Improving influenza vaccination rates in the elderly.

BACKGROUND: Vaccination coverage for influenza in the elderly remains low when the physician is the only person responsible for immunization. Integration of other health care workers may improve the coverage rate of at-risk groups. OBJECTIVES: To estimate vaccination coverage rate by using a strategy based on the systematic intervention of a health care professional proposing vaccination before the doctor's consultation, to evaluate the changes in coverage rates before and after introduction of this strategy, and to assess the feasibility of this intervention and the achieved coverage rate in family physician offices. STUDY DESIGN: Prospective study in a medical outpatient clinic and 5 family physician practices in Switzerland. POPULATION: Participants consisted of all patients 65 years or older attending a medical outpatient clinic during the vaccination period in 1999 (n = 401), patients 65 years or older regularly followed at a medical outpatient clinic in 1998 and 1999 (n = 195), and patients 65 years or older presenting to 5 family physician offices in 1999 (n = 598). OUTCOME MEASURED: Rates of vaccination coverage. RESULTS: Among all participants, vaccination coverage rates in 1999 were 85% at the medical outpatient clinic and 83% in family physician offices. Among participants regularly followed at the medical outpatient clinic, vaccination coverage increased from 48% in 1998 to 76% in 1999. Rates of refusal were 9% at the medical outpatient clinic and 14% in the family physician offices. CONCLUSIONS: The systematic intervention of a health care professional to suggest vaccination before the doctor's visit is an effective measure to achieve high coverage rate. Such a strategy also improves outpatient clinic or private practice efficiency by reducing pressures on physicians.

Trachea, lung, and tracheobronchial lymph nodes are the major sites where antigen-presenting cells are detected after nasal vaccination of mice with human papillomavirus type 16 virus-like particles.

Vaccination by the nasal route has been successfully used for the induction of immune responses. Either the nasal-associated lymphoid tissue (NALT), the bronchus-associated lymphoid tissue, or lung dendritic cells have been mainly involved. Following nasal vaccination of mice with human papillomavirus type 16 (HPV16) virus-like-particles (VLPs), we have previously shown that interaction of the antigen with the lower respiratory tract was necessary to induce high titers of neutralizing antibodies in genital secretions. However, following a parenteral priming, nasal vaccination with HPV16 VLPs did not require interaction with the lung to induce a mucosal immune response. To evaluate the contribution of the upper and lower respiratory tissues and associated lymph nodes (LN) in the induction of humoral responses against HPV16 VLPs after nasal vaccination, we localized the immune inductive sites and identified the antigen-presenting cells involved using a specific CD4(+) T-cell hybridoma. Our results show that the trachea, the lung, and the tracheobronchial LN were the major sites responsible for the induction of the immune response against HPV16 VLP, while the NALT only played a minor role. Altogether, our data suggest that vaccination strategies aiming to induce efficient immune responses against HPV16 VLP in the female genital tract should target the lower respiratory tract.

Influenza vaccination in solid-organ transplant recipients.

PURPOSE OF REVIEW: We reviewed the most recent literature on solid-organ transplant (SOT) recipients regarding the clinical significance of influenza and the immunogenicity and safety of influenza vaccine in this population. RECENT FINDINGS: In SOT recipients, influenza is associated with significant graft dysfunction and even mortality. Early initiation of antiviral therapy is associated with a reduced risk for influenza-associated complications, mainly pneumonia. The main preventive strategy against influenza in SOT recipients remains the administration of yearly influenza vaccine. Although most studies have shown that influenza vaccination is safe after transplantation, impaired responses are expected in more immunosuppressed patients. A lower immunogenicity of influenza vaccine has been described in patients receiving mycophenolate and mammalian target of rapamycin inhibitors. The optimal timing of vaccination after transplant remains to be determined, although vaccination during the early posttransplant period appears to be safe. Novel vaccination strategies, such as intradermal vaccination or use of adjuvanted vaccines, have been evaluated in SOT recipients, with inconclusive results to date. SUMMARY: The administration of influenza vaccination is strongly recommended in SOT recipients and their relatives. Further research is needed for improving the immunogenicity of influenza vaccine in this population.

Narcolepsie avec cataplexie après vaccination anti-H1N1

IntroductionIt has been suggested that the H1N1 vaccine may be a trigger for the onset of narcolepsy-cataplexy, a rare disease whose autoimmune origin is suspected.ObservationsWe report two patients (a 9-year-old boy and an 18-year-old man) with severe narcolepsy-cataplexy, in whom the illness appeared within 3-4 weeks after H1N1 vaccination. In both cases, symptoms developed unusually abruptly and they presented with severe daytime sleepiness and multiple daily cataplexy attacks. Other similar cases have been recently reported associated with H1N1 vaccine.ConclusionAlthough no formal link can be established, the unusual characteristics of the reported cases and the striking temporal relationship suggests that narcolepsy may be the result of an autoimmune reaction triggered by H1N1 vaccination in susceptible individuals.

Risk factors for positive tuberculin skin tests among migrant and resident children in Lausanne, Switzerland

Résumé en français Cadre : Policlinique pédiatrique à Lausanne en Suisse, pays rencontrant une proportion importante de tuberculose au sein de la population de migrants. But : Déterminer les facteurs de risque associés à un test tuberculinique positif (ou test de Mantoux), notamment l'influence du BCG (Bacille Calmette Guérin) et d'un contact avec un personne ayant une tuberculose active. Les patients concernés étaient des enfants examinés dans le cadre d'un contrôle de santé ou dans le cadre d'une étude d'entourage d'un cas déclaré de tuberculose. Méthode : Etude descriptive comprenant des enfants ayant eu un test tuberculinique (2 unités RT23) entre novembre 2002 et avril 2004. L'âge, le sexe, l'anamnèse de contact avec une personne ayant une tuberculose active, la vaccination par le BCG, le pays d'origine et le lieu de naissance (en Suisse ou hors de la Suisse) étaient répertoriés. Résultats : Parmi les 234 enfants de l'étude, 176 (75%) avaient une réaction tuberculinique égal à zéro et 31 (13%) avaient une réaction positive (> 10mm). Dans le modèle de régression linéaire, la taille de la réaction tuberculinique variait significativement selon l'anamnèse de contact avec une personne ayant une tuberculose active, l'âge, l'incidence de la tuberculose dans le pays d'origine et la vaccination par le BCG. Le sexe ou le lieu de naissance n'influençait pas la taille de la réaction. Dans le modèle de régression logistique incluant toutes les valeurs répertoriées, les paramètres significativement associés avec un Mantoux positif étaient l'âge (Odds Ratio = 1.21, 95% CI 1.08 ; 1.35), l'anamnèse de contact avec une personne ayant une tuberculose active (OR = 7.31, 95% CI 2.23 ; 24) et l'incidence de la tuberculose dans le pays d'origine (OR = 1.01, 95% CI 1.00 ; 1.02). Le sexe (OR = 1.18, 95% CI 0.50 ; 2.78) et la vaçcination par le BCG (OR = 2.97, 95% CI 0.91 ; 9.72) n'étaient pas associés avec une réaction tuberculinique positive. Conclusions : L'incidence de la tuberculose dans le pays d'origine, la vaccination par le BCG et l'âge influencent le test de Mantoux (taille ou proportion de réaction > 10mm). Toutefois, le facteur de risque le plus important d'avoir une réaction tuberculinique positive est l'anamnèse de contact avec. une personne ayant une tuberculose active.

Vaccination against human papillomavirus in Switzerland: simulation of the impact on infection rates.

OBJECTIVES: Human papillomavirus (HPV) is a sexually transmitted infection of particular interest because of its high prevalence rate and strong causal association with cervical cancer. Two prophylactic vaccines have been developed and different countries have made or will soon make recommendations for the vaccination of girls. Even if there is a consensus to recommend a vaccination before the beginning of sexual activity, there are, however, large discrepancies between countries concerning the perceived usefulness of a catch-up procedure and of boosters. The main objective of this article is to simulate the impact on different vaccination policies upon the mid- and long-term HPV 16/18 age-specific infection rates. METHODS: We developed an epidemiological model based on the susceptible-infective-recovered approach using Swiss data. The mid- and long-term impact of different vaccination scenarios was then compared. RESULTS: The generalization of a catch-up procedure is always beneficial, whatever its extent. Moreover, pending on the length of the protection offered by the vaccine, boosters will also be very useful. CONCLUSIONS: To be really effective, a vaccination campaign against HPV infection should at least include a catch-up to early reach a drop in HPV 16/18 prevalence, and maybe boosters. Otherwise, the protection insured for women in their 20s could be lower than expected, resulting in higher risks to later develop cervical cancer.

Impact of a Nurse Vaccination Program on Hepatitis B Immunity in a Swiss HIV Clinic.

ABSTRACT: We evaluated the impact of a nurse program for hepatitis B virus vaccination in a center from the Swiss HIV Cohort Study. Immunity (anti-HBs >10 IU/mL) increased from 32% to 76% in the intervention center (n = 238) where vaccine management was endorsed by nurses, but only from 33% to 39% in control centers (n = 2712, P < 0.001) where management remained in charge of physicians. Immunity against HBV in the HIV population is insufficient in Switzerland. Specific nurse vaccination program may efficiently improve health care.

Decreased specific CD8+ T cell cross-reactivity of antigen recognition following vaccination with Melan-A peptide.

The aim of T cell vaccines is the expansion of antigen-specific T cells able to confer immune protection against pathogens or tumors. Although increase in absolute cell numbers, effector functions and TCR repertoire of vaccine-induced T cells are often evaluated, their reactivity for the cognate antigen versus their cross-reactive potential is rarely considered. In fact, little information is available regarding the influence of vaccines on T cell fine specificity of antigen recognition despite the impact that this feature may have in protective immunity. To shed light on the cross-reactive potential of vaccine-induced cells, we analyzed the reactivity of CD8(+) T cells following vaccination of HLA-A2(+) melanoma patients with Melan-A peptide, incomplete Freund's adjuvant and CpG-oligodeoxynucleotide adjuvant, which was shown to induce strong expansion of Melan-A-reactive CD8(+) T cells in vivo. A collection of predicted Melan-A cross-reactive peptides, identified from a combinatorial peptide library, was used to probe functional antigen recognition of PBMC ex vivo and Melan-A-reactive CD8(+) T cell clones. While Melan-A-reactive CD8(+) T cells prior to vaccination are usually constituted of widely cross-reactive naive cells, we show that peptide vaccination resulted in expansion of memory T cells displaying a reactivity predominantly restricted to the antigen of interest. Importantly, these cells are tumor-reactive.

Vaccination of melanoma patients with Melan-A/Mart-1 peptide and Klebsiella outer membrane protein p40 as an adjuvant.

Toll-like receptor ligands are potentially useful adjuvants for the development of clinical T cell vaccination. Here we investigated the novel Toll-like receptor2 ligand P40, the outer membrane protein A derived from Klebsiella pneumoniae. Seventeen human leukocyte antigen-A*0201 positive stage III/IV melanoma patients were vaccinated with P40 and Melan-A/Mart-1 peptide subcutaneously in monthly intervals. Adverse reactions were mild-to-moderate. Fourteen patients received at least 8 vaccinations and were thus evaluable for clinical tumor and immune responses. Seven patients experienced progressive disease, whereas 2 patients had stable disease throughout the trial period, 1 of them with regression of multiple skin metastases. The remaining 5 patients had no measurable disease. Melan-A/Mart-1 specific CD8 T cells were analyzed ex vivo, with positive results in 6 of 14 evaluable patients. Increased percentages of T cells were found in three patients, memory/effector T cell differentiation in 4 patients, and a positive interferon-gamma Elispot assay in 1 patient. Antibody responses to P40 were observed in all patients. We conclude that vaccination with peptide and P40 was feasible and induced ex vivo detectable tumor antigen specific T cell responses in 6 of 14 patients with advanced melanoma.

Support for Seasonal Influenza Vaccination Requirements among US Healthcare Personnel.

Objective. To measure support for seasonal influenza vaccination requirements among US healthcare personnel (HCP) and its associations with attitudes regarding influenza and influenza vaccination and self-reported coverage by existing vaccination requirements. Design. Between June 1 and June 30, 2010, we surveyed a sample of US HCP ([Formula: see text]) recruited using an existing probability-based online research panel of participants representing the US general population as a sampling frame. Setting. General community. Participants. Eligible HCP who (1) reported having worked as medical doctors, health technologists, healthcare support staff, or other health practitioners or who (2) reported having worked in hospitals, ambulatory care facilities, long-term care facilities, or other health-related settings. Methods. We analyzed support for seasonal influenza vaccination requirements for HCP using proportion estimation and multivariable probit models. Results. A total of 57.4% (95% confidence interval, 53.3%-61.5%) of US HCP agreed that HCP should be required to be vaccinated for seasonal influenza. Support for mandatory vaccination was statistically significantly higher among HCP who were subject to employer-based influenza vaccination requirements, who considered influenza to be a serious disease, and who agreed that influenza vaccine was safe and effective. Conclusions. A majority of HCP support influenza vaccination requirements. Moreover, providing HCP with information about the safety of influenza vaccination and communicating that immunization of HCP is a patient safety issue may be important for generating staff support for influenza vaccination requirements.

Opportunity for catch-up HPV vaccination in young women after first delivery.

Background Early age at first delivery has been identified as a risk factor for high-risk HPV-type infection and cervical cancer development. Methods A cross-sectional study was carried out in a large public maternity hospital in Sao Paulo, Brazil. During June 2006 to February 2007, 301 women aged 15-24 years who gave birth to their first child were recruited between 43 and 60 days after delivery. Detection of HPV DNA in cervical specimens was performed using a standardised PCR protocol with PGMY09/11 primers. The association of selected factors with HPV infection was assessed by using a Generalised Linear Model. Results HPV DNA was detected in 58.5% (95% CI 52.7% to 64.0%) of the enrolled young women. The most common types of HPV found were: HPV16, HPV51, HPV52, HPV58 and HPV71. The overall prevalence of HPV types targeted by the HPV prophylactic vaccines was: HPV 16-12.0%, HPV 18-2.3% and HPV 6 and 11 4.3%. In the multivariate analysis, only age (inversely, p for trend=0.02) and smoking habits were independently associated with HPV infection. Conclusions The findings show that these young primiparous women had high cervical HPV prevalence, suggesting that this is a high-risk group for cervical cancer development. Nevertheless, 17.3% were positive for any of the four HPV types included in HPV vaccines (HPV6, 11, 16 or 18), with 13.3% positive for HPV 16 or 18 and only 1.0% having both vaccine related-oncogenic HPV types. Thus, young primiparous women could benefit from catch-up HPV vaccination programmes.

Vaccination Strategies against Highly Pathogenic Arenaviruses: The Next Steps toward Clinical Trials.

Vaccination is one of the most valuable weapons against infectious diseases and has led to a significant reduction in mortality and morbidity. However, for most viral hemorrhagic fevers caused by arenaviruses, no prophylactic vaccine is available. This is particularly problematic as these diseases are notoriously difficult to diagnose and treat. Lassa fever is globally the most important of the fevers caused by arenaviruses, potentially affecting millions of people living in endemic areas, particularly in Nigeria. Annually, an estimated 300,000 humans are infected and several thousands succumb to the disease. The successful development of the vaccine "Candid#1" against Junin virus, the causative agent of Argentine hemorrhagic fever, proved that an effective arenavirus vaccine can be developed. Although several promising studies toward the development of a Lassa fever vaccine have been published, no vaccine candidate has been tested in human volunteers or patients. This review summarizes the immunology and other aspects of existing experimental arenavirus vaccine studies, discusses the reasons for the lack of a vaccine, and proposes a plan for overcoming the final hurdles toward clinical trials.

Vaccination-induced functional competence of circulating human tumor-specific CD8 T-cells.

T-cells specific for foreign (e.g., viral) antigens can give rise to strong protective immune responses, whereas self/tumor antigen-specific T-cells are thought to be less powerful. However, synthetic T-cell vaccines composed of Melan-A/MART-1 peptide, CpG and IFA can induce high frequencies of tumor-specific CD8 T-cells in PBMC of melanoma patients. Here we analyzed the functionality of these T-cells directly ex vivo, by multiparameter flow cytometry. The production of multiple cytokines (IFNγ, TNFα, IL-2) and upregulation of LAMP-1 (CD107a) by tumor (Melan-A/MART-1) specific T-cells was comparable to virus (EBV-BMLF1) specific CD8 T-cells. Furthermore, phosphorylation of STAT1, STAT5 and ERK1/2, and expression of CD3 zeta chain were similar in tumor- and virus-specific T-cells, demonstrating functional signaling pathways. Interestingly, high frequencies of functionally competent T-cells were induced irrespective of patient's age or gender. Finally, CD8 T-cell function correlated with disease-free survival. However, this result is preliminary since the study was a Phase I clinical trial. We conclude that human tumor-specific CD8 T-cells can reach functional competence in vivo, encouraging further development and Phase III trials assessing the clinical efficacy of robust vaccination strategies.

Activation of human melanoma reactive CD8+ T cells by vaccination with an immunogenic peptide analog derived from Melan-A/melanoma antigen recognized by T cells-1.

PURPOSE: As compared with natural tumor peptide sequences, carefully selected analog peptides may be more immunogenic and thus better suited for vaccination. However, T cells in vivo activated by such altered analog peptides may not necessarily be tumor specific because sequence and structure of peptide analogs differ from corresponding natural peptides. EXPERIMENTAL DESIGN: Three melanoma patients were immunized with a Melan-A peptide analog that binds more strongly to HLA-A*0201 and is more immunogenic than the natural sequence. This peptide was injected together with a saponin-based adjuvant, followed by surgical removal of lymph node(s) draining the site of vaccination. RESULTS: Ex vivo analysis of vaccine site draining lymph nodes revealed antigen-specific CD8+ T cells, which had differentiated to memory cells. In vitro, these cells showed accelerated proliferation upon peptide stimulation. Nearly all (16 of 17) of Melan-A-specific CD8+ T-cell clones generated from these lymph nodes efficiently killed melanoma cells. CONCLUSIONS: Patient immunization with the analog peptide leads to in vivo activation of T cells that were specific for the natural tumor antigen, demonstrating the usefulness of the analog peptide for melanoma immunotherapy.

Recommandations de vaccination pour les patients atteints de maladie chronique [Immunization guidelines regarding patients with a chronic disease].

Some chronic diseases--like renal failure, liver insufficiency, chronic lung disease, cardiac involvement, diabetes mellitus, asplenia--present limited defects of the immune system and/or a higher risk of infection; therefore, patients with such pathologies should get selective vaccinations. The efficacy of immunization decreases with disease progression; for this reason, these patients should be immunized as soon as possible. At the beginning of their disease, these patients do not need a specialized treatment and are followed by the general practitioner alone who is in charge of immunizing them as well as contact people of any immunocompromised patient. OFSP's regular vaccinations programme is recommended, as well as selective vaccinations against influenza, pneumococci and viral hepatitis, depending on the underlying chronic disease.