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Background: Delayed graft function (DGF) increases the renal allograft failure risk. Late‐onset Cytomegalovirus (CMV) infection's effect on the association between DGF and allograft failure has not been determined. Methods: In this retrospective cohort, we included all renal allograft recipients at London Health Sciences Centre from January 1, 2014 to December 30, 2017, and continued clinical follow‐up until February 28, 2020. We determined whether late‐onset CMV infection affects the association between DGF and allograft failure in stratified and Cox proportional hazard analyses. Results: Of 384 patients (median age [interquartile range]: 55 [43.3–63]; 38.7% female), 57 recipients (14.8%) were diagnosed with DGF. Patients with DGF were at a greater risk of CMV infection than patients without DGF (22.8% vs. 11.3%, p =.017). Late‐onset CMV infection (odds ratio [OR]: 4.7, 95% CI: 2.07–10.68) and rejection (OR: 9.59, 95% CI: 4.15–22.16) significantly increased the risk of allograft failure in recipients with DGF. Patients with DGF had a significantly greater risk of graft failure than those without DGF (17.5% vs. 6.1%, p =.007). In the adjusted Cox hazard model, CMV infection significantly increased the risk of allograft failure (aHR: 3.19, 95% CI: 1.49–6.84). Conclusion: Late‐onset CMV infection considerably increased the risk of graft failure in patients with DGF. A hybrid preventive model including prophylaxis followed by CMV‐specific cell‐mediated immunity monitoring may decrease the risk of allograft failure in recipients with DGF. [ABSTRACT FROM AUTHOR]

Background: Solid organ transplant (SOT) recipients are at risk of Pneumocystis pneumonia (PCP). PCP is associated with significant morbidity and mortality. The effect of acute T cell‐mediated rejection (TCMR) on post‐transplant PCP has not been determined yet. Methods: In this case‐control study, we estimated the risk of PCP following acute TCMR during a lookback period of 180 days. We also determined the effects of contributing factors such as CMV infection. Results: We compared 15 SOT (8 kidney, 4 heart, 2 liver, and 1 kidney‐pancreas) recipients with PCP with 60 matched recipients who did not develop PCP (control group) during the study period (December 2013 to February 2016). PCP occurred after a complete course of prophylaxis (ie, late‐onset PCP) in 60% of patients. Patients with PCP frequently required intensive care unit (ICU) admission (73.3%). Post‐transplant PCP was associated with considerable allograft loss (53.4%) and mortality (26.7%). In the 6‐month lookback period, acute TCMR (OR: 13.1, 95% CI: 3.2, 53.2), and CMV infection (OR: 15.1,95% CI: 4.0, 53.2.1) were significantly associated with post‐transplant PCP. Conclusions: Post‐transplant PCP is associated with substantial risk of ICU admission, allograft failure, and mortality. Anti‐Pneumocystis prophylaxis for at least 6 months following acute TCMR may reduce the risk. [ABSTRACT FROM AUTHOR]

Renal transplant recipients remain at risk of delayed‐onset cytomegalovirus (CMV) infection occurring beyond a complete course of prophylaxis. In this retrospective cohort, all 278 patients who received renal allografts from deceased donors from 2014 to 2016 were followed until September 1, 2019. We determined the effect of early–vs late‐onset acute rejection (EAR vs LAR [ie, occurring beyond 12 months after transplantation]) on CMV infection and subsequently long‐term allograft outcome. Median (IQR) duration of follow‐up was 1186.0 (904.7‐1531.2) days. Seventy patients including 49 patients with EAR and 21 with LAR received augmented immunosuppression. In the same interval, 40 patients developed CMV infection (36 patients beyond 90 days after transplantation [90%]). In logistic regression analysis, D+/R‐ CMV serostatus (OR: 5.5, 95% CI: 2.5‐12.2) and LAR (OR: 7.9, 95% CI: 2.8‐22.2) significantly increased the risk of CMV infection. In Cox proportional hazard model, delayed‐onset CMV infection (HR: 2.51, 95% CI: 1.08‐5.86) and LAR (HR: 5.46, 95% CI: 2.26‐13.14) significantly increased the risk of allograft loss. Patients with LAR are at risk of late‐onset CMV infection. Post‐LAR, targeted prophylaxis may reduce the risk of CMV infection and subsequently allograft loss. Further studies are required to demonstrate the effect of targeted prophylaxis following LAR. [ABSTRACT FROM AUTHOR]

Human leukocyte antigen (HLA) class I presentation pathway plays a central role in natural killer (NK) cell and cytotoxic T‐cell activities against BK polyomavirus (BKPyV) DNAemia. We determined the risk of sustained BKPyV DNAemia in 175 consecutive renal transplant recipients considering the simultaneous effect of donor/recipient HLA class I antigens and pre‐ or post‐transplant variables. Median (IQR) age was 53 (44‐64) years, and 37% of patients were female. 40 patients (22.9%) developed sustained BKPyV DNAemia [median (IQR) viral load: 9740 (4350‐17 125) copies/ml]. In the Cox proportional hazard analysis, HLA‐A1 (HR: 3.06, 95% CI: 1.51‐6.17) and HLA‐B35‐Cw4 (HR: 4.63, 95% CI: 2.12‐10.14) significantly increased the risk of sustained BKPyV DNAemia, while 2 HLA‐C mismatches provided a marginally protective effect (HR: 0.32, 95% CI: 0.10‐0.98). HLA‐Cw4 is a ligand for NK cell inhibitory receptor, and HLA‐B35 is in strong linkage disequilibrium with the HLA‐Cw4 allele. The association between HLA‐B35‐Cw4 expression and sustained BKPyV DNAemia supports the important role of cytotoxic T cells and NK cells that would normally control BKPyV activation through engagement with immunoglobulin‐like killer receptors (KIRs). Further studies are required to investigate the effect of HLA‐C alleles along with NK cell activity against BKPyV DNAemia. [ABSTRACT FROM AUTHOR]

Pneumocystis pneumonia (PCP) outbreaks may occur in solid organ transplant (SOT) patients. Transmissibility of Pneumocystis jirovecii among SOT and non‐SOT patients has not been investigated. Ten SOT (ie, 4 heart, 4 kidney, 2 liver allograft recipients) and 11 non‐SOT (ie, 7 HIV‐infected, 3 hematologic malignancies, and 1 stem cell transplant) patients with PCP were admitted to London Health Sciences Center (LHSC) from October 2014 to August 2016. We investigated the course of illness and outcome of PCP in SOT and non‐SOT patients. Post‐transplant PCP was frequently an acute‐onset disease (90% vs. 18.2%, p =.01) requiring ICU admission (70% vs. 20%, p =.03) and hemodialysis (60% vs. 0, p =.003). Mortality was more frequent in SOT patients (40% vs. 18.1%, p =.36). Multilocus sequence typing (MLST) demonstrated circulation of a single genotype of P. jirovecii among SOT patients. However, 8 different genotypes were detected from non‐SOT patients. Reinstitution of prophylaxis successfully controlled post‐transplant cluster until end of observation period in October 2019. No transmission was detected from non‐SOT patients to SOT recipients. Detection of a single P. jirovecii genotype from all SOT recipients highlights the likelihood of nosocomial transmission. No source control method is recommended by current guidelines. Improvement of preventive strategies is required. [ABSTRACT FROM AUTHOR]

Background: Invasive fungal infection (IFI) in solid organ transplant (SOT) recipients is associated with significant morbidity and mortality. The long‐term probability of post‐transplant IFI is poorly understood. Methods: We conducted a population‐based cohort study using linked administrative healthcare databases from Ontario, Canada, to determine the incidence rate; 1‐, 5‐, and 10‐year cumulative probabilities of IFI; and post‐IFI all‐cause mortality in SOT recipients from 2002 to 2016. We also determined post‐IFI, death‐censored renal allograft failure. Results: We included 9326 SOT recipients (median follow‐up: 5.35 years). Overall, the incidence of IFI was 8.3 per 1000 person‐years. The 1‐year cumulative probability of IFI was 7.4% for lung, 5.4% for heart, 1.8% for liver, 1.2% for kidney‐pancreas, and 1.1% for kidney‐only allograft recipients. Lung transplant recipients had the highest incidence rate and 10‐year probability of IFI: 43.0 per 1000 person‐years and 26.4%, respectively. The 1‐year all‐cause mortality rate after IFI was 34.3%. IFI significantly increased the risk of mortality in SOT recipients over the entire follow‐up period (hazard ratio: 6.50, 95% CI: 5.69‐7.42). The 1‐year probability of death‐censored renal allograft failure after IFI was 9.8%. Conclusion: Long‐term cumulative probability of IFI varies widely among SOT recipients. Lung transplantation was associated with the highest incidence of IFI with considerable 1‐year all‐cause mortality. [ABSTRACT FROM AUTHOR]

Abstract: A growing number of publications have reported the outbreaks of post‐transplant pneumocystis pneumonia (PJP). In most studies, the onset of PJP was beyond 6‐12 months of prophylaxis. Cytomegalovirus (CMV) infection and allograft rejection have been repeatedly reported as probable risk factors for post‐transplant PJP. In this systematic review and meta‐analysis, we determined the pooled effect estimates of these 2 variables as risk factors. Data sources included PUBMED, MEDLINE‐OVID, EMBASE‐OVID, Cochrane Library, Networked Digital Library of Theses and Dissertations, World Health Organization, and Web of Science. We excluded publications related to hematopoietic stem cell transplantation (HSCT) or Human Immunodeficiency Virus (HIV) patients. Eventually, 15 studies remained for the final stage of screening. Cytomegalovirus infection (OR: 3.30, CI 95%: 2.07‐5.26, I2: 57%, P = 0.006) and allograft rejection (OR:2.36, CI95%: 1.54‐3.62, I2: 45.5%, P = 0.05) significantly increased the risk of post‐transplant PJP. Extended prophylaxis targeting recipients with allograft rejection or CMV infection may reduce the risk of PJP. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Previous studies showed HIV‐negative immunocompromised patients are susceptible to Pneumocystis pneumonia (PCP). However, the PCP outcome has not been compared among HIV‐negative immunocompromised patients.In this retrospective cohort study at the University Health Network, we included all HIV‐negative immunocompromised patients who fulfilled the European Organization for Research and Treatment of Cancer (EORTC) PCP diagnosis criteria from December 2018 to December 2019. We compared the demographics, comorbidities, course of illness, and PCP outcome (28‐day mortality and composite outcome [i.e., death or intensive care unit (ICU) admission]) between solid organ transplant (SOT) and non‐SOT patients.Of 160 non‐HIV patients with PCP diagnoses, 118 patients fulfilled EORTC criteria (76 males [64.4%], median [range] age: 65.5 [21–87] years). PCP presentation in SOT recipients (n = 14) was more severe than non‐SOT patients (n = 104): acute presentation (onset <7 days before admission: 11/14 [78.6%] vs. 51/104 [56%], p = .037), shortness of breath (100% vs. 75/104 [74.3%], p = .037), median [range] O2 saturation (88% [75%, 99%] vs. 92%[70%, 99%], p = .040), and supplemental O2 requirement (12/14 [85.7%] vs. 59/104 [56.7%], p = .044). The mortality [4/14, (28.6%) vs. 15/104 (14.4%), p = .176], ICU admission (10/14 [71.4%] vs. 18/104 [17.3%], p < .0001), and mechanical ventilation (8/14 [57.1%] vs. 18/104 [17.3%], p = .0007) in SOT patients was different from non‐SOT patients. In multivariable analysis, SOT recipients were at greater risk of composite outcome than non‐SOT patients (aOR [CI95%]: 12.25 [3.08–48.62], p < .001).PCP presentation and outcomes in SOT recipients are more severe than in non‐SOT patients. Further studies are required to explore the biological reasons for this difference. [ABSTRACT FROM AUTHOR]