Humoral and cellular response after varicella vaccination in VZV IgG seronegative kidney transplant candidates

BackgroundIn immunocompromised patients, primary infection with VZV may have a disastrous clinical course. Vaccination of VZV-seronegative patients on the waiting list for renal transplantation may prevent severe disease. However, the immunologic response of end-stage renal disease patients to peptide vaccines is far from optimal. Our question was whether end-stage renal disease patients with undetectable VZV-IgG levels were able to mount an adequate humoral and cellular response to a live attenuated varicella vaccine.MethodsKidney transplant candidates with undetectable VZV levels were vaccinated twice with a live attenuated varicella vaccine at an interval of 6 weeks. VZV IgG levels were analysed till 2 years after vaccination. The VZV-specific T-cell reactivity was determined prior to vaccination and after transplantation.ResultsSeventy-seven percent (40/52) of the vaccinees reached positive VZV-IgG levels after vaccination (responders). Eighty-two percent (9/11) showed an increase in VZV-specific CD4⁺ memory T-cells (both central and effector memory cells). The percentage VZV-specific CD8⁺ memory T-cells did not increase. None of the non-responders suffered from primary VZV after transplantation. No severe vaccine-related adverse events were reported, only spontaneously resolving local skin irritation.ConclusionThe live attenuated varicella vaccine evokes positive VZV IgG-levels and VZV-specific memory T-cells in VZV-seronegative potential kidney transplant candidates.     

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.     

Differences in avidity of IgG antibodies to pertussis toxin after acellular pertussis booster vaccination and natural infection

Background

Pertussis toxin (PT) is a specific virulence factor of Bordetella pertussis and it is included in all acellular pertussis vaccines (aP). Although immunity after infection seems to persist longer than that after vaccination, the exact mechanism(s) is not known. Primary aim of this study was to develop an ELISA method for measuring avidity index (AI) of IgG-anti-PT antibodies and to compare antibody responses after booster vaccination and infection. Secondary aim was to evaluate if the AI-ELISA has potential in the serodiagnosis of pertussis.

Material

Serum samples from a total of 409 subjects were included in the study. Paired sera were taken from 97 adolescents who received booster vaccine ten years ago (dTpa-004) and from 80 young adults who received a second booster dose ten years after the previous booster vaccine (dTpa-040). Thirty-two paired sera from culture-confirmed pertussis patients, 161 single sera from serologically diagnosed patients and 39 single sera from healthy controls were included. AI of IgG-anti-PT antibodies were determined with newly developed ELISA using diethylamine (DEA) as a bond breaking agent. The IgG-anti-PT antibodies were measured by standardized ELISA.

Results

A significant increase was found in antibody concentrations and AI between PRE and one month POST vaccination ten years ago [GMC for antibody: 7.9 IU/ml vs. 98.3 IU/ml (p = 0.0001); for AI: 40.4% vs. 56.1% (p = 0.0001)]. Similar result was observed after the second booster dose [GMC for antibody: 9.2 IU/ml vs. 92.4 IU/ml (p = 0.0001); for AI: 36.1% vs. 59.5% (p = 0.0001)] and between the first and second sera of culture-confirmed patients [GMC for antibody: 6.9 IU/ml vs. 285.1 IU/ml (p = 0.0001); for AI: 40.5% vs. 68.4% (p = 0.0001)]. Healthy controls showed lower levels of both antibodies and AI.

Conclusions

Our results suggest that there may be difference in quality and quantity of antibodies to PT after vaccination and after infection. Furthermore, AI could be a help for vaccine studies.     

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.     

Differences of IgG antibody avidity after an acellular pertussis (aP) booster in adolescents after a whole cell (wcP) or aP primary vaccination

Compared to whole cell pertussis (wcP) vaccines, acellular pertussis vaccines (aP) have a better safety profile with lower reactogenicity, although their short and long-term efficacy was found to be slightly lower. Up to now, no established serological parameter to predict long-term protection exists. IgG-anti-pertussis avidity possibly determines the effect of different pertussis vaccines and boosting intervals on long-term immunity. Thus, the avidity of a tetanus-diphtheria-aP booster at 10–14 years was tested in three groups of adolescents who had been previously immunized with either five doses of aP (5aP) at 2, 4, 6, 15–18 months and 5–6 years of age, four doses of aP (4aP) or four doses of wcP (4wcP) at 2, 4, 6 and 15–18 months of age.     

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。     

测定巨细胞病毒特异性抗体亲和指数的诊断价值

目的以快速、简便的人巨细胞病毒特异性抗体亲和指数（CMV—IgGAI）检测方法作为有效的诊断工具，用于区分孕妇CMV原发感染与非原发感染。方法以标准的间接ELISA方法，8．0mol／L尿素作为温和蛋白变性剂，用标准曲线方法定量测定标本中的CMV—IgG含量。结果共检测218例标本，其中187例为CMV既往感染标本，31例为继发或再感染、可疑原发感染和原发感染标本。以抗体亲和指数〈35．0％作为阳性判断标准，此时方法的灵敏度为75．0％，特异度为91．4％，可用度为67．2％。既往感染、继发或再感染、可疑原发感染、原发感染4组的平均AI值分别是（61．42±25．69）％，（70．38±21．88）％，（66．73±23．62）％，（29．78±25．93）％，原发感染组与其它3组非原发感染比较，差异有统计学意义（P〈0．01））。结论以8．0mol／L尿素作为温和蛋白变性剂，用标准曲线方法定量测定标本中CMV—IgG含量适用于检测巨细胞病毒IgG抗体亲和指数（CMV—IgGAI），认为CMV—IgM联合CMV—IgGAI检测是区分原发与非原发感染的血清学方法之一。     

Responses of varicella zoster virus (VZV)-specific immunity in seropositive adults after inhalation of inactivated or live attenuated varicella vaccine

To examine boostering of varicella zoster virus (VZV)-specific immunity in seropositive adults after nasal inhalation of heat-inactivated or live attenuated varicella vaccine, we determined specific cellular immunity, IgG antibody in sera and secretory IgA antibody in saliva before and after the inhalation. The mean titers in specific IgG antibody and skin test findings significantly increased following inhalation of both vaccines. However, the ratio of a two-fold or more increase in the levels of IgG antibody or skin test did not show significant difference after inhalation of the inactivated vaccine in comparison with those in the control. After inhalation of the live vaccine, the ratio showed significant difference but transmission of the live vaccine virus to others was suspected. No significant increase in VZV-secretory IgA antibody levels in saliva was noted following inhalation. The results of this study suggested that nasal inhalation of the live vaccine could increase specific immunity in adults. This method would be similar to the natural infection and simpler than subcutaneous injection.     

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。     

Cross-reactivity and avidity of antibody responses induced in humans by the oral inactivated multivalent enterotoxigenic Escherichia coli (ETEC) vaccine ETVAX

We investigated whether the oral inactivated, multivalent enterotoxigenic Escherichia coli (ETEC) vaccine ETVAX, consisting of four E. coli strains over-expressing the colonisation factors (CFs) CFA/I, CS3, CS5 and CS6, combined with the toxoid LCTBA, could induce cross-reactive antibodies to CFs related to the CFA/I and CS5 families. We also evaluated the avidity of vaccine induced antibodies against the toxoid and CFs.Cross-reactivity was analysed in mucosal (faecal and antibodies in lymphocyte supernatants, ALS) samples, and antibody avidity in serum and ALS samples, from two phase I trials: a primary vaccination study, where two oral doses of ETVAX were given ± the double mutant heat labile toxin (dmLT) adjuvant at a 2-week interval, and a booster vaccination study, where a single booster dose of ETVAX was given 13–23 months after primary vaccinations.We found that 65–90% of subjects who had responded to CFA/I in ALS or faecal specimens also developed cross-reactive antibodies to the related CFs tested, i.e. CS1, CS14 and CS17, and that approximately 80% of those responding to CS5 also responded to the closely related CS7. For subjects who had developed cross-reactive antibodies, the magnitudes of responses against vaccine CFs and related non-vaccine CFs were comparable. Using both a simple method of antibody avidity determination based on limiting antigen dilution, as well as a chaotropic ELISA method, we found that the avidity of serum and ALS antibodies to key vaccine antigens increased after a late booster dose compared to after primary vaccination.Our results suggest that the cross-reactive antibody responses against multiple CFs may result in expanded ETEC strain coverage of ETVAX and that repeated vaccinations induce vaccine-specific antibodies with increased binding capacity.     

Varicella vaccination coverage in Bavaria (Germany) after general vaccine recommendation in 2004

Since 2004, general varicella vaccination has been recommended for all children 11–14 months of age in Germany. The objective of this study was to examine vaccination coverage in children and factors associated with parental acceptance during the first years after recommendation. In a regional surveillance area, cross-sectional parent surveys were conducted in 2006, 2007 and 2008 in random samples (n = 600) of children aged 18–36 months; data were obtained for 372, 364 and 352 children, respectively. Parents were questioned on their child's varicella disease history, and on varicella vaccination status as recorded in the child's vaccination booklet. Overall coverage increased from 38% in 2006 to 51% in 2007 and stagnated at 53% in 2008; in susceptible children (without previous varicella disease until vaccination or time of survey) coverage was 42%, 61% and 59%, respectively. Recommendation by the paediatrician as reported by the parents increased from 48% (2006) to 57% (2007) and 60% (2008), and was the main independent factor associated with parental acceptance. In 32–35% of unvaccinated children parents had not yet decided whether to vaccinate against varicella. Additional programmes targeting paediatricians’ and parents’ acceptance of varicella vaccination are needed to achieve the WHO-defined goal of at least 85% coverage.     

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.     

Persistence and avidity maturation of antibodies to A(H1N1)pdm09 in healthcare workers following repeated annual vaccinations

Healthcare workers are at increased risk of influenza infection through direct patient care, particularly during the early stages of a pandemic. Although influenza vaccination is widely recommended in Healthcare workers, data on long-term immunogenicity of vaccination in healthcare workers are lacking.The present study was designed to assess the persistence of the humoral response after pandemic vaccination as well as the impact of repeated annual vaccination in healthcare workers (n = 24).Pandemic influenza vaccination resulted in a significant increase in haemagglutination inhibition (HI) antibody titers with 93–100% of subjects achieving protective titers 21-days post each of the three annual vaccinations. Seroprotective antibodies measured by HI, microneutralization and single radial hemolysis assays were present in 77–94% of healthcare workers 6 months post-vaccination. Repeated vaccination resulted in an increased duration of seroprotective antibodies with seroprotective titers increasing from 35–62% 12 months after 2009 pandemic vaccination to 50–75% 12 months after 2010 vaccination. Furthermore, repeated annual vaccination augmented the avidity of influenza-specific IgG antibodies.In conclusion, we have shown that A(H1N1)pdm09 vaccination induces high seroprotective titers that persist for at least 6 months. We demonstrate that repeated vaccination is beneficial to healthcare workers and results in further avidity maturation of vaccine-induced antibodies.     

Cost-effectiveness of Recombinant Zoster Vaccine (RZV) and Varicella Vaccine Live (VVL) against herpes zoster and post-herpetic neuralgia among adults aged 65 and over in Japan

BackgroundThe approval of the extended use of 1-dose varicella vaccine (VVL) in adults aged 50 and older against herpes zoster (HZ) in 2016 and the 2-dose recombinant zoster vaccine (RZV) in 2018 raised the need to evaluate the value for money between these two vaccines.MethodsWe conducted a cost-effectiveness analysis with Markov modelling to evaluate the efficiency of the immunisation programmes from payer’s perspective. Eight strategies with different ages to receive VVL or RZV were set, namely: 65–84 year old (y.o.), 70–84 y.o., 75–84 y.o., and 80–84 y.o. VVL- or RZV-strategy. Incremental cost-effectiveness ratios (ICERs) compared with curative care scenario were calculated. The health statuses following the target cohort were as follows: acute HZ followed by recovery, post-herpetic neuralgia followed by recovery, post HZ/PHN, recurrence of HZ, and general death.ResultsAt the vaccination cost ¥8000 (US$73) for 1-dose ZVL and ¥30,000 (US$273) for 2-dose RZV, ICERs ranged from ¥2,633,587/US$23,942 (age 80–84 y.o.) to ¥3,434,267 or US$31,221 (age 65–84 y.o.)/QALY gained for VVL-strategies; from ¥5,262,227 or US$47,838 (age 80–84 y.o.) to ¥6,278,557 or US$57,078/QALY gained (age 65–84 y.o.) for RZV-strategies. Cost-effectiveness acceptability curves derived from probabilistic sensitivity analyses showed that if the cost-effective threshold was at ¥3,000,000 or US$27,273/QALY, the acceptability was 90.7% and 8.8% for 65–84 VVL-strategy and 65–84 RZV-strategy, respectively; if at ¥5,000,000 or US$45,455/QALY, 56.2% and 43.8%, and if at ¥10,000,000 or US$90,909/QALY 11.9% and 88.1%, respectively.ConclusionVaccinating individuals aged 65–84 y.o., 70–84 y.o., 75–84 y.o., 80–84 y.o. with VVL or RZV to prevent HZ-associated disease in Japan can be cost-effective from payer’s perspective, with vaccination costs at ¥8,000 per shot for VVL, ¥30,000 for 2-dose RZV. While the results suggesting that only 65–84 VVL-strategy and 65–84 RZV strategy should be considered when introducing HZ immunisation programme. The optimal strategy varies depending on the willingness-to-pay threshold.     

A practical approach to tuberculosis diagnosis and treatment in liver transplant recipients in a low-prevalence area

Solid organ transplant candidates/recipients are at risk of mycobacterial infections. Although guidelines on the management of latent tuberculosis infection and active tuberculosis are available for solid organ transplant recipients, limited guidance focuses on end-stage liver disease or liver transplant recipients who require management in a referral center. Therapeutic challenges arise from direct antituberculosis drug-related hepatotoxicity, and substantial metabolic interactions between immunosuppressive and antituberculosis drugs. Another issue is the optimal timing of therapy with regards to the time of transplantation. This review focuses on the importance of tuberculosis screening with immunological tests, challenges in the diagnosis, management, and treatment of latent tuberculosis infection and active tuberculosis, as well as risk assessment for active tuberculosis in the critical peri-liver transplantation period. We detail therapeutic adjustments required for the management of antituberculosis drugs in latent tuberculosis infection and active tuberculosis, particularly when concomitantly using rifampicin and immunosuppressive drugs.     

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.     

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.     

Cryptosporidiosis and microsporidiosis as causes of diarrhea in kidney and/or pancreas transplant recipients

IntroductionGastrointestinal disorders in solid organ recipients may have various origins including cryptosporidiosis and microsporidiosis. The prevalence of these infections is poorly known in solid organ transplant (SOT) patients in industrialized countries.MethodsWe prospectively assessed the infectious causes of diarrhea in SOT patients. Secondary objectives were to gain further insight into the main characteristics of cryptosporidiosis, and to assess risk factors for this infection. All adult kidney and/or pancreas recipients presenting with diarrhea and admitted to our facility between May 1, 2014 and June 30, 2015 were enrolled. A stool sample was analyzed using a standardized protocol including bacteriological, virological, and parasitological investigations. Data related to clinical symptoms, immunosuppression, and environmental potential risk factors were collected through a self-administered questionnaire and computerized medical records.ResultsOut of 73 enrolled patients, 36 had infectious diarrhea (49.3%). Viruses ranked first (17/36), followed by parasites and fungi (11/17). Cryptosporidiosis was the most common parasitic disease (n = 6 patients). We observed four microsporidiosis cases. The estimated prevalence of cryptosporidiosis and microsporidiosis in this cohort was 3.7 and 2.4⁰/₀₀, respectively_. No significant risk factor for cryptosporidiosis or microsporidiosis, neither environmental nor immunological, could be evidenced.ConclusionBoth cryptosporidiosis and microsporidiosis represent a significant cause of diarrhea in kidney transplant recipients.