José-María Bayas

Safety and reactogenicity profile of an adjuvanted H5N1 pandemic candidate vaccine in adults within a phase III safety trial

A multicentre, randomized, phase III clinical trial in 5071 healthy adults was conducted to evaluate the safety and reactogenicity of a 15 microg HA dose of a candidate oil-in-water emulsion-based adjuvant system (AS)-adjuvanted split-virion H5N1 (AS-H5N1) vaccine compared to a licensed seasonal influenza vaccine, Fluarix.(1) Stringent criteria were used to evaluate adverse events and reactogenicity profile. Overall, 96.7% of the 5071 vaccinated subjects completed the study. Significantly more participants in the AS-H5N1 vaccine group reported general or local adverse events. Pain was the most common symptom in both treatment groups. Less than 1% of subjects withdrew from the study due to adverse events and no withdrawals were due to serious adverse events related to vaccination. The safety and reactogenicity profile of the AS-H5N1 candidate vaccine can be considered clinically acceptable in the context of its use against pandemic influenza.

Hepatitis B vaccination in prisons: The Catalonian experience

A pilot programme of hepatitis B vaccination was set up in three prisons to assess the feasibility and results of this method of reaching a high-risk population. Hepatitis B vaccine was offered to all inmates who lacked serological markers for hepatitis B virus. The antibody response was assessed in those who received two or three doses of vaccine. Candidates for vaccination were 41% of 1755 imprisoned men (20% of intravenous drug users (IVDU) and 63% of non-IVDU), but complete vaccination could be given to only 33% of candidates. A further 29% received two doses. Seroconversion to anti-HBs (titres > 10 IU l-1) occurred in 33% of vaccinees after two doses and in 76% after three doses. The overall rate of susceptible inmates who became protected for hepatitis B was 34%. The seroconversion rate was higher when the interval between the first two doses was shorter than 3 weeks (91%), than in cases with an interval of 3-6 weeks (79%) or longer than 6 weeks (33%). Age greater than 35 years and history of IVDU were associated with a lower response to the vaccine, while anti-HIV seropositivity did not influence the response. In conclusion, vaccination of prisoners susceptible to HBV may achieve protection in at least a third of cases. Shortening intervals between the priming doses of vaccine may improve compliance and increases the response.

Cervical cancer vaccination indications, efficacy, and side effects

Due to the limited contact of the human papillomavirus (HPV) with the immune system, past infection does not guarantee lasting protection. Two preventive vaccines (Gardasil and Cervarix) that can impede persistent HPV infection and its consequences are now available. They use structural L1 capsular proteins obtained by genetic recombination and antigens for genotypes 16 and 18, which are responsible for around 70% of cases of uterine cancer worldwide. Evaluation of their protective efficacy is based on the capacity of the vaccine to prevent persistent infection and cervical intraepithelial neoplasia (CIN). Phase I and II trials showed the safety of these vaccines and their capacity to produce very-high titers of antibodies (low or non-existent after natural infection). Phase II and III trials have confirmed these aspects and shown an efficacy of nearly 100% in the protocol analysis in preventing infection and the CIN associated with oncogenic vaccine genotypes. Some trials have also shown cross-protection against infections produced by other genotypes (such as 45 and 31). The optimal vaccination strategy is vaccination of girls aged 8-14 years. Other strategies should include the catch-up of adolescent and women not yet sexually-active, as well as the vaccination of sexually-active women. The progressive development of primary prevention strategies should coexist with secondary prevention with redesigned screening programs. The successful development of vaccination programs will require the support of public health authorities, the coordination of health workers from different areas and increased public awareness.

Hepatitis B and A vaccination in HIV-infected adults: A review

Hepatitis B and A account for considerable morbidity and mortality worldwide. Immunization is the most effective means of preventing hepatitis B and A. However, the immune response to both hepatitis vaccines seems to be reduced in HIV-infected subjects. The aim of this review was to analyze the immunogenicity, safety, long-term protection and current recommendations of hepatitis B and A vaccination among HIV-infected adults. The factors most frequently associated with a deficient level of anti-HBs or IgG anti-HAV after vaccination are those related to immunosuppression (CD4 level and HIV RNA viral load) and to the frequency of administration and/or the amount of antigenic load per dose. The duration of the response to both HBV and HAV vaccines is associated with suppression of the viral load at vaccination and, in the case of HBV vaccination, with a higher level of antibodies after vaccination. In terms of safety, there is no evidence of more, or different, adverse effects compared with HIV-free individuals. Despite literature-based advice on the administration of alternative schedules, revaccination after the failure of primary vaccination, and the need for periodic re-evaluation of antibody levels, few firm recommendations are found in the leading guidelines.

Reactogenicity Profile of Tetanus‐Diphtheria (Adult‐Type) Vaccine: Results of a Naturalistic Study Performed at an Adult Vaccination Center

A prospective observational naturalistic study was conducted at a vaccination center to assess the reactogenicity of tetanus‐diphtheria (adult‐type) (Td) vaccine. In 1 year, 3072 adult subjects were invited to participate, of whom 1977 (62% women, mean age [± SD]: 39 [± 14.5] years [range: 18–85 years]) actively did so. A follow‐up diary card was provided to all subjects to record all local and general symptoms experienced during the following 4 days after vaccination. Of the study population (n = 1977), 280 received a second Td dose, and 30 received a third dose: the total number of diary cards collected was 2287. Td was always administered (i.m. route) in the left arm. The study population was grouped by age: 52%, 41%, and 7% were ages 18 to 35, 36 to 65, and > 65 years, respectively, most of them beingtravelers to developing countries. Close to two‐thirds of subjects received up to nine different vaccines (mainly hepatitis B, hepatitis A, and typhoid) in addition to Td. Adverse reactions were classified as mild, moderate, and severe. Overall, 50% of subjects reported some type of adverse reaction. Pain, discomfort with arm movement, swelling, malaise, and fever (axillary temperature ≥ 38°C) were recorded in 43%, 14%, 3.8%, 5.1%, and 1.7% of all diary cards, respectively. Local and general reactions were considered as mild by almost two‐thirds of vaccinees and lasted ≤ 48 hours in about three‐fourths of them. The incidence of moderate plus severe local reactions was significantly (p < 0.01) more commonly reported in the 18‐ to 35‐year‐old group than in the 36‐ to 65‐year‐old group. No statistically significant differences were observed when comparing the incidence of general adverse reactions of those receiving Td alone with those receiving additional vaccines or when comparing the duration and intensity by age groups. Only 5.2% of subjects required analgesic/antipyretic treatment. In conclusion, this study shows that Td vaccine is reasonably well tolerated when given alone or with other vaccines. Similar studies should be conducted with other vaccines routinely recommended to adults to assess how they are administered in usual clinical practice and the reactogenicity profile perceived by the vaccinees.

Factors associated with the immune response to hepatitis A vaccination in HIV-infected patients in the era of highly active antiretroviral therapy.

INTRODUCTION HIV seropositivity is considered a risk factor for complications in hepatitis A virus (HAV) infection. HAV vaccination schedules are widely implemented in HIV-infected patients, but the immune response remains impaired. METHODS We analysed the response to vaccination (antiHAV titres ≥20IU/l) in 282 HIV-infected patients included in a standard (1440 Elisa Units (EU) at 0, 6 months) or rapidly accelerated schedule (720 EU at 0, 7, 21 days and 6 months) between 1997 and 2009. Factors associated with the response to vaccination were analysed using logistic regression. RESULTS The overall response rate was 73.4%. Male sex (OR: 0.16, 95% CI 0.05-0.51) and hepatitis C virus co-infection (OR: 0.30, 95% CI 0.14-0.74) were associated with a lower probability of response. Protective antibody response was associated with a higher CD4/CD8 ratio (OR: 3.69, 95% CI 1.3-10.5) and having received two doses of standard schedule (compared with patients receiving only one dose of the same schedule) (OR: 2.51, 95% CI 1.22-5.15). Three doses of the rapidly accelerated schedule were not more effective than a single dose of 1440 EU (OR: 1.32, 95% CI 0.48-3.63). CONCLUSION The low responses observed in patients receiving a single dose suggest the need to emphasize adhesion to vaccination protocols to avoid failure. The CD4/CD8 ratio may be considered as an immune status marker which could help to better choose the moment of vaccination. Our findings underscore the importance of identifying strategies that optimize the timing and effectiveness of hepatitis A vaccination in HIV-infected patients and of the need for further studies on individual factors such as sex and hepatitis C co-infection that may affect the response to vaccination. Likewise, the sub-optimal effectiveness of three doses of 720 EU in the rapidly accelerated schedule, if confirmed in future studies, might lead to a revision of the current schedule recommended for HIV-infected travellers.

Validity of self-reported pneumococcal vaccination status in the elderly in Spain.

The objective of this study was to evaluate the validity of information reported by the elderly on 23-valent pneumococcal polysaccharide vaccine (23vPPV) vaccination status. A cross-sectional, observational study was carried out in patients aged >or=65 years admitted to five Spanish hospitals. Data on 23vPPV vaccination history were obtained through interview of the patient or close relative and review of written medical information. The validity of the patient self-report was compared to the written medical information by calculation of the sensitivity, specificity, concordance, positive predictive value (PPV) and negative predictive value (NPV). A total of 2484 patients were initially included of whom 1814 patients (73%) responded about their vaccination status. The global sensitivity of the patient self-report was 0.74 and the specificity 0.95. The PPV was 0.92, the NPV 0.84 and the concordance 87. Vaccination cards and centralized vaccination registries in primary health care centres and hospitals should be potentiated in order to ensure that neither more nor less vaccinations are administered than are necessary.

Influence of socioeconomic status on community-acquired pneumonia outcomes in elderly patients requiring hospitalization: a multicenter observational study.

BackgroundThe associations between socioeconomic status and community-acquired pneumonia outcomes in adults have been studied although studies did not always document a relationship.The aim of this multicenter observational study was to determine the association between socioeconomic status and community-acquired pneumonia outcomes in the elderly, in the context of a public health system providing universal free care to the whole population.MethodsA total of 651 patients aged ≥65 years hospitalized due to community-acquired pneumonia through the emergency departments of five Spanish public hospitals were recruited and followed up between May 2005 and January 2007. The primary outcomes studied were: length of stay, intensive care unit admission, overall mortality and readmission. Socioeconomic status was measured using both individual and community data: occupation [categorized in six social groups (I, II, III, IVa, IVb and V)], educational level (≤ primary level or ≥ secondary level) and disposable family income of the municipality or district of residence [>12,500 € (high municipality family income) and ≤12,500 € (low municipality family income)]. The six social groups were further categorized as upper/middle social class (groups I-IVb) and lower class (group V).Bivariate and multivariate analyses were performed. OR and their 95% confidence intervals were calculated. All statistical tests were two tailed and statistical significance was established as p < 0.05.Results17.7% of patients lived in a municipality or district with a high municipality family income and 63.6% were upper/middle social class (I-IVb). Only 15.7% of patients had a secondary education. The adjusted analysis showed no association between pneumonia outcomes and social class, educational level or municipality family income. However, length of stay increased significantly in patients in whom the factors, living alone and being a smoker or ex-smoker coincided (p < 0.001).ConclusionsWe measured socioeconomic status using both individual and community data and found no association between social class, educational level or municipality family income and the variables of pneumonia outcomes. The lack of differences between social classes supports the provision of universal, equitable health care by the public health system.

Susceptibilidad a la varicela en personal sanitario. Aceptación y respuesta a la vacunación

BACKGROUND AND OBJECTIVE To determine the prevalence of health care workers (HCW) susceptibility to varicella zoster virus (VZV). As a secondary objective, we describe the immunogenicity and reactogenicity of the vaccine. SUBJECTS AND METHODS A multicenter analytic cross-sectional study was conducted in 5 hospitals in Catalonia, Spain, in a total of 1,111 HCW, aged between 18-60 years. We studied the prevalence of anti-VZV antibodies (IgG) and obtained demographic, occupational and health related variables that were expected to be associated with immunogenicity, as well as past history of varicella. All susceptible HCW were vaccinated and we studied the immunogenicity (antibody detection) and reactogenicity of the 1st and 2nd doses of the vaccine. Detection of antibodies against VZV was obtained by ELISA. All negative results were confirmed with FAMA. RESULTS Forty two subjects (3.8%) were negative. Susceptibility to VZV was associated (p<0.05) with decreased age (29.6 years ± 8.5 vs. 32,5 ± 9,3 in non-susceptible individuals), having fewer siblings and having no previous clinical history of varicella. Postvaccination detection tests with ELISA showed a seroconversion rate of 52 and 86% after the 1st and 2nd doses of the vaccine respectively, and 100% when using FAMA. There were no significant adverse events. CONCLUSIONS Susceptibility to varicella among HCW is low. Positive past history of varicella is a good predictor of previous exposure to VZV, since 99% (687/696) of the individuals that declared having experienced the disease were immune. This would avoid prevaccination screening in nearly two thirds of HCW.

Influence of Prior Pneumococcal and Influenza Vaccination on Outcomes of Older Adults with Community‐Acquired Pneumonia

OBJECTIVES: To determine whether prior pneumococcal and seasonal influenza vaccination improves outcomes in older adults hospitalized for community‐acquired pneumonia (CAP).