A model based on the combination of ifn-γ, ip-10, ferritin and 25-hydroxyvitamin d for discriminating latent from active tuberculosis in children

Altres ajuts: This work was supported by grants from: (i) the Isolana Foundation, (ii) the Maria Francisca de Roviralta Foundation expedient AT/MA 1-19/07/2017, AT/MA 70-27/04/2016, and AT/MA 3-22/10/2014 and (vi) Fundació Recerca i Docència Mútua Terrassa.In recent years, pediatric research on tuberculosis (TB) has focused on addressing new biomarkers with the potential to be used as immunological non-sputum-based methods for the diagnosis of TB in children. The aim of this study was to characterize a set of cytokines and a series of individual factors (ferritin, 25-hydroxyvitamin D [25(OH)D], parasite infections, and nutritional status) to assess different patterns for discriminating between active TB and latent TB infection (LTBI) in children. The levels of 13 cytokines in QuantiFERON-TB Gold In-Tube (QFT-GIT) supernatants were analyzed in 166 children: 74 with active TB, 37 with LTBI, and 55 uninfected controls. All cytokines were quantified using Luminex or ELISA. Ferritin and 25(OH)D were also evaluated using CLIA, and Toxocara canis Ig-G antibodies were detected with a commercial ELISA kit. The combination of IP-10, IFN-γ, ferritin, and 25(OH)D achieved the best diagnostic performance to discriminate between active TB and LTBI cases in children in relation to the area under receiver operating characteristic (ROC) curve 0.955 (confidence interval 95%: 0.91-1.00), achieving optimal sensitivity and specificity for the development of a new test (93.2 and 90.0%, respectively). Children with TB showed higher ferritin levels and an inverse correlation between 25(OH)D and IFN-γ levels. The model proposed includes a combination of biomarkers for discriminating between active TB and LTBI in children to improve the accuracy of TB diagnosis in children. This combination of biomarkers might have potential for identifying the onset of primary TB in children

Tuberculosis infection in children visiting friends and relatives in countries with high incidence of tuberculosis: A study protocol

Introduction: Tuberculosis (TB) is a global infectious disease. In low-incidence countries, paediatric TB affects mostly immigrant children and children of immigrants. We hypothesize that these children are at risk of exposure to Mycobacterium tuberculosis when they travel to the country of origin of their parents to visit friends and relatives (VFR). In this study, we aim to estimate the incidence rate and risk factors associated to latent tuberculosis infection (LTBI) and TB in VFR children. Methods and analysis: A prospective study will be carried out in collaboration with 21 primary health care centres (PCC) and 5 hospitals in Catalonia, Spain. The study participants are children under 15 years of age, either immigrant themselves or born to immigrant parents, who travel to countries with high incidence of TB (≥ 40 cases/100,000 inhabitants). A sample size of 492 children was calculated. Participants will be recruited before traveling, either during a visit to a travel clinic or to their PCC, where a questionnaire including sociodemographic, epidemiological and clinical data will be completed, and a tuberculin skin test (TST) will be performed and read after 48 to 72 hours; patients with a positive TST at baseline will be excluded. A visit will be scheduled eight to twelve-weeks after their return to perform a TST and a QuantiFERON-TB Gold Plus test. The incidence rate of LTBI will be estimated per individual/month and person/year per country visited, and also by age-group

Performance of QuantiFERON-TB Gold Plus assays in children and adolescents at risk of tuberculosis: a cross-sectional multicentre study

Introduction: The QuantiFERON-TB Gold Plus (QFT-Plus) assay, which features two antigen-stimulated tubes (TB1 and TB2) instead of a single tube used in previous-generation interferon-gamma release assays (IGRAs), was launched in 2016. Despite this, data regarding the assay’s performance in the paediatric setting remain scarce. This study aimed to determine the performance of QFT-Plus in a large cohort of children and adolescents at risk of tuberculosis (TB) in a low-burden setting. Methods: Cross-sectional, multicentre study at healthcare institutions participating in the Spanish Paediatric TB Research Network, including patients <18 years who had a QFT-Plus performed between September 2016 and June 2020. Results: Of 1726 patients (52.8% male, median age: 8.4 years), 260 (15.1%) underwent testing during contact tracing, 288 (16.7%) on clinical/radiological suspicion of tuberculosis disease (TBD), 649 (37.6%) during new-entrant migrant screening and 529 (30.6%) prior to initiation of immunosuppressive treatment. Overall, the sensitivity of QFT-Plus for TBD (n=189) and for latent tuberculosis infection (LTBI, n=195) was 83.6% and 68.2%, respectively. The agreement between QFT-Plus TB1 and TB2 antigen tubes was excellent (98.9%, κ=0.961). Only five (2.5%) patients with TBD had discordance between TB1 and TB2 results (TB1+/TB2−, n=2; TB1−/TB2+, n=3). Indeterminate assay results (n=54, 3.1%) were associated with young age, lymphopenia and elevated C reactive protein concentrations. Conclusions: Our non-comparative study indicates that QFT-Plus does not have greater sensitivity than previous-generation IGRAs in children in both TBD and LTBI. In TBD, the addition of the second antigen tube, TB2, does not enhance the assay’s performance substantially

Q-SAPS?: què saben sobre salut pública a l’atenció primària?

Malalties; Declaració obligatòria; Brots epidèmicsEnfermedades; Declaración obligatoria; Brotes epidémicosDiseases; Mandatory declaration; Epidemic outbreaksEl treball d’aquesta comunitat de pràctica (CoP) pretén ajudar a detectar mancances de coneixement sobre la salut pública entre els professionals de l’atenció primària i elaborar un document de propostes per millorar el coneixement referit en aquest àmbit. Amb les següents propostes de valor: 1-Conèixer les funcions de cada actor en les malalties de declaració obligatòria (MDO), emergents i brots epidèmics. 2-Detectar mancances de coneixement i dificultats per a declarar. 3-Saber la utilitat de declarar MDO i brots epidèmics, ja que no és només un simple registre sinó que hi ha una actuació al darrere. 4-Conèixer les actuacions comunitàries que cal fer en cada malaltia per controlar-la, i brots epidèmics.El trabajo de esta comunidad de práctica (CoP) pretende ayudar a detectar carencias de conocimiento sobre la salud pública entre los profesionales de la atención primaria y elaborar un documento de propuestas para mejorar el conocimiento referido en este ámbito. Con las siguientes propuestas de valor: 1-Conocer las funciones de cada actor en las enfermedades de declaración obligatoria (MDO), emergentes y brotes epidémicos. 2-Detectar carencias de conocimiento y dificultades para declarar. 3-Saber la utilidad de declarar EDO y brotes epidémicos, ya que no es sólo un simple registro sino que hay una actuación detrás. 4-Conocer las actuaciones comunitarias a realizar en cada enfermedad para controlarla, y brotes epidémicos.The work of this community of practice (CoP) aims to help detect gaps in knowledge about public health among primary care professionals and prepare a document of proposals to improve the knowledge referred to in this area. With the following value propositions: 1-Know the functions of each actor in notifiable diseases, emerging diseases and epidemic outbreaks. 2-Detect knowledge gaps and difficulties in declaring. 3-Know the usefulness of declaring notifiable diseases and epidemic outbreaks, since it is not just a simple record but there is an action behind it. 4-Know the community actions to be carried out in each disease to control it, and epidemic outbreaks

Factors Associated with Tuberculosis Treatment Default in an Endemic Area of the Brazilian Amazon: A Case Control-Study

SETTING: Treatment default is a serious problem in tuberculosis control because it implies persistence of infection source, increased mortality, increased relapse rates and facilitates the development of resistant strains. OBJECTIVE: This study analyzed tuberculosis treatment default determinants in the Amazonas State to contribute in planning appropriate control interventions. DESIGN: Observational study with a retrospective cohort using Brazilian Disease Notification System data from 2005 to 2010. A nested case control study design was used. Patients defaulting from treatment were considered as 'cases' and those completing treatment as 'controls'. In the analysis, 11,312 tuberculosis patients were included, 1,584 cases and 9,728 controls. RESULTS: Treatment default was observed to be associated to previous default (aOR 3.20; p<0.001), HIV positivity (aOR 1.62; p<0.001), alcoholism (aOR 1.51; p<0.001), low education level (aOR 1.35; p<0.001) and other co-morbidities (aOR 1.31; p = 0.05). Older patients (aOR 0.98; p = 0.001) and DOT (aOR 0,72; p<0.01) were considered as protective factor for default. CONCLUSIONS: Associated factors should be considered in addressing care and policy actions to tuberculosis control. Information on disease and treatment should be intensified and appropriate to the level of education of the population, in order to promote adherence to treatment and counter the spread of multidrug resistance to anti-TB drugs

datosTB105.sav

Prevalence and Diagnosis of Latent Tuberculosis Infection in Young Children in the Absence of a Gold Standard. PlosOne 2016<br

Prevalence and Diagnosis of Latent Tuberculosis Infection in Young Children in the Absence of a Gold Standard.

For adequate disease control the World Health Organization has proposed the diagnosis and treatment of latent tuberculous infection (LTBI) in groups of risk of developing the disease such as children. There is no gold standard (GS) test for the diagnosis of LTBI. The objective of this study was to estimate the prevalence of LTBI in young children in contact with a household case of tuberculosis (TB-HCC) and determine the accuracy and precision of the Tuberculin Skin Test (TST) and QuantiFERON-TB Gold in-tube (QFT) used in the absence of a GS.We conducted a cross-sectional study in children up to 6 years of age in Manaus/Brazil during the years 2009-2010. All the children had been vaccinated with the BCG and were classified into two groups according to the presence of a TB-HCC or no known contact with tuberculosis (TB). The variables studied were: the TST and QFT results and the intensity and length of exposure to the index tuberculosis case. We used the latent class model to determine the prevalence of LTBI and the accuracy of the tests.Fifty percent of the children with TB-HCC had LTBI, with the prevalence depending on the intensity and length of exposure to the index case. The sensitivity and specificity of TST were 73% [95% confidence interval (CI): 53-91] and 97% (95%CI: 89-100), respectively, versus 53% (95%CI: 41-66) and 81% (95%CI:71-90) for QFT. The positive predictive value of TST in children with TB-HCC was 91% (95%CI: 61-99), being 74% for QFT (95%CI: 47-95).This is one of the first studies to estimate the prevalence of LTBI in children and the parameters of the main diagnostic tests using a latent class model. Our results suggest that children in contact with an index case have a high risk of infection. The accuracy and the predictive value of the two tests did not significantly differ. Combined use of the two tests showed scarce improvement in the diagnosis of LTBI

Probability of non LTBI (LTBI^c) in children up to 6 years of age according to the results of both tests in the latent class model (first phase).

<p>Probability of non LTBI (LTBI^c) in children up to 6 years of age according to the results of both tests in the latent class model (first phase).</p

Flow diagram of enrollment.

<p>TB: tuberculosis, QFT: QuantiFERON-TB Gold In-Tube, TST: Tuberculin Skin Test.</p