Tuberculosis y odontología

Se presenta en este artículo una revisión de los aspectos fundamentales de la tuberculosis y sus implicaciones en odontología. La tuberculosis, un importante problema de salud pública en la primera mitad del siglo pasado, disminuyó progresivamente su incidencia desde entonces a consecuencia de la mejoría en las condiciones de vida, las medidas de prevención y los progresos en el tratamiento. Sin embargo, la aparición de nuevas cepas de Mycobacterium tuberculosis resistentes a varios fármacos utilizados en el tratamiento y el aumento de su incidencia en inmunodeprimidos y otros grupos de población, agrava este problema. La tuberculosis se transmite, principalmente, por vía aérea. Cabe pues la posibilidad de que sea transmitida en el ejercicio de la profesión y aunque parece que el riesgo de transmisión es bajo, está indicado la introducción de medidas preventivas que reduzcan el riesgo.

Mycobacterium tuberculosis-specific CD8 T cells are functionally and phenotypically different between latent infection and active disease

Purpose/Objective: Tuberculosis (TB) is the second worldwide leading cause of death from an infectious disease after HIV infection. Protective immunity to Mycobacterium tuberculosis (Mtb) remains poorly understood and the role of Mtb-specific CD8 T-cells is controversial. We performed comprehensive functional and phenotypic characterizations of Mtb-specific CD8 T-cell responses in 273 subjects with either latent Mtb infection (LTBI) or active TB disease (TB) to assess their profile and relevance in TB. Materials and methods: Using multi-parametric flow cytometry, we assessed Mtb-specific CD8 T-cell functional (production of IFNgamma, IL-2 and TNF-alpha; proliferation capacity and cytotoxicity) and phenotypic (T-cell differentiation and exhaustion) profiles in cells isolated from peripheral blood and correlated these profiles with distinct clinical presentations. Results: Mtb-specific CD8 T-cells were detected in most TB patients and few LTBI subjects (65% and 15%, respectively; P < 0.00001) and were of similar magnitude with a comparable cytokines profile (IFNg+TNFa+IL2-) in both groups. Mtb-specific CD8 T-cells were mostly TEMRA (CD45RA+ CCR7-) co-expressing 2B4 and CD160 in LTBI subjects and mostly TEM (CD45RA-CCR7-) lacking PD-1/ CD160/2B4 in TB patients. Furthermore, Mtb-specific CD8 T-cells mostly expressed very little perforin and granulysin but contained granzymes A and B or lacked all these cytotoxic markers in TB and LTBI subjects, respectively. However, in vitro expanded Mtb-specific CD8 T-cells acquired perforin, granulysin and granzymes. Finally, Mtb-specific CD8 T-cell responses were more robust and prone to proliferate in patients with extrapulmonary compared to pulmonary TB. Conclusions: The clinical status and TB presentation are associated to specific profiles of Mtb-specific CD8 T-cell responses, thus indicating distinct dynamics between the mycobacteria, the CD8 T-cell response and the clinical outcome. Our data shed light on the controversial reached by studies performed in human and animal models, thus advancing the current knowledge on the complex dynamic of TB immunity.

Respiratory viruses in HIV-infected patients with suspected respiratory opportunistic infection.

OBJECTIVE: To assess the incidence and epidemiological pattern of respiratory viruses in HIV-infected patients and to evaluate their potential clinical impact. DESIGN AND METHODS: A prospective population-based cohort study was conducted at three Swiss university hospitals. Study participants were HIV-infected patients who underwent a bronchoalveolar lavage to rule out an opportunistic event. All bronchoalveolar lavage specimens were screened using a set of real-time reverse transcriptase-polymerase chain reaction assays targeting 17 different respiratory viruses. RESULTS: Between November 2003 and November 2006, 59 bronchoalveolar episodes from 55 HIV-infected patients were analysed. Eleven of 59 episodes (18.6%) were positive for at least one respiratory virus. Coronavirus OC43 was identified in three cases (27.3%) followed by influenza A in two (18.2%). Parainfluenza virus (PIV) 2, PIV 3, PIV 4, bocavirus, human rhinovirus A and human metapneumovirus were each identified in one case (9%). In the majority of these cases (63.6%) no other concomitant microorganism was isolated. CONCLUSIONS: Clinical investigation of respiratory viral infections in HIV-infected patients should not be restricted to prototype viruses and also need to target all the different family of viruses as it seems likely that these viruses contribute to pulmonary complications and morbidity in this population.

Cellular immune responses against mycobacterium tuberculosis

Mycobacterium tuberculosis (Mtb) infection is known to have two main outcomes: latent infection (LTBI) where the pathogen is in a dormant form or active tuberculosis disease (TB), which is, most of the time, highly transmissible. Over one-third of the world's population asymptomatically harbours a latent form of Mtb with a 10% risk of disease reactivation. Efficient vaccine strategies remain unknown and the existing BCG vaccine is believed to protect against only some forms of TB (extra-pulmonary TB in children). Moreover, timely identification of TB remains complex with the actual diagnosis based on clinical observations associated to low efficient tests. Furthermore, current therapies are expensive, heavy and long for patients, and present lesser and lesser efficiency against new drug-resistant strains of Mtb. It is thus important to develop our knowledge on host -Mtb relationship to propose new vaccines, diagnosis tools and medications for the future. This thesis aims at improving our understanding of human immunology in the field of TB. All along this work, the same algorithm has been used and points towards the discovery of new correlates of protection through the comparison of T-cell immune responses in patients with LTBI or TB. We performed a comprehensive analysis of T-cell immune responses to Mtb using polychromatic flow cytometiy to study the functional profile of Μ/ό-specific CD4 Τ cells. We observed a polyfunctional profile in LTBI where CD4 Τ cells mainly co-produced IFN-γ, TNF-α and IL-2. In contrast, in TB, Mtó-specific CD4 Τ cells were mostly single TNF-a positive. Thus, analysis of the cytokine profiles was a strong immunological measure discriminating TB and LTBI. We next analyzed Thl7 cells. Mtò-specific Thl7 cells lacked immediate {i.e. ex vivo) IL-17A effector function in both LTBI and TB individuals. Moreover, they were also absent in bronchoalveolar lavages (BALs). Interestingly, we noticed that Mtb- specific Thl7 cells from LTBI but not from TB subjects acquired the ability to produce IL- 17A following Mtb-specific T-cell expansion. We finally performed a comprehensive characterization of Mfè-specific CD8 Τ cells that were detected in most (60%) TB patients and few (15%) LTBI subjects. We observed differences in the phenotype, the cytotoxicity and the proliferative capacities but not in the cytokine profile of Mtò-specific CD8 Τ cells between LTBI and TB. We concluded that the activity of Mtb infection (i.e. latent versus active) and the clinical presentation were associated to distinct profiles of Mtó-specific CD8 T-cell responses. To conclude, a multiparametric analysis including both CD4 and CD8 T-cell responses to Mtb lead to the development of a significantly improved diagnostic test discriminating between LTBI and TB. All together, these results provide new insights into the interaction between Mtb and the host immune response and expand upon our prior knowledge of tuberculosis. - L'infection par Mycobacterium tuberculosis peut résulter en une infection tuberculeuse latente et asymptomatique ou encore en une forme active et la plupart du temps contagieuse, la tuberculose. Un tiers de la population mondiale serait infectée de manière chronique avec 10 % de risques de développer la maladie durant la vie. Il n'existe actuellement aucun vaccin efficace, le BCG ne conférant qu'une protection partielle contre certaines formes extrapulmonaires de la maladie chez l'enfant. D'autre part, il n'existe pas de méthode diagnostique fiable et rapide, celle-ci se basant dans un premier temps sur l'analyse de la situation clinique des patients. Enfin, les thérapies actuelles sont couteuses et contraignantes pour les patients et tendent à ne plus être efficaces contre les souches émergentes de mycobactérie multi-résistantes. Aussi, il est important de bien comprendre la relation hôte-pathogène de manière à pouvoir proposer de nouveaux outils vaccinaux, diagnostiques et thérapeutiques. Ce manuscrit s'inscrit dans cette direction et vise à améliorer nos connaissances de la réponse immunitaire humaine dans le cadre de la tuberculose. Nous avons suivi un algorithme similaire tout au long des études proposées en comparant les réponses immunes des patients latents à celles des patients actifs, et ce, dans le but de mettre en évidence de potentiels corrélats de protection. Nous avons réalisé par cytométrie en flux une analyse du profil fonctionnel des cellules lymphocytaires CD4 dans la réponse au pathogène. Dans le cas de la tuberculose active, les cellules CD4 sécrètent majoritairement du TNF-α quand, au contraire, elles sécrètent à la fois du TNF-α, de l'IFN-γ et de l'IL-2 (poly-fonctionnalité) dans l'infection latente. Cette observation nous a permis de proposer un nouveau test diagnostique de la maladie active. Nous avons aussi étudié les cellules CD4 Thl7, impliquées dans la réponse immunitaire cellulaire contre les pathogènes extracellulaires et les champignons. Nous avons souligné une variation dans la production d'IL-17 entre infection latente et tuberculose active qui pourrait être impliquée dans la protection de l'individu contre le pathogène. D'autre part, ce manuscrit propose une caractérisation des cellules Τ CD8 dites cytotoxiques dans la tuberculose. Des divergences dans la fréquence des réponses observées, le phénotype mais aussi les capacités prolifératives et cytotoxiques ont pu être mises en évidence entre latence et tuberculose active. Ces observations soulignent le rôle important de ce groupe cellulaire dans l'évolution de la maladie et permettent de proposer une amélioration de l'outil diagnostic précédemment proposé et se basant à la fois sur le profil fonctionnel des cellules Τ CD4 ainsi que sur la présence potentielle d'une réponse CD8 spécifique au pathogène. Ces diverses études réalisées sur les cellules Τ humaines répondant spécifiquement à Mtb nous permettent de faire un pas supplémentaire dans la compréhension de notre réponse immunitaire face à ce pathogène particulièrement dangereux qui continue à l'heure actuelle à tuer chaque année des millions de personnes. - La tuberculose (TB) résulte d'une infection bactérienne par Mycobacterium tuberculosis (Mtb) et existe sous deux formes majeures: une forme latente, lorsque la bactérie est en phase de dormance ainsi qu'une forme active durant laquelle la bactérie se divise activement, entraînant les symptômes de la maladie. La personne infectée devient alors contagieuse dans la plupart des cas. Aujourd'hui des études épidémiologiques assument que plus d'un tiers de la population mondiale serait infectée par la forme latente de la bactérie et que 10% des cas réactiveront donnant lieu à diverses présentations de la maladie. Il n'existe actuellement aucun vaccin réellement efficace chez l'adulte. D'autre part, les traitements antibiotiques utilisés sont très lourds pour les patients et les cliniciens doivent faire face à l'émergence de nouvelles souches bactériennes multi-résistantes non affectées par les thérapies existantes. Les autorités sanitaires sont, d'autre part, confrontées à l'absence d'un outil diagnostique rapide, fiable et efficace. En effet, la méthode de référence reste la culture microbiologique du pathogène qui prend généralement plusieurs semaines, pendant lesquelles le patient pourra contaminer d'autres personnes. En résumé, la lutte contre la tuberculose doit passer par l'élaboration d'un vaccin efficace, de nouvelles thérapies, mais aussi par la mise en place de nouveaux tests diagnostics plus rapides afin d'éviter la dissémination de la maladie. Aussi, la relation hôte-bactérie qui n'est actuellement que peu comprise doit être investiguée. Ce travail de thèse a pour but d'étudier la réponse immunitaire chez l'homme infecté par Mtb et vise plus particulièrement l'étude d'une population clé de cellules immunitaires: les lymphocytes T. L'étude des cellules Τ CD4 nous a permis dans un premier temps de proposer un nouveau test diagnostic de la maladie active. Nous avons aussi analysé plus en détail une population spécifique des cellules Τ CD4 (les cellules Thl7), nous permettant d'associer leur fonction avec un possible état physiologique de protection contre le pathogène. En second lieu nous avons réalisé une caractérisation des cellules Τ CD8, à la fois chez les personnes avec des infections latentes et chez les personnes malades. Nous avons mis en évidence des différences fonctionnelles chez les deux groupes de patients, nous permettant ainsi une meilleure compréhension de l'immunité contre Mtb. Enfin, nous avons combiné les différents profils immunologiques obtenus pour développer un test diagnostic plus performant et sensible que celui proposé antérieurement. Ces diverses études réalisées sur les cellules Τ humaines nous permettent de faire un pas supplémentaire dans la compréhension de la réponse immunitaire face à ce pathogène particulièrement dangereux qui continue à tuer chaque année des millions de personnes.

QuantiFERON-TB Gold assay for the diagnosis of latent tuberculosis infection.

Tuberculin skin test (TST) has been used for 100 years for the diagnosis of latent tuberculosis (TB) infection (LTBI). In recent years, increasing interest in the diagnosis of TB has led to the development of new assays. QuantiFERON-TB Gold (QFT-G) is an IFN-gamma-release assay that measures the release of interferon after stimulation in vitro by Mycobacterium tuberculosis antigens. The main advantage of this assay with respect to TST is the lack of crossreaction with bacillus Calmette-Guérin and most nontuberculous mycobacteria. QFT-G also eliminates the need for the patient to return for test reading in 48-72 h. In the immunocompromised host and in pediatric populations, studies suggest that the QFT-G better correlates with the risk of TB than the TST, but data remain inconclusive. In contrast to TST, there are no prospective studies regarding the association of the QFT-G result and the risk for development of TB. Given its advantages, the QFT-G may become the standard test for the diagnosis of LTBI.

Comparison of interferon-gamma release assay versus tuberculin skin test for tuberculosis screening in inflammatory bowel disease.

OBJECTIVES: Reactivation of latent tuberculosis (TB) in inflammatory bowel disease (IBD) patients treated with antitumor necrosis factor-alpha medication is a serious problem. Currently, TB screening includes chest x-rays and a tuberculin skin test (TST). The interferon-gamma release assay (IGRA) QuantiFERON-TB Gold In-Tube (QFT-G-IT) shows better specificity for diagnosing TB than the skin test. This study evaluates the two test methods among IBD patients. METHODS: Both TST and IGRA were performed on 212 subjects (114 Crohn's disease, 44 ulcerative colitis, 10 indeterminate colitis, 44 controls). RESULTS: Eighty-one percent of IBD patients were under immunosuppressive therapy; 71% of all subjects were vaccinated with Bacille Calmette Guérin; 18% of IBD patients and 43% of controls tested positive with the skin test (P < 0.0001). Vaccinated controls tested positive more often with the skin test (52%) than did vaccinated IBD patients (23%) (P = 0.011). Significantly fewer immunosuppressed patients tested positive with the skin test than did patients not receiving therapy (P = 0.007); 8% of patients tested positive with the QFT-G-IT test (14/168) compared to 9% (4/44) of controls. Test agreement was significantly higher in the controls (P = 0.044) compared to the IBD group. CONCLUSIONS: Agreement between the two test methods is poor in IBD patients. In contrast to the QFT-G-IT test, the TST is negatively influenced by immunosuppressive medication and vaccination status, and should thus be replaced by the IGRA for TB screening in immunosuppressed patients having IBD.

Cost evaluation and comparison of three decision strategies to revascularize : results of the suspected CAD protocol of the european CMR registry

Background: Cardiac magnetic resonance (CMR) is accepted as a method to assess suspected coronary artery disease (CAD). Nonetheless, invasive coronary angiography (CXA) combined or not with fractional flow reserve (FFR) remains the main diagnostic test to evaluate CAD. Little data exist on the economic impact of the use of these procedures in a population with a low to intermediate pre-test probability. Objective: To compare the costs of 3 decision strategies to revascularize a patient with suspected CAD: 1) strategy guided by CMR 2) hypothetical strategy guided by CXA-FFR, 3) hypothetical strategy guided by CXA alone.

Should pulmonary embolism be suspected in exacerbation of chronic obstructive pulmonary disease?

BACKGROUND: The cause of acute exacerbation of chronic obstructive pulmonary disease (COPD) is often difficult to determine. Pulmonary embolism may be a trigger of acute dyspnoea in patients with COPD. AIM: To determine the prevalence of pulmonary embolism in patients with acute exacerbation of COPD. METHODS: 123 consecutive patients admitted to the emergency departments of two academic teaching hospitals for acute exacerbation of moderate to very severe COPD were included. Pulmonary embolism was investigated in all patients (whether or not clinically suspected) following a standardised algorithm based on d-dimer testing, lower-limb venous ultrasonography and multidetector helical computed tomography scan. RESULTS: Pulmonary embolism was ruled out by a d-dimer value <500 microg/l in 28 (23%) patients and a by negative chest computed tomography scan in 91 (74%). Computed tomography scan showed pulmonary embolism in four patients (3.3%, 95% confidence interval (CI), 1.2% to 8%), including three lobar and one sub-segmental embolisms. The prevalence of pulmonary embolism was 6.2% (n = 3; 95% CI, 2.3% to 16.9%) in the 48 patients who had a clinical suspicion of pulmonary embolism and 1.3% (n = 1; 95% CI, 0.3% to 7.1%) in those not suspected. In two cases with positive computed tomography scan, the venous ultrasonography also showed a proximal deep-vein thrombosis. No other patient was diagnosed with venous thrombosis. CONCLUSIONS: The prevalence of unsuspected pulmonary embolism is very low in patients admitted in the emergency department for an acute exacerbation of their COPD. These results argue against a systematic examination for pulmonary embolism in this population.

Tobacco and tuberculosis

Smoking is not only the most important source of avoidable disability and death, but a risk factor for TB infection, disease and death. Even passive smoking exposure may increase the risk of infection and disease in adults and children exposed to TB. Considering the increase in tobacco consumption in developing countries, where the prevalence of TB is the highest, smoking may be responsible for a large part of the burden of disease. Therefore, medical advice and counselling in smoking cessation is an important activity for all care providers engaged in management of TB

Latent tuberculosis: which test in which situation?

Detection of latent tuberculosis infection (LTBI) is a cost-effective procedure in patients at high risk of developing tuberculosis later and who could benefit from preventive treatment. The commonest situation where screening is indicated is the search for infected contacts of an index case with pulmonary tuberculosis. As a screening procedure the current tendency is to replace the time-honoured tuberculin skin test by one of the new blood tests measuring the release of interferon gamma by sensitised T lymphocytes after stimulation by specific peptides from M. tuberculosis. The main advantage of the new tests is the absence of interference with BCG and non-tuberculous mycobacteria, which confers high specificity on the test. This allows a more selective choice of persons for whom preventive treatment is indicated. Some controversial issues remain, such as sensitivity in children and immunocompromised subjects, the predictive value of the blood test and interpretation of possible changes in test results over time. The technical aspects required for performance of the tests must be considered.

Iowa Tuberculosis Control Program 2014 Annual Report

This report provides a summary of Tuberculosis (TB) in Iowa and the activities and achievements of the TB Control Program and our partners during the 2014 calendar year. This report provides Iowa-specific TB rates, funding sources, and program-specific data, often in ten-year time lines to more accurately reflect trends. Previous reports included TB control efforts by the World Health Organization and the Centers for Disease Control and Prevention. Reports paid tribute to the role TB disease played in the history of man including historical TB treatments, myths, and bygone TB control practices. The 2014 Report does not include these overviews. Please refer to previous reports for this information. The annual report serves as an informational resource for stakeholders, local partners, policy makers and others interested in Iowa’s TB Control efforts.

Lack of Mycobacterium tuberculosis-specific interleukin-17A-producing CD4(+) T cells in active disease.

Protective immunity to Mycobacterium tuberculosis (Mtb) is commonly ascribed to a Th1 profile; however, the involvement of Th17 cells remains to be clarified. Here, we characterized Mtb-specific CD4(+) T cells in blood and bronchoalveolar lavages (BALs) from untreated subjects with either active tuberculosis disease (TB) or latent Mtb infection (LTBI), considered as prototypic models of uncontrolled or controlled infection, respectively. The production of IL-17A, IFN-γ, TNF-α, and IL-2 by Mtb-specific CD4(+) T cells was assessed both directly ex vivo and following in vitro antigen-specific T-cell expansion. Unlike for extracellular bacteria, Mtb-specific CD4(+) T-cell responses lacked immediate ex vivo IL-17A effector function in both LTBI and TB individuals. Furthermore, Mtb-specific Th17 cells were absent in BALs, while extracellular bacteria-specific Th17 cells were identified in gut biopsies of healthy individuals. Interestingly, only Mtb-specific CD4(+) T cells from 50% of LTBI but not from TB subjects acquired the ability to produce IL-17A following Mtb-specific T-cell expansion. Finally, IL-17A acquisition by Mtb-specific CD4(+) T cells correlated with the coexpression of CXCR3 and CCR6, currently associated to Th1 or Th17 profiles, respectively. Our data demonstrate that Mtb-specific Th17 cells are selectively undetectable in peripheral blood and BALs from TB patients.

Tuberculosis screening in patients with psoriasis before antitumour necrosis factor therapy: comparison of an interferon-gamma release assay vs. tuberculin skin test.

BACKGROUND: Antitumour necrosis factor (anti-TNF) treatments may reactivate latent tuberculosis infection (LTBI). For detecting LTBI, the tuberculin skin test (TST) has low sensitivity and specificity. Interferon-gamma release assays (IGRA) have been shown to be more sensitive and specific than TST. OBJECTIVE: To compare the TST and the T-SPOT.TB IGRA for identifying LTBI in patients with psoriasis before anti-TNF treatment. METHODS: A retrospective study was carried out over a 4-year period on patients with psoriasis requiring anti-TNF treatment. All were subjected to the TST, T-SPOT.TB and chest X-ray. Risk factors for LTBI and history of bacillus Calmette-Guérin (BCG) vaccination were recorded. The association of T-SPOT.TB and TST results with risk factors for LTBI was tested through univariate logistic regression models. Agreement between tests was quantified using kappa statistics. Treatment for LTBI was started 1 month before anti-TNF therapy when indicated. RESULTS: Fifty patients were included; 90% had prior BCG vaccination. A positive T-SPOT.TB was strongly associated with a presumptive diagnosis of LTBI (odds ratio 7.43; 95% confidence interval 1.38-39.9), which was not the case for the TST. Agreement between the T-SPOT.TB and TST was poor, kappa = 0.33 (SD 0.13). LTBI was detected and treated in 20% of the patients. In 20% of the cases, LTBI was not retained in spite of a positive TST but a negative T-SPOT.TB. All patients received an anti-TNF agent for a median of 56 weeks (range 20-188); among patients with a positive TST/negative T-SPOT.TB, no tuberculosis was detected with a median follow-up of 64 weeks (44-188). One case of disseminated tuberculosis occurred after 28 weeks of adalimumab treatment in a patient with LTBI in spite of treatment with rifampicin. CONCLUSION: This study is the first to underline the frequency of LTBI in patients with psoriasis (20%), and to support the use of IGRA instead of the TST for its detection. Nevertheless, there is still a risk of tuberculosis under anti-TNF therapy, even if LTBI is correctly diagnosed and treated.

Interferon-gamma release assays for the diagnosis of tuberculosis and tuberculosis infection in HIV-infected adults: a systematic review and meta-analysis.

Background: Despite the widespread use of interferon-gamma release assays (IGRAs), their role in diagnosing tuberculosis and targeting preventive therapy in HIV-infected patients remains unclear. We conducted a comprehensive systematic review to contribute to the evidence-based practice in HIV-infected people. Methodology/Principal Findings: We searched MEDLINE, Cochrane, and Biomedicine databases to identify articles published between January 2005 and July 2011 that assessed QuantiFERON H -TB Gold In-Tube (QFT-GIT) and T-SPOT H .TB (T-SPOT.TB) in HIV-infected adults. We assessed their accuracy for the diagnosis of tuberculosis and incident active tuberculosis, and the proportion of indeterminate results. The search identified 38 evaluable studies covering a total of 6514 HIV-infected participants. The pooled sensitivity and specificity for tuberculosis were 61% and 72% for QFT-GIT, and 65% and 70% for T-SPOT.TB. The cumulative incidence of subsequent active tuberculosis was 8.3% for QFT-GIT and 10% for T-SPOT.TB in patients tested positive (one study each), and 0% for QFT-GIT (two studies) and T-SPOT.TB (one study) respectively in those tested negative. Pooled indeterminate rates were 8.2% for QFT-GIT and 5.9% for T-SPOT.TB. Rates were higher in high burden settings (12.0% for QFT-GIT and 7.7% for T-SPOT.TB) than in low-intermediate burden settings (3.9% for QFT-GIT and 4.3% for T-SPOT.TB). They were also higher in patients with CD4 + T-cell count, 200 (11.6% for QFT-GIT and 11.4% for T-SPOT.TB) than in those with CD4 + T-cell count $ 200 (3.1% for QFT-GIT and 7.9% for T-SPOT.TB). Conclusions/Significance: IGRAs have suboptimal accuracy for confirming or ruling out active tuberculosis disease in HIV-infected adults. While their predictive value for incident active tuberculosis is modest, a negative QFT-GIT implies a very low short- to medium-term risk. Identifying the factors associated with indeterminate results will help to optimize the use of IGRAs in clinical practice, particularly in resource-limited countries with a high prevalence of HIV-coinfection.