Establishing the health and economic impact of influenza vaccination within the European Union 25 countries

BACKGROUND: In 2003, the World Health Assembly (WHA) issued a resolution for prevention and control of influenza pandemics and annual epidemics, which urges the European Union 25 (EU-25) Member States to (1) establish and implement strategies to increase vaccination coverage of all people at high risk, including the elderly and people with underlying disease, with the goal of attaining vaccination coverage of the elderly population of at least 50% by 2006 and 75% by 2010; (2) to assess the disease burden and economic impact of annual influenza epidemics as a basis for framing and implementing influenza prevention policies. This resolution was reinforced by the European Union (EU), where Member States agreed to make additional efforts to improve uptake on their territory in accordance with their own recommendations and to achieve the World Health Organisation (WHO) target of 75% in high risk groups before 2010. It was also noted that the changing demographic profile of the EU population would result in an increasing number of elderly people falling within the current target groups. OBJECTIVES: To establish the number of people who may be eligible for influenza vaccination in the EU, and estimate the costs and consequences of not vaccinating this population for five EU Member States, France, Germany, Italy, Spain, and the UK. METHODS: A mathematical model has previously been developed, in which vaccine distribution data are combined with demographic and health economics data to model the public health consequences of influenza and possible intervention strategies. We have extended that model using specific EU-25 demographic data on populations at risk of influenza during the inter-pandemic period. For each country, the total population and age breakdown was calculated to estimate the percentage of the population that falls under the WHA recommendations. Other target groups for influenza vaccination were identified by analysing estimating the proportion of the population with respiratory or cardiovascular related diseases, diabetes, AIDS or transplantation, as well as health care professionals. Target population size and possible vaccination coverage rates across the EU-25 Member States, along with the potential cost and health consequence impact is estimated. RESULTS: For the EU-25, it was estimated that up to 49.1% of the population (or 223.4 million people) should be vaccinated against influenza. This ranged from 41.6% in Cyprus to 56.4% in the UK. There were, on average, 174 vaccine doses distributed per 1000 population within the EU-25, which leads to an average vaccination rate of the target population of 35.4% based on current supply constraints. As a consequence, up to 144.4 million people who could be considered "at risk" may not currently be vaccinated. Implementing a 100% vaccination rate programme for all risk groups across the EU-25 would lead to an estimated reduction of number of influenza cases of 7.22 million, 1.96 million reduced PCP visits for influenza treatment, 796,743 less hospital admissions and 68,537 fewer influenza related deaths for all EU-25 countries. The implementation of a 100% vaccination rate programme for all risk groups in France, Germany, Italy, Spain and UK would require an additional 1.52 billion Euro. This would result in estimated savings of 39.45 million Euro of reduced primary care visits and further savings of 1.59 billion Euro in reduced hospitalisations respectively in these countries. CONCLUSIONS: There is a gap between current vaccination coverage and the EU recommendations. The public health consequences of low vaccination coverage include increased morbidity, hospitalisations and mortality associated with influenza-related complications. This model is a powerful tool to: (1) support EU public health officials in implementing recommendations; (2) to visualize the need for increased vaccination rates for better influenza control; (3) the consequences of low vaccine coverage.     

The Unenlarged Lymph Nodes of HIV-1–infected, Asymptomatic Patients with High CD4 T Cell Counts Are Sites for Virus Replication and CD4 T Cell Proliferation. The Impact of Highly Active Antiretroviral Therapy

The efficacy of triple drug therapy for HIV-1 infection encourages its early use to prevent damage to the immune system. We monitored the effects of such therapy on 12 patients with 14–75-mo histories of minimal disease, i.e., CD4⁺ counts constantly >500/μl and little or no lymph node enlargement. In this way, we could first determine the extent of viral replication and immunoarchitectural changes in unenlarged nodes early in disease, and second follow the response to triple therapy in plasma and lymphoid tissue in tandem. As is known for lymph nodes with more advanced disease, the germinal centers showed productively infected T cells, i.e., CD4⁺CD1a⁻CD68⁻ cells labeling intensely for HIV-1 RNA after in situ hybridization. The unenlarged nodes also showed extensive HIV-1 RNA retention on a well-preserved, follicular dendritic cell (FDC) network, and the follicles were abnormal. There were numerous CD8⁺ cells, many expressing TIA-1 granule antigen. Also, in contrast to normal follicles, CD4⁺ T cell proliferation was active, with marked increases in the number of cycling, Ki-67⁺CD4⁺CD45R0⁺ cells. After 28 d and 3 mo of therapy, productively infected T cells decreased dramatically and often were not apparent. The labeling of the FDC network for viral RNA also decreased, but not for gag protein. We conclude that HIV-1 replicates and accumulates in lymphoid organs before damage of the immune system, that at this stage of disease de novo production of T cells occurs in the lymphoid tissue, and that the infection is sensitive to triple drug therapy in both plasma and lymph nodes.     

Allogeneic haematopoietic stem cell transplantation in relapsed or refractory anaplastic large cell lymphoma of children and adolescents--a Berlin-Frankfurt-Münster group report

Patients with refractory or early relapsed anaplastic large cell lymphoma (ALCL) have a poor chance of survival. We report 20 children and adolescents with high-risk relapsed or refractory ALCL who underwent allogeneic haematopoietic stem cell transplantation (HSCT). We retrospectively analysed 20 patients who relapsed between December 1991 and April 2003 during (six patients) or soon after first-line Berlin-Frankfurt-Münster-type chemotherapy (14 patients) and underwent allogeneic HSCT. Nine patients received allogeneic HSCT after the first relapse and 11 after multiple relapses. Eight patients received their transplants from matched sibling donors, eight from unrelated donors and four from haploidentical family donors. The conditioning regimen was based on total body irradiation in 15 patients. Two patients relapsed after allogeneic HSCT and died. Three patients died of transplant-related toxicity. Event-free survival at 3 years after allogeneic transplant was 75 +/- 10%. There was no influence of donor type or conditioning regimen on outcome. Two of six patients with progressive disease during frontline therapy survived compared with 13/14 patients with a first relapse after frontline therapy. Two of three patients who were transplanted with active lymphoma and all five patients who received allogeneic HSCT for relapse following autologous HSCT survived disease-free. Allogeneic HSCT is effective and has acceptable toxicity as rescue therapy for high-risk ALCL relapse. It even offers cure for patients refractory to chemotherapy, suggesting a graft-versus-ALCL effect.     

Role of Energy Sensor TlpD of Helicobacter pylori in Gerbil Colonization and Genome Analyses after Adaptation in the Gerbil

Helicobacter pylori maintains colonization in its human host using a limited set of taxis sensors. TlpD is a proposed energy taxis sensor of H. pylori and dominant under environmental conditions of low bacterial energy yield. We studied the impact of H. pylori TlpD on colonization in vivo using a gerbil infection model which closely mimics the gastric physiology of humans. A gerbil-adapted H. pylori strain, HP87 P7, showed energy-dependent behavior, while its isogenic tlpD mutant lost it. A TlpD-complemented strain regained the wild-type phenotype. Infection of gerbils with the complemented strain demonstrated that TlpD is important for persistent infection in the antrum and corpus and suggested a role of TlpD in horizontal navigation and persistent corpus colonization. As a part of the full characterization of the model and to gain insight into the genetic basis of H. pylori adaptation to the gerbil, we determined the complete genome sequences of the gerbil-adapted strain HP87 P7, two HP87 P7 tlpD mutants before and after gerbil passage, and the original human isolate, HP87. The integrity of the genome, including that of a functional cag pathogenicity island, was maintained after gerbil adaptation. Genetic and phenotypic differences between the strains were observed. Major differences between the gerbil-adapted strain and the human isolate emerged, including evidence of recent recombination. Passage of the tlpD mutant through the gerbil selected for gain-of-function variation in a fucosyltransferase gene, futC (HP0093). In conclusion, a gerbil-adapted H. pylori strain with a stable genome has helped to establish that TlpD has important functions for persistent colonization in the stomach.     

Detectability of Fast Ripples (>250 Hz) on the Scalp EEG: A Proof-of-Principle Study with Subdermal Electrodes

To evaluate the possibility of detecting fast ripples (FRs) on the surface EEG of patients with focal pharmacoresistant epilepsy, and to investigate the relationship between scalp FRs and localization of the seizure onset zone (SOZ). We included 10 patients undergoing combined surface–intracranial EEG with ≥10 spikes in the surface EEG during the first 30 consecutive minutes of N3 sleep. FRs (≥4 consecutive oscillations above 250 Hz with an amplitude clearly exceeding that of the background) on the surface EEG (F3-C3, C3-P3, Fz-Cz, Cz-Pz, F4-C4, C4-P4) were visually marked, and verified by two EEG experts. FRs were categorized as related to the SOZ, if localized in the brain lobe of the SOZ. Low-amplitude FRs with a rate of 0.09/min were found in 6/10 patients: two exhibited events related to the SOZ, three showed no relationship with the SOZ, and in one patient the SOZ was not identified. It may be possible to detect FRs with surface EEG using subdermal electrodes in patients with focal epilepsy. The relationship between surface FRs and the SOZ remains unclear. Future studies aiming at a higher spatial EEG coverage are needed to elucidate their significance.     

Gene Deletions in Mycobacterium bovis BCG Stimulate Increased CD8+ T Cell Responses

Mycobacteria, the etiological agents of tuberculosis and leprosy, have coevolved with mammals for millions of years and have numerous ways of suppressing their host''s immune response. It has been suggested that mycobacteria may contain genes that reduce the host''s ability to elicit CD8⁺ T cell responses. We screened 3,290 mutant Mycobacterium bovis bacillus Calmette Guerin (BCG) strains to identify genes that decrease major histocompatibility complex (MHC) class I presentation of mycobacterium-encoded epitope peptides. Through our analysis, we identified 16 mutant BCG strains that generated increased transgene product-specific CD8⁺ T cell responses. The genes disrupted in these mutant strains had disparate predicted functions. Reconstruction of strains via targeted deletion of genes identified in the screen recapitulated the enhanced immunogenicity phenotype of the original mutant strains. When we introduced the simian immunodeficiency virus (SIV) gag gene into several of these novel BCG strains, we observed enhanced SIV Gag-specific CD8⁺ T cell responses in vivo. This study demonstrates that mycobacteria carry numerous genes that act to dampen CD8⁺ T cell responses and suggests that genetic modification of these genes may generate a novel group of recombinant BCG strains capable of serving as more effective and immunogenic vaccine vectors.     

Calcium absorption is not increased by caseinophosphopeptides

BACKGROUND: One of the suggested health benefits of caseinophosphopeptides (CPPs) is their ability to enhance calcium absorption. This possibility is based on the assumption that they resist proteolysis in the upper gastrointestinal tract and maintain calcium in a soluble form at alkaline pH in the distal ileum. OBJECTIVE: The effects of CPP-enriched preparations (containing candidate functional food ingredients) on calcium absorption from a calcium lactate drink were tested. DESIGN: A randomized crossover trial was undertaken in 15 adults in whom we measured the absorption of calcium from a calcium lactate drink (drink A: 400 mg Ca as lactate) and 2 preparations enriched with forms of CPP (1.7 g each; drinks B and C). Both drinks B and C contained 400 mg Ca as calcium lactate plus approximately 100 mg CPP-derived calcium). Each volunteer received the 3 drinks in random order. Absorption was measured by the dual-label calcium stable-isotope technique. RESULTS: The quantity of calcium absorbed was significantly lower from drink A (103 mg) than from drink B (117 mg; P = 0.012) or drink C (121 mg; P = 0.002), which indicated a positive effect of the CPPs. However, because the CPP preparations contributed additional calcium besides that found in the calcium lactate (drink A), fractional absorption of calcium from drink B (23%) was slightly but significantly (P = 0.015) lower than that from drink A (26%). CONCLUSIONS: The differences in calcium absorption are unlikely to have any biological significance. CPPs are unsuitable as candidate ingredients for functional foods that are designed to deliver improved calcium nutrition.     

Mycoplasma hominis impacts gene expression in Trichomonas vaginalis

Parasitology Research - In Europe, up to 90% of isolated Trichomonas vaginalis strains are naturally infected with Mycoplasma hominis, a facultative pathogen of the human genital tract. The...     

The assessment of disability in children and adolescents with headache: Adopting PedMIDAS in an epidemiological study

ObjectiveThe study aimed at the assessment of disability in children with headache (n = 1585, 11–14 yrs) from a randomly drawn population based sample. We explored the suitability of the PedMIDAS in epidemiological research by various indicators of response quality. Furthermore, predictors of disability were examined, as well as its association with measures of health care behaviour.MethodsThe PedMIDAS measures functional interference in different domains of life by asking the children for the number of days that their headache partially or totally interfered with their activities.ResultsThe examination of response behaviour revealed a marked attrition of responses (missing, invalid) in two items. As a consequence, the total score for disability could not be obtained for about 25% of the children. Analysis of homogeneity of the PedMIDAS items revealed low item/total correlations in two items. The grading of disability resulted in 81.2% of all children with headache showing no or low disability. Only 1.4% was “severely” disabled. Disability was predicted by frequency, type and intensity of headache. From all psychological variables only dysfunctional stress coping was significantly associated with disability. Disability itself was significantly associated with medical consultation.ConclusionsSuitability of the PedMIDAS for epidemiological research was supported, however with a caveat and recommendations for item revision. Severe disability due to headache was rare in the studied unselected sample when defined by behavioural interference. It is suggested to explore the construct of disability by a multi-method approach, including further instruments assessing headache related distress, (respectively) quality of life.