Immunization practices in solid organ transplant recipients

Vaccine-preventable diseases are a significant cause of morbidity and mortality in solid organ transplant recipients who undergo immunosuppression after transplantation. The primary strategy for immunizing transplant recipients is to deliver all potential vaccines prior to transplantation. However, time constraints limit the number of vaccines that may be delivered. In such cases, the administration of live attenuated vaccines that are contraindicated after transplantation should be prioritized. Simultaneous vaccination is also encouraged to maximize the number of vaccines delivered. Immunity induced by both inactivated and live vaccines wane after transplantation. The limited but available evidence suggests that immunization using inactivated vaccines in transplant recipients is both effective and safe. An increasing number of studies also suggest that once patients are under minimal immunosuppression, live attenuated vaccines may be given effectively and safely. The need for serologic monitoring and booster immunizations remain issues for future research.     

实体器官移植受者新型冠状病毒疫苗接种临床研究进展

器官移植受者是新型冠状病毒肺炎的高风险人群,为降低该类患者的感染率及重症化率,疫苗接种是有效的防控方法。本文介绍实体器官移植受者感染新型冠状病毒的临床预后,综合分析该人群接受新冠疫苗后免疫应答相关机制及强化免疫的研究进展,并对该类患者的免疫策略提出建议。     

器官移植供者来源感染防控效果研究

目的探讨供者来源感染(Donor derived infection,DDI)防控干预措施对降低实体器官移植患者医院感染发生率、耐碳青霉烯肺炎克雷伯菌(Carbapenem-Resistant Klebsiella Pneumoniae,CRKP)感染率以及DDI引起的CRKP感染率的效果。方法采用回顾性队列研究,选择在上海长海医院接受器官移植的所有患者为研究对象,2016年6月-2017年12月收集的患者586例为对照组,实施常规医院感染防控措施,2018年1月-2019年2月收集的患者289例为干预组,分别从供者感染状态评估分层后决定器官取舍、供者维护期间的感染防控及接受高风险供者器官移植后受者的防控三个方面实施DDI防控干预措施。观察对比干预前后实体器官移植患者医院感染发生率、医院感染患者中CRKP感染占比、由DDI引起的CRKP感染占比及CRKP感染患者病死率。结果干预组患者医院感染发生率为6.23%(18/289),低于对照组的9.22%(54/586)(P=0.131);干预组CRKP感染率为0.35%(1/289),低于对照组的1.71%(10/586)(P=0.169);干预组医院感染患者中CRKP感染占5.56%(1/18),低于对照组的18.52%(10/54)(P=0.344);干预组由DDI引起的CRKP感染百分比为0.00%,低于对照组的80.00%(P=0.273);干预组CRKP感染患者病死率为0.00%,低于对照组的40.00%(P>0.999),差异均无统计学意义。结论采取DDI防控干预措施能有效降低实体器官移植患者医院感染发生率、CRKP感染率、医院感染患者中CRKP感染占比,特别是由DDI引起的CRKP感染以及CRKP感染患者病死率。     

Immunogenicity of conjugate meningococcus C vaccine in pediatric solid organ transplant recipients

The present study was aimed to evaluate the immunogenicity of a single dose of conjugate Meningococcus C (Men C) vaccine by analyzing the serum bactericidal antibody (SBA) titers in 10 pediatric solid organ transplant (SOT) patients. Four patients showed a delayed immune response after 1 month, but all patients demonstrated an increase of SBA titers after vaccination. A significant decrease of SBA titers was seen after 6 months. However, all patients maintained protective SBA titers (≥1:8) despite rapidly waning titers. For patients with significantly decreasing titers, a booster dose may be discussed with close monitoring of SBA titers over time.     

实体器官移植供者来源感染防控研究进展

供者来源感染(Donor-derived infection)是实体器官移植工作面临的重大挑战。目前我国实体器官捐献者多为滞留ICU的患者,是多药耐药菌感染或定植的高危人群,由此引发的供者来源性感染,严重时可威胁受者生命安全。移植工作中既要避免供者来源感染的威胁又要充分利用稀缺的供者器官,需要加强信息沟通,多学科协作从源头上进行过程监控、主动监测,对潜在供者进行感染预防维护、对供者感染状况评估分层决定器官取舍以及对移植后受者进行感染防控。     

器官移植病人的营养支持

器官移植已成为各种器官终末期病人优先考虑的治疗方法 ,伴随营养不良的器官移植病术后并发症、死亡率。营养支持能够明显改善器官移植病人的预后     

Pneumococcal vaccination in adult solid organ transplant recipients: A review of current evidence

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.     

Safety and efficacy of early vaccination with live attenuated measles vaccine for hematopoietic stem cell transplant recipients and solid organ transplant recipients

Background and objectiveVaccination 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.MethodPubMed 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.ResultsA 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.ConclusionData 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.     

Reduced varicella-zoster-virus (VZV)-specific lymphocytes and IgG antibody avidity in solid organ transplant recipients

Background

Varicella-zoster-virus (VZV) infection may cause significant morbidity and mortality in immunocompromised patients. So far, only IgG-anti-VZV antibody concentrations were used to estimate immunity against VZV, but the antibody binding strength (avidity) together with VZV-specific cellular responses have not been evaluated in solid organ transplant (SOT) recipients.

Methods

Thus, we assessed the humoral and cellular immune responses to two doses of the VZV vaccine (vacc) and wild-type VZV infection (wt) in 23 kidney (KTx) and 19 liver transplant (LTx) recipients including children and adults compared to 48 healthy controls (HC) for measurement of IgG-anti-VZV relative avidity index (RAI) and frequency of VZV-specific peripheral blood mononuclear cells (PBMCs) in vaccinated individuals using an adapted ELISA and IFN-gamma ELISPOT, respectively.

Results

KTx(wt) (median RAI 72.3%) or LTx(wt) (79.2%) and KTx(vacc) (91.0%) or LTx(vacc) (72.5%) showed lower avidities compared to HC(wt) (84.5%) and HC(vacc) (94.0%), respectively, despite equally distributed IgG-anti-VZV concentrations. RAI > 60% (high avidity) was detected in all HC, but only in 69.0% of SOT patients. KTx(vacc) (median 64 spot forming units SFU/500,000 PBMCs) and LTx(vacc) (67 SFU) had significantly lower VZV-specific cellular responses compared to HC(vacc) (268 SFU).

Conclusions

The diminished cellular reactivity to VZV has to be considered in SOT patients receiving immunosuppressive treatments when evaluating immunity against VZV. IgG antibody avidity and VZV-specific cellular responses may serve as additional markers to evaluate immunity against VZV in SOT recipients. The role of wild-type exposures and endogenous VZV re-activation on long-term immunity in SOT patients has to be awaited to establish recommendations for vaccine spacing in these patients, considering immunogenicity and safety aspects.     

Nutrition assessment and support of organ transplant recipients

Timely nutrition assessment and intervention in organ transplant recipients may improve outcomes surrounding transplantation. A pretransplant nutrition assessment should include a variety of parameters including physical assessment, history, anthropometric measurements, and laboratory tests. Malnutrition compromises posttransplant survival; prolonged waiting times worsen outcomes when patients are already malnourished. Severe obesity may decrease graft function and survival in kidney transplant recipients. In the pretransplant phase, nutritional goals include optimization of nutritional status and treatment of nutrition-related symptoms induced by organ failure. Enteral tube feeding is indicated for patients with functional gastrointestinal tracts who are not eating adequately. Parenteral nutrition is rarely needed pretransplant except in cases of intestinal failure. When determining pretransplant nutrient requirements, nutritional status, weight, age, gender, metabolic state, stage and type of organ failure, malabsorption, induced losses, goals, and comorbid conditions must be considered. During the acute posttransplant phase, adequate nutrition is required to help prevent infection, promote wound healing, support metabolic demands, replenish lost stores, and perhaps mediate the immune response. Nutrient recommendations reflect posttransplant metabolic changes. The appropriateness of posttransplant nutrition support depends on the prevalence of malnutrition among patients with a specific type of organ failure and the benefits when nutrition support is given. Organ transplantation complications including rejection, infection, wound healing, renal insufficiency, hyperglycemia, and surgical complications require specific nutritional requirements and therapies. Many potential applications of nutrition in the pre- and posttransplant phases exist and require further study.     

Humoral,T-cell and B-cell immune responses to seasonal influenza vaccine in solid organ transplant recipients receiving anti-T cell therapies

BackgroundWe analyzed the impact of the anti-T-cell agents basiliximab and antithymocyte globulins (ATG) on antibody and cell-mediated immune responses after influenza vaccination in solid-organ transplant recipients.Methods71 kidney and heart transplant recipients (basiliximab [n = 43] and ATG [n = 28]) received the trivalent influenza vaccine. Antibody responses were measured at baseline and 6 weeks post-vaccination by hemagglutination inhibition assay; T-cell responses were measured by IFN-γ ELISpot assays and intracellular cytokine staining (ICS); and influenza-specific memory B-cell (MBC) responses were evaluated using ELISpot.ResultsMedian time of vaccination from transplantation was 29 months (IQR 8–73). Post-vaccination seroconversion rates were 26.8% for H1N1, 34.1% for H3N2 and 4.9% for influenza B in the basiliximab group and 35.7% for H1N1, 42.9% for H3N2 and 14.3% for influenza B in the ATG group (p = 0.44, p = 0.61, and p = 0.21, respectively). The number of influenza-specific IFN-γ-producing cells increased significantly after vaccination (from 35 to 67.5 SFC/10⁶ PBMC, p = 0.0007), but no differences between treatment groups were observed (p = 0.88). Median number of IgG-MBC did not increase after vaccination (H1N1, p = 0.94; H3N2 p = 0.34; B, p = 0.79), irrespective of the type of anti-T-cell therapy.ConclusionsAfter influenza vaccination, a significant increase in antibody and T-cell immune responses but not in MBC responses was observed in transplant recipients. Immune responses were not significantly different between groups that received basiliximab or ATG.     

Cryptococcus neoformans infection in organ transplant recipients: variables influencing clinical characteristics and outcome

Unique clinical characteristics and other variables influencing the outcome of Cryptococcus neoformans infection in organ transplant recipients have not been well defined. From a review of published reports, we found that C. neoformans infection was documented in 2.8% of organ transplant recipients (overall death rate 42%). The type of primary immunosuppressive agent used in transplantation influenced the predominant clinical manifestation of cryptococcosis. Patients receiving tacrolimus were significantly less likely to have central nervous system involvement (78% versus 11%, p =0.001) and more likely to have skin, soft-tissue, and osteoarticular involvement (66% versus 21%, p = 0.006) than patients receiving nontacrolimus- based immunosuppression. Renal failure at admission was the only independently significant predictor of death in these patients (odds ratio 16.4, 95% CI 1.9-143, p = 0.004). Hypotheses based on these data may elucidate the pathogenesis and may ultimately guide the management of C. neoformans infection in organ transplant recipients.     

Baseline serum interleukin-6 to interleukin-2 ratio is associated with the response to seasonal trivalent influenza vaccine in solid organ transplant recipients

BackgroundThe analysis of pre- and post-vaccination B-cell-associated cytokines might be useful in predicting the immunogenicity of seasonal trivalent influenza vaccine (TIV) in solid organ transplant (SOT) recipients.MethodsWe performed a subanalysis of a clinical trial that compared the safety and efficacy of high-dose intradermal (ID) versus intramuscular (IM) TIV in SOT recipients. Serum levels of selected cytokines (interferon [IFN]-γ, interleukin [IL]-2, IL-4, IL-5, IL-6, IL-12 and IL-21, and tumor necrosis factor [TNF]-α) were measured pre- and one month post-vaccination in 155 patients (with 84 and 71 receiving the ID and IM vaccines, respectively). Cytokine profiles were compared according to vaccine response (seroconversion [≥4-fold increase in hemagglutination inhibition antibody titers] to ≥1 influenza vaccine antigen).ResultsMean baseline IL-6 levels were higher (1.20 versus 0.65 pg/mL; P-value = 0.021) and IL-2 levels were lower (0.01 versus 0.50 pg/mL; P-value = 0.051) in patients achieving vaccine response. After adjusting for clinical variables, baseline IL-6/IL-2 ratio remained predictive of vaccine response (odds ratio per 10-unit increment: 1.06; 95% confidence interval: 1.02–1.10; P-value = 0.002). Vaccination induced an increase in TNF-α (P-value <0.0001) and a decrease in IL-5 levels (P-value = 0.0007). There were no significant differences in cytokine kinetics between vaccine responders and non-responders. Mean baseline TNF-α levels were higher in patients experiencing moderate-to-severe adverse events after vaccination (1.93 versus 1.72 pg/mL; P-value = 0.009).ConclusionsBaseline serum IL-6 and IL-2 levels, two cytokines that modulate the role of CD4⁺ T follicular helper cells and the terminal differentiation of B-cells, predict vaccine response in SOT recipients.     

Contraceptive use among solid organ transplant patients: a systematic review

Background

Women undergoing solid organ transplantation are advised to avoid pregnancy for up to 24 months following transplant surgery.

Study Design

We conducted a systematic review of the literature, from database (PubMed) inception through February 2009, to evaluate evidence on the safety and effectiveness of contraceptive use among women having undergone solid organ transplantation.

Results

From 643 articles, eight articles from seven studies satisfied review inclusion criteria; six articles pertained to kidney transplant patients, and two reported on liver transplant patients. Two reports of one prospective cohort of 36 kidney transplant recipients taking combined oral contraceptives (COCs) or using the transdermal contraceptive patch reported no significant changes in biochemical measures after 18 months of use for either group, although 13 women modified antihypertensive medication, and two women discontinued the study because of serious medical complications. Four case reports of five kidney recipients using intrauterine devices reported inconsistent findings, including both beneficial health effects and contraceptive failures. One retrospective, noncomparative study of 15 liver transplant recipients using COCs or the transdermal contraceptive patch found no significant changes in any biochemical measures obtained, no discontinuations or severe complications and no pregnancies after a 12-month follow up. One case report of a liver transplant recipient on cyclosporine and prednisone documented the development of cholestasis associated with high-dose (50 mcg ethinyl estradiol) COC use as treatment for heavy uterine bleeding.

Conclusions

Very limited evidence on COC and transdermal contraceptive patch use among kidney and liver transplant recipients indicated no pregnancies and no overall changes in biochemical measures. Excluding case reports, evidence on other contraceptive methods or contraception among other types of solid organ transplants was not identified.     

Drug-nutrient interactions in transplant recipients

Drug-nutrient interaction refers to an alteration of kinetics or dynamics of a drug or a nutritional element, or a compromise in nutritional status as a result of the addition of a drug. The potentials for drug-nutrient interaction increase with the number of drugs taken by the patient. Organ transplant recipients are therefore at high risk for drug-nutrient interactions because multiple medications are used to manage graft rejection, opportunistic infections, and other associated complications. Unrecognized or unmanaged drug-nutrient interactions in this patient population can have an adverse impact on their outcomes. This paper reviews the importance of recognizing drug-nutrient interaction when using cyclosporine-based regimens.     

Hickman catheter complications in marrow transplant recipients

The complications associated with the insertion and use of 95 single lumen and 312 double lumen Hickman right atrial catheters in 357 marrow transplant recipients were retrospectively analyzed. Three-hundred (84%) first inserted catheters were in place for a median of 93 days (range, 16-209) without complications and were removed electively. Thirty-nine (9.6%) of all catheters were removed for infections and 24 (5.9%) for mechanical complications. Ninety-five patients (26.6%) had 111 episodes of septicemia involving 128 separate organisms and 25 patients had 25 episodes of localized catheter infection with 26 separate organisms. The most frequently isolated organism was coagulase-negative staphylococcus. Twelve of 24 removals due to mechanical complications were caused by accidental pulling of the catheter by the patient.     

Bronchiolitis obliterans syndrome in lung transplant recipients

Bronchiolitis obliterans syndrome in lung transplant recipients. The leading cause of late graft loss after lung transplantation is bronchiolitis obliterans syndrome. The process is a manifestation of chronic rejection, and is characterized by an excessive fibroproliferation in the small airways, leading progressively to luminal obliteration and graft injury. Both alloantigen-dependent (acute rejection, histocompatibility) and alloantigen-independent (ischaemia-reperfusion injury, cytomegalovirus infection, gastroesophageal reflux disease) risk factors may contribute to the development of the disease. Early in the process, damage to the airway epithelium occurs, which then triggers a massive influx of alloreactive T-cells into the graft tissue. Activated T-cells release a wide range of cytokines and growth factors, which in turn are capable of stimulating cellular proliferation and matrix protein synthesis in fibroblasts as well as in airway smooth muscle cells. Clinically, a decline in lung functions together with nonspecific symptoms can usually be observed in these patients, while later in the disease course recurrent respiratory tract infections are more common. Up till now, no effective therapy is available for bronchiolitis obliterans syndrome, however, certain immunosuppressive regimens may slow down the progression of the disease.