Surveillance of congenital rubella and rubella infections in pregnancy in EU/EEA countries, 2012: Current status and future perspective to monitor elimination.

INTRODUCTION: Rubella elimination and congenital rubella syndrome (CRS) prevention are targets for achievement by 2015 in the WHO-EURO Region. This paper describes the existing surveillance systems for CRS and rubella in pregnancy in order to critically interpret the findings in relation to the 2012 WHO-EURO surveillance guidelines. METHODS: In 2012 we conducted a survey to collect information on surveillance of CRS and rubella in pregnancy in 29 EU/EEA countries. Questionnaires explored the characteristics of the surveillance systems, case definition, epidemiological investigation and follow-up of cases, reference laboratories and types of tests performed. RESULTS: Twenty-eight countries had surveillance systems for CRS, mostly nationwide, mandatory, passive and case-based; 23 collected information on the origin of the infection; 11 reported asymptomatic infections; 6 required zero-reporting. Case definitions varied among countries, although 24 used the EU definition. Laboratories reported cases in 18 countries. Twenty countries collected information on pregnancy within the rubella surveillance system and 5 had specific surveillance for rubella in pregnancy. Two countries did not monitor outcomes of suspected infections in pregnancy; infants with CRS were monitored in all the remaining countries; asymptomatic infected infants in 15; stillbirths and fetal deaths in 13; therapeutic and spontaneous abortions in 8 and 7. Twenty-seven countries had a national reference laboratory for CRS and rubella in pregnancy; genotyping was performed in 15. DISCUSSION: The current surveillance systems allow adequate CRS monitoring in EU. Further efforts are needed to improve their quality, including uniform case definitions, collection of information on the origin of infection, and promotion of reporting from laboratories. Follow-up of pregnant women with suspected infection should be strengthened because it is an entry point for CRS, including detection of fetal deaths, stillbirths and abortions. Laboratory capacity for confirming congenital rubella infections and infections in pregnancy is good in EU, however the use of genotyping should be encouraged.

Vaccine-preventable diseases: the role of the European Centre for Disease Prevention and Control.

The role of the European Centre for Disease Prevention and Control (ECDC) is to strengthen the capacity of the European Union (EU) Member States to protect human health through the prevention and control of infectious diseases. The main objective of the programme on vaccine-preventable diseases and invasive bacterial infections (VPD) is to provide robust evidence and high-quality technical support to the EU Member States to help them in their efforts to prevent and control VPD. Since the establishment of ECDC, several existing VPD surveillance networks have been transferred to ECDC, namely EU-IBIS, DIPNET and EUVAC. In addition to surveillance of diseases, ECDC is collecting information and monitoring other parameters that are of crucial importance for a well-functioning immunization system, including vaccination coverage. The VPD programme also provides independent scientific opinions in the area of immunization and initiates and coordinates scientific studies in the area of vaccination to answer specific questions of public health importance, including risk perception and analysis of behaviour in different population groups. One of the overall ECDC priorities over recent years is the Centre's involvement in measles elimination. The 'Message' tool and the 'Measles Atlas' are examples of work aiming at supporting the efforts of Member States in the elimination phase.

The usefulness of 111indium-oxine autologous platelet gel graft imaging to evaluate osteoinduction in patients undergoing surgery of jaw bone defects.

Autologous platelet gel (AGP) is a source of concentrated growth factors contained in the platelet granules used to enhance bone quality and, especially, quicken bone formation in regeneration techniques, and also ameliorate the haemostasis in anti-coagulated patient management. The purpose of this study is to describe a technique to perform labelling of autologous platelet-gel with 111In -Oxine and to evaluate its usefulness, as a marker of bone osteoinduction by means of scintigraphy, after in vivo application in patients with jaw bone defects following cystic lesion enucleation and the extraction of deeply impacted lower third molar. All patients included in the study presented mandible bone defects following cyst enucleation or deeply impacted lower third molar extraction. In sterile conditions, 111In-Oxine AGP was added during the bone-milling phase of the graft preparation and then applied to the bone defects. The scintigraphy was performed 2 hours after the application of labelled AGP (early scan) and at 24, 48, 72, 384 hours (delayed scan). At early scan all the patients presented a high concentration of 111In-Oxine AGP, which was easily recognized at the level of jaw defect. Limited diffusion of AGP was seen in the tissue surrounding the bone defect; this activity was attributed to the presence, in the PRP, of a quote of autologous granulocytes, as marker of inflammatory process, which was labelled with 111In-Oxine. In order to demonstrate the persistence and stability of labelling AGP, abdominal scintigraphies were performed to assess the presence of activity in the liver, spleen and bone marrow. None of the patients presented appreciable activity in these organs. The labelled AGP topically applied showed high uptake values, without statistically significant activity in the surrounding tissues or in critical organs during the early phase, as well as in delayed controls, and confirmed a very low grade of loss of 111In-Oxine from the bone defect. The scintigraphy represents a useful method of assessing the success of surgical procedure for jaw bone defects performed with autogenous grafts. It is well accepted by the patients, offering at the same time a sensitive method of studying uptake of topically applied AGP and to follow up kinetics of AGP in order to correlate quantitative data of the platelet gel life span with evolution of the bone remodelling process. Finally, the labelled granulocytes around the bone defect allow to assess the inflammatory process evolution derived from the surgical technique.

Epidemiological and virological characterization of a large community-wide outbreak of hepatitis A in southern Italy.

A large outbreak of hepatitis A virus (HAV) infection occurred in 2004 in Campania, a region of southern Italy, with 882 cases reported between 1 January and 1 August. The local public health authorities and the Italian National Institute of Health carried out investigations in order to characterize the agent, identify the source of infection and the route of transmission, and implement appropriate control measures. A web-based reporting system enhanced the flow of information between public health authorities, providing real-time epidemic curves and frequency distributions. The same 1B HAV genotype was found in 90% of sera from a subset of patients with acute disease, suggesting a local common source. A case-control study in the municipality with the highest attack rate showed that raw seafood consumption, in particular if illegally sold in water, was strongly associated with HAV illness. Samples of seafood systematically collected from retailers were found contaminated by HAV.

Small bowel Crohn's disease: comparison of enteroclysis, bowel sonography and Tc-99m-HMPAO leukocyte scintigraphy.

BACKGROUND: Crohn's disease (CD) frequently involves the small bowel. Actually, the diagnosis of CD is made by ileocolonoscopy (IC) and small bowel enteroclysis (SBE), while trans-abdominal bowel sonography (BS) and Tc-99m-HMPAO leukocyte scintigraphy (LS) are only partially used in spite of their minimal invasiveness. AIM: to compare the diagnostic accuracy of these procedures for the diagnosis of small bowel CD. PATIENTS AND METHODS: in about two years a series of consecutive subjects underwent IC, SBE, BS and LS for either suspected or known small bowel CD. RESULTS: Sensitivity, specificity, positive and negative predictive value for CD diagnosis of the studied procedures were respectively: 98%, 97%, 98% and 97% for SBE; 92%, 97%, 98%, and 88% for BS; 90%, 93%, 96% and 85% for LS. In addition, the parallel combined use of BS and LS led to overall sensitivity, specificity, positive and negative predictive value of 100%, 93%, 96%, 100%, respectively. CONCLUSION: SBE, BS and LS are accurate procedures for the diagnosis of small bowel Crohn's disease. The use of BS and LS, particularly in combination, can be proposed as early diagnostic approach to subjects with a suspicion of disease.

Abnormalities of renal endothelin during acute exacerbation in chronic obstructive pulmonary disease.

Circulating and urinary levels of endothelin (ET), an endothelium-derived vasoconstrictive and mitogenic peptide have been reported to increase in patients with chronic obstructive pulmonary disease (COPD), but the mechanisms of these abnormalities are not fully understood. Our study objectives were to evaluate pulmonary and renal ET clearance in COPD patients during an acute exacerbation. Our participants included nine consecutive patients with moderate to severe COPD without signs of right heart failure admitted for acute exacerbation and ten healthy volunteers (HV) as controls. ET was detected by radioimmunoassay in venous and arterial blood as well as in a timed urine specimen. For each subject, arterial/venous immunoreactive ET ratio (ir-ETart/ir-ETven) was evaluated as an index of its pulmonary clearance. Creatinine clearance was employed in each case to obtain a corrected renal ir-ET clearance. Glomerular filtration rate (GFR) was also assessed by dynamic(99m)Tc-diethylenetriamine pentaacetic acid renal scintigraphy in six COPD patients during acute exacerbation and at recovery. The ratio ir-ETart/ir-ETven was comparable in COPD patients (0.75+/-0.12) and in HV (0.82+/-0.09). A significant difference was found with respect to 24 h ir-ET urinary excretion between COPD patients during exacerbation as well as at recovery (respectively 142.1+/-12.8 ng/24 h and 89.0+/-15.1 ng/24 h) and HV (65.1+/-10.1 ng/24 h). ET renal clearance was higher in COPD patients than in HV (29.2+/-5.2 ml min(-1)in COPD during exacerbation; 17.5+/-3.9 ml min(-1)at recovery and 13.6+/-2.4 ml min(-1)in HV, P<0.001). GFR was 69.4+/-10.0 ml min(-1)in COPD patients during exacerbation and it significantly increased at the recovery (95.5+/-20.9 ml min(-1)P<0.001). Corrected renal clearance of the peptide was significantly correlated to GFR values during the exacerbation (r=-0.81, P<0.05). Furthermore change in renal ET production resulted associated with changes in paCO(2)(r=0.83, P<0.001) and in paO(2)(r=-0.73, P<0.05). Acute exacerbation in COPD patients causes an increase in renal ET production which is partially reversible at the recovery, in the absence of significant changes in ET-1 circulating levels. ET might contribute to the renal response to hypoxaemia and hypercapnia in COPD.

Colonoscopy and technetium-99m white cell scan in children with suspected inflammatory bowel disease.

OBJECTIVES: To determine the utility of the technetium-labeled autologous white cell scintigraphy (Tc-WCS) for detecting intestinal inflammation in children with suspected inflammatory bowel disease (IBD). Tc-WCS was compared with colonoscopy and histologic examination. STUDY DESIGN: Forty-eight children (26 boys; median age, 10 years; range, 2-17 years) with symptoms and signs suggesting IBD had colonoscopy with exploration of terminal ileum and mucosal biopsies. The scans were judged to be abnormal if activity was seen in the gut within the first hour. RESULTS: Twenty-one patients had a diagnosis of IBD (Crohn's disease, 13; ulcerative colitis, 5; indeterminate colitis, 3); results of scintigraphy were positive in 16 and negative in 5 (sensitivity, 76.2%); the latter had a moderate degree of intestinal inflammation. In 27 patients, IBD was ruled out. Results of scintigraphy were negative in children with non-specific colitis and in those with lymphoid hyperplasia of the terminal ileum, whereas results were positive in 6 of 12 patients with spondyloarthropathy. In children with IBD, there was a significant correlation between results of scintigraphy and endoscopy for the intensity of inflammation (r = 0.70); however, there was a poor correlation regarding the number of involved segments (r = 0.30) because in 16 patients, endoscopy revealed additional diseased segments as compared with scintigraphy. CONCLUSIONS: A positive Tc-WCS result indicates the presence of an inflammatory process of the gut, whereas a negative test result does not rule out intestinal inflammation, especially when the latter is of moderate degree. Colonoscopy and biopsy are the investigations of choice to establish the diagnosis of IBD and are superior to Tc-WCS in assessing topographic extension of IBD.

Measurement of glomerular filtration rate by the 99mTc-DTPA renogram is less precise than measured and predicted creatinine clearance.

The work was devised to compare measurements of glomerular filtration rate (GFR) by technetium-99m-diethylenetriaminepentacetic acid (99mTc-DTPA) renogram to those by creatinine clearance (measured and predicted by Cockroft and Gault) and by inulin clearance. A total number of 65 individuals were enrolled: 15 healthy controls and 50 patients with renal disease. Compared to inulin clearance used as the gold standard, 99mTc-DTPA overestimated at low and underestimated at high GFRs. 99mTc-DTPA measurements were less precise than creatinine clearance except for individuals with GFR >100 ml/min x 1.73 m2. Measured creatinine clearance had the highest correlation coefficient with inulin clearance, 99mTc-DTPA clearance the lowest. In correlation analyses, 81.5% of the interindividual variability for measured creatinine clearance could be explained by true differences in inulin clearance; this value dropped to 59.1 and 57.4% for predicted creatinine clearance and 99mTc-DTPA, respectively. In patients with GFR <25 ml/min x 1.73 m2, all 99mTc-DTPA measurements were out of the 95% confidence interval for the inulin measurement. It can be inferred that 99mTc-DTPA clearance from the renogram is less precise than measured and predicted creatinine clearance.

[Diagnostic accuracy and clinical significance of combined small bowel enema and scintigraphy with pure fractions of neutrophil granulocytes labeled with HMPAO-Tc99m in chronic intestinal inflammation]. / Accuratezza diagnostica e rilevanza clinica dell'integrazione tra enteroclisi del tenue e scintigrafia con frazioni pure di granulociti neutrofili marcati con HMPAO-Tc99m nell'infiammazione cronica intestinale.

Enema is the primary imaging method in the diagnosis of Crohn's disease in the small bowel, with clinical follow-up examinations performed by gastroenterologists as the gold standard. The information provided by small bowel enema, in addition to endoscopic findings, is usually sufficient for the gastroenterologist to make the definitive diagnosis and to plan the whole treatment. Scintigraphy with leukocytes labelled with HMPAO-Tc99m has several unique characteristics favoring its use as a diagnostic imaging method in Crohn's disease and ulcerative colitis. It is a noninvasive method requiring no bowel preparation and it is safe in severely ill patients in whom such conventional imaging methods as barium enema or colonscopy might be hazardous. In this study, the authors report the results of their experience with diagnostic small bowel enema and leukocyte scintigraphy with HMPAO-Tc99m in 28 patients with inflammatory bowel disease (Crohn's disease in 18 patients, ulcerative colitis in 7 and radiation-induced inflammatory stenosis of the sigma-rectum, bowel inflammation after appendicectomy and bladder surgery, respectively, in 1 patient each). Scintigraphy with autologous granulocytes with HMPAO-Tc99m was positive in 26 patients and negative in 2. Twenty-five patients were true positives and 1 was a false positive. Fifteen patients were also submitted to small bowel enema: 12 of them were positive (true positive) and 3 negative (1 false negative and 2 true negative). The results of granulocytes scintigraphy were compared with those of small bowel enema: the radionuclide study appeared superior in the assessment of bowel inflammation associated with Crohn's disease and ulcerative colitis. Indeed, scintigraphy depicted granulocyte uptake in the colon where enema had shown no major findings in 4 patients with Crohn's disease. In the author's opinion, the overall sensitivity, specificity and positive predictive value of combined leukocyte scintigraphy and small bowel enema play a major role in the early diagnosis of Crohn's disease and ulcerative colitis and in the assessment of disease extent and activity.

Treatment of advanced medullary thyroid carcinoma with a combination of recombinant interferon alpha-2b and octreotide.

BACKGROUND: The medical treatment of advanced medullary thyroid carcinoma (MTC) is still questionable. Results of chemotherapy are disappointing with almost no curative responses, few partial responses, and many side-effects. A recent report has suggested the activity of combination recombinant interferon alpha-2b (rIFN-alpha-2b) and octreotide, a somatostatin analogue, in the treatment of a metastatic carcinoid tumor. This new therapeutic schedule may be used in other neuroendocrine tumors. In this study we evaluated the therapeutic effectiveness of octreotide and rIFN-alpha-2b in patients with advanced MTC. METHODS: Eight patients affected by advanced MTC received octreotide at a daily dose of 150 micrograms for 6 months and subsequently at a daily dose of 300 micrograms for another 6 months, subcutaneously, and rIFN-alpha-2b at a daily dose of 5.000.000 IU intramuscularly 3 times a week for 12 months. Plasma calcitonin, carcinoembryonic antigenic levels, and morphologic staging were evaluated at 0, 1, 3, 6, and 12 months. RESULTS: The therapy was stopped in two patients because of diarrhea and toxicity of drugs used. Pre-existing diarrhea in four patients and flushing in one significantly improved during treatment. A maximum decrease of calcitonin was reached after 1 month in 2 patients and after 3 months in 4. In all of the patients carcinoembryonic antigen levels decreased during treatment. No significant changes of size of metastases were observed. CONCLUSIONS: The combination of octreotide and interferon is well tolerated and can be recommended for the treatment of advanced MTC.