Urine NMR-based TB metabolic fingerprinting for the diagnosis of TB in children

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

Clinical presentations and outcomes related to tuberculosis in children younger than 2 years of age in Catalonia

Introduction: Children younger than 2 years have an increased risk of complications associated with tuberculosis (TB) due to the immaturity of t he innate and adaptive immune response. We aimed to identify TB clinical presentations and outcomes as well as risk factors for complications in this age group. Materials and Methods: Multicenter, retrospective, cross-sectional study of TB cases in children aged <2 years in Catalonia (2005-2013). Epidemiological and clin ical data were collected from the hospital medical records. TB complications, sequelae included, were defined as any tissue damage generating functional or an atomical impairment after being diagnosed or after TB treatment being completed. Statistical analyses were based on bivariate chi-square and multivariate logistic regression, and it was carried out with Stata ® version 13.1. Odds ratios (OR) and its 95% confidence intervals were calculated (CI). Results: A total of 134 patients were included, 50.7% were male, the median [IQR] age was 13[8-18] months, and 18.7% (25/134) showed TB-assoc iated complications. Pulmonary TB was diagnosed in 94.0% (126/134) of children, and the most common complications were lobar collapse (6/126). TB menin gitis was diagnosed in 14/134 (10.4%), and hydrocephalus and mental impairment occurred in 1 and 2 patients, respectively. Two patients with spinal TB develo ped vertebral destruction and paraplegia, respectively. Only one of the patients died. At multivariate level, tachypneaSoriano-Arandes et al. Tuberculosis Complications in Children (OR = 4.24; 95% CI 1.17-15.35) and meningeal (OR = 52.21; 95% CI 10.05-271.2) or combined/extrapulmonary forms (OR = 11.3; 95% CI 2.85-45.1) were associated with the development of TB complications. Discussion: TB complications are common in children under 2 years old. Extrapulmonary TB forms in this pediatric age remain a challenge and require prompt diagnosis and treatment in order to prevent them. The presence of tachypnea at the time of TB diagnosis is an independent associated factor to the development of TB complications in infants. This clinical sign should be closely monitored in patients in this age group. It is necessary to perform further studies in this age group in a prospective design in order to understand whether there are other factors associated to TB complications