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The risk of progression from Mycobacterium tuberculosis (M.tb) infection to active tuberculosis (TB) disease varies markedly with age. TB disease is significantly less likely in pre-adolescent children above 4 years of age than in very young children or post-pubescent adolescents and young adults. We hypothesized that pro-inflammatory responses to M.tb in pre-adolescent children are either less pronounced or more regulated, than in young adults. Inflammatory and antimicrobial mediators, measured by microfluidic RT-qPCR and protein bead arrays, or by analyzing published microarray data from TB patients and controls, were compared in pre-adolescent children and adults. Multivariate analysis revealed that M.tb-uninfected 8-year-old children had lower levels of myeloid-associated pro-inflammatory mediators than uninfected 18-year-old young adults. Relative to uninfected children, those with M.tb-infection had higher levels of similar myeloid inflammatory responses. These inflammatory mediators were also expressed after in vitro stimulation of whole blood from uninfected children with live M.tb. Our findings suggest that myeloid inflammation is intrinsically lower in pre-pubescent children than in young adults. The lower or more regulated pro-inflammatory responses may play a role in the lower risk of TB disease in this age group.

Eradication of tuberculosis (TB), the world's leading cause of death due to infectious disease, requires a highly efficacious TB vaccine. Many TB vaccine candidates are in pre-clinical and clinical development but only a few can be advanced to large-scale efficacy trials due to limited global resources. We aimed to perform a statistically rigorous comparison of the antigen-specific T cell responses induced by six novel TB vaccine candidates and the only licensed TB vaccine, Bacillus Calmette-Guérin (BCG). We propose that the antigen-specific immune response induced by such vaccines provides an objective, data-driven basis for prioritisation of vaccine candidates for efficacy testing. We analyzed frequencies of antigen-specific CD4 and CD8 T cells expressing IFNγ, IL-2, TNF and/or IL-17 from adolescents or adults, with or without Mycobacterium tuberculosis (M.tb) infection, who received MVA85A, AERAS-402, H1:IC31, H56:IC31, M72/AS01E, ID93+GLA-SE or BCG. Two key response characteristics were analyzed, namely response magnitude and cytokine co-expression profile of the memory T cell response that persisted above the pre-vaccination response to the final study visit in each trial. All vaccines preferentially induced antigen-specific CD4 T cell responses expressing Th1 cytokines; levels of IL-17-expressing cells were low or not detected. In M.tb-uninfected and -infected individuals, M72/AS01E induced higher memory Th1 cytokine-expressing CD4 T cell responses than other novel vaccine candidates. Cytokine co-expression profiles of memory CD4 T cells induced by different novel vaccine candidates were alike. Our study suggests that the T cell response feature which most differentiated between the TB vaccine candidates was response magnitude, whilst functional profiles suggested a lack of response diversity. Since M72/AS01E induced the highest memory CD4 T cell response it demonstrated the best vaccine take. In the absence of immunological correlates of protection, the likelihood of finding a protective vaccine by empirical testing of candidates may be increased by the addition of candidates that induce distinct immune characteristics., Author summary Tuberculosis (TB) causes more deaths than any other single infectious disease, and a new, improved vaccine is needed to control the epidemic. Many new TB vaccine candidates are in clinical development, but only one or two can be advanced to expensive efficacy trials. In this study, we compared magnitude and functional attributes of memory T cell responses induced in recently conducted clinical trials by six TB vaccine candidates, as well as BCG. The results suggest that these vaccines induced CD4 and CD8 T cell responses with similar functional attributes, but that one vaccine, M72/AS01E, induced the largest responses. This finding may indicate a lack of diversity in T cell responses induced by different TB vaccine candidates. A repertoire of vaccine candidates that induces more diverse immune response characteristics may increase the chances of finding a protective vaccine against TB.

Objective To present our cases of ureteral obstruction after endoscopic treatment of vesicoureteral reflux (VUR) with dextranomer/hyaluronic acid (Dx/HA). Patients and methods We collected data from patients who had suffered ureteral obstruction after endoscopic treatment of VUR with Dx/HA in our institution. Results From April 2002 to April 2011 we treated endoscopically 475 ureters with VUR, and detected 5 ureteral obstructions. Median age at reflux treatment was 39 months. Reflux grade before treatment was III in one patient and IV in four. Three ureterovesical junctions (UVJ) were blocked after a second endoscopic treatment. The median of Dx/HA injected was 1 ml (0.6–1.1). In two patients ureteral obstruction presented acutely and was treated with a ureteral stent. In the other three, the ureteral obstruction appeared gradually and was detected by ultrasound scans and MAG3 diuretic renogram; one underwent nephrectomy because of poor renal function, and the other two were treated with endoscopic dilatation of the UVJ. In all these patients both reflux and obstructions have resolved. Conclusions On preoperative cystography, three of the patients had a narrowed distal ureter, and probably had a refluxing and obstructive megaureter. Other causes are not clear, except for those patients with acute presentation in whom edema of the UVJ was found. Ureteral obstruction after endoscopic treatment of VUR is rare. Endoscopic intervention such as ureteral stent placement or high-pressure balloon dilatation of the UVJ has good results as a treatment of acute and delayed obstruction.

Purpose To compare efficacy of Cohen's ureteral reimplantation and endoscopic treatment with Dx/HA in patients with primary VUR grades II, III and IV. Methods From April 2002 to June 2004, patients over 1 year old with VUR grade I, II, III or IV were included. Patients were randomized into two groups: endoscopic treatment (ET) or ureteral reimplantation (UR). In the ET group, an ultrasonography study was performed 24 h and 1 month after surgery, and two voiding cystourethrographies at 3 and 6 months post treatment. In the UR group, an ultrasonography study was done 7 days and 1 month after surgery and a micturial cystography 6 months post surgery. A postoperative nuclear direct cystogram was performed 5 years later in both groups. Results A total of 41 patients were included in this study: in ET 22 patients with 35 refluxing ureters and in UR 19 patients with 32 refluxing ureters. The VUR grades in ET were: 16 grade II, 16 grade III and 3 grade IV; and in UR: 15 grade II, 12 grade III and 5 grade IV. VUR was resolved in 91% (32/35) of ET (28% of ureters needed a second injection), and in 100% of UR group. Five years after the procedure, VUR was still resolved in 30/32 of ET and 32/32 of UR. Conclusion Short- and long-term follow up shows that multiple endoscopic treatment of VUR grades II, III and IV with Dx/HA is as effective as ureteral reimplantation.

Two patients with congenital esophageal stenosis associated with an H-type tracheoesophageal fistula in one and esophageal atresia with distal fistula in the other are presented. In both patients the correct preoperative diagnosis was made by esophagram. Satisfactory results were obtained with surgical excision. Histologic studies revealed fibromuscular stenosis and membranous esophageal mucosa, respectively.

Objectives : Three new cases of xanthogranulomatous pyelonephritis are described in children. Methods : Laboratory examinations including white and red blood cell counts, erythrocyte sedimentation rate, renal function, urinalysis and cystography were performed. Results : All of the patients had a palpable abdominal mass. Urine culture was positive (Proteus mirabilis) in only 1 patient. Associated urological abnormalities were found in 2 cases. Urographically a functionless kidney was encountered in 2 children and a renal mass in the other. None could be diagnosed preoperatively. Conclusions : Although nephrectomy has been said to be the treatment of choice, conservative treatment can be successful as shown by 1 of our patients.