For psoriatic patients who need to receive nonlive or live vaccines, evidence-based recommendations are needed regarding whether to pause or continue systemic therapies for psoriasis and/or psoriatic arthritis.

To evaluate literature regarding vaccine efficacy and safety and to generate consensus-based recommendations for adults receiving systemic therapies for psoriasis and/or psoriatic arthritis receiving nonlive or live vaccines.

Using a modified Delphi process, 22 consensus statements were developed by the National Psoriasis Foundation Medical Board and COVID-19 Task Force, and infectious disease experts.

Key recommendations include continuing most oral and biologic therapies without modification for patients receiving nonlive vaccines; consider interruption of methotrexate for nonlive vaccines. For patients receiving live vaccines, discontinue most oral and biologic medications before and after administration of live vaccine. Specific recommendations include discontinuing most biologic therapies, except for abatacept, for 2-3 half-lives before live vaccine administration and deferring next dose 2-4 weeks after live vaccination.

Studies regarding infection rates after vaccination are lacking.

Interruption of antipsoriatic oral and biologic therapies is generally not necessary for patients receiving nonlive vaccines. Temporary interruption of oral and biologic therapies before and after administration of live vaccines is recommended in most cases.

Prevention of infections is crucial in solid organ transplant (SOT) candidates and recipients. These patients are exposed to an increased infectious risk due to previous organ insufficiency and to pharmacologic immunosuppression. Besides infectious-related morbidity and mortality, this vulnerable group of patients is also exposed to the risk of acute decompensation and organ rejection or failure in the pre- and post-transplant period, respectively, since antimicrobial treatments are less effective than in the immunocompetent patients. Vaccination represents a major preventive measure against specific infectious risks in this population but as responses to vaccines are reduced, especially in the early post-transplant period or after treatment for rejection, an optimal vaccination status should be obtained prior to transplantation whenever possible. This review reports the currently available data on the indications and protocols of vaccination in SOT adult candidates and recipients.

COVID-19 infections can lead to worse outcomes in an immunocompromised population with multiple comorbidities, e.g., heart transplant patients. We used the National Inpatient Sample database to compare heart transplant outcomes in patients with COVID-19 vs. influenza. A total of 2460 patients were included in this study: heart transplant with COVID-19 (n = 1155, 47.0%) and heart transplant with influenza (n = 1305, 53.0%) with the primary outcome of in-hospital mortality. In-hospital mortality (n = 120) was significantly higher for heart transplant patients infected with COVID-19 compared to those infected with influenza (9.5% vs. 0.8%, adjusted OR: 51.6 [95% CI 4.3-615.9], p = 0.002) along with significantly higher rates of mechanical ventilation, acute heart failure, ventricular arrhythmias, and higher mean total hospitalization cost compared to the influenza group. More studies are needed on the role of vaccination and treatment to improve outcomes in this vulnerable population.

Solid organ transplant recipients (SOTR) have diminished humoral immune responses to COVID-19 vaccination and higher rates of COVID-19 vaccine breakthrough infection than the general population. Little is known about COVID-19 disease severity in SOTR with COVID-19 vaccine breakthrough infections.

Between 4/7/21 and 6/21/21 we requested case reports via the Emerging Infections Network (EIN) listserv of SARS-CoV-2 infection following COVID-19 vaccination in SOTR. Online data collection included patient demographics, dates of COVID-19 vaccine administration and clinical data related to COVID-19. We performed a descriptive analysis of patient factors and evaluated variables contributing to critical disease or need for hospitalization.

Sixty-six cases of SARS-CoV-2 infection after vaccination in SOTR were collected. COVID-19 occurred after the second vaccine dose in 52 (78.8%) cases of which 43 (82.7%) occurred ≥14 days post-vaccination. There were 6 deaths, 3 occurring in fully vaccinated individuals (7.0%, n = 3/43). There was no difference in the percentage of patients who recovered from COVID-19 (70.7% vs 72.2%, p = 0.90) among fully and partially vaccinated individuals. We did not identify any differences in hospitalization (60.5% vs. 55.6%, p = 0.72) or critical disease (20.9% vs. 33.3%, p = 0.30) among those who were fully vs. partially vaccinated.

SOTR vaccinated against COVID-19 can still develop severe, and even critical, COVID-19 disease. Two doses of mRNA COVID-19 vaccine may be insufficient to protect against severe disease and mortality in SOTR. Future studies to define correlates of protection in SOTR are needed. This article is protected by copyright. All rights reserved.

COVID-19 is associated with increased morbidity and mortality in transplant recipients. There are no efficacy data available regarding these patients with any of the available SARS-CoV-2 vaccines. We analyzed the humoral response following full vaccination with the BNT162b2 (Pfizer-BioNTech) in 136 kidney transplant recipients, and compared it to 25 controls. In order to exclude prior exposure to the virus, only participants with negative serology to SARS-CoV-2 nucleocapsid protein were included. All controls developed a positive response to spike protein, while only 51 of 136 transplant recipients (37.5%) had positive serology (p < .001). Mean IgG anti-spike level was higher in the controls (31.05 [41.8] vs. 200.5 [65.1] AU/mL, study vs. control, respectively, p < .001). Variables associated with null humoral response were older age (odds ratio 1.66 [95% confidence interval 1.17-2.69]), high-dose corticosteroids in the last 12 months (1.3 [1.09-1.86]), maintenance with triple immunosuppression (1.43 [1.06-2.15]), and regimen that includes mycophenolate (1.47 [1.26-2.27]). There was a similar rate of side effects between controls and recipients, and no correlation was found between the presence of symptoms and seroconversion. Our findings suggest that most kidney transplant recipients remain at high risk for COVID-19 despite vaccination. Further studies regarding possible measures to increase recipient's response to vaccination are required.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus causing Coronavirus disease 2019 (COVID-19), has had a huge impact on health services, with a high mortality associated with complications including pneumonia and acute respiratory distress syndrome. Patients with systemic lupus erythematosus (SLE) are at increased risk of viral infections, and recent data suggests they may be at an increased risk of poor outcomes with COVID-19. This may be particularly true for those on rituximab or high dose steroids. A huge international effort from the scientific community has so far resulted in the temporary authorisation of three vaccines which offer protection against SARS-CoV-2, with over 30 other vaccines being evaluated in ongoing trials. Although there has historically been concern that vaccines may trigger disease flares of SLE, there is little convincing evidence to show this. In general lupus patients appear to gain good protection from vaccination, although there may be reduced efficacy in those with high disease activity or those on immunosuppressive therapies, such as rituximab or high dose steroids. Recent concerns have been raised regarding rare clotting events with the AstraZeneca/Oxford vaccine and it is currently unknown whether this risk is higher for those patients with secondary antiphospholipid syndrome. With the possibility of annual COVID vaccination programmes in the future, prospective data collection and registries looking at the effect of vaccination on SLE disease control, the incidence of COVID-19 in SLE patients and severity of COVID-19 disease course would all be useful. As mass vaccination programmes begin to roll out across the world, we assess the evidence of the use of vaccines in SLE patients and in particular vaccines targeting SARS-CoV-2.

Patients with immune-mediated diseases on immunosuppressive therapies have more infectious episodes than healthy individuals, yet vaccination practices by physicians for this patient population remain suboptimal.

To evaluate the safety and efficacy of vaccines in individuals exposed to immunosuppressive therapies and provide evidence-based clinical practice recommendations.

A literature search for vaccination safety and efficacy in patients on immunosuppressive therapies (2009-2017) was conducted. Results were assessed using the Grading of Recommendation, Assessment, Development, and Evaluation system.

Several immunosuppressive therapies attenuate vaccine response. Thus, vaccines should be administered before treatment whenever feasible. Inactivated vaccines can be administered without treatment discontinuation. Similarly, evidence suggests that the live zoster vaccine is safe and effective while on select immunosuppressive therapy, although use of the subunit vaccine is preferred. Caution regarding other live vaccines is warranted. Drug pharmacokinetics, duration of vaccine-induced viremia, and immune response kinetics should be considered to determine appropriate timing of vaccination and treatment (re)initiation. Infants exposed to immunosuppressive therapies through breastmilk can usually be immunized according to local guidelines. Intrauterine exposure to immunosuppressive agents is not a contraindication for inactivated vaccines. Live attenuated vaccines scheduled for infants and children ⩾12 months of age, including measles, mumps, rubella, and varicella, can be safely administered as sufficient time has elapsed for drug clearance.

Immunosuppressive agents may attenuate vaccine responses, but protective benefit is generally maintained. While these recommendations are evidence based, they do not replace clinical judgment, and decisions regarding vaccination must carefully assess the risks, benefits, and circumstances of individual patients.

This narrative review summarizes the current literature relating to pneumococcal vaccination in adult solid organ transplant (SOT) recipients, who are at risk of invasive pneumococcal disease (IPD) with its attendant high morbidity and mortality. The effect of the pneumococcal polysaccharide vaccine has been examined in several small cohort studies in SOT recipients, most of which were kidney transplant recipients. The outcomes for these studies have been laboratory seroresponses or functional antibody titers. Overall, in most of these studies the transplant recipients were capable of generating measurable serological responses to pneumococcal vaccination but these responses were less than those of healthy controls. A mathematical model estimated the effectiveness of polysaccharide vaccination in SOT recipients to be one third less than those of patients with HIV. The evidence for the efficacy of the pneumococcal conjugate vaccine in SOT is based on a small number of randomized controlled trials in liver and kidney transplant recipients. These trials demonstrated that SOT recipients mounted a serological response following vaccination however there was no benefit to the use of prime boosting (conjugate vaccine followed by polysaccharide vaccine). Currently there are no randomized studies investigating the clinical protection rate against IPD after pneumococcal vaccination by either vaccine type or linked to vaccine titers or other responses against pneumococcus. Concerns that vaccination may increase the risk of adverse alloresponses such as rejection and generation of donor specific antibodies are not supported by studies examining this aspect of vaccine safety. Pneumococcal vaccination is a potentially important strategy to reduce IPD in SOT recipients and is associated with excellent safety. Current international recommendations are based on expert opinion from conflicting data, hence there is a clear need for further high-quality studies in this high-risk population examining optimal vaccination regimens. Such studies should focus on strategies to optimize functional immune responses.

Streptococcus pneumoniae is one of the main causative bacteria in patients with pneumonia; however, there are no data regarding serotype changes in adult patients with pneumonia after the introduction of the pneumococcal vaccine (PCV7) for childhood immunization in Japan. We herein evaluated the serotype distribution in adult patients with pneumonia.

This retrospective epidemiological study was performed at the University of Occupational and Environmental Health, Japan from January 2011 to December 2013. The serotypes of pneumococcal isolates obtained from patients with pneumonia were evaluated along with the patients' clinical information.

A total of 81 patients with pneumococcal pneumonia (89 episodes) from whom S. pneumoniae was isolated were included. The numbers (percentages) of sample types were as follows: sputum 55 (61.8%), intratracheal tube suction 15 (16.9%), intrabronchial sampling 5 (5.6%) and bronchoalveolar lavage fluid 14 (15.7%). The PCV7 serotypes decreased significantly among the patients with pneumococcal pneumonia from 46.4% in 2011 to 20.0% in 2013 (p < 0.05). Conversely, PCV13 and 23-valent pneumococcal polysaccharide vaccination (PPSV23) serotypes other than PCV7 serotypes mildly increased during this period. In addition, the frequency of serotypes 19F, 23F and 4 (which are covered by PCV7) decreased annually; however, the changes in the frequencies of the other serotypes were not significant.

This study demonstrated the yearly decrease of PCV7 serotypes in adult pneumococcal pneumonia patients after introducing PCV7 into the childhood immunization schedule in Japan. Continued surveillance of pneumococcal serotype changes is important for the proper use of different pneumococcal vaccines.

International travellers with immunocompromising conditions such as human immunodeficiency virus (HIV) infection, solid organ transplantation (SOT) and haematopoietic stem cell transplantation (HSCT) are at a significant risk of travel-related illnesses from both communicable and non-communicable diseases, depending on the intensity of underlying immune dysfunction, travel destinations and activities. In addition, the choice of travel vaccinations, timing and protective antibody responses are also highly dependent on the underlying conditions and thus pose significant challenges to the health-care providers who are involved in pre-travel risk assessment. This review article provides a framework of understanding and approach to aforementioned groups of immunocompromised travellers regarding pre-travel risk assessment and management; in particular travel vaccinations, infectious and non-infectious disease risks and provision of condition-specific advice; to reduce travel-related mortality and morbidity.

Bloodstream infections (BSIs) remain important causes of morbidity and mortality among solid organ transplant (SOT) recipients and still threaten the success of SOT. In general, among SOT recipients, risk factors for BSIs are associated with prior ICU admission, catheterization, older recipient or donor age…etc. Pulmonary focus, nosocomial source of BSIs, lack of appropriate antibiotic therapy and other variables have significant impacts on BSIs-related mortality in SOT. Most of BSIs in SOT are caused by gram-negative bacteria. However, all aspects including microbiological spectrum, morbidity and mortality rates, risk factors of BSIs and BSIs-related death depend on the type of transplantation. The purpose of this review is to summarize the epidemiology, microbiologic features including antimicrobial resistance of organisms, and associated risk factors for morbidity and mortality of BSIs according to different type of transplantation to better understand the characteristics of BSIs and improve the outcomes after SOT.

Patients with chronic inflammatory rheumatic diseases often have an intrinsic and therapy associated increased susceptibility to infections which substantially contributes to morbidity and mortality of the patients. A large proportion of these infections are preventable by vaccination. For this reason in 2005 the standing vaccination committee (STIKO) recommended for patients with immunosuppression vaccination against pneumococcus, influenza, Haemophilus influenza b and meningococcus in addition to standard vaccinations, independent of age. Every patient should therefore be informed about a possible increase in susceptibility to infections and the recommended prevention by vaccination before implementation of immunosuppressive therapy.

Systemic lupus erythematosus (SLE) is a chronic immune-mediated inflammatory multisystem disease. The onset of viral and bacterial infections may favor the exacerbation of the disease, amplify autoimmune processes and contribute to mortality and morbidity. The prevention of influenza and Streptococcus pneumoniae infections with vaccination should receive particular attention in SLE patients considering their elevated incidence, their high attack rate in epidemic periods, their potentially severe complications as well as the immunocompromised state of the host. The use of non-adjuvanted vaccine preparations should be preferred in order to avoid the onset of the "Autoimmune (auto-inflammatory) Syndrome Induced by Adjuvants" or "ASIA". In this review, we report that influenza and pneumococcal vaccinations in SLE patients are: 1) recommended to reduce the risk of development of these infections; 2) strongly suggested in elderly subjects and in those receiving high dose immunosuppressive treatments; 3) efficacious, even if specific immune responses may be lower than in the general population, as generally the humoral response fulfills the criteria for vaccine immunogenicity; and 4) safe in inactive disease although may favor a transient increase in autoantibody levels and rarely disease flares.

The development of vaccination is a major achievement in modern medicine. However, children treated with immunosuppression may not at all, or only in part, receive routine immunization due to uncertainty of its risks and effect. There is a substantial lack of pediatric studies concerning the efficacy and safety of vaccination in this patient group. Experience from similar adult groups and children with HIV infection can be used as a model for other disease categories. With increasing knowledge of the immunologic basis of vaccination and how immunosuppressive drugs interfere with the immune system, improved vaccines could be tailored, and adequate, individualized guidelines issued.

Immunocompromised patients are all at risk of invasive pneumococcal disease, of different degrees and timings. However, considerable progress in pneumococcal immunization over the last 30 years should benefit these patients. The 23-valent polysaccharide vaccine has been widely evaluated in these populations, but due to its low immunogenicity, its efficacy is sub-optimal, or even low. The principle of the conjugate vaccine is that, through the protein conjugation with the polysaccharide, the vaccine becomes more immunogenic, T-cell dependent, and thus providing a better early response and a boost effect. The 7-valent conjugate vaccine has been the first one to be evaluated in different immunocompromised populations. We review here the efficacy and safety of the different antipneumococcal vaccines in cancer, transplant and HIV-positive patients and propose a critical appraisal of the current guidelines.

An international panel of experts prepared an evidenced-based guideline for vaccination of immunocompromised adults and children. These guidelines are intended for use by primary care and subspecialty providers who care for immunocompromised patients. Evidence was often limited. Areas that warrant future investigation are highlighted.

Supported by several epidemiological studies and a large number of animal studies, certain polyfluorinated alkyl acids are believed to be immunotoxic, affecting particularly humoral immunity. Our aim was to investigate the relationship between the antibody response following vaccination with an inactivated trivalent influenza vaccine and circulating levels of perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS). The study population consisted of 411 adults living in the mid-Ohio region of Ohio and West Virginia where public drinking water had been inadvertently contaminated with PFOA. They participated in a larger cross-sectional study in 2005/2006 and were followed up in 2010, by which time serum levels of PFOA had been substantially reduced but were still well above those found in the general population. Hemagglutination inhibition tests were conducted on serum samples collected preinfluenza vaccination and 21 ± 3 days postvaccination in 2010. Serum samples were also analyzed for PFOA and PFOS concentrations (median: 31.5 and 9.2 ng/ml, respectively). Questionnaires were conducted regarding the occurrence and frequency of recent (during the last 12 months) respiratory infections. Our findings indicated that elevated PFOA serum concentrations are associated with reduced antibody titer rise, particularly to A/H3N2 influenza virus, and an increased risk of not attaining the antibody threshold considered to offer long-term protection. Although the direct relationship between weakened antibody response and clinical risk of influenza is not clear, we did not find evidence for an association between self-reported colds or influenza and PFOA levels nor between PFOS serum concentrations and any of the endpoints examined.

Resolution of acute of infection caused by capsular Streptococcus pneumoniae infection in the absence of effective antibiotic therapy requires tight regulation of immune and inflammatory responses. To provide new mechanistic insight of the requirements needed for innate host defenses against acute S. pneumoniae infection, we examined how IL-23 deficiency mediated acute pulmonary resistance. We found that IL-23 deficient mice were more susceptible to bacterial colonization in the lungs corresponding with greater bacterial dissemination. The lack of IL-23 was found to decrease IL-6 and IL-12p70 cytokine levels in bronchiolar lavage within the initial day after infection. Pulmonary leukocytes isolated from infected IL-23 deficient mice demonstrated a dramatic decrease in IL-17A and IFN-γ in response to heat-killed organisms. These findings corresponded with significant abrogation of neutrophilic infiltrate in the lungs compared to IL-23 competent mice. Whereas previous studies have shown opposing influences of IL-12/IL-23 regulation, our findings suggest a concordant dependency of IL-23 expression on Th1 and Th17-related responses.

Infectious diseases after solid organ transplantation (SOT) are one of the major complications in transplantation medicine. Vaccination-based prevention is desirable, but data on the response to active vaccination after SOT are conflicting.

In this systematic review, we identify the serologic response rate of SOT recipients to post-transplantation vaccination against tetanus, diphtheria, polio, hepatitis A and B, influenza, Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitides, tick-borne encephalitis, rabies, varicella, mumps, measles, and rubella.

Of the 2478 papers initially identified, 72 were included in the final review. The most important findings are that (1) most clinical trials conducted and published over more than 30 years have all been small and highly heterogeneous regarding trial design, patient cohorts selected, patient inclusion criteria, dosing and vaccination schemes, follow up periods and outcomes assessed, (2) the individual vaccines investigated have been studied predominately only in one group of SOT recipients, i.e. tetanus, diphtheria and polio in RTX recipients, hepatitis A exclusively in adult LTX recipients and mumps, measles and rubella in paediatric LTX recipients, (3) SOT recipients mount an immune response which is for most vaccines lower than in healthy controls. The degree to which this response is impaired varies with the type of vaccine, age and organ transplanted and (4) for some vaccines antibodies decline rapidly.

Vaccine-based prevention of infectious diseases is far from satisfactory in SOT recipients. Despite the large number of vaccination studies preformed over the past decades, knowledge on vaccination response is still limited. Even though the protection, which can be achieved in SOT recipients through vaccination, appears encouraging on the basis of available data, current vaccination guidelines and recommendations for post-SOT recipients remain poorly supported by evidence. There is an urgent need to conduct appropriately powered vaccination trials in well-defined SOT recipient cohorts.

Little is known about the long-term antibody response to the 2009-H1N1 vaccine in solid organ transplant recipients (SOTR) and its clinical repercussion on the efficacy of following 2010-2011 influenza vaccine.

We performed a multicenter prospective study in SOTR receiving one dose of the nonadjuvant 2010-2011 seasonal influenza vaccine and determined the immunological response at 5 weeks after vaccination.

One hundred SOTR were included. Long-term antibody titers to the previous vaccine were only detected in one third of the patients. Patients with baseline titers had significantly higher seroprotection for the 2009-H1N1 strain (100% vs. 73%, relative risks [RR] 1.37, 95% confidence intervals [CI] 1.19-1.57; P=0.006), for H3N2 strain (100% vs. 62.2%, RR 1.61, 95% CI 1.36-1.90; P=0.005), and for B strain (100% vs. 69%; P=0.02). The seroconversion rate in patients with baseline titers was 90.9% vs. 73% (RR 2.97, 95% CI 0.75-11.74; P=0.07) for the 2009-H1N1 strain, 92.2% vs. 62.2% (RR 5.29, 95% CI 0.8-35.7; P=0.02) for the H3N2 strain, and 58.3% vs. 69% (P=0.45) for the B strain.

SOTR response to the 2010-2011 influenza vaccine was not optimal. The response was related to baseline titers; however, most of the patients did not exhibit detectable antibodies at vaccination lacking long-term response. New strategies are necessary to improve vaccination efficacy.

Immunocompromised patients are vulnerable to severe or complicated influenza infection. Vaccination is widely recommended for this group. This systematic review and meta-analysis assesses influenza vaccination for immunocompromised patients in terms of preventing influenza-like illness and laboratory confirmed influenza, serological response and adverse events.

Electronic databases and grey literature were searched and records were screened against eligibility criteria. Data extraction and risk of bias assessments were performed in duplicate. Results were synthesised narratively and meta-analyses were conducted where feasible. Heterogeneity was assessed using I(2) and publication bias was assessed using Begg's funnel plot and Egger's regression test. Many of the 209 eligible studies included an 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]=0.16-0.34; p<0.001) and laboratory confirmed influenza infection (OR=0.15; 95% CI=0.03-0.63; 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.

Infection 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.

Influenza A (H1N1) has emerged as a considerable threat for recipients of organ transplants. Vaccination against the novel influenza A (H1N1) virus has generally been advocated. There is limited experience with AS03-adjuvanted A/H1N1 pandemic influenza vaccines in immunosuppressed patients.

We conducted an observational, nonrandomized single-center study to assess antibody response and vaccine-related adverse effects in 47 heart transplant recipients (44 men; age, 56±13 years). The AS03-adjuvanted, inactivated split-virion A/California/7/2009 H1N1v pandemic vaccine was administered. Antibody titers were measured using hemagglutination inhibition; immunoglobulin G (IgG) response was assessed using a new pandemic influenza A IgG enzyme-linked immunosorbent assay (ELISA) test kit and compared with hemagglutination-inhibition titers. Adverse effects of vaccination were assessed by a questionnaire.

Postvaccination antibody titers of greater than or equal to 1:40 were found in only 15 patients, corresponding to a seroprotection rate of 32% (95% confidence interval, 19%-47%). Sensitivity, specificity, positive predictive value, and negative predictive value of ELISA testing were 80.0%, 68.8%, 54.5%, and 88.0%, respectively. Age, time posttransplantation, and immunosuppressive regimen did not impact antibody response. Vaccination was well tolerated.

Single-dose administration of an AS03-adjuvanted vaccine against the novel influenza A (H1N1) virus did not elicit seroprotective antibody concentrations in a substantial proportion of heart transplant recipients; the new pandemic influenza A IgG ELISA test kit proved to be of limited clinical use.

Data on the immunogenicity of the influenza vaccine in children after liver transplantation are sparse. Our study aims to evaluate the response of such patients to the trivalent influenza vaccine, administered by different protocols in 2 influenza seasons.

Children attending the Liver Transplantation Unit of a tertiary care medical center were prospectively recruited and immunized with the inactivated subvirion influenza vaccine during the influenza seasons of 2004/2005 (1 dose, n = 18) and 2005/2006 (2 doses 4-6 weeks apart, n = 32). Antibodies were measured by hemagglutination inhibition assay. Immunity was defined as a titer of ≥1:40, and response was defined as a ≥4-fold increase in antibody titer from baseline.

In 2004/2005, the proportions of patients with protective antibodies were similar before and after 1 dose of vaccine. We found significant difference after the first dose for the A/H3N2 Wisconsin strain (43.2% vs. 70.3%, P = 0.003) and B/Malaysia strains (8.1% vs. 35.1%, P = 0.003) and for A/H1N1 New Caledonia strain (48.6% vs. 64.9% vs. 75%, P = 0.08, 0.005, respectively) after the second dose in 2005/2006 season. In 2004/2005, geometric mean titers rose significantly (P = 0.03) for the A/H3N2 New York strain; in 2005/2006, geometric mean titers for A/H3N2 New York and B/Malaysia increased after the first dose and for A/H1N1 New Caledonia after the second dose. Antibody titers were unrelated to age at transplantation, time from transplantation, and number of immunosuppressive drugs used. No serious vaccine-related events were documented.

Liver-transplanted children respond to influenza vaccination. For some strains, the response is similar to that reported for healthy children. A second vaccine dose yielded no statistically significant benefit.

Patients with autoimmune or rheumatic diseases are at increased risk for infectious complications due to immunosuppressive therapy and/or the underlying immunological disease itself. To date, the consistent use of vaccinations in this patient group has been limited due to concerns about flair-ups or lack of efficacy. In prospective studies neither an increased risk of disease flair-ups nor of initiation of autoimmune disorders was found as yet; however, the data is still considered insufficient (small studies including only patients in remission). Vaccination with non-live vaccines can generally be regarded as safe and relatively effective, even in patients on immunosuppressive therapy. Since the immune response to vaccination may be markedly impaired depending on the medication used and the underlying autoimmune disease, monitoring of both serum titers and of patients' vaccination schedules should form an integral part of rheumatological care.

Cyclosporine is highly effective in the treatment of a multitude of dermatoses. Concern over its side effect profile has limited its use in dermatology. Adverse effects are, for the most part, dose dependent and related to duration of therapy. Using the recommended monitoring protocols results in a significant decrease in the incidence of cyclosporine-related toxicities. This article provides a comprehensive review of the pharmacokinetics of cyclosporine, potential drug interactions, adverse effects, and recommendations for monitoring in patients treated with cyclosporine. The use of cyclosporine in pregnancy and in the pediatric population is also addressed.

After completing this learning activity, participants should be familiar with the monitoring guidelines of cyclosporine, its contraindications, its possible drug interactions, its adverse effect profile, and its use in pregnancy and the childhood and adolescent populations.

Severe immune deficiency follows autologous stem cell transplantation for multiple myeloma and is associated with significant infectious morbidity. This study was designed to evaluate the utility of a pretransplantation vaccine and infusion of a primed autologous T-cell product in stimulating specific immunity to influenza. Twenty-one patients with multiple myeloma were enrolled from 2007 to 2009. Patients were randomly assigned to receive an influenza-primed autologous T-cell product or a nonspecifically primed autologous T-cell product. The study endpoint was the development of hemagglutination inhibition titers to the strain-specific serotypes in the influenza vaccine. Enzyme-linked immunospot assays were performed to confirm the development of influenza-specific B-cell and T-cell immunity. Patients who received the influenza-primed autologous T-cell product were significantly more likely to seroconvert in response to the influenza vaccine (P = .001). Seroconversion was accompanied by a significant B-cell response. No differences were observed in the global quantitative recovery of T-cell and B-cell subsets or in global T-cell and B-cell function. The provision of a primed autologous T-cell product significantly improved subsequent influenza vaccine responses. This trial was registered at www.clinicaltrials.gov as #NCT00499577.

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.

The risk of developing invasive pneumococcal disease in transplant patients is estimated at 28 to 36 per 1000 patients/year according to the type of organ transplanted. This rate is much higher than the estimated incidence in the general population. This study reviews the current experience regarding the different types of vaccinations against Streptococcus pneumoniae in transplant patients, the immunogenic response to pneumococcal vaccine in these patients, the clinical experience to date with the use of pneumococcal vaccines, and the utility of a sequential vaccination regime including the heptavalent vaccine and vaccine for the 23 serogroups. The immunogenicity produced by pneumococcal vaccines in transplant patients is lower and not as long-lasting as in immunocompetent individuals, and the revaccination regimen inducing the most favorable immunological response is unknown. Nonetheless, pneumococcal vaccination provides clear benefits to transplant recipients and should be given before transplantation whenever possible.

Although effective in the treatment of immunodysregulatory diseases such as psoriasis, targeted immunosuppressive agents may confer risks of both enhanced susceptibility to infection and decreased responsiveness to vaccination. In a recent study, Krueger et al. (this issue) investigated these issues by testing the immune response to both a model antigen and a therapeutic vaccination in psoriasis patients during and after treatment with an LFA-1 inhibitor, efalizumab.

Active immunization is the most important way to protect immunocompromised patients from vaccine-preventable infectious diseases. Although live vaccines are contraindicated for most immunocompromised patients, many inactivated or conjugate vaccines are safe and generally recommended. Some vaccines are known to be of suboptimal immunogenicity in transplant recipients. As a consequence, this may be associated with an impaired ability to mount protective immunity. Nevertheless, even partial protection has been shown to confer significant benefit to this vulnerable patient group. To increase efficacy in generating protective immunity, patients should complete the full complement of recommended vaccinations early in the course of disease before transplantation. This review summarizes the general recommendations for vaccinations of adult transplant recipients and candidates including special considerations for household contacts and health care workers.

Patients who have chronic rheumatic or autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, or vasculitides, show a risk of infection that is at least 2-fold greater than that for healthy individuals. This increased risk is not only a result of the aberrant immunologic reaction itself but also can be attributed to the immunosuppressive therapy required to control the activity of the underlying disease and the associated organ complications. Vaccination is an option for a substantial number of these infections. In this context, pneumococcal and influenza vaccines are the best evaluated and are recommended by standard vaccination guidelines. Some studies have found mildly impaired immune responses to vaccines among patients receiving long-term immunosuppressive therapy, but postvaccination antibody titers are usually sufficient to provide protection for the majority of immunized individuals. The accumulated data on the safety and effectiveness of vaccines warrant immunization with the majority of vaccines for patients with chronic autoimmune or rheumatic diseases, especially vaccination against influenza and pneumococci. Vaccination protocols for this population should be better implemented in daily clinical practice.

Efalizumab is a humanized monoclonal CD11a antibody approved for treatment of psoriasis. Its immunomodulatory effects led us study how immune responses are modified and the possible consequences for vaccinations in clinical practice. This was a randomized, single-blind, placebo-controlled, parallel-group study of 12 weeks of subcutaneous efalizumab treatment of patients with moderate psoriasis. Bacteriophage phiX174 was used as a model neoantigen to assess T-cell-dependent humoral immunity. Tetanus booster vaccine, pneumococcal vaccine, and intracutaneous skin tests were administered to further evaluate humoral and cellular immune responses. During efalizumab treatment, both primary and secondary antibody responses to phiX174, including IgM/IgG isotype switch, were reduced. There appeared to be naïve T-cell anergy to a neoantigen (phiX174) during active CD11a blockade, without tolerance to the antigen after efalizumab withdrawal. Secondary humoral immune responses to tetanus booster during treatment were reduced, but antibody titer increases led to protective levels. Responses to pneumococcal vaccination 6 weeks after withdrawal from efalizumab were not affected. Cellular immune responses to intracutaneous recall antigens were reduced during treatment and returned to pretreatment conditions after withdrawal. These results expand our knowledge of how immune responses are modulated in humans by CD11a blockade and have implications for vaccinations of patients treated with this agent.

Annual influenza vaccination is routinely recommended for pediatric solid organ transplant recipients. However, there are limited data defining the immune response to the inactivated vaccine in this population.

This prospective study compared the humoral and cell-mediated immune responses to the trivalent subvirion influenza vaccine in pediatric liver transplant recipients with those in their healthy siblings. All subjects received inactivated influenza vaccine. Hemagglutination inhibition and interferon-gamma (IFN-gamma) enzyme-linked immunosorbent spot assays for New Caledonia and Shanghai strains were performed at baseline, after each vaccine dose, and 3 months after the series. Seroconversion was defined as a 4-fold increase in antibody titers; seroprotection was defined as an antibody titer > or =1:40. An increase in the number of T cells secreting IFN-gamma was considered to be a positive enzyme-linked immunosorbent spot response.

After 1 dose of vaccine, transplant recipients achieved rates of antibody seroprotection and seroconversion that were similar to those achieved by their healthy siblings. However, for both influenza strains, IFN-gamma responses by enzyme-linked immunosorbent spot were significantly attenuated in transplant recipients after 2 doses of vaccine. No cases of influenza or vaccine-related serious adverse events were documented in the study.

The diminished cell-mediated immune response to influenza vaccination that was observed in pediatric liver transplant recipients suggests that the current vaccine strategy may not provide optimal protection. Because of concerns regarding potential emergence of more virulent influenza strains, further studies are warranted to determine if IFN-gamma responses are predictive of efficacy and to identify the optimal vaccination strategy to protect populations with a high risk of infection.

The growing success of solid organ transplantation poses unique challenges for the implementation of effective immunization strategies. Although live attenuated vaccines have proven benefits for the general population, immunosuppressed patients are at risk for unique complications such as infection from the vaccine because of lack of both clearance and containment of a live attenuated virus. Moreover, while vaccination strategies using killed organisms or purified peptides are believed to be safe for immunosuppressed patients, they may have reduced efficacy in this population. The current lack of knowledge of the basic safety and efficacy of vaccination strategies in the immunosuppressed has limited the development of guidelines regarding vaccination in this population. Recent fears of influenza pandemics and potential attacks by weaponized pathogens such as smallpox heighten the need for increased knowledge. Herein, we review the current understanding of the effects of immunosuppressants on the immune system and the ability of the suppressed immune system to respond to vaccination. This review highlights the need for systematic, longitudinal studies in both humans and nonhuman primates to understand better the defects in innate and adaptive immunity in transplant recipients, thereby aiding the development of strategies to vaccinate these individuals.

Different immunosuppressant regimens vary in their effects on antibody responses to vaccination. The combination of prednisolone and azathioprine has only a minor effect, whereas the addition of ciclosporin attenuates protective antibody responses to influenza vaccination. The effect of sirolimus, a new immunosuppressant, on vaccine responses has been little studied. Thirty-two hepatic or renal transplant patients randomized to calcineurin inhibitor-based or sirolimus-based immunosuppression were vaccinated against influenza and pneumococcus. Following tri-valent influenza vaccination, a similar rise in antibody titer occurred in sirolimus and calcineurin inhibitor (CNI) treated patients, though sirolimus treated patients developed a 'protective' titer to more influenza antigens. The pneumococcal polysaccharide vaccine was equally effective in both groups. Hence, vaccination guidelines in place for CNI treated patients are likely to be appropriate for transplant recipients maintained on sirolimus.

The aim of this study was to compare response to inactivated influenza vaccine in healthy children and pediatric patients with inflammatory bowel disease (IBD).

A prospective, open-label, controlled clinical trial during influenza seasons of 2002-2004 was performed. Single-dose inactive trivalent influenza vaccine was administered. Immune response to vaccination was measured by pre-immunization and postimmunization hemagglutinin inhibition titers. A postimmunization hemagglutinin inhibition titer of 40 or higher was considered protective against influenza. IBD activity and adverse events were recorded.

Eighty subjects were enrolled (29 healthy controls, 51 IBD patients). One patient did not complete the study. Patients were divided into 3 subgroups: infliximab and immunomodulatory (16), immunomodulatory (20), and anti-inflammatory therapy (14). Immunomodulatory therapy included corticosteroids, 6-mercaptopurine, or methotrexate. Overall, there was a statistically significant decrease in immune response in patients compared with healthy controls who received 1 influenza vaccine antigen (B/Hong Kong, P = .0125). Patients receiving infliximab and immunomodulatory therapy were less likely to respond to 2 influenza vaccine antigens (A/New Caledonia/20/99 and B/Hong Kong/330/2001, P = .018 and .0002, respectively). Fifteen subjects (19%) reported 19 mild adverse events: 11 (14%) reported soreness at the site, 4 (5%) reported having a cold, 3 (4%) reported flu-like symptoms, and 1 (1%) reported a headache. The clinical activity of IBD was not affected by vaccination.

The serologic conversion rate to influenza vaccine in patients with IBD ranged from 33% to 85%. Patients on concomitant infliximab and immunomodulatory therapy are at risk of inadequate response to vaccination. The vaccine was safe and did not affect IBD activity.

Patients with rheumatic diseases who are undergoing immunosuppressive therapy have a substantially increased risk of infection compared to the normal population, and are thus candidates for preventive measures. In accordance with the recommendations of the Standing Vaccination Commission of the Robert Koch Institute (Ständigen Impfkommission, STIKO), these individuals, in analogy with other patients with chronic diseases, belong to a risk group for which vaccination against pneumococci and influenza is recommended. Published studies indicate that a limited immune response is possible for patients undergoing immunosuppressive therapy. Here, methotrexate in particular appears to interfere with the success of vaccination against pneumococci. However, a limited immune response against influenza antigens was observed under immunosuppression with mycophenolate mufti, cyclosporine und azathioprine. Consideration must be given to the fact that a patient under continual immunosuppression has a reduced duration of protective immune response. New studies on tumor necrosis factor (TNF) inhibitors indicate that there should be no interference with pneumococcus infection. The possibly variable vaccination success of patients undergoing TNF inhibitor treatment is qualified by the fact that all published results show that the expected immune response after an influenza vaccination is very good. Vaccination strategies in cases in which the use of rituximab and abatacept is planned are currently unclear.