Imported Methicillin-Resistant Staphylococcus aureus, Sweden

Knowledge of different risks for infection will improve control measures

Discovery of a novel class of highly conserved vaccine antigens using genomic scale antigenic fingerprinting of pneumococcus with human antibodies

Pneumococcus is one of the most important human pathogens that causes life-threatening invasive diseases, especially at the extremities of age. Capsular polysaccharides (CPSs) are known to induce protective antibodies; however, it is not feasible to develop CPS-based vaccines that cover all of the 90 disease-causing serotypes. We applied a genomic approach and described the antibody repertoire for pneumococcal proteins using display libraries expressing 15–150 amino acid fragments of the pathogen's proteome. Serum antibodies of exposed, but not infected, individuals and convalescing patients identified the ANTIGENome of pneumococcus consisting of ∼140 antigens, many of them surface exposed. Based on several in vitro assays, 18 novel candidates were preselected for animal studies, and 4 of them showed significant protection against lethal sepsis. Two lead vaccine candidates, protein required for cell wall separation of group B streptococcus (PcsB) and serine/threonine protein kinase (StkP), were found to be exceptionally conserved among clinical isolates (>99.5% identity) and cross-protective against four different serotypes in lethal sepsis and pneumonia models, and have important nonredundant functions in bacterial multiplication based on gene deletion studies. We describe for the first time opsonophagocytic killing activity for pneumococcal protein antigens. A vaccine containing PcsB and StkP is intended for the prevention of infections caused by all serotypes of pneumococcus in the elderly and in children

Forecasting drug utilization and expenditure in a metropolitan health region

<p>Abstract</p> <p>Background</p> <p>New pharmacological therapies are challenging the healthcare systems, and there is an increasing need to assess their therapeutic value in relation to existing alternatives as well as their potential budget impact. Consequently, new models to introduce drugs in healthcare are urgently needed. In the metropolitan health region of Stockholm, Sweden, a model has been developed including early warning (horizon scanning), forecasting of drug utilization and expenditure, critical drug evaluation as well as structured programs for the introduction and follow-up of new drugs. The aim of this paper is to present the forecasting model and the predicted growth in all therapeutic areas in 2010 and 2011.</p> <p>Methods</p> <p>Linear regression analysis was applied to aggregate sales data on hospital sales and dispensed drugs in ambulatory care, including both reimbursed expenditure and patient co-payment. The linear regression was applied on each pharmacological group based on four observations 2006-2009, and the crude predictions estimated for the coming two years 2010-2011. The crude predictions were then adjusted for factors likely to increase or decrease future utilization and expenditure, such as patent expiries, new drugs to be launched or new guidelines from national bodies or the regional Drug and Therapeutics Committee. The assessment included a close collaboration with clinical, clinical pharmacological and pharmaceutical experts from the regional Drug and Therapeutics Committee.</p> <p>Results</p> <p>The annual increase in total expenditure for prescription and hospital drugs was predicted to be 2.0% in 2010 and 4.0% in 2011. Expenditures will increase in most therapeutic areas, but most predominantly for antineoplastic and immune modulating agents as well as drugs for the nervous system, infectious diseases, and blood and blood-forming organs.</p> <p>Conclusions</p> <p>The utilisation and expenditure of drugs is difficult to forecast due to uncertainties about the rate of adoption of new medicines and various ongoing healthcare reforms and activities to improve the quality and efficiency of prescribing. Nevertheless, we believe our model will be valuable as an early warning system to start developing guidance for new drugs including systems to monitor their effectiveness, safety and cost-effectiveness in clinical practice.</p

2000. Recurrence of pneumonia in relation to the antibody response after pneumococcal vaccination in middle-aged and elderly

We have recently studied the efficacy of pneumococcal vaccine in preventing pneumonia recurrences after hospital treatment for community-acquired pneumonia in non-immunocompromised patients aged 50 -85 y. Among these patients, we have now compared the antibody response to the pneumococcal vaccine between patients who developed pneumonia (n =50) and patients without pneumonia recurrences (n= 100), during a mean follow-up period of 32 months after vaccination. The antibody levels of 5 pneumococcal serotypes were measured before, and 4 weeks, 1 y and 3 y after vaccination. A lower risk of pneumonia recurrences was seen in patients with antibody fold increases (FIs) \ 4 from pre-vaccination to post-vaccination compared with patients with lower FIs (p =0.02). The results suggest that in this patient category, the antibody response to pneumococcal vaccination is of importance for the risk of pneumonia recurrence

Antibody Response to Pneumococcal Polysaccharide Vaccination Predicts Pneumococcal Disease in Splenectomized Patients with Hematological Diseases

Abstract Patients with hematological diseases undergoing diagnostic or therapeutic splenectomy are at increased risk of acquiring fulminant pneumococcal infections. Vaccination is a straightforward option in reducing these infections. Certain patient subgroups showing inadequate immunological response to pneumococcal vaccination may be candidates for alternative prophylactic measures. We prospectively studied the antibody response to vaccination with 23-valent pneumococcal capsular polysaccharide vaccine (Pneumovax N) in splenectomized patients with hematological disorders in relation to clinical characteristics and pneumococcal disease. A total of 76 splenectomized patients (Hodgkin s lymphoma 26, indolent lymphoma 10, aggressive lymphoma 8, immune hemolytic anemia 6, immune thrombocytopenic purpura 22, and others 4) with a median age of 52 years (range 18–82) were included. Antibody titers were determined using an enzyme-linked immunosorbent assay before and 12 months after vaccination. A weak immunological response was observed in 27 (35%) patients (poor responders) and an adequate response in 49 (65%) (good responders). During the follow-up period of 5–9 years after vaccination and despite repeated revaccination in many cases, a total of 5 episodes of microbiologically verified pneumococcal infections were reported in poor responders, while only one episode was noted among good responders (p=.01). Underlying malignant hematological diseases were more frequent among poor responders than among good responders (p=.002). The distribution of patients according to age, gender, immunoglobulin levels, time between splenectomy and vaccination (), time between preceding chemotherapy/radiotherapy and vaccination () and/or previous radiotherapy did not differ between poor and good responders. In conclusion, a significant number of splenectomized patients with hematological diseases respond poorly to pneumococcal vaccination and have a significantly increased risk of post-splenectomy pneumococcal infections despite vaccination. In the absence of clinical parameters that can reliably predict a poor antibody response, measurement of antibody titers 12 months after vaccination seems to be the most adequate method for identification of patients in this subgroup. Poor responders may be offered other prophylactic measures such as antibiotic prophylaxis and/or immunization with pneumococcal conjugate vaccines. Studies to further elucidate the last alternative are ongoing

Poor antibody response to pneumococcal polysaccharide vaccination suggests increased susceptibility to pneumococcal infection in splenectomized patients with hematological diseases

Patients with hematological diseases undergoing diagnostic or therapeutic splenectomy are at increased risk of pneumococcal infections. Vaccination is a straightforward option in preventing these infections. A well-defined cohort of splenectomized patients with hematological disorders was followed according to response to 23-valent pneumococcal capsular polysaccharide (Pneumovax N ®) vaccination. A total of 76 splenectomized patients (Hodgkin lymphoma, HL 26, non-Hodgkin lymphoma, NHL 19, immune-mediated cytopenias 28, and others 3) with a median age of 52 years (range 18–82 years) were included. Pneumococcal polysaccharide (PS) antibodies were determined using an enzyme-linked immunosorbent assay before vaccination, at peak, and follow-up. A poor response to vaccination was observed in 21 (28%) patients and a good response in 55 (72%), respectively. During the follow-up period of 7.5 years (range 3.5–10.5 years) after vaccination, and despite repeated revaccination in many cases, a total of five episodes (in three patients) of pneumococcal infections were reported, all confined to the poor responder group. Revaccination did not improve antibody levels in this group. The median age at vaccination was significantly higher in the group of poor responders ( p = 0.0006). None of the following factors could predict a poor antibody response: gender, disease activity or aggressiveness in hematological malignancies, previous radiotherapy and/or chemotherapy, time between splenectomy and pneumococcal vaccination, time between chemotherapy/radiotherapy and study pneumococcal vaccination (1 year), or the presence of hypogammaglobulinemia. In conclusion, a substantial proportion of splenectomized patients with hematological diseases mounted a poor PS antibody response and remained at risk for pneumococcal infections despite vaccination. In the absence of apt indirect clinical predictors of antibody response, with the exception of age, measurement of antibody levels seems to be a feasible method for early identification of this patient subgroup. Poor responders do not benefit from revaccination, and should be offered other prophylactic measures