Alessia Stival

Pertussis re-emergence in the post-vaccination era

BackgroundResurgence of pertussis in the post-vaccination era has been reported in Western countries. A shift of cases from school-age children to adolescents, adults and children under 1 year of age has been described in the last decade, and mortality rates in infants are still sustained. We aimed to review and discuss the possible vaccination strategies which can be adopted in order to improve the pertussis control, by searches of Pubmed, and websites of US and European Centers for Disease Control and Prevention, between 1st January 2002, and 1st March 2013.DiscussionThe following vaccination strategies have been retrieved and analysed: the cocooning strategy, the immunization of pregnant women and newborns, vaccination programs for preschool children, adolescents, adults and health-care workers. Cost-effectiveness studies provide some contrasting data, mainly supporting both maternal vaccination and cocooning. Adolescent and/or adult vaccination seems to be cost-effective, however data from observational studies suggest that this vaccination strategy, used alone, leads to a reduced pertussis burden globally, but does not affect the disease incidence in infants. Moreover, substantial logistical and economic difficulties have to be overcome to vaccinate the largest number of individuals.SummaryThe simultaneous use of more than one strategy, including cocooning strategy plus vaccination of adolescents and adults, seems to be the most reasonable preventive measure. The development of new highly immunogenic and efficacious pertussis vaccines continues to be a primary objective for the control of pertussis.

Vaccine effectiveness against severe laboratory-confirmed influenza in children: results of two consecutive seasons in Italy

OBJECTIVE To evaluate the effectiveness of seasonal influenza vaccine in preventing Emergency Department (ED) visits and hospitalisations for influenza like illness (ILI) in children. METHODS We conducted a test negative case-control study during the 2011-2012 and 2012-2013 influenza seasons. Eleven paediatric hospital/wards in seven Italian regions participated in the study. Consecutive children visiting the ED with an ILI, as diagnosed by the doctor according to the European Centre for Disease Control case definition, were eligible for the study. Data were collected from trained pharmacists/physicians by interviewing parents during the ED visit (or hospital admission) of their children. An influenza microbiological test (RT-PCR) was carried out in all children. RESULTS Seven-hundred and four children, from 6 months to 16 years of age, were enrolled: 262 children tested positive for one of the influenza viruses (cases) and 442 tested negative (controls). Cases were older than controls (median age 46 vs. 29 months), though with a similar prevalence of chronic conditions. Only 25 children (4%) were vaccinated in the study period. The overall age-adjusted vaccine effectiveness (VE) was 38% (95% confidence interval -52% to 75%). A higher VE was estimated for hospitalised children (53%; 95% confidence interval -45% to 85%). DISCUSSION This study supports the effectiveness of the seasonal influenza vaccine in preventing visits to the EDs and hospitalisations for ILI in children, although the estimates were not statistically significant and with wide confidence intervals. Future systematic reviews of available data will provide more robust evidence for recommending influenza vaccination in children.

Sexual dimorphism in tuberculosis incidence: children cases compared to adult cases in Tuscany from 1997 to 2011.

Background In most countries, men seem to be more susceptible to tuberculosis (TB) than women, but only few studies have investigated the reasons of this gender incidence difference. The effect of sexual hormones on immunity is possible. Methods Data from children and adults, living in Tuscany, hospitalized for TB in all the thirty-one regional hospitals from January 1st 1997 to December 31st 2011, were analyzed using the International Classification of Disease, 9th Revision, Clinical Modification. Results During the study period, 10,744 patients were hospitalized with TB diagnosis, precisely 279 (2.6%) children [0–14 years], 205 (1.9%) adolescents [15–18 years] and 10,260 (95.5%) adults [≥18 years]. The male population ranged from 249 patients (51.4%) in children and adolescents, to 6,253 (60.9%) in adults. Pulmonary TB was the most common form both in children and adults. Men were more likely than women to have pulmonary TB after puberty, while no significant differences were found between males and females in the hospitalized children. The male gender also resulted the most affected for the extra-pulmonary disease sites, excluding the lymphatic system, during the reproductive age. Conclusions Our findings suggest a possible role of sexual hormones in the development of TB. No significant male-female difference was found in TB incidence among children, while a sex ratio significantly different from 1∶1 emerged among reproductive age classes. An increased incidence difference also persisted in older men, suggesting that male-biased risk factors could influence TB progression. Some limitations of the study are the sample size, the method of discharge diagnosis which could be deficient in accuracy in some cases, the increasing number of immigrants and the lack of possible individual risk factors (smoke and alcohol). Further studies are needed to investigate the possible hormone-driven immune mechanisms determining the sexual dimorphism in TB.

Blood-Brain Barrier and Breast Cancer Resistance Protein: A Limit to the Therapy of CNS Tumors and Neurodegenerative Diseases

The treatment of brain tumors and neurodegenerative diseases, represents an ongoing challenge. In Central Nervous System (CNS) the achievement of therapeutic concentration of chemical agents is complicated by the presence of distinct set of efflux proteins, such as ATP-Binding Cassette (ABC) transporters localized on the Blood-Brain Barrier (BBB). The activity of ABC transporters seems to be a common mechanism that underlies the poor response of CNS diseases to therapies. The molecular characterization of Breast Cancer Resistance Protein (BCRP/ABCG2), as an ABC transporter conferring multidrug resistance (MDR), has stimulated many studies to investigate its activity on the BBB, its involvement in physiology and CNS diseases and its role in limiting the delivery of drugs in CNS. In this review, we highlight the activity and localization of BCRP on the BBB and the action that this efflux pump has on many conventional drugs or latest generation molecules used for the treatment of CNS tumors and other neurodegenerative diseases.

The Use of Anthracyclines for Therapy of CNS Tumors

Despite being long lived, anthracyclines remain the “evergreen” drugs in clinical practice of oncology, showing a potent effect in inhibiting cell growth in many types of tumors, including brain neoplasms. Unfortunately, they suffer from a poor penetration into the brain when intravenously administered due to multidrug resistance mechanism, which hampers their delivery across the blood brain barrier. In this paper, we summarize the current literature on the role of anthracyclines in cancer therapy and highlight recent efforts on 1) development of tumor cell resistance to anthracyclines and 2) the new approaches to brain drug delivery across the blood brain barrier.