Vaccination against serogroup B Neisseria meningitidis: Perceptions and attitudes of parents

BackgroundA vaccine against serogroup B Neisseria meningitidis, major cause of bacterial meningitis in children and adults, has recently been developed. In a context of an increasing parental mistrust against vaccinations, understanding the reason for their choices is crucial in order to improve immunization coverage. Our study aimed at evaluating parental attitudes and perceptions towards serogroup B meningococcal invasive disease vaccination.MethodsA prospective observational study was conducted in different French independent-practice medical offices (general practitioners and paediatricians) and nurseries between May 1 and December 31, 2013, using a questionnaire distributed in electronic and paper forms to parents having at least one child between the ages of 2 months and 16 years old.Results1270 parents were included, of whom 671 (52.8%) spontaneously stated to be in favour of this vaccination. Their choice was mainly justified by the severity of the disease (63.8%) and the desire to protect their child (51.7%). In multivariate analysis, the young age of parents (OR 0.949 per additional year; p < 10⁻³), the history of vaccination against serogroup C meningococcal invasive diseases (OR 6.755; p < 10⁻³), and the prior knowledge of the vaccine (OR 2.081; p = 0.001) were associated with vaccination acceptance. The main reasons for refusal were the lack of hindsight on this new vaccine (50.6%) and the fear of side effects (45.5%). After objective information on the disease and the vaccine, only 6.3% of the entire responding population would refuse to consider vaccination.ConclusionsThe spontaneous acceptance rate of vaccination against serogroup B meningococcal invasive disease is insufficient. However, after objective information by their physician or public health authorities, only a few parents would in the end be completely resistant.     

Anti-tumor effect of the alphavirus-based virus-like particle vector expressing prostate-specific antigen in a HLA–DR transgenic mouse model of prostate cancer

The goal of this study was to determine if an alphavirus-based vaccine encoding human Prostate-Specific Antigen (PSA) could generate an effective anti-tumor immune response in a stringent mouse model of prostate cancer. DR2bxPSA F₁ male mice expressing human PSA and HLA-DRB1^*1501 transgenes were vaccinated with virus-like particle vector encoding PSA (VLPV–PSA) followed by the challenge with Transgenic Adenocarcinoma of Mouse Prostate cells engineered to express PSA (TRAMP–PSA). PSA-specific cellular and humoral immune responses were measured before and after tumor challenge. PSA and CD8 reactivity in the tumors was detected by immunohistochemistry. Tumor growth was compared in vaccinated and control groups. We found that VLPV–PSA could infect mouse dendritic cells in vitro and induce a robust PSA-specific immune response in vivo. A substantial proportion of splenic CD8 T cells (19.6 ± 7.4%) produced IFNγ in response to the immunodominant peptide PSA_65–73. In the blood of vaccinated mice, 18.4 ± 4.1% of CD8 T cells were PSA-specific as determined by the staining with H-2D^b/PSA_65–73 dextramers. VLPV–PSA vaccination also strongly stimulated production of IgG2a/b anti-PSA antibodies. Tumors in vaccinated mice showed low levels of PSA expression and significant CD8+ T cell infiltration. Tumor growth in VLPV–PSA vaccinated mice was significantly delayed at early time points (p = 0.002, Gehan–Breslow test). Our data suggest that TC-83-based VLPV–PSA vaccine can efficiently overcome immune tolerance to PSA, mediate rapid clearance of PSA-expressing tumor cells and delay tumor growth. The VLPV–PSA vaccine will undergo further testing for the immunotherapy of prostate cancer.     

Immunogenicity and safety of an E. coli-produced bivalent human papillomavirus (type 16 and 18) vaccine: A randomized controlled phase 2 clinical trial

BackgroundThis study aimed to investigate the dosage, immunogenicity and safety profile of a novel human papillomavirus (HPV) types 16 and 18 bivalent vaccine produced by E. coli.MethodsThis randomized, double-blinded, controlled phase 2 trial enrolled women aged 18–25 years in China. Totally 1600 eligible participants were randomized to receive 90 μg, 60 μg, or 30 μg of the recombinant HPV 16/18 bivalent vaccine or the control hepatitis B vaccine on a 0, 1 and 6 month schedule. The designated doses are the combined micrograms of HPV16 and 18 VLPs with dose ratio of 2:1. The immunogenicity of the vaccines was assessed by measuring anti-HPV 16 and 18 neutralizing antibodies and total IgG antibodies. Safety of the vaccine was assessed.ResultsAll but one of the seronegative participants who received 3 doses of the HPV vaccines seroconverted at month 7 for anti-HPV 16/18 neutralizing antibodies and IgG antibodies. For HPV 16, the geometric mean titers (GMTs) of the neutralizing antibodies were similar between the 60 μg (GMT = 10,548) and 90 μg (GMT = 12,505) HPV vaccine groups and were significantly higher than those in the 30 μg (GMT = 7596) group. For HPV 18, the GMTs of the neutralizing antibodies were similar among the 3 groups. The HPV vaccine was well tolerated. No vaccine-associated serious adverse events were identified.ConclusionThe prokaryotic-expressed HPV vaccine is safe and immunogenic in women aged 18–25 years. The 60 μg dosage formulation was selected for further investigation for efficacy.Clinical trials registration: NCT01356823.     

Congenital rubella syndrome (CRS) in Vietnam 2011–2012—CRS epidemic after rubella epidemic in 2010–2011

BackgroundRubella is endemic in Vietnam with epidemics occurring every 4–5 years. In 2011, Vietnam experienced the large nationwide rubella epidemic. During the rubella epidemic, many infants born with congenital rubella syndrome (CRS) were identified and reported from the neonatal units or cardiology departments of the national hospitals. To understand the burden of CRS, National Expanded Program on Immunization (NEPI) established sentinel CRS surveillance system.MethodThree national paediatric hospitals in Hanoi and Ho Chi Minh City (HCMC) were selected as CRS sentinel surveillance sites. Blood specimens from the infants were collected for rubella specific IgM and ELISA testing was performed at the national measles and rubella laboratory.ResultsFrom January 2011 to December 2012, 424 infants with suspected CRS were identified and reported. Among them 406 (96%) had specimens obtained, 284 (70%) cases were IgM positive including 279 laboratory confirmed CRS and 5 Congenital Rubella Infection (CRI). 13 cases were clinically confirmed and 127 (30%) were discarded. Total 292 infants were confirmed as CRS. Of the 292 infants with CRS, 69% of mothers had a history of “fever and rash” during pregnancy, of which 85% was in the first trimester. The most common clinical defects were congenital heart disease and cataract(s). However, 81.9% of the infants had a combination of major and minor signs and symptoms. Low birth weight in full term infants with confirmed CRS was observed in 114 infants (39%).ConclusionsThe newly established CRS sentinel surveillance system documented the significant burden of CRS in Vietnam and provided evidence to the policy makers for the introduction of rubella containing vaccine (RCV) into Vietnam. This report highlights the importance of countries with rubella epidemic to establish CRS surveillance rapidly in order to support the introduction of RCV into the routine Expanded Programme on Immunization (EPI) immunization.     

Estimating the herd immunity effect of rotavirus vaccine

IntroductionDiarrhea is one of the leading causes of death in children under 5, and an estimated 39% of these deaths are attributable to rotavirus. Currently two live, oral rotavirus vaccines have been introduced on the market; however, the herd immunity effect associated with rotavirus vaccine has not yet been quantified. The purpose of this meta-analysis was to estimate the herd immunity effects associated with rotavirus vaccines.MethodsWe performed a systematic literature review of articles published between 2008 and 2014 that measured the impact of rotavirus vaccine on severe gastroenteritis (GE) morbidity or mortality. We assessed the quality of published studies using a standard protocol and conducted meta-analyses to estimate the herd immunity effect in children less than one year of age across all years presented in the studies. We conducted these analyses separately for studies reporting a rotavirus-specific GE outcome and those reporting an all-cause GE outcome.ResultsIn studies reporting a rotavirus-specific GE outcome, four of five of which were conducted in the United States, the median herd effect across all study years was 22% [19–25%]. In studies reporting an all-cause GE outcome, all of which were conducted in Latin America, the median herd effect was 24.9% [11–30%].ConclusionsThere is evidence that rotavirus vaccination confers a herd immunity effect in children under one year of age in the United States and Latin American countries. Given the high variability in vaccine efficacy across regions, more studies are needed to better examine herd immunity effects in high mortality regions.     

Systemic immune responses to an inactivated,whole H9N2 avian influenza virus vaccine using class B CpG oligonucleotides in chickens

Commercial vaccines against avian influenza viruses (AIV) in chickens consist mainly of inactivated AIV, requiring parenteral administration and co-delivery of an adjuvant. Limitations in T helper 1 or T helper 2 biased responses generated by these vaccines emphasize the need for alternative, more efficacious adjuvants. The Toll-like receptor (TLR) 21 ligand, CpG oligodeoxynucleotides (ODN), has been established as immunomodulatory in chickens. Therefore, the objective of this study was to investigate the adjuvant potential of high (20 μg) and low (2 μg) doses of CpG ODN 2007 (CpG 2007) and CpG ODN 1826 (CpG 1826) when administered to chickens with a formalin-inactivated H9N2 AIV. Antibody responses in sera were evaluated in 90 specific pathogen free (SPF) chickens after intramuscular administration of vaccine formulations at 7 and 21 days post-hatch. Antibody responses were assessed based on haemagglutination inhibition (HI) and virus neutralization (VN) assays; virus-specific IgM and IgY antibody responses were evaluated by ELISA. The results suggest that the vaccine formulation containing low dose CpG 2007 was significantly more effective at generating neutralizing (both HI and VN) responses than formulations with high or low doses of CpG 1826 or high dose CpG 2007. Neutralizing responses elicited by low dose CpG 2007 significantly exceeded those generated by a squalene-based adjuvanted vaccine formulation during peak responses. A significantly higher IgM response was elicited by the formulation containing low dose CpG 2007 compared to high and low doses of 1826. Although the low dose of CpG 2007 elicited a higher IgY response than CpG 1826, the difference was not statistically significant. In conclusion, 2 μg of CpG 2007 is potentially promising as a vaccine adjuvant when delivered intramuscularly with inactivated H9N2 virus to chickens. Future studies may be directed at determining the mucosal antibody responses to the same vaccine formulations.     

Immunogenicity and safety of the new intradermal influenza vaccine in adults and elderly: A randomized phase 1/2 clinical trial

BackgroundRecent clinical evidence indicates that an intradermal (ID) delivery of vaccines confers superior immunogenicity as compared to a standard intramusclular or subcutaneous (SC) delivery.MethodsIn this exploratory study, 600 healthy adults were randomized to 6 study groups with subgroups of young adults (20–64 years old) and older adults (65 years and older). The subjects were either injected by a novel ID injection system with a single dose of 6, 9, or 15 μg HA or two doses (21 days apart) of 15 μg HA per strain or injected by an SC injection method with a single or two doses (21 days apart) of 15 μg HA per strain. Immunogenicity was assessed using hemagglutination inhibition (HAI) titer and microneutralization titer on Days 0, 10, 21, and 42. Solicited and unsolicited adverse events were recorded for 7 and 21 days post-vaccination, respectively.ResultsIn both young adults and older adults groups, the geometric titer (GMT) ratios of HAI in the ID 15 μg HA group were higher than those in the SC 15 μg HA group on both Day 10 and Day 21, while those in the ID 6 and ID 9 μg HA groups were comparable with those in the SC 15 μg HA group. The kinetics of GMTs of HAI suggested that the ID vaccine has the potential to induce the prompt immune response, which is rather hampered in older adults as seen in the SC vaccine groups. The injection-site AEs were generally mild and transient, and did not occur in a dose or dosage-dependent manner.ConclusionsThe results of this study clearly suggest that the immunologic profile of the ID vaccine is better than that of the SC vaccine, while the safety profile of the ID vaccine is similar to that of the SC vaccine. In this exploratory study with almost 100 subjects per each group, single or two-dose administration of the ID vaccine containing 15 μg HA was suggested to be an appropriate regimen in order to prevent influenza and to reduce the associated disease burden.Trial registrationJAPIC Clinical Trials Information (JapicCTI-132096).     

Functional Status Is Associated With 30-Day Potentially Preventable Hospital Readmissions After Inpatient Rehabilitation Among Aged Medicare Fee-for-Service Beneficiaries

ObjectivesTo determine the association between patients' functional status at discharge from inpatient rehabilitation and 30-day potentially preventable hospital readmissions. A secondary objective was to examine the conditions resulting in these potentially preventable readmissions.DesignRetrospective cohort study.SettingInpatient rehabilitation facilities submitting claims to Medicare.ParticipantsNational cohort (N=371,846) of inpatient rehabilitation discharges among aged Medicare fee-for-service beneficiaries in 2013 to 2014. The average age was 79.1±7.6 years. Most were women (59.7%) and white (84.5%).InterventionsNot applicable.Main Outcome Measures(1) Observed rates and adjusted odds of 30-day potentially preventable hospital readmissions after inpatient rehabilitation and (2) primary diagnoses for readmissions.ResultsThe overall rate of any 30-day hospital readmission after inpatient rehabilitation was 12.4% (n=46,265), and the overall rate of potentially preventable readmissions was 5.0% (n=18,477). Functional independence was associated with lower observed rates and adjusted odds ratios for potentially preventable readmissions. Observed rates for the highest versus lowest quartiles within each functional domain were as follows: self-care: 3.4% (95% confidence interval [CI], 3.3–3.5) versus 6.9% (95% CI, 6.7–7.1), mobility: 3.3% (95% CI, 3.2–3.4) versus 7.2% (95% CI, 7.0–7.4), and cognition: 3.5% (95% CI, 3.4–3.6) versus 6.2% (95% CI, 6.0–6.4), respectively. Similarly, adjusted odds ratios were as follows: self-care: .70 (95% CI, .67–.74), mobility: .64 (95% CI, .61–.68), and cognition: .84 (95% CI, .80–.89). Infection-related conditions (44.1%) were the most common readmission diagnoses followed by inadequate management of chronic conditions (31.2%) and inadequate management of other unplanned events (24.7%).ConclusionsFunctional status at discharge from inpatient rehabilitation was associated with 30-day potentially preventable readmissions in our sample of aged Medicare beneficiaries. This information may help identify at-risk patients. Future research is needed to determine whether follow-up programs focused on improving functional independence will reduce readmission rates.     

Foot disorders in the elderly: A mini-review

Ageing process is associated with changes to the aspect, biomechanics, structure and function of the foot, it may be related with a marked presence of foot conditions, pain, disability and other overall health problems that constitute a major public health concern.Also, the prevalence of epidemiologic research found an incidence of foot problems which is even higher as a consequence of increasing life expectation. Several studies have also suggested that such foot disorders currently affect between 71 and 87% of older patients and are a frequent cause of medical and foot care.Thus, these kind problems are extremely common conditions in the general population, especially in the elderly who are associated with poor quality of life, balance impairment, increase the risk of falls, dificulty on putting shoes, fractures, restrict mobility and performance of activities of daily living that turn can produce serious physical, mental and social consequences in the older people.The role of the physician in the assessment, evaluation, and examination of foot problems is very important, yet it is often an overlooked and undervalued component of geriatric health care.The purpose of this article is to review and to provide an overview of the most common foot deformities precipitating factors, clinical presentation, evidence-based diagnostic evaluation, and treatment recommendations with a view to preventing medical conditions or deformities affecting the feet that may alter foot condition and general health amongst the elderly.     

Preliminary evidence of disparities in physical activity among adolescents with bipolar disorder

Physical activity can potentially mitigate the symptomatic burden and cardiovascular risk associated with bipolar disorder (BD). Studies have found that adults with BD are less physically active than controls. However, no previous study has examined this topic among adolescents with BD. This study compares physical activity among adolescents with BD vs. healthy controls without major psychiatric disorders, and examines characteristics associated with physical activity among adolescents with BD. Subjects were 86 adolescents with a diagnosis of BD via gold-standard psychiatric interviews, and 50 controls. The Quick Weight, Activity & Excess Screener (WAVE) was used to assess physical activity. Between-group analyses examined for differences in achieving recommended benchmarks for three types of physical activity: working out, “working in” (incidental physical activity), and screen time. Exploratory within-group analyses were based on a median split (high vs. low) of the total physical activity scores among BD adolescents. Adolescents with BD were significantly less likely to report working out regularly (6%) as compared to controls (22%; χ² = 7.98, p = 0.005). There were no significant between-group differences in working in or screen time. BD adolescents with low levels of physical activity were less likely to have a family history of substance use disorder (p = 0.03). Adolescents with BD are less likely than their peers to achieve the recommended benchmark for regular working out. Future studies are warranted to determine what factors explain this difference, and to identify strategies for optimizing physical activity among adolescents with BD.