Expanded data regarding the safety and immunogenicity of live viral vaccines (LVV) during the posttransplant period has resulted in updated recommendations endorsing LVVs for select pediatric liver transplant (LT) recipients, a significant change from historical guidelines. The goal of this survey study was to understand current LVV practices among pediatric LT centers.

A 20-question email survey detailing center-specific pre- and post-LT LVV practices was distributed between May 1, 2024, and August 1, 2024, to a representative from each US center participating in the Society of Pediatric Liver Transplantation (SPLIT).

The overall survey response rate was 95% (41/43 centers). In the pretransplant period, 85% of centers (35/41) administer LVVs starting at 6 months of age, 7% (3/41) wait until 9 months, and another 7% start at 12 months. The majority of centers (83%, 34/41) require a 4-week interval between LVVs and active transplant listing. In the posttransplant period, 39% of centers (16/41) never recommend LVVs, citing perceived limited safety data (63%, 10/16) and inability to reach provider consensus (31%, 5/16) as reasons. Among the 25 centers that offer LVVs, barriers faced in implementing LVV protocols include parental concerns about change from historical recommendation (48%, 12/25) and parental concerns about safety/efficacy (36%, 9/25).

The majority of pediatric LT centers across the US now recommend LVVs for select LT recipients. However, these centers face barriers in vaccinating all nonimmune eligible transplant recipients. Research is needed to understand and overcome barriers to widespread acceptance and implementation of evidence-based LVV recommendations.

Patients with cirrhosis and liver transplant recipients are at increased risk of infections. Malnutrition, multiple hospital admissions, immune dysfunction related to cirrhosis, and immunosuppressive agents used for liver transplantation predispose the recipient to various life-threatening infections. Some of these infections are preventable with vaccines. With the COVID-19 pandemic, there has been an accelerated research in vaccination technology and platforms, which in turn may also improve awareness of physicians regarding this healthy and often ignored aspect of management of patients with cirrhosis and transplant recipients. The organ transplant candidates should complete the recommended vaccination schedule as early as possible (especially patients with compensated cirrhosis) or at least during their pretransplant work-up so as to prevent or reduce the severity of various infections.

Recently, live-attenuated measles, rubella, varicella, and mumps vaccines have been administered to carefully selected post-liver transplant patients. Although attention has been focused on post-vaccination antibody titers and adverse events, the real-life clinical benefits remain unclear. A comprehensive analysis of breakthrough infections and natural boosters (asymptomatic cases with significant elevation in virus antibody titers) following immunization post-liver transplantation was conducted from 2002-2023, exploring the timing, frequency, correlation with domestic outbreaks, and degree of antibody elevation. During the median 10-year observation period among 68 post-liver transplant patients, breakthrough infections occurred only in chickenpox, with 7 mild cases (1 episode/64 person-years). A total of 59 natural booster episodes (1, 5, 20, and 33 for measles, rubella, chickenpox, and mumps, respectively) were observed, with incidence rates of 1 per 569, 110, 22, and 17 person-years, respectively. The timing of natural boosters closely correlated with domestic outbreaks (P < .05 in chickenpox and mumps), influenced by local vaccine coverage. The degree of antibody elevation was significantly higher in individuals with breakthrough infections than in those with natural boosters (P < .05). These findings suggest that immunization with live-attenuated vaccines for post-liver transplant patients has demonstrated clinical benefits. Furthermore, mass vaccination has a positive impact on post-transplant patient outcomes.

A recent conditional recommendation suggests considering live-attenuated vaccines for solid organ transplant recipients, yet the conditions of their safe and effective administration remain unclear.

This prospective study was conducted at Keio University Hospital from 2002 to August 2023. We gave a live-attenuated vaccine to liver transplant (LT) recipients fulfilling criteria for live-attenuated vaccines, including criteria for humoral and cell-mediated immunity. Patient background information, immunization date, vaccine strain, immunosuppressive agents at the time of vaccination, and antibody titers were collected. Factors related to primary and secondary vaccine failure were evaluated to enhance the effectiveness of the live-attenuated vaccine program after LT.

Among 67 LT recipients, 54, 55, 47, and 55 received at least one dose of live-attenuated vaccine for measles, rubella, varicella, and mumps, respectively. The difference in vaccine strains, but not the use of two or more immunosuppressive agents, was associated with a lower risk of vaccine failures. Measles vaccine with the AIK-C strain exhibited significantly lower primary and secondary failure rates than the CAM-70 strain (1/38 vs. 4/16, odds ratio: 0.08, 95 % confidence interval [CI]: 0.01-0.80, p = 0.02, and hazard ratio: 0.54, 95 % CI: 0.34-0.85, p = 0.01, respectively). No primary failures were observed with the TO-336 strain of rubella, whereas 4 of 10 LT recipients with the Matsuura strain of rubella did not seroconvert. For mumps, the Hoshino strain showed lower primary failure rates than the Torii strain (15/52 vs. 3/3, p = 0.03).

According to a 20-year long-term study, vaccine strains are the most critical factor influencing primary and secondary vaccine failure in post-transplant live-attenuated vaccination.

Liver transplantation (LT) recipients are susceptible to infections, including measles. Concerns about the safety and efficacy of live-attenuated vaccines, such as the measles-mumps-rubella (MMR) vaccine, have led to hesitancy among providers in administering them to immunocompromised patients. This 9-year interventional study assessed seroprotection against measles following MMR vaccination in pediatric LT recipients. Of 119 participants enrolled, 60 (50%) were seroprotected against measles after transplantation. Among the 59 nonseroprotected participants, 56 fulfilled safety criteria and received MMR vaccination with a seroprotection rate of 90% (95% confidence interval [CI], 73%-98%) after a first dose, 95% (95% CI, 85%-99%) after primary vaccination with 1 to 3 doses, comparable to nonimmunocompromized populations. However, measles antibodies declined over time, suggesting the need for regular monitoring, and booster doses. Half of the vaccinees (26/53, 49%) subsequently lost seroprotection. Among them, 23 received additional doses of MMR, with a high seroconversion rate. At their last follow-up (median, 6.1 years; interquartile range, 3.0-8.1 after inclusion), 63% (95% CI, 49%-75%) of all vaccinees were seroprotected against measles. In conclusion, MMR vaccination in pediatric LT recipients offers seroprotection against measles, but long-term immunity should be monitored closely.

Solid organ transplant (SOT) candidates and recipients are a fragile population, in which the presence of a pre-transplant disease leading to organ insufficiency and the post-transplant immunosuppressive treatment expose them to an increased risk of infectious diseases. The best intervention to guarantee efficient prevention of infections, with optimal cost-benefit ratio, is represented by vaccination programs; however, the response to vaccines needs that the immune system maintains a good function. This is even more relevant at paediatric age, when specific immunological conditions make transplant candidates and recipients particularly vulnerable. Paediatric patients may be naïve to most infections and may have incomplete immunization status at the time of transplant listing due to their age. Moreover, the unaccomplished development of a mature immune system and the immunosuppressive regimen adopted after transplant might affect the efficacy of post-transplant vaccinations. Therefore, every effort should be made to obtain the widest vaccination coverage before the transplantation, whenever possible. This review reports the most relevant literature, providing information on the current approach to the vaccinations in paediatric SOT candidates and recipients.

Emerging evidence has figured that serum conversion rate of mumps is a crucial link of mumps disease. Nevertheless, a rising number of mumps outbreaks caused our attention and studies examining the serum conversion cases were conducted in small samples previously; this meta-analysis was conducted to assess the immunogenicity and safety of a mumps containing vaccine (MuCV) before 2019. We identified a total of 17 studies from the year of 2002-2017. In the case-control studies, the vaccine effectiveness (VE) of MuCV in preventing laboratory-confirmed mumps was 68% (odds risk: 0.32; 95% confidence interval [CI], 0.14-0.70) while in the cohort studies and randomised control trials, 58% (relative risk [RR]: 0.42; 95% CI, 0.26-0.69). Similar intervals of effectiveness rates were found during non-outbreak periods compared with outbreak periods (VE: 66%; RR: 0.34; 95% CI, 0.18-0.68 versus VE: 49%; RR: 0.51; 95% CI, 0.21-1.27). In addition, the MuCV group with two and three doses did not show enhanced laboratory-confirmed mumps than one dose (VE: 58%; RR: 0.42; 95% CI, 0.20-0.88 versus VE: 65%, RR: 0.35; 95% CI, 0.20-0.61) for the reason of the overlap of 95% CI. MuCV had comparable effectiveness comparing non-outbreak and outbreak period, one dose, and two or three doses. MuCV displayed acceptable adverse event profiles.

Infections are a serious short- and long-term problem after pediatric organ transplantation. In immunocompromised patients, they can lead to transplant rejection or a severe course with a sometimes fatal outcome. Vaccination is an appropriate means of reducing morbidity and mortality caused by vaccine-preventable diseases. Unfortunately, due to the disease or its course, it is not always possible to establish adequate vaccine protection against live-attenuated viral vaccines (LAVVs) prior to transplantation. LAVVs such as measles, mumps, and rubella (MMR) are still contraindicated in solid organ transplant recipients receiving immunosuppressive therapy (IST), thus creating a dilemma.

This review discusses whether, when, and how live-attenuated MMR vaccines can be administered effectively and safely to pediatric liver transplant recipients based on the available data.

We searched PubMed for literature on live-attenuated MMR vaccination in pediatric liver transplantation (LT).

Nine prospective observational studies and three retrospective case series were identified in which at least 833 doses of measles vaccine were administered to 716 liver transplant children receiving IST. In these selected patients, MMR vaccination was well tolerated and no serious adverse reactions to the vaccine were observed. In addition, an immune response to the vaccine was demonstrated in patients receiving IST.

Due to inadequate vaccine protection in this high-risk group, maximum efforts must be made to ensure full immunization. MMR vaccination could also be considered for unprotected patients after LT receiving IST following an individual risk assessment, as severe harm from live vaccines after liver transplantation has been reported only very rarely. To this end, it is important to establish standardized and simple criteria for the selection of suitable patients and the administration of the MMR vaccine to ensure safe use.

Live attenuated varicella vaccine (LAVV) has historically been contraindicated in children who are immunocompromised due to solid organ transplant (SOT) because of safety concerns. Recently, clinical guidelines were developed that support post-transplant varicella vaccination in selected SOT recipients based on emerging evidence of LAVV safety. This qualitative study sought to explore barriers and facilitators to implementing the new guidelines, as well as acceptability of LAVV among healthcare providers (HCPs) and parents.

HCPs and parents of transplant recipients were recruited from four sites using purposive sampling. Data from semi-structured interviews were analyzed using an Interpretive Description approach that incorporated data from the interviews, academic knowledge and clinical experience, and drew from Grounded Theory and Thematic Analysis. The theoretical framework used was Adaptive Leadership.

Thirty-four participants (16 HCPs and 18 parents) were included in the analysis. Parents developed skills in adaptive leadership that included strategies to protect their child against infectious diseases. Foundational information that live vaccines were absolutely contraindicated post-transplant "stuck" with parents and led them to develop strategies other than vaccination to keep their child safe. Some parents struggled to understand that information previously presented as a certainty (contraindication of LAVV) could change. Their approach to adaptive leadership informed their appraisal of the new vaccination guidelines and willingness to accept vaccination.

HCPs should adopt a family-centered approach to communicating changing guidelines that considers parents' approach to adaptive leadership and discusses the changing nature of medical evidence. Trust between HCPs and parents can facilitate these conversations.

The use of live attenuated vaccines in patients with immunosuppressive agents is contraindicated in package inserts and guidelines in Japan and other countries. However, patients receiving immunosuppressants have a high risk of infectious disease becoming severe, and the necessity to prevent infectious disease is high. To date, 2,091 vaccinations have been reported in 25 reports of live attenuated vaccines in people receiving immunosuppressants. Twenty-three patients (1.1%) became infected with the virus strain used in the vaccine, which was varicella virus in 21 patients. No reports have described life-threatening complications. A prospective study at the National Center for Child Health and Development conducted under certain immunological conditions (CD4 cell count ≥ 500/mm3, stimulation index of lymphocyte blast transformation by phytohemagglutinin (PHA) ≥ 101.6, serum immunoglobulin G ≥ 300 mg/dL) confirmed the serological effectiveness and safety. The evidence suggests that live attenuated vaccines can be used even in combination with immunosuppressants. Further evidence must be gathered and immunological criteria investigated to determine the conditions for safe use. Depending on the results of these investigations, the wording in package inserts and guidelines may need to be revised.

This study aimed to synthesize the available evidence on the immunogenicity, safety, and effectiveness of live-attenuated varicella vaccine in solid organ transplant recipients. Medline and EMBASE were searched using predefined search terms to identify relevant studies. The included articles reported varicella vaccine administration in the posttransplant period in children and adults. A pooled proportion of transplant recipients who seroconverted and who developed vaccine-strain varicella and varicella disease was generated. Eighteen articles (14 observational studies and 4 case reports) were included, reporting on 711 transplant recipients who received the varicella vaccine. The pooled proportion was 88.2% (95% confidence interval 78.0%-96.0%, 13 studies) for vaccinees who seroconverted, 0% (0%-1.2%, 13 studies) for vaccine-strain varicella, and 0.8% (0%-4.9%, 9 studies) for varicella disease. Most studies followed clinical guidelines for administering live-attenuated vaccines, with criteria that could include being at least 1 year posttransplant, 2 months postrejection episode, and on low-dose immunosuppressive medications. Varicella vaccination in transplant recipients was overall safe in the included studies, with few cases of vaccine-strain-induced varicella or vaccine failure, and although it was immunogenic, the proportion of recipients who seroconverted was lower than that seen in the general population. Our data support varicella vaccination in select pediatric solid organ transplant recipients.

Live vaccines (measles-mumps-rubella [MMR] and varicella-zoster virus [VZV]) have not been recommended after solid organ transplant due to concern for inciting vaccine strain infection in an immunocompromised host. However, the rates of measles, mumps, and varicella are rising nationally and internationally, leaving susceptible immunocompromised children at risk for life-threating conditions.

To determine the safety and immunogenicity of live vaccines in pediatric liver and kidney transplant recipients.

This cohort study included select pediatric liver and kidney transplant recipients who had not completed their primary MMR and VZV vaccine series and/or who displayed nonprotective serum antibody levels at enrollment between January 1, 2002, and February 28, 2023. Eligibility for live vaccine was determined by individual US pediatric solid organ transplant center protocols.

Exposure was defined as receipt of a posttransplant live vaccine. Transplant recipients received 1 to 3 doses of MMR vaccine and/or 1 to 3 doses of VZV vaccine.

Safety data were collected following each vaccination, and antibody levels were obtained at 0 to 3 months and 1 year following vaccination. Comparisons were performed using Mann-Whitney U test, and factors associated with development of postvaccination protective antibodies were explored using univariate analysis.

The cohort included 281 children (270 [96%] liver, 9 [3%] kidney, 2 [1%] liver-kidney recipients) from 18 centers. The median time from transplant to enrollment was 6.3 years (IQR, 3.4-11.1 years). The median age at first posttransplant vaccine was 8.9 years (IQR, 4.7-13.8 years). A total of 202 of 275 (73%) children were receiving low-level monotherapy immunosuppression at the time of vaccination. The majority of children developed protective antibodies following vaccination (107 of 149 [72%] varicella, 130 of 152 [86%] measles, 100 of 120 [83%] mumps, and 124 of 125 [99%] rubella). One year post vaccination, the majority of children who initially mounted protective antibodies maintained this protection (34 of 44 [77%] varicella, 45 of 49 [92%] measles, 35 of 42 [83%] mumps, 51 of 54 [94%] rubella). Five children developed clinical varicella, all of which resolved within 1 week. There were no cases of measles or rubella and no episodes of graft rejection within 1 month of vaccination. There was no association between antibody response and immunosuppression level at the time of vaccination.

The findings suggest that live vaccinations may be safe and immunogenic after solid organ transplant in select pediatric recipients and can offer protection against circulating measles, mumps, and varicella.

Immunizations are a relatively safe and cost-effective intervention to prevent morbidity and mortality associated with vaccine preventable infection (VPIs). As such, immunizations are a critical part of the care of pre and posttransplant patients and should be prioritized. New tools are needed to continue to disseminate and implement the most up-to-date vaccine recommendations for the SOT population. These tools will help both primary care providers and multi-disciplinary transplant team members taking care of transplant patients to stay abreast of evidence-based best practices regarding the immunization of the SOT patient.

Although live-attenuated vaccines are contraindicated under immunosuppression, the immune status of patients with inflammatory bowel disease (IBD) has not been fully assessed prior to immunosuppressive therapy.

To investigate antiviral serostatus against viruses requiring live vaccines for prevention in IBD patients undergoing immunosuppressive therapy.

This multicenter study included IBD patients who were aged <40 years and were treated with thiopurine monotherapy, molecular-targeted monotherapy, or combination therapy. Gender- and age-matched healthy subjects (HS) living in the same areas were included as control group. Antibody titers against measles, rubella, mumps, and varicella were measured by enzyme-linked immunosorbent assays.

A total of 437 IBD patients (163 ulcerative colitis [UC] and 274 Crohn's disease [CD]) and 225 HS were included in the final analysis. Compared with HS, IBD patients had lower seropositivity rates for measles (IBD vs. HS = 83.91% vs. 85.33%), rubella (77.55% vs. 84.89%), mumps (37.50% vs. 37.78%), and varicella (91.26% vs. 96.44%). Gender- and age-adjusted seropositivity rates were lower in UC patients than in both CD patients and HS for measles (UC, CD, and HS = 81.60%, 85.29%, and 85.33%), rubella (76.40%, 78.23%, and 84.89%), mumps (27.16%, 43.70%, and 37.78%), and varicella (90.80%, 91.54%, and 96.44%); the difference was significant for all viruses except measles. Divided by the degree of immunosuppression, there were no significant differences in seropositivity rates among IBD patients.

IBD patients, especially those with UC, exhibit reduced seropositivity rates and may benefit from screening prior to the initiation of immunosuppressive therapy.

Low-vaccination rates worldwide have led to the re-emergence of vaccine-preventable infections, including measles. Immunocompromised patients, including pediatric solid organ transplant (SOT) recipients, are at risk for measles because of suboptimal vaccination, reduced or waning vaccine immunity, lifelong immunosuppression, and global re-emergence of measles.

To review published cases of measles in pediatric SOT recipients to heighten awareness of its clinical manifestations, summarize diagnostic and treatment strategies, and identify opportunities to optimize prevention.

We conducted a literature review of published natural measles infections in SOT recipients ≤21 years of age, summarizing management and outcomes. We describe measles epidemiology, recommended diagnostics, treatment, and highlight prevention strategies.

There are seven published reports of measles infection in 12 pediatric SOT recipients, the majority of whom were unvaccinated or incompletely vaccinated. Subjects had atypical or severe clinical presentations, including lack of rash and complications, most frequently with encephalitis and pneumonitis, resulting in 33% mortality. Updated recommendations on testing and vaccination are provided. Treatment options beyond supportive care and vitamin A are limited, with no approved antivirals.

While measles is infrequently reported in pediatric SOT recipients, morbidity and mortality remain significant. A high index of suspicion is warranted in susceptible SOT recipients with clinically compatible illness or exposure. Providers must recognize this risk, educate families, and be aware of both classic and atypical presentations of measles to rapidly identify, isolate, and diagnose measles in pediatric SOT recipients. Continued efforts to optimize measles vaccination both pre- and post-SOT are warranted.

Following the outbreak of coronavirus disease 2019 (COVID-19), a disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the field of liver transplantation, along with many other aspects of healthcare, underwent drastic changes. Despite an initial increase in waitlist mortality and a decrease in both living and deceased donor liver transplantation rates, through the implementation of a series of new measures, the transplant community was able to recover by the summer of 2020. Changes in waitlist prioritization, the gradual implementation of telehealth, and immunosuppressive regimen alterations amidst concerns regarding more severe disease in immunocompromised patients, were among the changes implemented in an attempt by the transplant community to adapt to the pandemic. More recently, with the advent of the Pfizer BNT162b2 vaccine, a powerful new preventative tool against infection, the pandemic is slowly beginning to subside. The pandemic has certainly brought transplant centers around the world to their limits. Despite the unspeakable tragedy, COVID-19 constitutes a valuable lesson for health systems to be more prepared for potential future health crises and for life-saving transplantation not to fall behind.

Vaccine preventable illnesses are important sources of morbidity, mortality, and increased healthcare costs in pediatric LT recipients. Our aim was to measure the seroprevalence of antibodies to measles and VZV in this population.

We conducted a retrospective chart review of 44 patients who received LT before age 18 at UCLA Mattel Children's Hospital from January 2008 to December 2017.

Median age at transplantation was 2.5 years (IQR 1.2-7.7). Post-transplant measles antibodies were present in 17 of 37 patients (46%); risk factors for seronegativity included younger age at transplant (p = .02) and greater time from transplant to testing (p = .04). Post-transplant VZV antibodies were present in 17 of 39 patients (44%); risk factors for seronegativity included greater time from transplant to testing (p = .04). 6 of 16 patients (38%) who tested positive for pre-transplant VZV antibodies tested negative after transplantation. Fourteen of 20 patients (70%) with at least 1 documented dose of the MMR vaccine tested positive for post-transplant measles antibodies. Ten of 20 of patients (50%) with at least 1 documented dose of the VZV vaccine tested positive for post-transplant VZV antibodies. We also describe 10 patients who received post-transplant measles and VZV vaccines without documented complications.

Our study suggests that pediatric LT patients are at greater risk of contracting measles and VZV despite vaccination status, and that prevalence of measles and VZV antibodies decreases as time from transplantation increases. This should weigh into the institutional risk-benefit assessment when deciding whether or not to administer LAVs to these patients.

A quality improvement approach was used to increase pediatric liver transplant recipient live and inactive vaccination rates by assessing titers and recommending vaccinations.

A new screening and immunization process for both live and inactive vaccines was discussed with families at their annual visit. Antibody titers for varicella, measles, mumps, rubella, Haemophilus influenzae type B, hepatitis A, and hepatitis B were obtained. Specific criteria were developed for live virus vaccination candidacy. Vaccines were recommended based on patient titers and vaccination candidacy criteria. Surveillance for adverse effects to live vaccines was performed. Repeat titers were obtained approximately 1-month post-vaccine administration.

After PDSA cycle 1, 99% (71/72) of pediatric liver transplant patients had titers obtained. Live vaccines were recommended for 32 patients and 16 (50%) were vaccinated. Inactive vaccines were recommended to 64 patients, and 31 (48%) were vaccinated. Eight of 13 (62%) patients with follow-up titers achieved immunity for inactive vaccines. Zero patients had an adverse reaction to any live vaccine. Ten of 12 (83%) patients with follow-up titers achieved immunity from live vaccines. The most common barriers to receive live vaccines included not scheduling appointment with primary care provider (n = 3) and "non-vaccinators" (n = 3).

Administering live and inactive vaccines to select pediatric liver transplant patients appears to be safe and effective in our studied population. For PDSA cycle 2, we will continue our current practice and consider offering vaccines in transplant clinic, since this was a barrier to vaccination identified during PDSA cycle 1.

LAVV have historically been avoided in children after solid organ transplantation. However, it has been reported that post-transplant, children without severe immunosuppression can generate anti-varicella antibody after immunization but the duration of the response is not clear. Furthermore, the origin of the varicella virus in immunosuppressed patients who develop varicella after vaccination is often unclear.

A female child received LAVV 30 months after a living donor liver transplant at the age of 2 months. Varicella rash appeared on the trunk 16 days after vaccination and gradually spread over the body. The patient was treated with intravenous acyclovir followed by oral therapy and recovered fully. The virus detected in blisters was derived from the vaccine-type strain. Paired sera before and after the onset of varicella showed an increase in antibody titer. However, 2 years after onset, the antibody titer decreased to undetectable again.

This was an informative case of varicella due to vaccine strain attenuated virus. Antibody levels were not maintained over many years. Although varicella was caused by the vaccine-type strain, repeated vaccinations may be necessary for post-transplant patients who develop varicella.

Inborn errors of metabolism (IEM) are genetic disorders due to a defective metabolic pathway. The incidence of each disorder is variable and depends on the respective population. Some disorders such as urea cycle disorders (UCD) and organic acidurias, pose a high risk for a metabolic crisis culminating in a life-threatening event, especially during infections; thus, vaccines may play a crucial role in prevention. However, there are different triggers for decompensations including the notion that vaccines themselves can activate fever and malaise. Additionally, many of the IEM include immunodeficiency, placing the patients at an increased risk for infectious diseases and possibly a weaker response to immunizations. Since metabolic crises and vaccine regimens intersect in the first years of life, the question whether to vaccinate the child occupies parents and medical staff. Many metabolic experts hesitate to vaccinate IEM patients, disregarding the higher risk from the direct infections. In this paper we summarize the published data regarding the safety and recommendations for vaccinations in IEM patients, with reference to the risk for decompensations and to the immunogenic component.

Content available: Author Audio Recording.

Recent guidelines suggest that LAVs may be given to LT recipients meeting certain criteria. However, information is still limited. We sought to evaluate the safety of LAVs, including measles, mumps, rubella, and varicella to LT recipients following our clinically based immunization protocol for LT recipients. We conducted a case-series analysis on safety of LAVs for measles, rubella, varicella, and mumps given to LT recipients at our institution from July 2010 to July 2019. Patients who underwent LT at age <20 years who visited our immunization clinic were included. LT recipients were vaccinated if 2 years had lapsed from LT, had no signs of rejection within 6 months, and were on minimal immunosuppressants. Patient demographics, underlying diseases, type and number of vaccines administered, date of vaccination, and adverse events occurring within 4 weeks after vaccination were extracted from their medical records. During the study period, LAVs were administered 422 times to 209 patients who met criteria and included 225 doses of MR combination vaccine, 224 doses of varicella vaccine, and 215 doses of mumps vaccine. Underlying diseases included cholestatic liver diseases (n = 125), followed by metabolic diseases (n = 33) and acute liver failure (n = 19). Nine non-critical adverse events (2.1%) possibly associated with LAVs were reported, but there were no serious adverse events, including hospitalizations or deaths. In conclusion, LAVs administered to LT recipients were safe without any serious adverse events following our relatively simple institutional protocol.

Live attenuated vaccines are contraindicated for patients on immunosuppressive agents or biological agent, except for live attenuated varicella vaccine, although previous reports showed their effectiveness and safety. This study is the nationwide cross-sectional research about the current utilization of live attenuated vaccines for patients on immunosuppressive agents or biological agents in Japan. We sent questionnaires to pediatric centers and examined whether each institution offered live attenuated vaccines to patients with immunosuppressive agents or biological agents (institutional research). We also examined adverse events associated with live attenuated vaccines between 2013 and 2017 (patient research). In the institutional research, 46 out of 334 institutions (13.8%) administered live attenuated vaccines to patients receiving immunosuppressive agents. In contrast, only six out of 270 institutions (2.2%) administered live attenuated vaccines to patients receiving biological agents. However, 66.3% of physicians answered that patients receiving immunosuppressive agents should be immunized with live attenuated vaccines, and only 7.0% disagreed with them. In the patient research, data for 781 patients were collected. Vaccine-associated infections were observed in only two patients (0.3%), both of whom had varicella, although they recovered promptly. No life-threatening adverse events were noted.

In pediatric centers, the demand for live attenuated vaccines in patients receiving immunosuppressive agents was high and most physicians think they should be immunized. Immunization with live attenuated vaccines appeared safe in patients receiving immunosuppressive agents, although further studies are needed for patients receiving biological agents What is known: • Live attenuated vaccines (LAV) are generally contraindicated for patients on immunosuppressive agents (IS) or biological agents (BA), except for live attenuated varicella vaccine, as immunocompromised patients are at greater risk for serious viral infection from the vaccine strains. • Viral infections, such as measles and varicella, cause serious complications in children receiving IS. • Several previous reports showed that LAV is relatively effective and safe for patients receiving IS. What is new: • In Japan, the demand for LAV in patients receiving IS was high, and most physicians hoped they should be immunized. • Vaccine-associated infection is rarely observed in patients with IS after LAV administration. • Immunization with LAV appeared safe in patients receiving IS.

University Hospital Medical Information Network (UMIN).

UMIN000029176.Date of registration: 2017/09/19.

Tacrolimus is widely used to prevent graft rejection after allogeneic transplantation by suppressing T cells in a non-antigen-specific fashion. Global T-cell suppression makes transplant recipients more susceptible to infection, especially infection by opportunistic intracellular pathogens. Infection followed by secondary challenge with the opportunistic intracellular bacterial pathogen, Listeria monocytogenes, was used to probe when tacrolimus most significantly impacts antimicrobial host defense. Tacrolimus-treated mice showed no difference in innate susceptibility following primary infection, whereas susceptibility to secondary challenge was significantly increased. Modifying the timing of tacrolimus initiation with respect to primary infection compared with secondary challenge showed significantly reduced susceptibility in tacrolimus-treated mice where tacrolimus was discontinued prior to secondary challenge. Thus, tacrolimus overrides protection against secondary infection primed by primary infection (and presumably live attenuated vaccines), with the most critical window for tacrolimus-induced infection susceptibility being exposure immediately prior to secondary challenge. These results have important implications for strategies designed to boost antimicrobial T-cell-mediated immunity in transplant recipients.

Vaccination with the live attenuated measles vaccine is currently recommended two years after hematopoietic stem cell transplantation (HSCT) and generally contraindicated after solid organ transplantation (SOT) due to safety concerns. However, in the last few years new data on the administration of the measles vaccine to HSCT recipients less two years post-transplantation and to SOT recipients have become available. This new data may change current guidelines and practices. The objective of this review is to provide an overview of the current data on the safety and efficacy of early measles vaccination for HSCT- and SOT recipients.

PubMed and EMBASE were searched from the earliest date available through October 2019 to identify all research that reported on the safety and efficacy of measles vaccination after SOT or less than two years after HSCT.

A total of ten studies was included in this review. In the six studies that evaluated the efficacy of measles vaccination after SOT, seroconversion rates ranged from 41 to 100% after one dose and 73 to 100% after two doses. In the four studies that evaluated the efficacy of measles vaccination less than two years after HSCT, seroconversion rates ranged from 33 to 100% after one dose and 100% after two doses. In all studies, the administration of the measles vaccine after transplantation was considered to be safe. There were no cases of infection with the attenuated vaccine strain, and there were no adverse events related to the vaccination.

Data on the administration of the measles vaccine after SOT and less than two years after HSCT is scarce. However, the current data available suggest that it is efficacious and well tolerable. Therefore, early measles vaccination could be considered in selected groups of SOT- and HSCT recipients during increased measles transmission or an outbreak setting.

As the number of living pediatric solid organ transplant (SOT) recipients continues to grow, there is an increased likelihood that primary care providers (PCPs) will encounter pediatric SOT recipients in their practices. In addition, as end-stage organ failure is replaced with chronic medical conditions in transplant recipients, there is a need for a comprehensive approach to their management. PCPs can significantly enhance the care of immunosuppressed hosts by advising parents of safety considerations and avoiding adverse drug interactions. Together with subspecialty providers, PCPs are responsible for ensuring that appropriate vaccinations are given and can play an important role in the diagnosis of infections. Through early recognition of rejection and posttransplant complications, PCPs can minimize morbidity. Growth and development can be optimized through frequent assessments and timely referrals. Adherence to immunosuppressive regimens can be greatly improved through reinforcement at every encounter, particularly among adolescents. PCPs can also improve long-term outcomes by easing the transition of pediatric SOT recipients to adult providers. Although guidelines exist for the primary care management of adult SOT recipients, comprehensive guidance is lacking for pediatric providers. In this evidence-based overview, we outline the main issues affecting pediatric SOT recipients and provide guidance for PCPs regarding their management from the first encounter after the transplant to the main challenges that arise in childhood and adolescence. Overall, PCPs can and should use their expertise and serve as an additional layer of support in conjunction with the transplant center for families that are caring for a pediatric SOT recipient.

Varicella and measles infections can be life-threatening after solid organ transplantation (SOT) but may be preventable with live-attenuated vaccines (LAV).

This survey conducted in January 2019 among subscribers of the International Pediatric Transplantation Association listserv aimed to explore the current strategies to prevent and manage both infections in the pediatric SOT population, including recommending LAV after SOT.

The answers given by 95 pediatric SOT healthcare workers show that these strategies are not yet optimal and call for further education. In particular, 59% of respondents are unnecessarily waiting for a SOT candidate to be >1 year of age to start administrating LAV before SOT. Interestingly, most respondents are willing to administer LAV after SOT (57%), and a fifth (21%) are already doing so, off-label. The survey queried the precautions taken to improve safety evaluations after LAV, and identified knowledge gaps and practitioners' concerns.

The results of this survey could be used as a starting point for education and promotion of the safe administration of LAV in carefully selected SOT recipients; in turn, this would increase available data that would contribute to the development of evidence-based guidelines by the transplant societies and ultimately prevent these infections after SOT.

Historically, the IDSA and the AST have recommended that live vaccines not be administered post-transplant due to concern for induction of vaccine-strain disease in immunocompromised hosts. However, recent prospective studies and revised AST guidelines published in April 2019 suggest that in the current era of immunosuppression minimization, live vaccines may be safely administered to select transplant recipients with resulting immunoprotection. The goal of this study was to assess current post-transplant live vaccine practices at individual pediatric liver transplant centers following the updated AST guidelines.

A six-item email survey detailing center-specific post-transplant live vaccine practices followed by up to three response-specific questions were distributed between July 2019 and May 2020 to a representative from each center participating in the SPLIT consortium.

The overall survey response rate was 93% (41/44 centers). Only 29% (12/41) of centers offer live vaccines post-transplant; each of these 12 centers uses different eligibility criteria for live vaccines. There was no difference between large (ten or more transplants per year) and small (less than ten transplants per year) centers in likelihood to offer live vaccines post-transplant. The main reasons for a center not offering post-transplant live vaccines were safety concerns and inability to reach group consensus.

The majority of pediatric liver transplant centers are reluctant to offer live vaccines post-transplant despite the updated AST guidelines. Prospective multicenter studies are needed to confirm safety and immunogenicity of live vaccines post-transplant.

Patients receiving immunosuppressive agents are at risk of life-threatening infections. However, live vaccines are generally contraindicated in them. We conducted a prospective study regarding live attenuated vaccines for them. Patients elder than one year of age with immunosuppressive agents who showed negative or borderline antibody titers (virus-specific IgG levels < 4.0) against one or more of measles, rubella, varicella, and mumps and fulfilled the criteria (CD4 cell counts ≥ 500/mm3, stimulation index of lymphocyte blast transformation by PHA ≥ 101.6, serum IgG level ≥ 300 mg/dl, no steroid use or prednisolone < 1 mg/kg/day or < 2 mg/kg/2 days, trough levels of tacrolimus or cyclosporine were < 10 ng/ml or < 100 ng/ml and under good control of primary disease) were enrolled. Sixty-four vaccinations were administered to 32 patients. The seroconversion rates for measles, rubella, varicella, and mumps were 80.0%, 100.0%, 59.1%, and 69.2%, respectively. No life-threatening adverse events were observed, although one patient suffered from vaccine-strain varicella who showed cellular and humoral immunodeficiency (CD4 cell counts = 511/mm3, stimulation index of lymphocyte blast transformation by PHA = 91.1, serum IgG level = 208 mg/dl). This girl was immunized before we established the criteria for vaccination. Immunization with live attenuated vaccines for patients receiving immunosuppressive agents might be effective and safe if their cellular and humoral immunological parameters are within normal levels. However, determining the criteria for vaccination by immunological parameters should be established to guarantee the safety of live vaccines in the future. Clinical Trial Registration: UMIN Clinical Trials Registry (UMIN-CTR) UMIN000007710. The date of registration: 2012/4/13.

Measles outbreaks occur rather frequently in Germany. Patients with chronic inflammatory diseases are often treated with immunosuppressants. A recent study showed that about 7% of such patients are not protected against measles according to the lack of documentation in the vaccination card or the absence of protective antibodies. The Standing Committee on Immunization (STIKO) recommends a first vaccination against measles as a measles-mumps-rubella combined vaccination (MMR) in children aged 11-14 months and a second vaccination at 14-23 months. For adults born after 1970, vaccination against measles is recommended if they have not yet been vaccinated against measles or have only been vaccinated once against measles or if their vaccination status is unclear. In April 2019, STIKO published instructions for vaccinations recommended for immunodeficiency. Since March 1, 2020, measles vaccination have been compulsory in Germany.

Live viral vaccines have historically been avoided in children after solid organ transplantation. Multiple reports of safety and immunogenicity, largely in the pediatric liver transplant population, have led to a reconsideration of this recommendation. Here, we report the case of a 4-year-old boy who inadvertently received the live attenuated MMR-varicella vaccine (MMRV) at a routine well-child visit 16 months after receiving a living donor kidney transplant. This was not known until after he was admitted with rash and documented disseminated varicella infection 5 weeks later. He was treated with intravenous acyclovir followed by oral therapy and recovered fully. This case and its discussion illustrate what is still unknown about the risk-to-benefit ratio of live viral vaccination in any individual transplant recipient. Criteria to determine which patients should receive these vaccines should be evaluated before their use after transplant becomes routine, and all recipients and their families should be counseled to have a low threshold to seek medical care for any febrile illness or rash after live viral vaccination.

Growing evidence suggests receipt of live-attenuated viral vaccines after solid organ transplant (SOT) has occurred and is safe and needed due to lapses in herd immunity. A 2-day consortium of experts in infectious diseases, transplantation, vaccinology, and immunology was held with the objective to review evidence and create expert recommendations for clinicians when considering live viral vaccines post-SOT. For consideration of VV and MMR post-transplant, evidence exists only for kidney and liver transplant recipients. For MMR vaccine post-SOT, consider vaccination during outbreak or travel to endemic risk areas. Patients who have received antiproliferative agents (eg. mycophenolate mofetil), T cell-depleting agents, or rituximab; or have persistently elevated EBV viral loads, or are in a state of functional tolerance, should be vaccinated with caution and have a more in-depth evaluation to define benefit of vaccination and net state of immune suppression prior to considering vaccination. MMR and/or VV (not combined MMRV) is considered to be safe in patients who are clinically well, are greater than 1 year after liver or kidney transplant and 2 months after acute rejection episode, can be closely monitored, and meet specific criteria of "low-level" immune suppression as defined in the document.

The NCCN Guidelines for Survivorship provide screening, evaluation, and treatment recommendations for common physical and psychosocial consequences of cancer and cancer treatment to help healthcare professionals who work with survivors of adult-onset cancer in the posttreatment period. This portion of the guidelines describes recommendations regarding the management of anthracycline-induced cardiotoxicity and lymphedema. In addition, recommendations regarding immunizations and the prevention of infections in cancer survivors are included.

Until recently, measles exposures were relatively rare and so, consequently, were an afterthought for cancer patients and/or blood and marrow transplant recipients and their providers. Declines in measles herd immunity have reached critical levels in many communities throughout the United States due to increasing vaccine hesitancy, so that community-based outbreaks have occurred. The reemergence of measles as a clinical disease has raised serious concerns among immunocompromised patients and those who work within the cancer and hematopoietic cell transplantation (HCT) community. Since live attenuated vaccines, such as measles, mumps, and rubella (MMR), are contraindicated in immunocompromised patients, and with no approved antiviral therapies for measles, community exposures in these patients can lead to life-threatening infection. The lack of data regarding measles prevention in this population poses a number of clinical dilemmas. Herein specialists in Infectious Diseases and HCT/cellular therapy endorsed by the American Society of Transplant and Cellular Therapy address frequently asked questions about measles in these high-risk cancer patients and HCT recipients and provide expert opinions based on the limited available data.

Pediatric kidney transplant (KT) candidates should be fully immunized according to routine childhood schedules using age-appropriate guidelines. Unfortunately, vaccination rates in KT candidates remain suboptimal. With the exception of influenza vaccine, vaccination after transplantation should be delayed 3-6 months to maximize immunogenicity. While most vaccinations in the KT recipient are administered by primary care physicians, there are specific schedule alterations in the cases of influenza, hepatitis B, pneumococcal, and meningococcal vaccinations; consequently, these vaccines are usually administered by transplant physicians. This article will focus on those deviations from the normal vaccine schedule important in the care of pediatric KT recipients. The article will also review human papillomavirus vaccine due to its special importance in cancer prevention. Live vaccines are generally contraindicated in KT recipients. However, we present a brief review of live vaccines in organ transplant recipients, as there is evidence that certain live virus vaccines may be safe and effective in select groups. Lastly, we review vaccination of pediatric KT recipients prior to international travel.

Live-attenuated vaccines are currently contraindicated in solid-organ transplant recipients. However, the risk of vaccine-preventable infections is lifelong, and can be particularly severe after transplantation. In this prospective interventional national cohort study, 44 pediatric liver transplant recipients with measles IgG antibodies <150 IU/L (below seroprotection threshold) received measles-mumps-rubella vaccine (MMR) at a median of 6.3 years posttransplantation (interquartile range, 4.0 to 10.9). A maximum of two additional doses were administered in nonresponders or when seroprotection was lost. Vaccine responses occurred in 98% (95% confidence interval [CI], 88-100) of patients. Seroprotection at 1-, 2-, and 3-year follow-up reached 62% (95% CI, 45-78), 86% (95% CI, 70-95), and 89% (95% CI, 67-99), respectively. All patients responded appropriately to the booster dose(s). Vaccinations were well tolerated and no serious adverse event attributable to vaccination was identified during the 8-week follow-up period (or later), using a multimodal approach including standardized telephone interviews, diarized side effect reporting, and monitoring of vaccinal virus shedding. We conclude that live attenuated MMR vaccine can be administered in liver transplant recipients fulfilling specific eligibility criteria (>1 year posttransplantation, low immunosuppression, lymphocyte count ≥0.75 G/L), inducing seroprotection in most subjects. (Clinicaltrials.gov number NCT01770119).

This article discusses the recommended vaccines used before and after solid organ transplant period, including data regarding vaccine safety and efficacy and travel-related vaccines. Vaccination is an important part of the preparation for solid organ transplantation, because vaccine-preventable diseases contribute to the morbidity and mortality of these patients. A pretransplantation protocol should be encouraged in every transplant center. The main goal of vaccination is to provide seroprotection before transplantation, because iatrogenically immunosuppressed patients posttransplant have a lower seroresponse to vaccines.

Infections significantly impact outcomes for solid organ and hematopoietic stem cell transplantation in children. Vaccine-preventable diseases contribute to morbidity and mortality in both early and late posttransplant time periods. Several infectious diseases and transplantation societies have published recommendations and guidelines that address immunization in adult and pediatric transplant recipients. In many cases, pediatric-specific studies are limited in size or quality, leading to recommendations being based on adult data or mixed adult-pediatric studies. We therefore review the current state of evidence for selected immunizations in pediatric transplant recipients and highlight areas for future investigation. Specific attention is given to studies that enrolled only children.

To conduct a prospective study to evaluate the immunogenicity and safety of live attenuated vaccines in patients with nephrotic syndrome receiving immunosuppressive agents.

Patients with nephrotic syndrome receiving immunosuppressive agents with negative or borderline antibody titers (virus-specific IgG levels <4.0) against measles, rubella, varicella, and/or mumps fulfilling the criteria of cellular and humoral immunity were enrolled. Virus-specific IgG levels were measured using an enzyme immunoassay. The primary endpoint was the seroconversion rate (ie, achievement of virus-specific IgG levels ≥4.0) at 2 months after vaccination. Virus-specific IgG levels at 1 year, breakthrough infections (wild-type infections), and adverse events were also evaluated.

A total of 116 vaccinations were administered to 60 patients. Seroconversion rates were 95.7% for measles, 100% for rubella, 61.9% for varicella, and 40.0% for mumps. More patients with a borderline antibody titer before vaccination achieved seroconversion than those with negative antibody titer, with statistical significance after varicella and mumps vaccination. The rate of patients who maintained seropositivity at 1 year after vaccination was 83.3% for measles, 94.1% for rubella, 76.7% for varicella, and 20.0% for mumps. No patient experienced breakthrough infection. No serious adverse events, including vaccine-associated infection, were observed.

Immunization with live attenuated vaccines may be immunogenic and is apparently safe in our cohort of patients with nephrotic syndrome receiving immunosuppressive agents if their cellular and humoral immunologic measures are within clinically acceptable levels.

UMIN-CTR UMIN 000007710.