Systematic review and meta-analysis on the utility of Interferon-gamma release assays for the diagnosis of Mycobacterium tuberculosis infection in children: A 2013 update

BACKGROUND: Previous meta-analyses regarding the performance of interferon-gamma release assays (IGRAs) for tuberculosis diagnosis in children yielded contrasting results, probably due to different inclusion/exclusion criteria. METHODS: We systematically searched PubMed, EMBASE and Cochrane databases and calculated pooled estimates of sensitivities and specificities of QuantiFERON-TB Gold In Tube (QFT-G-IT), T-SPOT.TB, and tuberculin skin test (TST). Several sub-analysis were performed: stratification by background (low income vs. high income countries); including only microbiological confirmed TB cases; including only studies performing a simultaneous three-way comparison of the three tests, and including immunocompromised children. RESULTS: Overall, 31 studies (6183 children) for QFT-G-IT, 14 studies (2518 children) for T-SPOT.TB and 34 studies (6439 children) for TST were included in the analyses. In high income countries QFT-G-IT sensitivity was 0.79 (95%IC: 0.75-0.82) considering all the studies, 0.78 (95%CI:0.70-0.84) including only studies performing a simultaneous three-way comparison and 0.86 (95%IC 0.81-0.90) considering only microbiologically confirmed studies. In the same analyses T-SPOT.TB sensitivity was 0.67 (95%IC 0.62-0.73); 0.76 (95%CI: 0.68 to 0.83); and 0.79 (95%IC 0.69-0.87), respectively. In low income countries QFT-G-IT pooled sensitivity was significantly lower: 0.57 (95%IC:0.52-0.61), considering all the studies, and 0.66 (95%IC 0.55-0.76) considering only microbiologically confirmed cases; while T-SPOT.TB sensitivity was 0.61 (95%IC 0.57-0.65) overall, but reached 0.80 (95%IC 0.73-0.86) in microbiologically confirmed cases. In microbiologically confirmed cases TST sensitivity was similar: 0.86 (95%IC 0.79-0.91) in high income countries, and 0.74 (95%IC 0.68-0.80) in low income countries. Higher IGRAs specificity with respect to TST was observed in high income countries (97-98% vs. 92%) but not in low income countries (85-93% vs. 90%). CONCLUSIONS: Both IGRAs showed no better performance than TST in low income countries

Vaccine against tuberculosis: what's new?

BACKGROUND: one of the World Health Organization Millennium Development Goal is to reduce tuberculosis incidence by 2015. However, more of 8.5 million tuberculosis cases have been reported in 2011, with an increase of multidrug-resistant strains. Therefore, the World Health Organization target cannot be reach without the help of a vaccine able to limit the spread of tuberculosis. Nowadays, bacille Calmette-Guérin is the only vaccine available against tuberculosis. It prevents against meningeal and disseminated tuberculosis in children, but its effectiveness against pulmonary form in adolescents and adults is argued. METHOD: a systematic review was performed by searches of Pubmed, references of the relevant articles and Aeras and ClinicalTrial.gov websites. RESULTS: 100 articles were included in this review. Three viral vectored booster vaccines, five protein adjuvant booster vaccines, two priming vaccines and two therapeutic vaccines have been analyzed. CONCLUSIONS: Several vaccines are in the pipeline, but further studies on basic research, clinical trial and mass vaccination campaigns are needed to achieve the TB eradication target by 2050

2,3,7,8-tetrachlorodibenzo-p-dioxin and the viral infection

Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a widespread highly toxic environmental contaminant, suppresses immune response and leads to an increased susceptibility to infectious agents. In particular, several studies have provided evidence that TCDD decreases resistance to numerous viruses. Indeed, in vivo and in vitro investigations showed that the presence of TCDD is able to interfere with the replication of both human and animal viruses, such as influenza A viruses, coxsackie virus B3, immunodeficiency virus type-1 (HIV-1), cytomegalovirus (CMV), herpes simplex II, and bovine herpesvirus 1. Moreover, TCDD could induce an exacerbation of latent infection produced by HIV-1, CMV or Epstein-Barr virus. In this review, we first describe the general effects of TCDD exposure on mammalian cells, then we focus on its influence on the viral infections. Overall, the available data support the concept that TCDD exposure may act as an additional risk factor in promoting of viral diseases

Clinical peculiarities of tuberculosis

The ongoing spread of tuberculosis (TB) in poor resource countries and the recently increasing incidence in high resource countries lead to the need of updated knowledge for clinicians, particularly for pediatricians. The purpose of this article is to provide an overview on the most important peculiarities of TB in children. Children are less contagious than adults, but the risk of progression to active disease is higher in infants and children as compared to the subsequent ages. Diagnosis of TB in children is more difficult than in adults, because few signs are associated with primary infection, interferon-gamma release assays and tuberculin skin test are less reliable in younger children, M. tuberculosis is more rarely detected in gastric aspirates than in smears in adults and radiological findings are often not specific. Treatment of latent TB is always necessary in young children, whereas it is recommended in older children, as well as in adults, only in particular conditions. Antimycobacterial drugs are generally better tolerated in children as compared to adults, but off-label use of second-line antimycobacterial drugs is increasing, because of spreading of multidrug resistant TB worldwide. Given that TB is a disease which often involves more than one member in a family, a closer collaboration is needed between pediatricians and clinicians who take care of adults

Vitamin D status and predictors of hypovitaminosis D in internationally adopted children

To evaluate vitamin D status in internationally adopted children at first medical evaluation in Italy and to identify possible risk factors for hypovitaminosis D in this population.25-hydroxyvitamin D [25(OH)D] levels were analyzed in internationally adopted children consecutively recruited at one Italian Center between 2010 and 2014 as part of the first screening protocol. Demographic, clinical and laboratory data were prospectively collected. Serum 25(OH)D levels <10 ng/mL, <20 ng/mL, and <30 ng/mL were used to define severe vitamin D deficiency, vitamin D deficiency and hypovitaminosis D, respectively.962 internationally adopted children (median age: 5.47 years; IQR:3.14-7.93) were included in the study. Median 25(OH)D level was 22.0 ng/mL (IQR:15.0-30.0 ng/mL); 710/962 (73.8%) children showed hypovitaminosis D (<30 ng/mL), 388/962 (40.3%) had vitamin D deficiency (<20 ng/dL), and 92/962 (9.6%) had severe vitamin D deficiency (<10ng/mL). No case of clinical rickets was observed. Hypovitaminosis D was particularly frequent (>90%) in children adopted from Ethiopia, Peru, India, Bulgaria and Lithuania. At multivariate analysis an increased risk of hypovitaminosis D was found to be associated with: age ≥ 6 years, time spent in Italy ≥ 3 months, blood sample taken in winter, spring or fall, compared to summer. Gender, ethnicity/continent of origin, tubercular infection, intestinal parassitosis and BMI-z-score < -2 were not associated with vitamin D status.Hypovitaminosis D is common in internationally adopted children, from all ethnic group. The evaluation of serum 25(OH)D level could be useful early after the adoption to promptly start vitamin D supplementation/treatment if needed

Update on the management of acute pharyngitis in children

Streptococcal pharyngitis is a very common pathology in paediatric age all over the world. Nevertheless there isn't a joint agreement on the management of this condition. Some authors recommend to perform a microbiological investigation in suspected bacterial cases in order to treat the confirmed cases with antibiotics so to prevent suppurative complications and acute rheumatic fever. Differently, other authors consider pharyngitis, even streptococcal one, a benign, self-limiting disease. Consequently they wouldn't routinely perform microbiological tests and, pointing to a judicious use of antibiotics, they would reserve antimicrobial treatment to well-selected cases. It has been calculated that the number of patients needed to treat to prevent one complication after upper respiratory tract infections (including sore throat), was over 4000

Heat-shock pretreatment inhibits sorbitol-induced apoptosis in K562, U937 and HeLa cells.

The aim of this study was to determine whether heat-shock pretreatment exerted a protective effect against sorbitol-induced apoptotic cell death in K562, U937 and HeLa cell lines and whether such protection was associated with a decreased cytochrome c release from mithocondria and a decreased activation of caspase-9 and -3. Following heat-shock pretreatment (42 6 0.3C for 1 hr), these cell lines were exposed to sorbitol for 1 hr. Apoptosis was evaluated by DNA fragmentation, whereas caspase-9,-3 activation, cytochrome c release and heat-shock protein70 (HSP70) were assayed by Western Blot. Sorbitol exposure-induced apoptosis in these different cell lines with a marked activation of caspase-9 and caspase- 3, whereas heat-shock pretreatment before sorbitol exposure, induced expression of HSP70 and inhibited sorbitol-mediated cytochrome c release and subsequent activation of caspase-9 and caspase- 3. Similarly, overexpression of HSP70 in the three cell lines studied prevented caspase-9 cleavage and activation as well as cell death. Furthermore, we showed that the mRNA expression of iNOS decreased during both the heat-shock treatment and heat-shock pretreatment before sorbitol exposure. By contrast, the expression of Cu-Zn superoxide dismutase (SOD) and Mn-SOD proteins increased during heat-shock pretreatment before sorbitol exposure. We conclude that, heat-shock pretreatment protects different cell lines against sorbitol-induced apoptosis through a mechanism that is likely to involve SOD family members

The ever-expanding conundrum of primary osteoporosis: aetiopathogenesis, diagnosis, and treatment.

In recent years, as knowledge regarding the etiopathogenetic mechanisms of bone involvement characterizing many diseases has increased and diagnostic techniques evaluating bone health have progressively improved, the problem of low bone mass/quality in children and adolescents has attracted more and more attention, and the body evidence that there are groups of children who may be at risk of osteoporosis has grown. This interest is linked to an increased understanding that a higher peak bone mass (PBM) may be one of the most important determinants affecting the age of onset of osteoporosis in adulthood. This review provides an updated picture of bone pathophysiology and characteristics in children and adolescents with paediatric osteoporosis, taking into account the major causes of primary osteoporosis (PO) and evaluating the major aspects of bone densitometry in these patients. Finally, some options for the treatment of PO will be briefly discussed