Control of targeting ligand display by pH-responsive polymers on gold nanoparticles mediates selective entry into cancer cells.

Selective targeting of cells for intracellular delivery of therapeutics represents a major challenge for pharmaceutical intervention in disease. Here we show pH-triggered receptor-mediated endocytosis of nanoparticles via surface ligand exposure. Gold nanoparticles were decorated with two polymers: a 2 kDa PEG with a terminal folate targeting ligand, and a di-block copolymer including a pH-responsive and a hydrophilic block. At the normal serum pH of 7.4, the pH-responsive block (apparent pKa of 7.1) displayed a hydrophilic extended conformation, shielding the PEG-folate ligands, which inhibited cellular uptake of the nanoparticles. Under pH conditions resembling those of the extracellular matrix around solid tumours (pH 6.5), protonation of the pH-responsive polymer triggered a coil-to-globule polymer chain contraction, exposing folate residues on the PEG chains. In line with this, endocytosis of folate-decorated polymer-coated gold nanoparticles in cancer cells overexpressing folate receptor was significantly increased at pH 6.5, compared with pH 7.4. Thus, the tumour acidic environment and high folate receptor expression were effectively exploited to activate cell binding and endocytosis of these nanoparticles. These data provide proof-of-concept for strategies enabling extracellular pH stimuli to selectively enhance cellular uptake of drug delivery vectors and their associated therapeutic cargo.

Is HCMV vaccine an unmet need? The state of art of vaccine development.

Congenital HCMV infection is the most frequent congenital infection, with an incidence of 0.2- 2.5 percent among all live births. About 11 percent of infected newborns show symptoms at birth, including hepato-splenomegaly, thrombocytopenia, neurologic involvement, hearing impairment and visual deficit. Moreover, 5-25 percent of the asymptomatic congenital HCMV-infected neonates will develop sequelae over months or even years. The relevant social burden, the economic costs of pre-natal screening, post-natal diagnosis, follow-up and possible therapy, although still limited, are the major factors to be considered. Several types of vaccines have been explored in order to develop an effective and safe HCMV vaccine: live attenuated, subunit, vectored, peptide, DNA, and subviral ones, but none are available for use. This review illustrates the different vaccine types studied to date, focusing on the possible vaccination strategy to be implemented once the HCMV vaccine is available, in terms of target population.

Psychopathological chronic sequelae of the 2009 earthquake in L'Aquila, Italy.

BACKGROUND: To date, there are no data available among the general adult population on the long-term psychological sequelae of the earthquake that occurred in the town of L'Aquila, Italy in 2009. We investigated the prevalence of post-traumatic stress disorder (PTSD) and major depression (MD) and identified risk factors for these disorders among adult survivors more than one year after the earthquake. METHODS: Telephone interviews were conducted among a random sample of 957 resident adults. The interviews were performed using a questionnaire on exposure to the earthquake, the Mini-International Neuropsychiatric Interview for PTSD, and the Patient Health Questionnaire 8 for MD. Univariate and multivariate logistic regression analyses were conducted to assess potential risk factors. RESULTS: The prevalence rates of PTSD and MD were 4.1% (95% CI=3.0-5.5) and 5.8% (95% CI=4.5-7.5), respectively. The risk factors for PTSD were economic difficulties not necessarily related to the earthquake, chronic disease, death of a relative or friend, and serious economic difficulties as consequence of the earthquake, whereas those for MD were female gender, economic difficulties not necessarily related to the earthquake, not having a permanent job and living in L'Aquila. LIMITATIONS: The major limitations were the cross sectional design and the uncertain accuracy of the diagnoses compared with clinical diagnoses. CONCLUSIONS: Psychological symptoms are frequent even 14-19 months after the L'Aquila earthquake. The mental health care providers in the area of L'Aquila should be aware of the possibility of PTSD or MD among their users.

Epidemiological surveillance of West Nile neuroinvasive diseases in Italy, 2008 to 2011.

We describe the geographical and temporal distribution of West Nile neuroinvasive diseases (WNND) cases in Italy from 2008 to 2011. The increasing number of confirmed human cases from eight in 2008 to 18 in 2009 and the occurrence of the virus in a larger geographical area in 2009 (moving from east to west) prompted the Ministry of Health to publish, in spring 2010, a national programme for WNND human surveillance, comprising veterinary and vector surveillance. Subsequently, in 2011, a new national plan on integrated human surveillance of imported and autochthonous vector-borne diseases (chikungunya, dengue and West Nile disease) was issued. Between 2008 and 2011, 43 cases of WNND were reported from five regions in Italy with a case fatality rate of 16%. The incidence of WNND during the entire study period was 0.55 per 100,000 population (range: 0.06­0.23 per 100,000). During 2011, two new regions (Friuli-Venezia Giulia and Sardinia) reported confirmed cases in humans. Integrated human, entomological and animal surveillance for West Nile virus is a public health priority in Italy and will be maintained during 2012.

Response to the 2009 influenza A(H1N1) pandemic in Italy.

In Italy, the arrival of the 2009 pandemic influenza A(H1N1) virus triggered an integrated response that was mainly based on the 2006 National Pandemic Preparedness and Response Plan. In this article we analyse the main activities implemented for epidemiological surveillance, containment and mitigation of the pandemic influenza and the lesson learned from this experience. Overall, from week 31 (27 July ­ 2 August) of 2009 to week 17 (26 April ­ 2 May) of 2010, we estimate that there were approximately 5,600,000 cases of influenza-like illness (ILI) who received medical attention (with almost 2,000 laboratory-confirmed cases of pandemic influenza from May to October 2009). A total of 1,106 confirmed cases were admitted to hospital for serious conditions, of whom 532 were admitted to intensive care units. There were 260 reported deaths due to pandemic influenza. Approximately 870,000 first doses of the pandemic vaccine were administered, representing a vaccine coverage of 4% of the target population. One of the possible reasons for the low uptake of the pandemic vaccine in the target population could be the communication strategy adopted, for both the general population and healthcare workers, which turned out to be a major challenge. Active involvement of all health professionals (at local, regional and national level) in influenza pandemic preparedness and response should be encouraged in the future.

Differences in national influenza vaccination policies across the European Union, Norway and Iceland 2008-2009.

In 2009 the second cross-sectional web-based survey was undertaken by the Vaccine European New Integrated Collaboration Effort (VENICE) project across 27 European Union (EU) member states (MS), Norway and Iceland (n=29) to determine changes in official national seasonal influenza vaccination policies since a survey undertaken in 2008 and to compare the estimates of vaccination coverage between countries using data obtained from both surveys. Of 27 responding countries, all recommended vaccination against seasonal influenza to the older adult population. Six countries recommended vaccination of children aged between six months and <18 years old. Most countries recommended influenza vaccination for those individuals with chronic medical conditions. Recommendations for vaccination of healthcare workers (HCW) in various settings existed in most, but not all countries. Staff in hospitals and long-term care facilities were recommended vaccination in 23 countries, and staff in out-patient clinics in 22 countries. In the 2009 survey, the reported national estimates on vaccine coverage varied by country and risk group, ranging from 1.1% - 82.6% for the older adult population; to between 32.9% -71.7% for clinical risk groups; and from 13.4% -89.4% for HCW. Many countries that recommend the influenza vaccination do not monitor the coverage in risk groups. In 2008 and 2009 most countries recommended influenza vaccination for the main risk groups. However, despite general consensus and recommendations for vaccination of high risk groups, many countries do not achieve high coverage in these groups. The reported vaccination coverage still needs to be improved in order to achieve EU and World Health Organization goals.

West Nile virus transmission with human cases in Italy, August - September 2009.

In 2009, to date 16 human cases of West Nile neuroinvasive disease (WNND) have been reported in Italy, in three regions: Veneto, Emilia-Romagna and Lombardia. The number of cases is higher compared with last year when nine cases were identified (eight cases of WNND and one case of West Nile fever) and the geographical distribution indicates spread from east to west.

The current state of introduction of HPV vaccination into national immunisation schedules in Europe: results of the VENICE 2008 survey.

Three surveys have been undertaken in European Union (EU) member states since January 2007, within the European Commission funded Vaccine European New Integrated Collaboration Effort (VENICE) project, to monitor the decision status regarding the introduction of human papillomavirus (HPV) vaccination into national immunisation schedules. A web-based questionnaire was developed and completed online by the 28 countries participating in VENICE. According to the last update (31st December 2008), 15 countries have decided to introduce HPV vaccination into their national immunisation schedule, while another six have started the decision-making process with a recommendation favouring introduction. Varying target populations have been selected by the countries which have introduced vaccination. The number of countries which have made a decision or recommendation has increased from 12 to 21 between October 2007 and December 2008. This survey demonstrates the rapidly evolving nature of HPV vaccine introduction in Europe. A further update should be available in the second half of 2009.

Enhanced epidemiological surveillance of influenza A(H1N1)v in Italy.

As of 7 July 2009, a total of 158 laboratory-confirmed cases of influenza A(H1N1)v were reported in Italy, from half of the 21 Italian regions. To date all cases have had symptoms consistent with seasonal influenza and no severe or fatal cases have been reported. An active surveillance of cases has been set up in Italy in order to undertake appropriate measures to slow down the spread of the new virus. This report describes the routine and enhanced surveillance currently ongoing in Italy.

Characterisation of Neisseria meningitidis C strains causing two clusters in the north of Italy in 2007 and 2008.

Two clusters of invasive meningococcal disease in the north of Italy both due to serogroup C/ST-11 clonal complex are here described. The objective of the investigation was to analyse the phenotype and the genotype of meningococci involved in the two clusters which were of national relevance due to the fatal outcome of the majority of cases (six of the total of 10 cases). All the strains were C:2a:P1.5 ST-11/ET-37 clonal complex. Two pulsed field gel electrophoresis (PFGE) and variable number tandem repeats (VNTR) profiles were identified, one for each cluster. VNTRs were different from those detected in Italy for C/ST-11 strains isolated from sporadic cases in the same period. This laboratory surveillance report highlights the importance and the crucial role of molecular characterisation to confirm the relatedness among meningococci responsible for clusters of cases.

National seasonal influenza vaccination survey in Europe, 2008.

A cross-sectional survey was undertaken with the European Union (EU) Member States and Norway and Iceland to describe seasonal influenza immunisation in the 2006-7 season, in particular to identify country-specific recommendations for risk groups, obtain vaccine uptake information and allow comparison with global recommendations. A standardised questionnaire was completed electronically by each country's project gatekeeper. Of the 29 countries surveyed, 28 recommended seasonal influenza vaccination for older age groups (22 for those aged > 65 years), and in one country vaccine was recommended for all age groups. All countries recommended vaccinating patients with chronic pulmonary and cardiovascular diseases and most countries advised to immunise patients with haematologic or metabolic disorders (n=28), immunologic disorders (n=27) and renal disease (n=27), as well as residents of long-term care facilities (n=24). Most countries recommended vaccination for staff in hospitals (n=25), long-term care facilities (n=25) and outpatient clinics (n=23), and one-third had such recommendations for workers in essential (n=10), military (n=10) and veterinary services (n=10) and poultry industry (n=13). Eight countries recommended vaccine for pregnant women; and five advised to vaccinate children (with age limits ranging from 6 months to 5 years). Twenty countries measured influenza vaccine uptake among those aged > 65 years (range 1.8%-82.1%), seven reported uptake in healthcare workers (range 14%-48%) and seven assessed coverage in persons with underlying medical conditions (range 27.6%-75.2%). The data provided by this study can assist EU states to assess and compare their influenza vaccination programme performance with other countries. The information provides a comprehensive overview of policies and programmes and their outcomes and can be used to inform joint discussions on how the national policies in the EU might be standardised in the future to achieve optimal coverage. Annual surveys could be used to monitor changes in these national policies.

Introduction of human papillomavirus (HPV) vaccination into national immunisation schedules in Europe: Results of the VENICE 2007 survey.

The European Union Member States are simultaneously considering introducing HPV vaccination into their national immunisation schedules. The Vaccine European New Integrated Collaboration Effort (VENICE) project aims to develop a collaborative European vaccination network. A survey was undertaken to describe the decision status and the decision-making process regarding the potential introduction of human papillomavirus (HPV) vaccination in to their national immunisation schedules. A web-based questionnaire was developed and completed online in 2007 by 28 countries participating in VENICE. As of 31 October 2007,five countries had decided to introduce HPV vaccination into the national immunisation schedule, while another seven had started the decision-making process with a recommendation favouring introduction. Varying target populations were selected by the five countries which had introduced the vaccination. Half of the surveyed countries had undertaken at least one ad hoc study to support the decision-making process. According to an update of the decision-status from January 2008, the number of countries which had made a decision or recommendation changed to 10 and 5 respectively. This survey demonstrates the rapidly evolving nature of HPV vaccine introduction in Europe and the existence of expertise and experience among EU Member States. The VENICE network is capable of following this process and supporting countries in making vaccine introduction decisions. A VENICE collaborative web-space is being developed as a European resource for the decision-making process for vaccine introduction.

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.