La pandemia de covid-19 amenaza la lucha contra la tuberculosis

Por primera vez parece posible acabar con la tuberculosis, infección milenaria que causa más de 10 millones enfermos y 1 millón de muertos cada año. Sin embargo, la irrupción de la pandemia de covid-19 amenaza ahora la “Estrategia Fin de la Tuberculosis” de la Organización Mundial de la Salud

Reply to von Reyn and Horsburgh

The study by Muñoz et al [1] demonstrates that the need for treatment of healthy household contacts of active tuberculosis can be safely reduced by 20% when an interferon γ release assay is used to exclude false-positive tuberculin skin test (TST) results. Because the study was conducted in Spain, 28% of trial participants had been previously immunized with Bacille Calmette Guerin (BCG) vaccine, a factor that seemed to be the predominant cause of false-positive TST results. The authors surmise that the remaining proportion of false-positive results may have been due to exposure to nontuberculous mycobacteria (NTM)

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

Editorial: Tuberculosis and non-tuberculous mycobacteria infections: control, diagnosis and treatment

Tuberculosis (TB), is one of the top 10 causes of death worldwide (WHO). According to the last Global TB report from the World Health Organization, 10 million persons were estimated to have had TB in 2019 worldwide, causing about 1.6 million deaths. Tuberculosis has not only a dramatic impact on the quality of life for the patients, but also has raised many socio-economic issues at a community level, especially in medium and high burden regions, such as India, China, and Indonesia. In 2014, WHO adopted the "End TB strategy" which aimed to reduce TB deaths by 90% between 2015 and 2030, to prevent new cases by 80% during the same period and to decrease the socioeconomic impact of the disease at a family level. Even though tuberculosis global incidence has decreased significantly, efforts still need to be made to reach these goals. Non-tuberculous mycobacteria (NTM), in contrast to Mycobacterium tuberculosis, are bacteria widely spread in the environment and can be found in a broad range of ecosystems such as soils and water, including drinking water systems. NTM are opportunistic pathogens associated with both pulmonary and extrapulmonary infections. This Research Topic collected articles addressing: (i) TB and NTMs associated diseases, diagnostic, control, and public health, (ii) mycobacterial genomics, (iii) and antimycobacterial drugs and resistanc

Tumor necrosis factor antagonists for paradoxical inflammatory reactions in the central nervous system tuberculosis: Case report and review

Rationale: Paradoxical reaction/immune reconstitution inflammatory syndrome is common in patients with central nervous system tuberculosis. Management relies on high-dose corticosteroids and surgery when feasible. Patient concern: We describe 2 cases of HIV-negative patients with corticosteroid-refractory paradoxical reactions of central nervous system tuberculosis. Diagnoses: The 2 patients experienced clinical impairment shortly after starting therapy for TB, and magnetic resonance imaging showed the presence of tuberculomas, leading to the diagnosis of a paradoxical reaction. Interventions: We added infliximab, an anti-tumor necrosis factor (TNF)-alpha monoclonal antibody, to the dexamethasone. Outcomes: Both patients had favorable outcomes, 1 achieving full recovery but 1 suffering neurologic sequelae. Lessons: Clinicians should be aware of the risk of paradoxical reactions/immune reconstitution inflammatory syndrome when treating patients with tuberculosis of the central nervous system and should consider the prompt anti-TNF-α agents in cases not responding to corticosteroids

Management of tuberculosis: are the practices homogeneous in high-income countries?

Objectives: to evaluate and compare practices regarding the diagnosis, isolation measures, and treatment of tuberculosis (TB) in high-income countries and mainly in Europe. Materials and Methods: a survey was conducted from November 2018 to April 2019 within the European Society of Clinical Microbiology and Infectious Diseases Study Group for Mycobacterial Infections (ESGMYC). The practices observed were compared to the main international guidelines. Results: among 136 ESGMYC members, 64 (17 countries) responded to the questionnaire. In their practice, two (20.7%) or three sputum samples (79.3%) were collected for the diagnosis of pulmonary TB, alternatively induced sputum (n = 37, 67.2%), bronchoscopy (34, 58.6%), and gastric aspirates (15, 25.9%). Nucleic acid amplification tests (NAATs) were performed by 41 (64%) respondents whatever the smear result and by 47 (73%) in case of smear-positive specimens. NAAT and adenosine deaminase measurement were used for extrapulmonary TB diagnosis in 83.6 and 40.4% of cases, respectively. For isolation duration, 21 respondents (42.9%) were keeping isolation until smear negativity. An initial treatment without ethambutol was offered by 14% (n = 9) of respondents. Corticosteroid therapy, cerebrospinal fluid opening pressure testing, and repeated lumbar puncture were carried out for central nervous system TB by 79.6, 51.9, and 46.3% of the respondents, respectively. For patients with human immunodeficiency virus-TB coinfection, the preferred antiretroviral therapy included dolutegravir 50 mg twice a day (56.8%). Comparing with the recommendations of the main guidelines, the practices are not totally consistent. Conclusion: this study shows heterogeneous practices, particularly for diagnosis, and isolation, although rapid molecular testing is implemented in most centers. More standardization might be needed

Immunodiagnostic tests' predictive values for progression to tuberculosis in transplant recipients. A prospective cohort study

Background: Little is known about the predictive value for progression to tuberculosis (TB) of interferon-γ release assays and how they compare with the tuberculin skin test (TST) in assessing the risk of TB infection in transplant recipients. Methods: We screened 50 liver transplant (LT) and 26 hematopoietic stem cell transplant (HSCT) recipients with both QuantiFERON-TB Gold In-tube (QFT-GT) and TST and prospectively followed them for a median of 47 months without preventive chemoprophylaxis. Results: In the LT cohort, 1 in 22 (4.5%) QFT-GT-positive patients developed posttransplant TB, compared with none of the QFT-GT-negative patients. In the HSCT cohort, none of the 7 QFT-GT-positive patients developed TB, whereas 1 case (5.3%) progressed to active TB among the 19 QFT-GT-negative patients. Comparable results were obtained with the TST: in the LT group, 1 of 23 TST-positive and none of the 27 TST-negative patients developed TB; and in the HSCT group, none of the 8 TST-positive and one of the 18 TST-negative patients progressed to active TB. Conclusions: In this cohort of transplant recipients, the positive predictive value of QFT-GT for progression to active TB was low and comparable to that of TST. Although the risk of developing TB in patients with negative results at baseline is very low, some cases may still occur

Clinical significance of indeterminate QuantiFERON-TB Gold Plus assay results in hospitalized COVID-19 patients with severe hyperinflammatory syndrome

Performance of the QuantiFERON-TB Gold Plus (QFT-Plus) assay could be affected by conditions of immune dysregulation. Little is known about the reliability of QTF-Plus in COVID-19 patients. Our aim was to determine the prevalence and the factors related to an indeterminate QFT-Plus test in COVID-19 hospitalized patients, and to analyze its relationship with in-hospital mortality. A retrospective analysis of all hospitalized COVID-19 patients on whom a QTF-Plus assay was performed in a tertiary care public hospital during the first epidemic wave in Spain (March-April 2020). Out of a total of 96 patients included, 34 (35.4%) had an indeterminate result, in all cases due to a lack of response in the mitogen control. Factors related to COVID-19 severity, such as higher lactate dehydrogenase (LDH) (odds ratio [OR] 1.005 [95% confidence interval [CI] 1.002-1.008]) and previous administration of corticosteroids (OR 4.477 [95% CI 1.397-14.345]), were independent predictors for indeterminate QFT-Plus assay. Furthermore, indeterminate results were more frequent among COVID-19 patients who died during hospitalization (29.1% vs. 64.7%; p = 0.005). We conclude that QFT-Plus assay yielded an unexpected, high prevalence of indeterminate results in severe COVID-19 patients. Factors related to worse COVID-19 outcome, such as LDH, as well as corticosteroid use before the QFT-Plus assay, seem to be predictors for an indeterminate result. The role of an indeterminate QFT-Plus result in predicting COVID-19 severity and mortality should be evaluated

Infectiousness of patients with smear-negative pulmonary tuberculosis, assessed by Real-time Polymerase Chain Reaction, Xpert®MTB/RIF

Currently, pulmonary tuberculosis (TB) isolation recommendations are based on serial sputum smear microscopy. To assess infectiousness of smear-negative/GeneXpert-positive (Sm-/GXpert+) pulmonary TB, we evaluated 511 contacts of pulmonary TB patients attended at a teaching hospital in Spain (2010-2018). There were no statistically significant differences in rates of Mycobacterium tuberculosis infection (46.2% contacts of smear-positive and 34.6% contacts of Sm-/GXpert+ pulmonary TB patients, p=0.112). Sm-/GXpert+ pulmonary TB poses a substantial risk of transmission of M. tuberculosis infection. Our results add evidence to support including Real-time Polymerase Chain Reaction (Xpert®MTB/RIF) in the work-up diagnosis of suspected pulmonary TB cases to make decisions on air-borne isolation

Antimicrobial susceptibility testing of mycobacterium tuberculosis complex isolates - the EUCAST broth microdilution reference method for MIC determination

Scope:Several methods are used worldwide for antibiotic susceptibility testing (AST) for theMycobac-terium tuberculosiscomplex (MTBC). The variability in the results obtained with these methods hamperssetting epidemiological cut-off (ECOFF) values and clinical breakpoints according to EUCAST guidelines.Methods for susceptibility testing and determination of the minimal inhibitory concentrations (MICs)need to be standardized for MTBC isolates for old and new agents. Our objective was to establish astandardized reference method for MIC determination for MTBC.Methods:The EUCAST antimycobacterial susceptibility testing subcommittee (AMST) compared pro-tocols of MIC determination with regard to medium, inoculum preparation, antituberculous agentpreparation, incubation, reading of the results and interpretation.Recommendations:The EUCAST reference method of MIC determination for MTBC is the broth micro-dilution method in Middlebrook 7H9-10% OADC medium. Thefinal inoculum is a 105CFU/mL suspension,obtained from a 10 2dilution of a 0.5 McFarland suspension prepared after vortexing bacterial colonieswith glass beads before suspending them in sterile water. The culture is maintained in a U-shaped 96-well polystyrene microtitre sterile plate with a lid incubated at 36 ±1 C. Reading is done using aninverted mirror as soon as the 1:100 diluted control (i.e. 103CFU/mL suspension) shows visual growth.The MIC, expressed in mg/L, is the lowest concentration that inhibits visual growth.MycobacteriumtuberculosisH37Rv ATCC 27294 is used as the reference strain and its targeted MIC values are within therange 0.03e0.12 for isoniazid, 0.12e0.5 for levofloxacin and 0.25e1 mg/L for amikacin.Conclusions:The EUCAST reference method for MTBC was endorsed by EUCAST after public consultationand will from now on be used to define EUCAST ECOFFs and clinical breakpoints. This reference methodis not primarily intended to be used under routine conditions and the AST methods will need to b