RESUMEN
BACKGROUND: Non-tuberculous mycobacteria (NTM) are generally free-living organism, widely distributed in the environment, with sporadic potential to infect. In recent years, there has been a significant increase in the global incidence of NTM-related disease, spanning across all continents and an increased mortality after the diagnosis has been reported. The decisions on whether to treat or not and which drugs to use are complex and require a multidisciplinary approach as well as patients' involvement in the decision process. METHODS AND RESULTS: This review aims at describing the drugs used for treating NTM-associated diseases emphasizing the efficacy, tolerability, optimization strategies as well as possible drugs that might be used in case of intolerance or resistance. We also reviewed data on newer compounds highlighting the lack of randomised clinical trials for many drugs but also encouraging preliminary data for others. We also focused on non-pharmacological interventions that need to be adopted during care of individuals with NTM-associated diseases CONCLUSIONS: Despite insufficient efficacy and poor tolerability this review emphasizes the improvement in patients' care and the needs for future studies in the field of anti-NTM treatments.
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Antibacterianos , Infecciones por Mycobacterium no Tuberculosas , Micobacterias no Tuberculosas , Humanos , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Infecciones por Mycobacterium no Tuberculosas/microbiología , Micobacterias no Tuberculosas/efectos de los fármacos , Antibacterianos/uso terapéutico , ItaliaRESUMEN
Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a significant global health problem. In immunocompetent individuals, the microorganism can remain in a latent, non-contagious form, however, it may become active under conditions of immunosuppression. Tumour necrosis factor (TNF) inhibitors, which are frequently used for the management of immune-mediated disorders like psoriasis, have been associated with a significantly increased risk of reactivating latent TB. Consequently, international guidelines recommend TB screening and preventive treatment before starting anti-TNF therapy. These recommendations have extended to IL-12/23, IL-17, IL-23 and TYK2 inhibitors under a caution principle, despite their different mechanisms of action. However, current evidence suggests that some of these agents are arguably not associated with an increased risk of TB reactivation or development of TB disease after infection, which calls for a critical reassessment of these guidelines. We have conducted a literature search evaluating the risk of TB reactivation associated with these innovative therapies, integrating findings from both randomized clinical trials and real-world evidence. The identified evidence is limited but the low number of identified cases of reactivation with IL-17 and IL-23 inhibitors prompts reconsidering the need for preventive treatment for latent TB in all cases, regardless of biologic class or individual patient's risk of TB reactivation or drug toxicity. This review, along with the clinical insight of a panel of experts on behalf of the SPIN-FRT, led to the development of these consensus recommendations for managing psoriasis treatment in patients with latent TB infection or at risk of TB infection, who are receiving or are intended to receive biologic and non-biologic targeted therapies. These recommendations highlight the need for updates to the existing guidelines, aiming to provide a more differentiated approach that reflects the evolving landscape of psoriasis treatment and its implications for TB management.
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BACKGROUND: Mycobacterium tuberculosis (MTB), the aetiological agent of tuberculosis (TB), is capable of interfering with the phagosome maturation pathway, by inhibiting phagosome-lysosome fusion and the autophagic process to ensure survival and replication in macrophages. Thus, it has been proposed that the modulation of autophagy may represent a therapeutic approach to reduce MTB viability by enhancing its clearance. OBJECTIVE: The aim of this study was to investigate whether transglutaminase type 2 (TG2) is involved in the pathogenesis of MTB. RESULTS: We have shown that either genetic or pharmacological inhibition of TG2 leads to a marked reduction in MTB replicative capacity. Infection of TG2 knockout mice demonstrated that TG2 is required for MTB intracellular survival in macrophages and host tissues. The same inhibitory effect can be reproduced in vitro using Z-DON, a specific inhibitor of the transamidating activity of TG2. Massive cell death observed in macrophages that properly express TG2 is hampered by the absence of the enzyme and can be largely reduced by the treatment of wild-type macrophages with the TG2 inhibitor. Our data suggest that reduced MTB replication in cells lacking TG2 is due to the impairment of LC3/autophagy homeostasis. Finally, we have shown that treatment of MTB-infected murine and human primary macrophages with cystamine, a TG2 inhibitor already tested in clinical studies, causes a reduction in intracellular colony-forming units in human macrophages similar to that achieved by the anti-TB drug capreomycin. CONCLUSION: These results suggest that inhibition of TG2 activity is a potential novel approach for the treatment of TB.
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Proteínas de Unión al GTP/metabolismo , Mycobacterium tuberculosis/patogenicidad , Transglutaminasas/metabolismo , Tuberculosis/metabolismo , Animales , Autofagia , Western Blotting , Células Cultivadas , Modelos Animales de Enfermedad , Macrófagos/metabolismo , Macrófagos/ultraestructura , Masculino , Ratones , Ratones Endogámicos C57BL , Microscopía Confocal , Microscopía Electrónica de Transmisión , Proteína Glutamina Gamma Glutamiltransferasa 2 , Tuberculosis/microbiología , Tuberculosis/patologíaRESUMEN
Cystic echinococcosis (CE) immunodiagnosis is still imperfect. We recently set-up a whole-blood test based on the interleukin (IL)-4 response to the native Antigen B (AgB) of Echinococcus granulosus. However, AgB is encoded by a multigene family coding for five putative subunits. Therefore, the aims of this study were to analyse the IL-4 response to peptides spanning the immunodominant regions of the five AgB subunits and to evaluate the accuracy of this assay for CE diagnosis. Peptides corresponding to each subunit were combined into five pools. A pool containing all peptides was also used (total pool). IL-4 evaluated by enzyme-linked immunosorbent assay was significantly higher in patients with CE compared to those without (NO-CE subjects) when whole-blood was stimulated with AgB1 and with the total pool. Moreover, IL-4 levels in response to the total pool were significantly increased in patients with active cysts. Receiver Operator Curve analysis identified a cut-off point of 0.59 pg/mL predicting active cysts diagnosis with 71% sensitivity and 82% specificity in serology-positive CE patients. These data, if confirmed in a larger cohort, offer the opportunity to develop new diagnostic tools for CE based on a standardized source of AgB as the peptides.
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Anticuerpos Antihelmínticos/sangre , Antígenos Helmínticos/inmunología , Equinococosis/diagnóstico , Echinococcus granulosus/inmunología , Proteínas del Helminto/inmunología , Interleucina-4/inmunología , Lipoproteínas/inmunología , Adulto , Anciano , Animales , Anticuerpos Antihelmínticos/inmunología , Antígenos Helmínticos/genética , Pruebas Diagnósticas de Rutina/métodos , Equinococosis/inmunología , Equinococosis/parasitología , Ensayo de Inmunoadsorción Enzimática , Femenino , Proteínas del Helminto/genética , Humanos , Pruebas Inmunológicas/métodos , Interleucina-4/sangre , Lipoproteínas/genética , Masculino , Persona de Mediana Edad , Dominios Proteicos/genética , Dominios Proteicos/inmunología , Sensibilidad y EspecificidadRESUMEN
Heparin-binding haemagglutinin (HBHA) has been proposed as an immunological biomarker for discriminating active tuberculosis (TB) from latent TB infection (LTBI) and to identify those at higher risk of progressing to active disease. Few data are available in immune-compromised patients, which are those with increased risk of TB reactivation. The aim of this stusy was to evaluate the immune response to HBHA in HIV-infected subjects with LTBI (HIV-LTBI) or active TB (HIV-TB) in comparison with the immune response to additional Mycobacterium tuberculosis (Mtb) or HIV and CMV antigens. The responses are evaluated in relation to TB status and in the LTBI subjects with the progression to active TB within 2 years. Forty-one HIV-infected antiretroviral-naïve subjects were prospectively enrolled: 18 were HIV-TB and 23 HIV-LTBI. Whole blood was in vitro stimulated overnight with several antigens and mitogen. Interferon-γ response in the harvested plasma was evaluated by ELISA. Despite that CD4 cell count was significantly different between HIV-LTBI and HIV-TB, no differences were observed in response to Mtb- or HIV-specific antigens. Differently, low responses to HBHA were observed in both HIV-LTBI and HIV-TB subjects. Importantly, none of the six HIV-LTBI responding to HBHA developed TB, while two of 17 non-HBHA responders developed active disease. HIV-TB-coinfected subjects, regardless of their TB status, showed low responses to HBHA despite maintaining detectable responses to other antigens; moreover, among the HIV-LTBI, the lack of HBHA responses indicated an increased risk to develop active TB. These results, although preliminary, suggest that a positive response to HBHA in HIV-LTBI correlates with Mtb containment.
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Proteínas Bacterianas/inmunología , Infecciones por VIH/diagnóstico , Huésped Inmunocomprometido/inmunología , Tuberculosis Latente/diagnóstico , Proteínas de la Membrana/inmunología , Mycobacterium tuberculosis/inmunología , Tuberculosis Pulmonar/diagnóstico , Adulto , Biomarcadores/sangre , Células Cultivadas , Diagnóstico Diferencial , Femenino , Estudios de Seguimiento , Antígenos VIH/inmunología , Infecciones por VIH/complicaciones , Humanos , Interferón gamma/sangre , Tuberculosis Latente/complicaciones , Activación de Linfocitos , Masculino , Pronóstico , Estudios Prospectivos , RiesgoRESUMEN
Caused by Mycobacterium tuberculosis, TB is the leading cause of death from an infectious disease. HIV and diabetes are recognised risk factors for progression of TB disease and both have a strong impact on the diagnosis and management of TB, threatening efforts to end TB globally. Here we provide the latest data on the complex interplay between these conditions. TB patients with HIV present systemic immune activation, increased HIV viral load, more severe clinical presentations and reduced success of TB therapy. Similarly, TB patients with diabetes are characterised by an exaggerated adaptive immunity, worsening of the clinical presentations and a higher risk for multidrug resistance and treatment failure. It is important to strengthen resources to prevent these comorbidities from occurring and to implement screening, early diagnosis and appropriate management strategies.
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Diabetes Mellitus , Infecciones por VIH , Mycobacterium tuberculosis , Tuberculosis , Humanos , Tuberculosis/diagnóstico , Tuberculosis/tratamiento farmacológico , Tuberculosis/epidemiología , Factores de Riesgo , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiología , Infecciones por VIH/complicaciones , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Antituberculosos/uso terapéuticoRESUMEN
BACKGROUND: Tuberculosis (TB) preventive therapy (TPT) decreases the risk of developing TB disease and its associated morbidity and mortality. The aim of these clinical standards is to guide the assessment, management of TB infection (TBI) and implementation of TPT.METHODS: A panel of global experts in the field of TB care was identified; 41 participated in a Delphi process. A 5-point Likert scale was used to score the initial standards. After rounds of revision, the document was approved with 100% agreement.RESULTS: Eight clinical standards were defined: Standard 1, all individuals belonging to at-risk groups for TB should undergo testing for TBI; Standard 2, all individual candidates for TPT (including caregivers of children) should undergo a counselling/health education session; Standard 3, testing for TBI: timing and test of choice should be optimised; Standard 4, TB disease should be excluded prior to initiation of TPT; Standard 5, all candidates for TPT should undergo a set of baseline examinations; Standard 6, all individuals initiating TPT should receive one of the recommended regimens; Standard 7, all individuals who have started TPT should be monitored; Standard 8, a TBI screening and testing register should be kept to inform the cascade of care.CONCLUSION: This is the first consensus-based set of Clinical Standards for TBI. This document guides clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage TBI.
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Tuberculosis Latente , Tuberculosis , Cuidadores , Niño , Humanos , Tamizaje Masivo , Estándares de Referencia , Tuberculosis/diagnóstico , Tuberculosis/prevención & controlRESUMEN
We conducted a systematic review and meta-analysis to compare the accuracy of the QuantiFERON-TB® Gold In-Tube (QFT-G-IT) and the T-SPOT®.TB assays with the tuberculin skin test (TST) for the diagnosis of latent Mycobacterium tuberculosis infection (LTBI). The Medline, Embase and Cochrane databases were explored for relevant articles in November 2009. Specificities, and negative (NPV) and positive (PPV) predictive values of interferon-γ release assays (IGRAs) and the TST, and the exposure gradient influences on test results among bacille Calmette-Guérin (BCG) vaccinees were evaluated. Specificity of IGRAs varied 98-100%. In immunocompetent adults, NPV for progression to tuberculosis within 2 yrs were 97.8% for T-SPOT®.TB and 99.8% for QFT-G-IT. When test performance of an immunodiagnostic test was not restricted to prior positivity of another test, progression rates to tuberculosis among IGRA-positive individuals followed for 19-24 months varied 8-15%, exceeding those reported for the TST (2-3%). In multivariate analyses, the odd ratios for TST positivity following BCG vaccination varied 3-25, whereas IGRA results remained uninfluenced and IGRA positivity was clearly associated with exposure to contagious tuberculosis cases. IGRAs may have a relative advantage over the TST in detecting LTBI and allow the exclusion of M. tuberculosis infection with higher reliability.
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Interferón gamma/metabolismo , Tuberculosis Latente/diagnóstico , Infecciones por Mycobacterium/diagnóstico , Infecciones por Mycobacterium/microbiología , Mycobacterium tuberculosis/metabolismo , Tuberculosis/diagnóstico , Tuberculosis/microbiología , Algoritmos , Vacuna BCG , Ensayos Clínicos como Asunto , Humanos , Análisis Multivariante , Oportunidad Relativa , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Prueba de TuberculinaRESUMEN
Vaccine strategies aimed at blocking virus entry have so far failed to induce protection against heterologous viruses. Thus, the control of viral infection and the block of disease onset may represent a more achievable goal of human immunodeficiency virus (HIV) vaccine strategies. Here we show that vaccination of cynomolgus monkeys with a biologically active HIV-1 Tat protein is safe, elicits a broad (humoral and cellular) specific immune response and reduces infection with the highly pathogenic simian-human immunodeficiency virus (SHIV)-89.6P to undetectable levels, preventing the CD4+ T-cell decrease. These results may provide new opportunities for the development of a vaccine against AIDS.
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Vacunas contra el SIDA/inmunología , Productos del Gen tat/inmunología , VIH-1/inmunología , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Síndrome de Inmunodeficiencia Adquirida del Simio/terapia , Vacunas contra el SIDA/genética , Animales , Formación de Anticuerpos , Linfocitos T CD4-Positivos/virología , Inmunidad Celular , Macaca fascicularis , Virus de la Inmunodeficiencia de los Simios/inmunología , Virus de la Inmunodeficiencia de los Simios/patogenicidad , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/metabolismo , Vacunación , Replicación Viral/inmunología , Productos del Gen tat del Virus de la Inmunodeficiencia HumanaRESUMEN
We report preventive measures adopted after tuberculosis(TB) transmission from a nurse to a newborn assessed in late July 2011. All exposed neonates born between January and July 2011 were clinically evaluated and tested by QuantiFERON TB gold in-tube; newborns testing positive were referred for prophylaxis.Of 1,340 newborns, 118 (9%) tested positive and no other active cases of TB were found. Active surveillance for TB will be continued over the next three years for all those exposed.
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Brotes de Enfermedades , Hospitales Pediátricos , Hospitales Universitarios , Transmisión de Enfermedad Infecciosa de Profesional a Paciente , Enfermería Maternoinfantil , Servicio de Ginecología y Obstetricia en Hospital , Tuberculosis Pulmonar/transmisión , Tuberculosis Esplénica/transmisión , Adulto , Antituberculosos/uso terapéutico , Trazado de Contacto , Salud de la Familia , Femenino , Humanos , Inmunidad Celular , Lactante , Recién Nacido , Transmisión de Enfermedad Infecciosa de Profesional a Paciente/prevención & control , Interferón gamma/metabolismo , Masculino , Tamizaje Masivo , Mycobacterium tuberculosis/aislamiento & purificación , Vigilancia de la Población , Embarazo , Ciudad de Roma/epidemiología , Esputo/microbiología , Prueba de Tuberculina , Tuberculosis Pulmonar/epidemiología , Tuberculosis Pulmonar/prevención & control , Tuberculosis Esplénica/prevención & controlRESUMEN
Evidence is accumulating on the interaction between tuberculosis (TB) and COVID-19. The aim of the present review is to report the available evidence on the interaction between these two infections. Differences and similarities of TB and COVID-19, their immunological features, diagnostics, epidemiological and clinical characteristics and public health implications are discussed. The key published documents and guidelines on the topic have been reviewed. Based on the immunological mechanism involved, a shared dysregulation of immune responses in COVID-19 and TB has been found, suggesting a dual risk posed by co-infection worsening COVID-19 severity and favouring TB disease progression. The available evidence on clinical aspects suggests that COVID-19 happens regardless of TB occurrence either before, during or after an active TB diagnosis. More evidence is required to determine if COVID-19 may reactivate or worsen active TB disease. The role of sequeale and the need for further rehabilitation must be further studied Similarly, the potential role of drugs prescribed during the initial phase to treat COVID-19 and their interaction with anti-TB drugs require caution. Regarding risk of morbidity and mortality, several risk scores for COVID-19 and independent risk factors for TB have been identified: including, among others, age, poverty, malnutrition and co-morbidities (HIV co-infection, diabetes, etc.). Additional evidence is expected to be provided by the ongoing global TB/COVID-19 study.
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COVID-19/epidemiología , Coinfección/epidemiología , Salud Pública/métodos , Tuberculosis/epidemiología , COVID-19/patología , Coinfección/patología , Comorbilidad , Humanos , SARS-CoV-2 , Tuberculosis/patologíaRESUMEN
Infection with HIV is the greatest risk factor for tuberculosis (TB) in Africa. Tuberculin skin test (TST), QuantiFERON-TB Gold In-Tube (QFT-G-IT) and T-Spot.TB assays were performed in newly diagnosed HIV-infected individuals with and without active TB and in HIV-uninfected subjects at a university outpatient clinic in Kampala, Uganda. A total of 135 individuals were enrolled: 109 with a new diagnosis of HIV-1 infection but no active TB, 19 with HIV-1 infection and active TB, and seven HIV-uninfected healthy subjects. In control subjects immune responses were positive in 57.2% by TST and in 100% by at least one interferon-gamma release assay. In HIV-1 infected patients without active TB, induration in the TST (mm) (rho = 0.41, p-value <0.0001) and concentration of interferon (IFN)-gamma in the QFT-G-IT tube with Mycobacterium tuberculosis-specific antigens (rho = 0.38; p = 0.0001) were negatively correlated to numbers of circulating CD4+ T-cells, while numbers of IFN-gamma producing cells (rho = 0.03-0.13; p-value = 0.21-0.77) and frequencies of positive test results for the T-Spot.TB test among groups of patients with different levels of immunodeficiency remained constant (p-value = 0.46). In HIV-1 infection, TST and QFT-G-IT immune responses are both strongly related to the degree of immunodeficiency, while results of the T-Spot.TB are independent of the level of CD4+ T-cell depletion.
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Recuento de Linfocito CD4 , Infecciones por VIH/inmunología , Interferón gamma/análisis , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/inmunología , Adulto , Estudios de Casos y Controles , Femenino , Infecciones por VIH/complicaciones , Humanos , Tuberculosis Latente/complicaciones , Masculino , Juego de Reactivos para Diagnóstico , Sensibilidad y Especificidad , Prueba de Tuberculina , Carga ViralRESUMEN
Interferon-gamma release assays based on region of difference 1 antigens have improved diagnosis of latent tuberculosis infection (LTBI). However, these tests cannot discriminate between recently acquired infection (higher risk of progression to active tuberculosis) and remote LTBI. The objective of the present study was to evaluate the T-cell interferon-gamma responses to Mycobacterium tuberculosis DosR-regulon-encoded antigens (latency antigens) compared with QuantiFERON TB-Gold In-Tube (QFT-GIT) in subjects at different stages of tuberculosis. A total of 16 individuals with remote LTBI and 23 with recent infection were studied; 15 controls unexposed to M. tuberculosis and 50 patients with active tuberculosis and 45 with cured tuberculosis were also analysed. The results indicated that subjects with remote LTBI showed significantly higher whole-blood interferon-gamma responses to M. tuberculosis latency antigen Rv2628 than did individuals with recent infection, active tuberculosis and controls (p<0.003), whereas no significant differences between these groups were found for other latency antigens tested (Rv2626c, Rv2627c, Rv2031c and Rv2032). The proportion of responders to Rv2628 was five-fold higher among QFT-GIT-positive-individuals with remote infection than among those with recently acquired infection. These data suggest that responses to M. tuberculosis latency antigen Rv2628 may associate with immune-mediated protection against tuberculosis. In contact-tracing investigations, these preliminary data may differentiate recent (positive QFT-GIT results without responses to Rv2628) from remote infection (positive to both tests).
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Antígenos Bacterianos/inmunología , Tuberculosis Latente/diagnóstico , Mycobacterium tuberculosis/inmunología , Adulto , Proteínas Bacterianas/genética , Proteínas Bacterianas/inmunología , Proteínas de Unión al ADN , Femenino , Humanos , Interferón gamma/inmunología , Tuberculosis Latente/tratamiento farmacológico , Tuberculosis Latente/inmunología , Proteínas Quinasas/genética , Proteínas Quinasas/inmunología , Linfocitos T/inmunologíaRESUMEN
Anti-tumour necrosis factor (TNF) monoclonal antibodies or soluble TNF receptors have become an invaluable treatment against chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease and psoriasis. Individuals who are treated with TNF antagonists are at an increased risk of reactivating latent infections, especially tuberculosis (TB). Following TNF antagonist therapy, the relative risk for TB is increased up to 25 times, depending on the clinical setting and the TNF antagonist used. Interferon-γ release assays or, as an alternative in individuals without a history of bacille Calmette-Guérin vaccination, tuberculin skin testing is recommended to screen all adult candidates for TNF antagonist treatment for the presence of latent infection with Mycobacterium tuberculosis. Moreover, paediatric practice suggests concomitant use of both the tuberculin skin test and an interferon-γ release assay, as there are insufficient data in children to recommend one test over the other. Consequently, targeted preventive chemotherapy is highly recommended for all individuals with persistent M. tuberculosis-specific immune responses undergoing TNF antagonist therapy as it significantly reduces the risk of progression to TB. This TBNET consensus statement summarises current knowledge and expert opinions and provides evidence-based recommendations to reduce the TB risk among candidates for TNF antagonist therapy.
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Anticuerpos Monoclonales/efectos adversos , Mycobacterium tuberculosis/inmunología , Tuberculosis Pulmonar/epidemiología , Tuberculosis Pulmonar/inmunología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Antiinflamatorios/efectos adversos , Antirreumáticos/efectos adversos , Humanos , Huésped Inmunocomprometido , Factores de RiesgoRESUMEN
Little is known about the relationship between the COVID-19 and tuberculosis (TB). The aim of this study is to describe a group of patients who died with TB (active disease or sequelae) and COVID-19 in two cohorts. Data from 49 consecutive cases in 8 countries (cohort A) and 20 hospitalised patients with TB and COVID-19 (cohort B) were analysed and patients who died were described. Demographic and clinical variables were retrospectively collected, including co-morbidities and risk factors for TB and COVID-19 mortality. Overall, 8 out of 69 (11.6%) patients died, 7 from cohort A (14.3%) and one from cohort B (5%). Out of 69 patients 43 were migrants, 26/49 (53.1%) in cohort A and 17/20 (85.0%) in cohort B. Migrants: (1) were younger than natives; in cohort A the median (IQR) age was 40 (27-49) VS. 66 (46-70) years, whereas in cohort B 37 (27-46) VS. 48 (47-60) years; (2) had a lower mortality rate than natives (1/43, 2.3% versus 7/26, 26.9%; p-value: 0.002); (3) had fewer co-morbidities than natives (23/43, 53.5% versus 5/26-19.2%) natives; p-value: 0.005). The study findings show that: (1) mortality is likely to occur in elderly patients with co-morbidities; (2) TB might not be a major determinant of mortality and (3) migrants had lower mortality, probably because of their younger age and lower number of co-morbidities. However, in settings where advanced forms of TB frequently occur and are caused by drug-resistant strains of M. tuberculosis, higher mortality rates can be expected in young individuals.
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Coinfección/mortalidad , Infecciones por Coronavirus/mortalidad , Neumonía Viral/mortalidad , Migrantes/estadística & datos numéricos , Tuberculosis Pulmonar/mortalidad , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Antimaláricos/uso terapéutico , Antituberculosos/uso terapéutico , Betacoronavirus , COVID-19 , Estudios de Cohortes , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/terapia , Femenino , Humanos , Hidroxicloroquina/uso terapéutico , Tiempo de Internación , Masculino , Persona de Mediana Edad , Ventilación no Invasiva , Terapia por Inhalación de Oxígeno , Pandemias , Neumonía Viral/complicaciones , Neumonía Viral/terapia , Estudios Retrospectivos , SARS-CoV-2 , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/tratamiento farmacológicoRESUMEN
Screening for active tuberculosis (TB) and latent TB infection (LTBI) is mandatory prior to the initiation of tumour necrosis factor-alpha inhibitor therapy. However, no agreement exists on the best strategy for detecting LTBI in this population. The aim of the present study was to analyse the performance of the tuberculin skin test (TST) and QuantiFERON-TB Gold in-tube (QFT-GIT) on LTBI detection in subjects with immunomediated inflammatory diseases (IMID). The TST and QFT-GIT were prospectively performed in 398 consecutive IMID subjects, 310 (78%) on immunosuppressive therapy and only 16 (4%) had been bacillus Calmette-Guérin (BCG) vaccinated. Indeterminate results to QFT-GIT were found in five (1.2%) subjects. Overall, 74 (19%) out of 393 subjects were TST-positive and 52 (13%) were QFT-GIT-positive. Concordance between TST and QFT-GIT results was good (87.7%): 13 were QFT-GIT-positive/TST-negative and 35 QFT-GIT-negative/TST-positive. By multivariate analysis both tests were significantly associated with older age. Only the TST was associated with BCG vaccination and radiological lesions of past TB. Use of immunosuppressive drugs differently modulated QFT-GIT or TST scoring. Use of the QuantiFERON-TB Gold in-tube, as a screening tool for latent tuberculosis among immunomediated inflammatory disease subjects, is feasible. Until further data will elucidate discordant tuberculin skin test/QuantiFERON-TB Gold in-tube results, a strategy of simultaneous tuberculin skin and QuantiFERON-TB Gold in-tube testing in a low prevalence bacillus Calmette-Guérin vaccinated population, should maximise potentials of latent tuberculosis diagnosis.
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Enfermedades Autoinmunes/sangre , Enfermedades Autoinmunes/complicaciones , Prueba de Tuberculina/instrumentación , Prueba de Tuberculina/métodos , Tuberculosis/complicaciones , Tuberculosis/inmunología , Adulto , Anciano , Enfermedades Autoinmunes/diagnóstico , Vacuna BCG/inmunología , Femenino , Humanos , Inmunosupresores/uso terapéutico , Inflamación , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Prospectivos , Tuberculosis/diagnóstico , Factor de Necrosis Tumoral alfa/biosíntesisRESUMEN
Tuberculosis control relies on the identification and preventive treatment of individuals who are latently infected with Mycobacterium tuberculosis. However, direct identification of latent tuberculosis infection is not possible. The diagnostic tests used to identify individuals latently infected with M. tuberculosis, the in vivo tuberculin skin test and the ex vivo interferon-gamma release assays (IGRAs), are designed to identify an adaptive immune response against, but not necessarily a latent infection with, M. tuberculosis. The proportion of individuals who truly remain infected with M. tuberculosis after tuberculin skin test or IGRA conversion is unknown. It is also uncertain how long adaptive immune responses towards mycobacterial antigens persist in the absence of live mycobacteria. Clinical management and public healthcare policies for preventive chemotherapy against tuberculosis could be improved, if we were to gain a better understanding on M. tuberculosis latency and reactivation. This statement by the TBNET summarises knowledge and limitations of the currently available tests used in adults and children for the diagnosis of latent tuberculosis infection. In summary, the main issue regarding testing is to restrict it to those who are known to be at higher risk of developing tuberculosis and who are willing to accept preventive chemotherapy.
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Pruebas Inmunológicas/métodos , Mycobacterium tuberculosis/inmunología , Selección de Paciente , Tuberculosis/diagnóstico , Tuberculosis/inmunología , Antígenos Bacterianos , Antituberculosos/farmacología , Trazado de Contacto , Medicina Basada en la Evidencia , Humanos , Tamizaje Masivo/métodos , Técnicas de Diagnóstico Molecular , Valor Predictivo de las Pruebas , Prueba de Tuberculina , Tuberculosis/tratamiento farmacológico , Tuberculosis/transmisiónRESUMEN
Forkhead box P3 (FoxP3) is a transcription factor whose expression characterizes regulatory T cells (T(reg)), but it is also present on activated T cells, thus hindering correct T(reg) identification. Using classical markers for T(reg) recognition, discordant results were found in terms of T(reg) expansion during active tuberculosis (TB) disease. Recently CD39 has been shown to be an accurate marker for T(reg) detection. The objectives of this study were: (i) to identify T(reg) expressing CD39 in patients with TB and to compare the results with those obtained by the standard phenotypic markers; (ii) to evaluate if T(reg) are expanded in vitro by exogenous interleukin (IL)-2 or by antigen-specific stimulation; and (iii) to characterize T(reg) function on the modulation of antigen-specific responses. We enrolled 13 patients with pulmonary TB and 12 healthy controls. T(reg) were evaluated by flow cytometry ex vivo and after antigen-specific in vitro stimulation using CD25, FoxP3, CD127 and CD39 markers. Results indicate that CD39(+) cells within the CD4(+)CD25(high) cells have T(reg) properties (absence of interferon-gamma production and transforming growth factor-beta1 release upon stimulation). Ex vivo analysis did not show significant differences between TB patients and controls of T(reg) by classical or novel markers. In contrast, a significantly higher percentage of T(reg) was found in TB patients after antigen-specific stimulation both in the presence or absence of IL-2. Depletion of CD39(+) T(reg) increased RD1-specific responses significantly. In conclusion, CD39 is an appropriate marker for T(reg) identification in TB. These results can be useful for future studies to monitor Mycobacterium tuberculosis-specific response during TB.
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Antígenos CD/análisis , Apirasa/análisis , Subgrupos de Linfocitos T/inmunología , Linfocitos T Reguladores/inmunología , Tuberculosis Pulmonar/inmunología , Adulto , Anciano , Proteínas Bacterianas/inmunología , Biomarcadores/análisis , Células Cultivadas , Citocinas/biosíntesis , Femenino , Humanos , Inmunofenotipificación , Interleucina-2/inmunología , Subunidad alfa del Receptor de Interleucina-2/análisis , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
The evaluation of diagnostic accuracy of new in vitro diagnostic assays for tuberculosis infection has been hampered by the lack of a standard reference test. The aim of this study was to compare sensitivity and specificity of interferon gamma assays for latent tuberculosis infection by assessing the association of test results with tuberculosis occupational exposure and by using latent class analysis. We analysed data from 115 healthcare workers on whom tuberculin skin test (TST) and the following in vitro tests were performed: in-house ELISPOT for RD1 proteins, T.SPOT-TB and Quantiferon-TB Gold. Results of all tests were associated with increased occupational risk of exposure to Mycobacterium tuberculosis, but only TST was associated with Bacillus Calmette-Guerin (BCG) vaccination. Sensitivity/specificity (95% confidence intervals) estimated by a latent class model were: 99.9%/64.2% (53.0-74.1) for TST, 95.3% (61.8-99.6)/87.5% (78.0-93.2) for in-house ELISPOT, 96.7% (69.3-99.7)/85.6%(75.3-92.0) for T.SPOT-TB, and 76.3% (55.9-89.1)/93.6% (85.4-97.3) for Quantiferon. The estimated specificity of in vitro assays was higher than that of TST also among individuals who were not BCG-vaccinated. In conclusion, when used in healthcare workers, in vitro assays may provide a significant increase of specificity for tuberculosis infection compared to TST, even among non vaccinated individuals, at the cost of some sensitivity.
Asunto(s)
Interferón gamma/sangre , Cuerpo Médico , Tuberculosis/sangre , Tuberculosis/diagnóstico , Adulto , Femenino , Humanos , Italia , Masculino , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
OBJECTIVES: We examined the data reported in studies for diagnostic purposes and to discuss whether their intended use could be extended to triage, as rule-in or rule-out tests to select individuals who should undergo further confirmatory tests. METHODS: We searched Scopus, PubMed and Web of Science with the terms 'acute phase proteins,' 'IP-10,' 'tuberculosis,' 'screening' and 'diagnosis,' extracted the sensitivity and specificity of the biomarkers and explored methodologic differences to explain performance variations. Summary estimates were calculated using random-effects models for overall pooled accuracy. The hierarchical summary receiver operating characteristic model was used for meta-analysis. RESULTS: We identified 14, four and one studies for C-reactive protein (CRP), interferon γ-induced protein 10 (IP-10) and alpha-1-acid glycoprotein (AGP). The pooled CRP sensitivity/specificity (95% confidence interval) was 89% (80-96) and 57% (36-65). Sensitivity/specificity were higher in high-tuberculosis-burden countries (90%/64%), HIV-infected individuals (91%/61%) and community-based studies (90%/62%). IP-10 sensitivity/specificity in TB vs. non-TB studies was 85%/63% and in TB and HIV coinfected vs. other lung conditions 94%/21%. However, IP-10 studies included diverse populations and a high risk of bias, resulting in very low-quality evidence. AGP had 86%/93% sensitivity/specificity. CONCLUSIONS: Few studies have evaluated CRP, IP-10 and AGP for the triage of symptomatic patients. Their high sensitivity and moderate specificity warrant further prospective studies exploring whether their combined use could optimize performance.