Nevertheless, our study supports national and international public health policy recommendations for the targeting of immunocompromised patients for influenza vaccination. == Supporting Information == Summary of risk of bias using the Cochrane Collaboration tool (n=191). unclear or high risk of bias. Meta-analyses showed a significant effect of preventing influenza-like illness (odds ratio [OR] = 0.23; 95% confidence interval [CI] = 0.160.34; p<0.001) and laboratory confirmed influenza contamination (OR = 0.15; 95% CI = 0.030.63; p = 0.01) through vaccinating immunocompromised patie nts compared to placebo or unvaccinated controls. We found no difference in the odds of influenza-like illness compared to vaccinated immunocompetent controls. The pooled odds of seroconversion were lower in vaccinated patients compared to immunocompetent controls for seasonal influenza A(H1N1), A(H3N2) and B. A similar trend was identified for seroprotection. Meta-analyses of seroconversion showed higher odds in vaccinated patients compared to placebo or unvaccinated controls, although this reached significance for influenza B only. Publication bias was not detected and narrative synthesis supported our findings. No consistent evidence of safety concerns was identified. == Conclusions/Significance == Contamination prevention and control strategies should recommend vaccinating immunocompromised patients. Potential for bias and confounding and the presence of heterogeneity mean the evidence reviewed is generally weak, although the directions of effects are consistent. Areas for further research are identified. == Introduction == Respiratory disease is usually a leading cause of global mortality to which seasonal and pandemic influenza both make substantial contributions. For example, in the USA an estimated average 225,000 hospitalisations and 36,000 deaths per annum are attributable to seasonal influenza[1],[2]. Even the mild 2009 influenza A(H1N1) pandemic was associated with substantial years of life lost due to mortality in younger age groups[3]. Patients with sub-optimal immune function due to disease or therapy (the immunocompromised) are recognised to be at increased risk from influenza-related complications, and are recommended for annual vaccination in many national vaccination guidelines. Concerns about influenza within immunocompromised populations include an impaired respo nse to vaccination and higher risk of complicated infection with increased mortality[4], greater and prolonged computer virus shedding with implications for control of transmission[5][8], the emergence of resistance to antiviral brokers[9]and possible Risperidone hydrochloride adverse effects of vaccination. The balance between potential benefit and harm resulting from vaccinating Risperidone hydrochloride these groups has been hard to Risperidone hydrochloride establish, with previous reviews finding few studies offering incontrovertible evidence of clinical protection[10][13]. There is uncertainty around thresholds for defining immunocompromise and the exte nt to which underlying aetiologies vary in their susceptibility to influenza and potentially their response to vaccine, with deference to clinical opinion in many cases[14]. A high burden of illness was recognised in immunocompromised patients during the 2009 influenza A(H1N1) pandemic, along with substantial nosocomial disease, proclaiming the need to re-visit the evidence base for influenza vaccination in these patients[8],[15][21]. We conducted a systematic review and meta-analysis to assess influenza vaccination for immunocompromised patients. We report the primary analysis and its interpretation from a public health policy perspective, to assess the overall evidence. A second manuscript will be submitted for publication which reports a secondary analysis of our data, stratified by aetiology of immunocompromise. == Methods == An abbreviated study protocol is available from the National Institute for Health Research international prospective register of systematic reviews (PROSPERO)[22], and the full protocol and PRISMA checklist are available as supporting information (seeProtocol S1andChecklist S1). Minor amendments to the original protocol were conducted to clarify the search strategy and eligibility criteria. The study populace of interest comprised all persons immunocompromised due to primary immunodeficiency (genetic defects) or secondary immunodeficiency (such SDF-5 as HIV contamination, Risperidone hydrochloride malignancy, or receipt of immunosuppressive drugs). Immunocompromised populations were derived from World Health Business (WHO) and United Kingdom (UK) Department of Health immunisation policy to prevent influenza contamination[14],[23]. We additionally included malnutrition and tuberculosis as conditions commonly associated with immunocompromise in developing countries. Interventions of interest comprised vaccination against seasonal influenza or 2009 influenza A(H1N1) pandemic; restricted to experimental designs for seasonal Risperidone hydrochloride influenza but with no limitation for pandemic studies where experimental approaches would have been ethically unfeasible in most circumstances. Comparative groups included vaccinated immunocompetent controls (VICT) and immunocompromised patients given placebo or no vaccination (PNV). Outcome measures corresponded to four research questions relevant to this review: prevention of clinically diagnosed influenza or influenza-like illness (ILI) and laboratory confirmed influenza contamination, serological response, and adverse events associated with vaccination. Criteria for inclusion and exclusion of studies, established in advance of executing the search str ategy, are presented inTable 1and information sources searched to identify relevant literature are shown inTable 2. == Table 1. Study eligibility criteria. == *Applied to respiratory and autoimmune conditions only; no specification of dosage or duration of therapy. == Table 2. Information sources. == == Search strategy and study selection == Single.