10.23749/mdl.v111i3.9983 -
Jornal Brasileiro de Nefrologia 2021
Topics: Humans; Kidney Transplantation; Latent Tuberculosis
PubMed: 34543376
DOI: 10.1590/2175-8239-JBN-2021-E008 -
Single-cell transcriptomics of blood reveals a natural killer cell subset depletion in tuberculosis.EBioMedicine Mar 2020Tuberculosis (TB) continues to be a critical global health problem, which killed millions of lives each year. Certain circulating cell subsets are thought to...
BACKGROUND
Tuberculosis (TB) continues to be a critical global health problem, which killed millions of lives each year. Certain circulating cell subsets are thought to differentially modulate the host immune response towards Mycobacterium tuberculosis (Mtb) infection, but the nature and function of these subsets is unclear.
METHODS
Peripheral blood mononuclear cells (PBMC) were isolated from healthy controls (HC), latent tuberculosis infection (LTBI) and active tuberculosis (TB) and then subjected to single-cell RNA sequencing (scRNA-seq) using 10 × Genomics platform. Unsupervised clustering of the cells based on the gene expression profiles using the Seurat package and passed to tSNE for clustering visualization. Flow cytometry was used to validate the subsets identified by scRNA-Seq.
FINDINGS
Cluster analysis based on differential gene expression revealed both known and novel markers for all main PBMC cell types and delineated 29 cell subsets. By comparing the scRNA-seq datasets from HC, LTBI and TB, we found that infection changes the frequency of immune-cell subsets in TB. Specifically, we observed gradual depletion of a natural killer (NK) cell subset (CD3-CD7+GZMB+) from HC, to LTBI and TB. We further verified that the depletion of CD3-CD7+GZMB+ subset in TB and found an increase in this subset frequency after anti-TB treatment. Finally, we confirmed that changes in this subset frequency can distinguish patients with TB from LTBI and HC.
INTERPRETATION
We propose that the frequency of CD3-CD7+GZMB+ in peripheral blood could be used as a novel biomarker for distinguishing TB from LTBI and HC. FUND: The study was supported by Natural Science Foundation of China (81770013, 81525016, 81772145, 81871255 and 91942315), National Science and Technology Major Project (2017ZX10201301), Science and Technology Project of Shenzhen (JCYJ20170412101048337) and Guangdong Provincial Key Laboratory of Regional Immunity and Diseases (2019B030301009). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Topics: Adolescent; Adult; Biomarkers; Female; Humans; Killer Cells, Natural; Latent Tuberculosis; Lymphocyte Count; Male; Middle Aged; Single-Cell Analysis; Transcriptome; Tuberculosis, Pulmonary
PubMed: 32114394
DOI: 10.1016/j.ebiom.2020.102686 -
JAMA Network Open May 2023
Topics: Humans; Latent Tuberculosis; Tuberculin Test; Mass Screening
PubMed: 37129898
DOI: 10.1001/jamanetworkopen.2023.12114