Responses of solid organ transplant recipients to the AS03-adjuvanted pandemic influenza vaccine

BACKGROUND: Solid organ transplant (SOT) recipients are a priority group for influenza vaccination and strategies enhancing immunogenicity are needed. METHODS: We determined adverse reactions, changes in biomarkers of graft function and immune responses to two doses of the AS03-adjuvanted influenza A/09/H1N1 vaccine in 216 SOT recipients and in 138 controls after one dose. Antibody responses were measured by haemagglutination inhibition and confirmed by microneutralization. We calculated geometric mean titres (GMT) and seroprotection rates (GMT≥40). RESULTS: Adverse reactions were fewer than in controls and graft function remained unaffected. Seroprotection was achieved by only 70.3% of SOT recipients, with significant differences between groups (lung 43.6%, heart 72.0%, kidney 83.3%, liver 83.3% and pancreas 85%), compared to 87% of controls (P<0.001). The weakest responses (seroprotection 43.5%) were elicited in lung transplant recipients. GMT remained threefold lower (115 versus 340) in SOT recipients than controls. Multivariate analyses identified increasing age, type of transplant and increasing blood levels of mycophenolate as independently associated to weaker responses. In contrast, even high blood levels of calcineurin inhibitors remained without significant influence on vaccine responses. CONCLUSIONS: The squalene-based adjuvanted A/09/H1N1 vaccine was safe in SOT recipients. However, even two doses of this adjuvanted influenza vaccine did not provide adequate protection for lung transplant recipients and those with high mycophenolate blood levels. Additional prophylactic measures should, therefore, be considered for these high-risk groups.     

Comparison of clinical presentation of respiratory tract infections in H1N1/09-positive and H1N1/09-negative patients

The true burden of influenza in children is difficult to assess and is probably underestimated as clinical signs are usually nonspecific, and formal viral identification is rarely searched. In this study, we compare the clinical features of infections related to the new H1N1/09 influenza virus with infections due to other respiratory viruses in children consulting in a tertiary care pediatric hospital in Geneva. Between October 1, 2009 and February 10, 2010, 109 patients were recruited, with a median of age of 7 years (range 0.1–18). There were 75 H1N1/09-positive patients (69%), and 32 (43%) had identified risk factors such as asthma or a history of wheezing. Fever (87%), cough (92%), and rhinitis (85%) were the most frequent reported presenting symptoms in both patient groups. H1N1/09-positive patients were significantly older (median of 8.2 vs. 4.6 years) and were more likely to have risk factors (43% vs. 24%) and myalgias (41% vs. 20%). H1N1/09-negative patients had more wheezing episodes (29% vs. 9%), higher rates of dyspnea (28% vs. 20%) and of hospital admissions (35% vs. 16%). Conclusion: Clinical signs cannot reliably differentiate H1N1/09-positive and H1N1/09-negative patients, although we found a higher proportion of myalgias in H1N1/09-positive patients. Severity of disease was lower in H1N1/09-positive than in H1N1/09-negative patients, mostly because of a higher proportion of asthma/wheezing episodes among H1N1/09-negative patients.     

Role of social networks in shaping disease transmission during a community outbreak of 2009 H1N1 pandemic influenza

Evaluating the impact of different social networks on the spread of respiratory diseases has been limited by a lack of detailed data on transmission outside the household setting as well as appropriate statistical methods. Here, from data collected during a H1N1 pandemic (pdm) influenza outbreak that started in an elementary school and spread in a semirural community in Pennsylvania, we quantify how transmission of influenza is affected by social networks. We set up a transmission model for which parameters are estimated from the data via Markov chain Monte Carlo sampling. Sitting next to a case or being the playmate of a case did not significantly increase the risk of infection; but the structuring of the school into classes and grades strongly affected spread. There was evidence that boys were more likely to transmit influenza to other boys than to girls (and vice versa), which mimicked the observed assortative mixing among playmates. We also investigated the presence of abnormally high transmission occurring on specific days of the outbreak. Late closure of the school (i.e., when 27% of students already had symptoms) had no significant impact on spread. School-aged individuals (6-18 y) facilitated the introduction and spread of influenza in households, but only about one in five cases aged >18 y was infected by a school-aged household member. This analysis shows the extent to which clearly defined social networks affect influenza transmission, revealing strong between-place interactions with back-and-forth waves of transmission between the school, the community, and the household.     

Graft-versus-host disease is the major determinant of humoral responses to the AS03-adjuvanted influenza A/09/H1N1 vaccine in allogeneic hematopoietic stem cell transplant recipients

Background

Responses to influenza vaccines are poorly characterized in immunocompromised patients. The goal of this study was to assess the efficacy of the AS03-adjuvanted influenza H1N1/A/09 vaccine in allogeneic hematopoietic stem cell transplant recipients.

Design and Methods

We enrolled 65 patients and 138 controls in an open prospective study. Controls received one dose and patients 2 doses of the AS03-adjuvanted influenza H1N1/A/09 vaccine at a 3-week interval. Geometric mean titers and seroprotection/seroconversion rates were determined by hemagglutination inhibition before and four weeks after the last immunization. Clinical and biological markers, including immunoglobulins, CD3⁺, CD4⁺, CD8⁺ and naïve CD4⁺ T-cell counts were assessed in all patients.

Results

Baseline seroprotection rates were low in patients (6.6%) and controls (14.8%). After 2 doses, patients (n=57, 92.3%) achieved similar seroprotection rates (84% vs. 87%, P=0.65) and antibody titers (305 vs. 340, P=0.88) as controls (n=131, 93.9%) after one dose. In univariate analysis, transplant-to-vaccination interval less than 12 months, active graft-versus-host disease, immunosuppressive drugs, hemoglobin less than 12g/L, lymphopenia less than1G/L, IgG less than 4g/L, IgA less than 0.5g/L, IgM less than 0.5g/L and naive CD4⁺ T cells less than 150/μL were significantly associated with weaker responses. Multivariate analysis identified transplant-to-vaccination interval and active graft-versus-host disease as the most powerful negative predictors of antibody responses (P=0.04 and P=0.002, respectively). Vaccination was well tolerated in both cohorts.

Conclusions

In allogeneic hematopoietic stem cell transplant recipients, 2 doses of an adjuvanted influenza vaccine elicited comparable responses to a single dose in healthy individuals. However, vaccine responses remained poor in patients with ongoing graft-versus-host disease, supporting the need for additional strategies in this high-risk patient population. (ClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT01022905","term_id":"NCT01022905"}}NCT01022905)     

Small airway remodeling in acute respiratory distress syndrome: a study in autopsy lung tissue

Introduction  

Airway dysfunction in patients with the Acute Respiratory Distress Syndrome (ARDS) is evidenced by expiratory flow limitation and dynamic hyperinflation. These functional alterations have been attributed to closure/obstruction of small airways. Airway morphological changes have been reported in experimental models of acute lung injury, characterized by epithelial necrosis and denudation in distal airways. To date, however, no study has focused on the morphological airway changes in lungs from human subjects with ARDS. The aim of this study is to evaluate structural and inflammatory changes in distal airways in ARDS patients.     

Pharmacological interventions in the treatment of the acute effects of cannabis: a systematic review of literature

Background

Medical cannabis dispensaries following the social or hybrid model offer supplementary holistic services in addition to dispensing medical cannabis. Historically, alternative physical health services have been the norm for these dispensaries, including services such as yoga, acupuncture, or chiropractor visits. A clinical service dearth remains for medical cannabis patients seeking substance use, misuse, dependence, and mental health services. This study examined patient desires for various clinical services and level of willingness to participate in specific clinical services.

Methods

Anonymous survey data (N = 303) were collected at Harborside Health Center (HHC), a medical cannabis dispensary in Oakland, CA. The sample was 70% male, 48% Caucasian and 21% African American. The mean male age was 38 years old and female mean age was 30. Sixty two percent of the male participants and 44% of the female participants are single. Sixteen percent of the population reported having a domestic partner. Forty six percent of the participants are employed full time, 41% have completed at least some college, and 49% make less than $40,000 a year.

Results

A significant portion of the sample, 62%, indicated a desire to participate in free clinical services at HHC, 34% would like more information about substances and use, and 41% want to learn more about reducing harms from substance use. About one quarter of the participants marked "would" or "likely would" participate in individual services such as consultation. Approximately 20% indicated "would" or "likely would" participate in psycho-educational forums, harm reduction information sharing sessions, online support groups, and coping, life, and social skills group. There was little interest in traditional NA/AA 12-step groups or adapted 12-step groups.

Conclusions

Desired clinical services can be qualified as a combination of harm reduction, educational, skills-based, peer support and therapeutic individual and group services. Results suggest that medical cannabis patients seek more information about various substances, including cannabis. Dispensaries can help to decrease gaps in substance education and clinical services and fulfill unmet clinical desires. More research is necessary in additional medical cannabis dispensaries in different geographic settings with different service delivery models.     

Immunization-safety monitoring systems for the 2009 H1N1 monovalent influenza vaccination program

The effort to vaccinate the US population against the 2009 H1N1 influenza virus hinged, in part, on public confidence in vaccine safety. Early in the vaccine program, >20% of parents reported that they would not vaccinate their children. Concerns about the safety of the vaccines were reported by many parents as a factor that contributed to their intention to forgo vaccination (see www.hsph.harvard.edu/news/press-releases/2009-releases/survey-40-adults-absolutely-certain-h1n1-vaccine.html and www.med.umich.edu/mott/npch/reports/h1n1.htm). The safety profiles of 2009 H1N1 monovalent influenza vaccines were anticipated to be (and have been) similar to those of seasonal influenza vaccines, for which an excellent safety profile has been demonstrated. Here we describe steps taken by the US government to (1) assess the key federal systems in place before 2009 for monitoring the safety of vaccines and (2) integrate and upgrade those systems for optimal vaccine-safety monitoring during the 2009 H1N1 monovalent influenza vaccination program. These efforts improved monitoring of 2009 H1N1 vaccine safety, hold promise for enhancing future national monitoring of vaccine safety, and may ultimately help improve public confidence in vaccines.