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      Immunogenicity and safety of intradermal influenza vaccine in immunocompromized patients: a meta-analysis of randomized controlled trials

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          Abstract

          Background

          The primary influenza prevention strategy is focused on annual vaccination according to the categories identified in the various countries as being at greatest risk of complications. Many studies were conducted in order to demonstrate that intradermal (ID) vaccine formulation represents a promising alternative to conventional intramuscular (IM) formulation, especially in subjects with an impaired immune system. However, there is no consensus whether the efficacy and safety of ID is equivalent to IM in these subjects. Therefore, we performed a meta-analysis of Randomized Controlled Trials (RCT) to compare the immunogenicity and safety of ID and IM influenza vaccines in subjects with a depleted immune system.

          Methods

          We conducted a search strategy of medical literature published until November 2014 in order to identify RCTs that evaluated the immunogenicity and safety of ID compared with IM influenza vaccines in immunocompromized patients.

          Results

          We identified a total of 269 citations through research in electronic databases and scanning reference lists. Of these, 6 articles were included in the meta-analysis, for a total of 673 subjects. The seroprotection rate induced by the ID vaccine is comparable to that elicited by the IM vaccine. The overall RR was 1.00 (95 % CI = 0.91 -1.10) for A/H1N1 strain, 1.00 (95 % CI = 0.90-1.12) for A/H3N2 and 0.99 (95 % CI = 0.84 -1.16) for B strain. No significant differences in the occurrence of systemic reactions were detected (17.7 % in the ID group vs 18.2 % in the IM group) with a pooled RR = 1.00 (95 % CI = 0.67 -1.51), whereas ID administration caused significantly more injection site reactions with a mean frequency of 46 % in the ID group compared to 22 % in the IM group, with a pooled RR = 1.89 (95 % CI = 1.40 -2.57).

          Conclusions

          The ID influenza vaccine has shown a similar immunogenicity and safety to the IM influenza vaccine in immunocompromized patients, and it may be a valid option to increase compliance to influenza vaccination in these populations.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s12879-015-1161-z) contains supplementary material, which is available to authorized users.

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          Most cited references27

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          Influenza in immunosuppressed populations: a review of infection frequency, morbidity, mortality, and vaccine responses.

          Patients that are immunosuppressed might be at risk of serious influenza-associated complications. As a result, multiple guidelines recommend influenza vaccination for patients infected with HIV, who have received solid-organ transplants, who have received haemopoietic stem-cell transplants, and patients on haemodialysis. However, immunosuppression might also limit vaccine responses. To better inform policy, we reviewed the published work relevant to incidence, outcomes, and prevention of influenza infection in these patients, and in patients being treated chemotherapy and with systemic corticosteroids. Available data suggest that most immunosuppressed populations are indeed at higher risk of influenza-associated complications, have a general trend toward impaired humoral vaccine responses (although these data are mixed), and can be safely vaccinated--although longitudinal data are largely lacking. Randomised clinical trial data were limited to one study of HIV-infected patients with high vaccine efficacy. Better trial data would inform vaccination recommendations on the basis of efficacy and cost in these at-risk populations.
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            A method for assessing the quality of a randomized control trial.

            A system has been constructed to evaluate the design, implementation, and analysis of randomized control trials (RCT). The degree of quadruple blinding (the randomization process, the physicians and patients as to therapy, and the physicians as to ongoing results) is considered to be the most important aspect of any trial. The analytic techniques are scored with the same emphasis as is placed on the control of bias in the planning and implementation of the studies. Description of the patient and treatment materials and the measurement of various controls of quality have less weight. An index of quality of a RCT is proposed with its pros and cons. If published papers were to approximate these principles, there would be a marked improvement in the quality of randomized control trials. Finally, a reasonable standard design and conduct of trials will facilitate the interpretation of those with conflicting results and help in making valid combinations of undersized trials.
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              Influenza vaccination in the organ transplant recipient: review and summary recommendations.

              Influenza virus causes a spectrum of illness in transplant recipients with a high rate of lower respiratory disease. Seasonal influenza vaccination is an important public health measure recommended for transplant recipients and their close contacts. Vaccine has been shown to be safe and generally well tolerated in both adult and pediatric transplant recipients. However, responses to vaccine are variable and are dependent on various factors including time from transplantation and specific immunosuppressive medication. Seasonal influenza vaccine has demonstrated safety and no conclusive evidence exists for a link between vaccination and allograft dysfunction. Annually updated trivalent inactivated influenza vaccines have been available and routinely used for several decades, although newer influenza vaccination formulations including high-dose vaccine, adjuvanted vaccine, quadrivalent inactivated vaccine and vaccine by intradermal delivery system are now available or will be available in the near future. Safety and immunogenicity data of these new formulations in transplant recipients requires investigation. In this document, we review the current state of knowledge on influenza vaccines in transplant recipients and make recommendations on the use of vaccine in both adult and pediatric organ transplant recipients.
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                Author and article information

                Contributors
                claudiapileggi@unicz.it
                francescalotito@libero.it
                a.bianco@unicz.it
                nobile@unicz.it
                ++39 961 712367 , pavia@unicz.it
                Journal
                BMC Infect Dis
                BMC Infect. Dis
                BMC Infectious Diseases
                BioMed Central (London )
                1471-2334
                14 October 2015
                14 October 2015
                2015
                : 15
                : 427
                Affiliations
                Department of Health Sciences, University of Catanzaro “Magna Græcia”, Via Tommaso Campanella, 88100 Catanzaro, Italy
                Article
                1161
                10.1186/s12879-015-1161-z
                4607009
                52e5e3df-8e7f-43e3-8ede-4097ffa75ef8
                © Pileggi et al. 2015

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 12 March 2015
                : 30 September 2015
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2015

                Infectious disease & Microbiology
                influenza vaccine,intradermal,intramuscular,immunocompromized patients

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