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Tuberculosis (TB) is a major cause of morbidity and mortality in children, and early diagnosis and treatment are crucial to reduce long-term morbidity and mortality. In this study, we explore whether urine nuclear magnetic resonance (NMR)-based metabolomics could be used to identify differences in the metabolic response of children with different diagnostic certainty of TB. We included 62 children with signs and symptoms of TB and 55 apparently healthy children. Six of the children with presumptive TB had bacteriologically confirmed TB, 52 children with unconfirmed TB, and 4 children with unlikely TB. Urine metabolic fingerprints were identified using high- and low-field proton NMR platforms and assessed with pattern recognition techniques such as principal components analysis and partial least squares discriminant analysis. We observed differences in the metabolic fingerprint of children with bacteriologically confirmed and unconfirmed TB compared to children with unlikely TB (p = 0.041 and p = 0.013, respectively). Moreover, children with unconfirmed TB with X-rays compatible with TB showed differences in the metabolic fingerprint compared to children with non-pathological X-rays (p = 0.009). Differences in the metabolic fingerprint in children with different diagnostic certainty of TB could contribute to a more accurate characterisation of TB in the paediatric population. The use of metabolomics could be useful to improve the prediction of TB progression and diagnosis in children.

Introduction: The aim of this project was to evaluate the psychopathological impact of home confinement and school closing between March and September 2020 on the mental health of Catalonian children. Methods: PEDSAME study: first cross-sectional section (beginning of the school year) and retrospective data (lockdown), carried out through the network of Primary Care pediatricians in the Catalan population between 5 and 14 years (included) from 09/14/2020 to 10/30/2020 in a random sample. Data were collected with an online survey through the RedCap platform at the beginning of the school year. The main variable was the result of the Strengths and Difficulties Questionnaire answered by parents to assess the risk of psychopathology, in addition to other related variable. Results: The results obtained at the beginning of the school year show that 9.8% of the patients were probable cases of psychopathology. The most affected group were those between 5 and 8 years. The perception of the children's level of concern for their health and that of their family was a risk factor for presenting psychopathology, while the good family environment was a protective factor. Emotional and behavioral symptoms, sleep disorders and problematic use of screens were detected more frequently during confinement than at the beginning of the school year. Conclusions: Confinement and the absence of schooling for 6 months had a negative impact on the mental health of the child–adolescent population who showed worse indicators than the previous year. Resumen: Introducción: El objetivo de este proyecto fue evaluar el impacto psicopatológico del confinamiento domiciliario y cierre escolar entre marzo y septiembre 2020 en la población pediátrica catalana. Métodos: Estudio PEDSAME: primer corte transversal (inicio de curso escolar) y datos retrospectivos (periodo de confinamiento), realizado a través de la red de pediatras de atención primaria en población catalana entre 5 y 14 años (incluidos) del 14/09/2020 al 30/10/2020 en una muestra aleatoria. Los datos fueron recogidos con una encuesta on line a través de la plataforma RedCap al inicio del curso. La variable principal fue el resultado del cuestionario Strengths and Difficulties Questionnaire contestado por los progenitores para evaluar el riesgo de psicopatología, además de otras variables relacionadas. Resultados: Los resultados obtenidos al inicio del curso escolar mostraron que el 9,8% de los pacientes eran casos probables de psicopatología. La franja más afectada fue la de los 5 a 8 años. La percepción del nivel de preocupación de los niños por su salud y la de su familia fue un factor de riesgo de presentar psicopatología, mientras que el buen ambiente familiar resultó protector. Durante el confinamiento se detectaron con mayor frecuencia síntomas emocionales, de conducta, trastornos del sueño y uso problemático de pantallas respecto al inicio del curso escolar. Conclusiones: El confinamiento y la ausencia de escolarización durante 6 meses supusieron un impacto negativo en la salud mental de la población infantojuvenil, con peores indicadores que el curso anterior.

Dientamoeba fragilis is a trichomonad parasite of the human intestine that is found worldwide. However, the biological cycle and transmission of this parasite have yet to be elucidated. Although its pathogenic capacity has been questioned, there is increasing evidence that clinical manifestations vary greatly. Different therapeutic options with antiparasitic drugs are currently available; however, very few studies have compared the effectiveness of these drugs. In the present longitudinal study, we evaluate 13,983 copro-parasitological studies using light microscopy of stools, during 2013–2015, in Terrassa, Barcelona (Spain). A total of 1150 (8.2%) presented D. fragilis. Of these, 739 episodes were finally analyzed: those that involved a follow-up parasitology test up to 3 months later, corresponding to 586 patients with gastrointestinal symptoms (53% under 15 years of age). Coinfection by Blastocystis hominis was present in 33.6% of the subjects. Our aim was to compare therapeutic responses to different antiparasitic drugs and the factors associated with the persistence of D. fragilis post-treatment. Gender, age, and other intestinal parasitic coinfections were not associated with parasite persistence following treatment. Metronidazole was the therapeutic option in most cases, followed by paromomycin: 65.4% and 17.5% respectively. Paromomycin was found to be more effective at eradicating parasitic infection than metronidazole (81.8% vs. 65.4%; p = 0.007), except in children under six years of age (p = 0.538). Although Dientamoeba fragilis mainly produces mild clinical manifestations, the high burden of infection means we require better understanding of its epidemiological cycle and pathogenicity, as well as adequate therapeutic guidelines in order to adapt medical care and policies to respond to this health problem., Graphical abstract Figure: Binucleate form of a trophozoite of D. fragilis, stained with trichrome Image courtesy of DPDx (Centers for Disease Control and Prevention).Image 1, Highlights • A high prevalence of D. fragilis was detected in individuals with gastrointestinal symptoms. • Paromomycin was more effective than metronidazole in the eradication of D. fragilis. • Persistence of infection by D. fragilis was not associated with age, gender or other parasitic coinfections.

In this cross-sectional study of 284 children and adolescents with clinically or radiologically suspected tuberculosis in a low-endemic country, the QuantiFERON-TB Gold Plus assay specificity, sensitivity, positive predictive value and negative predictive value were 91.5%, 87.3%, 86.4%, and 91.2%, respectively. The specificity was higher than that observed in tuberculin skin tests performed simultaneously, but similar to previous-generation interferon-gamma release assays. Sin financiación 3.806 JCR (2021) Q3, 105/161 Inmunology 1.104 SJR (2021) Q1, 29/320 Pediatrics, Perinatology and Child Health No data IDR 2021 UEM

Current diagnostics for tuberculosis (TB) only manage to confirm a small proportion of children with TB and require respiratory samples, which are difficult to obtain. There is a need for non-invasive biomarker-based tests as an alternative to sputum testing. Fujifilm SILVAMP TB lipoarabinomannan (FujiLAM), a lateral-flow test to detect lipoarabinomannan in urine, is a novel non-sputum-based point-of-care diagnostic reported to have increased sensitivity for the diagnosis of TB among human immunodeficiency virus (HIV)-infected adults. We evaluate the performance of FujiLAM in children with presumptive TB. Fifty-nine children attending a paediatric hospital in Haiti with compatible signs and symptoms of TB were examined using Xpert MTB/RIF, smear microscopy and X-rays, and classified according to the certainty of diagnosis into bacteriologically confirmed TB (n = 5), unconfirmed TB (bacteriologically negative, n = 50) and unlikely TB (n = 4). Healthy children (n = 20) were enrolled as controls. FujiLAM sensitivity and specificity were 60% and 95% among children with confirmed TB. FujiLAM’s high specificity and its characteristics as a point-of-care indicate the test has a good potential for the diagnosis of TB in children.

Objective To compare the cost–utility of microscopic observation drug-susceptibility assay (MODS) and Xpert® MTB/RIF implementation for tuberculosis (TB) diagnosis in rural northern Mozambique. Methods Stochastic transmission compartmental TB model from the healthcare provider perspective with parameter input from direct measurements, systematic literature reviews and expert opinion. MODS and Xpert® MTB/RIF were evaluated as replacement test of smear microscopy (SM) or as an add-on test after a negative SM. Costs were calculated in 2013 USD, effects in disability-adjusted life years (DALY). Willingness to pay threshold (WPT) was established at once the per capita Gross National Income of Mozambique. Results MODS as an add-on test to negative SM produced an incremental cost-effectiveness ratio (ICER) of 5647.89USD/DALY averted. MODS as a substitute for SM yielded an ICER of 5374.58USD/DALY averted. Xpert® MTB/RIF as an add-on test to negative SM yielded ICER of 345.71USD/DALY averted. Xpert® MTB/RIF as a substitute for SM obtained an ICER of 122.13USD/DALY averted. TB prevalence and risk of infection were the main factors impacting MODS and Xpert® MTB/RIF ICER in the one-way sensitivity analysis. In the probabilistic sensitivity analysis, Xpert® MTB/RIF was most likely to have an ICER below the WPT, whereas MODS was not. Conclusion Our cost–utility analysis favours the implementation of Xpert® MTB/RIF as a replacement of SM for all TB suspects in this rural high TB/HIV prevalence African setting.

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. Ethics and dissemination: The study protocol was approved by the Clinical Research Ethics Committee of the Hospital Universitari Mútua Terrassa (code 02/16) and the Clinical Research Ethics Committee of the Fundació Institut Universitari per a la Recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (code P16/094). Articles will be published in indexed scientific journals. Trial registration: Clinical-Trials.gov: NCT04236765

We aimed to identify challenges and to propose solutions for the implementation of tuberculosis (TB) programmes in rural Sub-Saharan Africa (SSA) by evaluating the outcomes of the TB programme in the Ancuabe district in rural Northern Mozambique.Retrospective descriptive study of the patients included in the TB programme in 2012-2013. Follow-up was continued till June 2014.Three hundred nineteen patients were registered, 62.1% male, mean age 36.3 (SD 14.4), estimated case detection rate (eCDR) of 24.24%. Two hundred seventy-two were new cases, 21 transferred-in, 11 back after lost to follow-up (LTFU), 10 relapsing TB, 5 previous treatment failures. 94.4% were tested for Human immunodeficiency virus (HIV), 41.9% HIV-positive. 87.5% of the new cases were pulmonary TB (PTB), 43.4% were HIV co-infected. Initial sputum results were available in 207 cases, with 145 smear-positive (SP) cases. Outcomes of new cases: 122 (44.9%) LTFU, 55 (20.2%) cured, 43 (15.8%) treatment completed (98-36%-treatment success), 31 (11.4%) died, 19 (7%) transferred out and 2 (0.7%) failures.A low eCDR and high proportion of LTFU demonstrate that few patients were identified and had a low probability of complete treatment, suggesting a fragile health system. This raises the hypothesis that, probably, to improve TB health care in rural SSA, interventions should aim at improving health systems. Special attention should be given to social protection and compensation of the financial burden associated with TB.

To compare the cost-utility of microscopic observation drug-susceptibility assay (MODS) and XpertStochastic transmission compartmental TB model from the healthcare provider perspective with parameter input from direct measurements, systematic literature reviews and expert opinion. MODS and XpertMODS as an add-on test to negative SM produced an incremental cost-effectiveness ratio (ICER) of 5647.89USD/DALY averted. MODS as a substitute for SM yielded an ICER of 5374.58USD/DALY averted. XpertOur cost-utility analysis favours the implementation of Xpert

The objective of the present study was to assess the diagnostic accuracy of the microscopic observation drug susceptibility (MODS) assay for tuberculosis (TB) diagnosis in HIV-infected patients.MEDLINE, EMBASE, LILACS, the Cochrane Central Register of Controlled Trials, African Index Medicus, ResearchGate, SciELO, and the abstracts of the main conferences on infectious diseases and tropical medicine were searched, and other sources investigated. Only studies including HIV-infected patients evaluating MODS for the diagnosis of TB and using culture-based diagnostic tests as a gold standard were analysed. Summary sensitivity and specificity were calculated with a bivariate model.3259 citations were found, 29 were selected for full-text review and 10 studies including 3075 samples were finally analysed. Overall diagnostic accuracy of MODS for the diagnosis of TB was a sensitivity of 88.3% (95% CI 86.18–90.2%) and specificity 98.2% (95% CI 97.75–98.55%). For multidrug-resistant (MDR)-TB, sensitivity was 89% (95% CI 66.07–97%) and specificity was 100% (95 CI 94.81–100%). For smear-negative pulmonary TB, a sensitivity of 88.2% (95% CI 86.1–89.9%) and specificity of 98.2% (95% CI 96.8–98.9%) were found. Costs varied between USD 0.72 and 7.31 per sample. Mean time to positivity was 8.24 days.MODS was found to have a good accuracy for the diagnosis of TB and MDR-TB in HIV-infected patients with low cost and fast results.

Introduction 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. Methods 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. Results 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). Conclusions 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.

Tuberculosis (TB) is one of the infectious diseases that contributes most to the morbidity and mortality of millions of people worldwide. Brazil is one of 22 countries that accounts for 80% of the tuberculosis global burden. The highest incidence rates in Brazil occur in the States of Amazonas and Rio de Janeiro. The aim of this study was to describe the temporal distribution of TB in the State of Amazonas. Between 2001 and 2011, 28,198 cases of tuberculosis were reported in Amazonas, distributed among 62 municipalities, with the capital Manaus reporting the highest (68.7%) concentration of cases. Tuberculosis was more prevalent among males (59.3%) aged 15 to 34 years old (45.5%), whose race/color was predominantly pardo (64.7%) and who had pulmonary TB (84.3%). During this period, 81 cases of multidrug-resistant TB were registered, of which the highest concentration was reported from 2008 onward (p = 0.002). The municipalities with the largest numbers of indigenous individuals affected were Sao Gabriel da Cachoeira (93%), Itamarati (78.1%), and Santa Isabel do Rio Negro (70.1%). The future outlook for this region includes strengthening the TB control at the primary care level, by expanding diagnostic capabilities, access to treatment, research projects developed in collaboration with the Dr. Heitor Vieira Dourado Tropical Medicine Foundation .;Fundacao de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD).; and financing institutions, such as the project for the expansion of the Clinical Research Center and the creation of a hospital ward for individuals with transmissible respiratory diseases, including TB.

Objective: This study evaluated the performance of the Tuberculin Skin Test (TST) and Quantiferon-TB Gold in-Tube (QFT) and the possible association of factors which may modify their results in young children (0–6 years) with recent contact with an index tuberculosis case. Materials and Methods: A cross-sectional study including 135 children was conducted in Manaus, Amazonas-Brazil. The TST and QFT were performed and the tests results were analyzed in relation to the personal characteristics of the children studied and their relationship with the index case. Results: The rates of positivity were 34.8% (TST) and 26.7% (QFT), with 14.1% of indeterminations by the QFT. Concordance between tests was fair (Kappa = 0.35 P,0.001). Both the TST and QFT were associated with the intensity of exposure (Linear OR = 1.286, P = 0.005; Linear OR = 1.161, P = 0.035 respectively) with only the TST being associated with the time of exposure (Linear OR = 1.149, P = 0.009). The presence of intestinal helminths in the TST+ group was associated with negative QFT results (OR = 0.064, P = 0.049). In the TST2 group lower levels of ferritin were associated with QFT+ results (Linear OR = 0.956, P = 0.036). Conclusions: Concordance between the TST and QFT was lower than expected. The factors associated with the discordant results were intestinal helminths, ferritin levels and exposure time to the index tuberculosis case. In TST+ group, helminths were associated with negative QFT results suggesting impaired cell-mediated immunity. The TST2&QFT+ group had a shorter exposure time and lower ferritin levels, suggesting that QFT is faster and ferritin may be a potential biomarker of early stages of tuberculosis infection.

BACKGROUND In young children, underdiagnosis and diagnostic delay have an adverse effect on morbidity and mortality of tuberculosis (TB). This study evaluated new strategies for early TB diagnosis using an outpatient protocol in children between 0 and 5 years of age, with a recent household TB contact. METHODS Case recruitment was performed in Manaus, Amazonas, Brazil, from 2008 to 2009. Epidemiologic and clinical data, tuberculin test, chest radiograph and 2 induced sputum respiratory samples from each participant were obtained. Laboratory diagnosis was based on Lowenstein-Jensen (LJ) culture, mycobacteria growth indicator tube (MGIT) and polymerase chain reaction. We conducted a study of comparison of diagnostic tests and a study of cases and controls to identify the clinical characteristics of the population with positive culture and polymerase chain reaction results. RESULTS A total of 102 children were evaluated. Thirty-two fulfilled criteria of suspicion of TB. MGIT was more sensitive (P = 0.035) and faster (P < 0.001) than LJ. Clinical score, MGIT, LJ and polymerase chain reaction presented no concordance or slight concordance. A positive MGIT culture was only associated with a strong tuberculin test reaction (P = 0.026). The combination of MGIT with the clinical score allowed the diagnosis of 33% more cases with little or no symptomatology compared with the exclusive use of the clinical classification. CONCLUSIONS The sensitivity and speed of MGIT demonstrate the utility of liquid cultures for the diagnosis in children. Furthermore, these results suggest that the use of MGIT in children presenting recent household TB contact and a strong tuberculin test reaction may be a strategy to improve early TB diagnosis.

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