Improving the TB case management: The International Standards for Tuberculosis Care.

Tuberculosis (TB) is currently the leading cause of death from a curable infectious disease. The World Health Organization (WHO) estimates that 8.9 million new TB cases occurred in 2004 (of which 3.9 million were sputum smear positive), although only about half of the estimated number were reported by public health systems. Whilst the highest TB incidence rate is in sub-Saharan Africa (estimated to be 356 new cases per 100,000 population per yr), in most countries of the former Soviet Union the estimated incidence rate exceeds 100 new cases per 100,000 population per yr. Although the rate of increase in the TB incidence rate is decreasing, the global TB notification grew by 1% between 2003 and 2004, the last year for which data are available. This continued increase is largely the result of the striking increase in cases in sub-Saharan Africa and, to a lesser extent, in the former USSR. Whilst the worsening of the TB incidence in Africa is due to the HIVepidemic compounded by an insufficient health infrastructure, it is due to different causes in Eastern Europe, including economic decline, increased poverty, social disruption and sub-standard health services. In addition, as a result of these factors, .10% of new TB cases in the Baltic states and in some parts of Russia are multidrug-resistant (MDR-TB), i.e. resistant to at least isoniazid and rifampicin. In the European region, 445,000 new TB cases and nearly 70,000 deaths were estimated to have resulted from TB in 2004. In the Eastern part of the region, the levels of directly observed treatment, short-course (DOTS) strategy coverage and case detection are the lowest among the world regions, and the overall treatment success rate is the second lowest (75%) after Africa

Cooperative Localization Enhancement through GNSS Raw Data in Vehicular Networks

The evolution and integration of communication networks and positioning technologies are evolving at a fast pace in the framework of vehicular systems. The mutual dependency of such two capabilities can enable several new cooperative paradigms, whose adoption is however slowed down by the lack of suitable open protocols, especially related to the positioning and navigation domain. In light of this, the paper introduces a novel vehicular message type, namely the Cooperative Enhancement Message (CEM), and an associated open protocol to enable the sharing of Global Navigation Satellite Systems (GNSS) raw measurements among connected vehicles. The proposed CEM aims at extending existent approaches such as Cooperative Awareness Messages (CAM) and Collective Perception Messages (CPM) by complementing their paradigms with a cooperative enhancement of the localization accuracy, precision, and integrity proposed by state-of-the-art solutions. Besides the definition of CEMs and a related protocol, a validation of the approach is proposed through a novel simulation framework. A preliminary analysis of the network performance is presented in the case where CEM and CAM transmissions coexist and are concurrently used to support cooperative vehicle applications

del (3) (q13.11q21.1): descrizione di un nuovo caso

La delezione interstiziale della regione prossimale del braccio lungo del cromosoma 3 (q11-q21) \ue8 un\u2019alterazione cromosomica molto rara ed \ue8 stata descritta solo in 13 pazienti. Riportiamo il caso di un bambino di 8 mesi nato con parto eutocico da genitori sani non consanguinei. Il cariotipo da sangue periferico ha mostrato la presenza di un\u2019ampia delezione sul braccio lungo del cromosoma 3: 46,XY,del(3)(q12q21) confermata per mezzo di FISH. L\u2019Array-CGH ha evidenziato che la delezione \ue8 pari a 18,97 Mb e si estende da q13.11 a q21.1 consentendo di definire in modo pi\uf9 preciso il cariotipo: 46,XY,del(3)(q13.11q21.1) Il cariotipo normale di entrambi i genitori ha confermato l\u2019insorgenza de novo della delezione. Il bambino presenta tratti dismorfici del volto (fronte ampia, epicanto bilaterale, radice nasale a sella, ipoplasia della parte mediana del volto, padiglioni auricolari a basso impianto), ipotono assiale con ritardo moderato nell\u2019acquisizione delle tappe di sviluppo, plagiocefalia, ipoplasia del corpo calloso, assottigliamento della sostanza bianca in sede peritrigonale bilaterale, anomala conformazione del tronco encefalico per lieve ipoplasia del ponte, tendenza all\u2019inversione della fisiologica lordosi cervicale, criptorchidismo sinistro ed ernia inguinale sinistra Per quanto riguarda la correlazione genotipo-fenotipo il gene CBLB (3q13.11) sembra responsabile delle alterazioni craniofacciali, il gene BOC (3q13.2) dell\u2019ipotonia muscolare, il gene DRD3 (3q13.3) del ritardo dello sviluppo. La comparazione delle caratteristiche cliniche del nostro paziente con quelle dei pazienti descritti in letteratura conferma che la delezione della regione prossimale del braccio lungo del cromosoma 3 determina un fenotipo eterogeneo che comprende dismorfismi a carico del volto, ipotonia, ritardo di sviluppo, difetti cardiaci, anomalie celebrali, anomalie scheletriche e genitourinarie. L\u2019espressivit\ue0 variabile del fenotipo potrebbe essere dovuta all\u2019ampiezza della delezione variabile per differenti punti di rottura e alla presenza in questa regione di geni sensibili al dosaggio e o allo smascheramento di alleli recessivi, che a seguito della delezione si troverebbero in una condizione di emizigosi

Pediatric Moyamoya Disease and Syndrome in Italy: A Multicenter Cohort

Background: Moyamoya is a rare progressive cerebral arteriopathy, occurring as an isolated phenomenon (moyamoya disease, MMD) or associated with other conditions (moyamoya syndrome, MMS), responsible for 6–10% of all childhood strokes and transient ischemic attacks (TIAs). Methods: We conducted a retrospective multicenter study on pediatric-onset MMD/MMS in Italy in order to characterize disease presentation, course, management, neuroradiology, and outcome in a European country. Results: A total of 65 patients (34/65 women) with MMD (27/65) or MMS (38/65) were included. About 18% (12/65) of patients were asymptomatic and diagnosed incidentally during investigations performed for an underlying condition (incMMS), whereas 82% (53/65) of patients with MMD or MMS were diagnosed due to the presence of neurological symptoms (symptMMD/MMS). Of these latter, before diagnosis, 66% (43/65) of patients suffered from cerebrovascular events with or without other manifestations (ischemic stroke 42%, 27/65; TIA 32%, 21/65; and no hemorrhagic strokes), 18% (12/65) of them reported headache (in 4/12 headache was not associated with any other manifestation), and 26% (17/65) of them experienced multiple phenotypes (≥2 among: stroke/TIA/seizures/headache/others). Neuroradiology disclosed ≥1 ischemic lesion in 67% (39/58) of patients and posterior circulation involvement in 51% (30/58) of them. About 73% (47/64) of patients underwent surgery, and 69% (45/65) of them received aspirin, but after diagnosis, further stroke events occurred in 20% (12/61) of them, including operated patients (11%, 5/47). Between symptom onset and last follow-up, the overall patient/year incidence of stroke was 10.26% (IC 95% 7.58–13.88%). At last follow-up (median 4 years after diagnosis, range 0.5–15), 43% (26/61) of patients had motor deficits, 31% (19/61) of them had intellectual disability, 13% (8/61) of them had epilepsy, 11% (7/61) of them had behavioral problems, and 25% (13/52) of them had mRS > 2. The proportion of final mRS > 2 was significantly higher in patients with symptMMD/MMS than in patients with incMMS (p = 0.021). Onset age <4 years and stroke before diagnosis were significantly associated with increased risk of intellectual disability (p = 0.0010 and p = 0.0071, respectively) and mRS > 2 at follow-up (p = 0.0106 and p = 0.0009, respectively). Conclusions: Moyamoya is a severe condition that may affect young children and frequently cause cerebrovascular events throughout the disease course, but may also manifest with multiple and non-cerebrovascular clinical phenotypes including headache (isolated or associated with other manifestations), seizures, and movement disorder. Younger onset age and stroke before diagnosis may associate with increased risk of worse outcome (final mRS > 2)

The health workforce crisis in TB control: a report from high-burden countries

BACKGROUND: Human resources (HR) constraints have been reported as one of the main barriers to achieving the 2005 global tuberculosis (TB) control targets in 18 of the 22 TB high-burden countries (HBCs); consequently we try to assess the current HR available for TB control in HBCs. METHODS: A standard questionnaire designed to collect information on staff numbers, skills, training activities and current staff shortages at different health service levels was sent to national TB control programme managers in all HBCs. RESULTS: Nineteen HBCs (86%) replied, and 17 (77%) followed the questionnaire format to provide data. Complete information on staff numbers at all service levels was available from nine countries and data on skill levels and training were complete in six countries. Data showed considerable variations in staff numbers, proportions of trained staff, length of courses and quality of training activities. Eleven HBCs had developed training materials, many used implementation guidelines for training and only three used participatory educational methods. Two countries reported shortages of staff at district health facility level, whereas 14 reported shortages at central level. There was no apparent association between reported staff numbers (and skills) and the country's TB burden or current case detection rates (CDR). CONCLUSION: There were few readily available data on HR for TB control in HBCs, particularly in the larger ones. The great variations in staff numbers and the poor association between information on workforce, proportion of trained staff, and length and quality of courses suggested a lack of valid information and/or poor data reliability. There is urgent need to support HBCs to develop a comprehensive HR strategy involving short-term and long-term HR development plans and strengthening their HR planning and management capabilities

Bacteriophage- based tests for the detection of Mycobacterium tuberculosis in clinical specimens: a systematic review and meta- analysis

BACKGROUND: Sputum microscopy, the most important conventional test for tuberculosis, is specific in settings with high burden of tuberculosis and low prevalence of non tuberculous mycobacteria. However, the test lacks sensitivity. Although bacteriophage-based tests for tuberculosis have shown promising results, their overall accuracy has not been systematically evaluated. METHODS: We did a systematic review and meta-analysis of published studies to evaluate the accuracy of phage-based tests for the direct detection of M. tuberculosis in clinical specimens. To identify studies, we searched Medline, EMBASE, Web of science and BIOSIS, and contacted authors, experts and test manufacturers. Thirteen studies, all based on phage amplification method, met our inclusion criteria. Overall accuracy was evaluated using forest plots, summary receiver operating (SROC) curves, and subgroup analyses. RESULTS: The data suggest that phage-based assays have high specificity (range 0.83 to 1.00), but modest and variable sensitivity (range 0.21 to 0.88). The sensitivity ranged between 0.29 and 0.87 among smear-positive, and 0.13 to 0.78 among smear-negative specimens. The specificity ranged between 0.60 and 0.88 among smear-positive and 0.89 to 0.99 among smear-negative specimens. SROC analyses suggest that overall accuracy of phage-based assays is slightly higher than smear microscopy in direct head-to-head comparisons. CONCLUSION: Phage-based assays have high specificity but lower and variable sensitivity. Their performance characteristics are similar to sputum microscopy. Phage assays cannot replace conventional diagnostic tests such as microscopy and culture at this time. Further research is required to identify methods that can enhance the sensitivity of phage-based assays without compromising the high specificity

Translational research for tuberculosis elimination: priorities, challenges, and actions

Christian Lienhardt and colleagues describe the research efforts needed to end the global tuberculosis epidemic by 2035