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1.
Gut ; 73(10): 1702-1711, 2024 Sep 09.
Article in English | MEDLINE | ID: mdl-38621922

ABSTRACT

OBJECTIVES: In high-income countries hepatitis E virus (HEV) is an uncommonly diagnosed porcine-derived zoonoses. After identifying disproportionate chronic HEV infections in persons with cystic fibrosis (pwCF) postlung transplant, we sought to understand its epidemiology and potential drivers. DESIGN: All pwCF post-transplant attending our regional CF centre were screened for HEV. HEV prevalence was compared against non-transplanted pwCF and with all persons screened for suspected HEV infection from 2016 to 2022 in Alberta, Canada. Those with chronic HEV infection underwent genomic sequencing and phylogenetic analysis. Owing to their swine derivation, independently sourced pancreatic enzyme replacement therapy (PERT) capsules were screened for HEV. RESULTS: HEV seropositivity was similar between transplanted and non-transplanted pwCF (6/29 (21%) vs 16/83 (19%); p=0.89). Relative to all other Albertans investigated for HEV as a cause of hepatitis (n=115/1079, 10.7%), pwCF had a twofold higher seropositivity relative risk and this was four times higher than the Canadian average. Only three chronic HEV infection cases were identified in all of Alberta, all in CF lung transplant recipients (n=3/29, 10.3%). Phylogenetics confirmed cases were unrelated porcine-derived HEV genotype 3a. Ninety-one per cent of pwCF were taking PERT (median 8760 capsules/person/year). HEV RNA was detected by RT-qPCR in 44% (47/107) of PERT capsules, and sequences clustered with chronic HEV cases. CONCLUSION: PwCF had disproportionate rates of HEV seropositivity, regardless of transplant status. Chronic HEV infection was evident only in CF transplant recipients. HEV may represent a significant risk for pwCF, particularly post-transplant. Studies to assess HEV incidence and prevalence in pwCF, and potential role of PERT are required.


Subject(s)
Cystic Fibrosis , Enzyme Replacement Therapy , Hepatitis E virus , Hepatitis E , Lung Transplantation , Cystic Fibrosis/surgery , Cystic Fibrosis/complications , Lung Transplantation/adverse effects , Humans , Hepatitis E/epidemiology , Male , Female , Animals , Swine , Adult , Hepatitis E virus/genetics , Hepatitis E virus/isolation & purification , Alberta/epidemiology , Phylogeny , Young Adult , Prevalence , Chronic Disease , Middle Aged , Adolescent , Transplant Recipients/statistics & numerical data , Genotype
2.
Am J Transplant ; 24(1): 11-19, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37659606

ABSTRACT

Current policies in organ and tissue donation and transplantation (OTDT) systems in Canada and the United States unnecessarily restrict access to donation for sexual and gender minorities (SGMs) and pose safety risks to transplant recipients. We compare SGM-relevant policies between the Canadian and United States systems. Policy domains include the risk assessment of living and deceased organ and tissue donors, physical examination considerations, viral testing recommendations, and informed consent and communication. Identified gaps between current evidence and existing OTDT policies along with differences in SGM-relevant policies between systems, represent an opportunity for improvement. Specific recommendations for OTDT system policy revisions to achieve these goals include the development of behavior-based, gender-neutral risk assessment criteria, a reduction in current SGM no-sexual contact period requirements pending development of inclusive criteria, and destigmatization of sexual contact with people living with human immunodeficiency virus. OTDT systems should avoid rectal examinations to screen for evidence of receptive anal sex without consent and mandate routine nucleic acid amplification test screening for all donors. Transplant recipients must receive enhanced risk-to-benefit discussions regarding decisions to accept or decline an offer of an organ classified as increased risk. These recommendations will expand the donor pool, enhance equity for SGM people, and improve safety and outcomes for transplant recipients.


Subject(s)
Sexual and Gender Minorities , Tissue and Organ Procurement , Humans , United States , Canada , Sexual Behavior , Policy
3.
Am J Transplant ; 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39326850

ABSTRACT

Bartonella quintana (BQ) infection is rarely described to be transmitted through solid organ transplant (SOT). We report a cluster of donor-derived BQ infection and attack rate from Bartonella seropositive donors. Retrospective study of SOT recipients that received an organ from an unhoused deceased donor (UDD) in Alberta in 2022-2023. Serology testing for Bartonella was performed with Indirect Immunofluorescent Assay from UDD and recipients from UDD with positive serology. Titers ≥1:64 considered positive. During the study period, 31/32 UDD had IgG to Bartonella (20 negative, 11 positives (D+) for B.quintana and/or B.henselae). 32 organs were transplanted from 11D+. Six SOT recipients developed bartonellosis secondary to BQ (4 SOT received organs from 3 D+, and 2 SOT from 1 UDD with no stored sample for testing). The attack rate for clinical disease from D+ was of 12.5% (4/32). The main presentation: skin nodules/papules (median 5.5 months) with bacillary angiomatosis in 4/6. Bartonella serology was positive in 5/6 (initially negative in 2), blood BQ-qPCR in two. None had visceral involvement. All donors had history of substance use. This outbreak of bartonellosis reinforces the potential for unexpected donor transmitted infections. Clinicians should be aware of high transmission of BQ through transplant from infected UDD.

4.
J Viral Hepat ; 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39109700

ABSTRACT

Co-existing chronic hepatitis B virus (CHB) infection and metabolic dysfunction associated steatotic liver disease (MASLD) can exert complex effects on hepatic metabolism, requiring mechanistic study. CHB participants were assessed for MASLD and the impact of hepatic steatosis/metabolic syndrome (MetS) on novel viral and immunological markers. In this prospective, cohort study, untreated CHB subjects were assessed for liver disease by non-invasive tests (i.e. FibroScan, controlled attenuation parameter, CAP). Subjects were tested for cytokines and IFN-γ ELISPOT assay to HBV Surface (S) and Core (C) proteins. Standard HBV serological, exploratory biomarkers and deep sequencing of HBV S and C genes were performed. In 53 subjects (median age 45 years [SD = 10.6], 35% F, 56% Asian, 20% Black, 3% White), 94% (50) HBeAg negative, 63% genotype B/C, mean HBV DNA 3.2 log10 IU/mL (SD = 1.8), quantitative HBsAg 2.9 log10 IU/mL (SD = 1.2) and HBV pgRNA 2.1 log10 copies/mL (SD = 1.3). In enrolled subjects, the mean ALT was 41.9 U/L (SD = 24.0), FibroScan was 5.7 kPa (SD = 1.9) and CAP was 306.4 dB/m (SD = 49.0). The mean BMI was 28.2 kg/m2 (SD = 4.2), 20% (11/53) had diabetes, 35% (19/53) dyslipidaemia and 24% (13/53) hypertension. Subjects with MetS and steatosis showed lower HBV markers (p < .01), higher HBV S diversity (p = .02) and greater frequency of HBV variants associated with host-anti-viral immune escape. Pro-inflammatory cytokine levels and HBV-specific cellular responses were higher in participants with hepatic steatosis. In CHB, MASLD/hepatic steatosis was associated with HBV variants and systemic immune responses potentially impacting liver disease progression despite low-level viraemia.

5.
Transpl Infect Dis ; 26(4): e14292, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38728099

ABSTRACT

BACKGROUND: Cytomegalovirus (CMV) mismatched, donor IgG-positive/recipient IgG-negative, solid organ transplant recipients (SOTRs) are at high risk of CMV invasive disease. Post-prophylaxis disease is an issue in this population. Some programs employ surveillance after prophylaxis (SAP) to limit the incidence of post-prophylaxis disease. METHODS: This was a single-center retrospective cohort study that included all CMV mismatched SOTRs from 2003 to 2017. Patients underwent SAP with weekly CMV plasma viral load for 12 weeks. The subjects were classified into three post-prophylaxis DNAemia patterns: no DNAemia, one episode of DNAemia, and multiple episodes of DNAemia. We calculated the cumulative incidence of each DNAemia pattern. We also determined 5-year mortality based on DNAemia pattern stratified by organ transplant type. RESULTS: Post-prophylaxis recurrent DNAemia occurred in 63% of lung recipients and 32% of non-lung recipients (p =  .003). Tissue invasive CMV disease was diagnosed in 3% of the population and CMV syndrome was diagnosed in 33%. Recurrent DNAemia was not associated with 5-year mortality. CONCLUSION: In this cohort, undergoing SAP tissue invasive disease was uncommon and CMV DNAemia recurrence did not have an impact on long-term mortality.


Subject(s)
Antiviral Agents , Cytomegalovirus Infections , Cytomegalovirus , DNA, Viral , Transplant Recipients , Viral Load , Humans , Cytomegalovirus Infections/prevention & control , Cytomegalovirus Infections/virology , Cytomegalovirus Infections/mortality , Retrospective Studies , Female , Male , Middle Aged , Cytomegalovirus/genetics , Cytomegalovirus/immunology , Antiviral Agents/therapeutic use , DNA, Viral/blood , Adult , Transplant Recipients/statistics & numerical data , Recurrence , Organ Transplantation/adverse effects , Aged , Incidence
6.
J Hepatol ; 79(5): 1121-1128, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37348788

ABSTRACT

BACKGROUND & AIMS: Canadian clinical practice guidelines currently recommend risk-based screening for HCV in pregnant individuals. However, no provinces or territories have ever compared the effectiveness of risk-based vs. universal screening for the prenatal diagnosis of HCV. We aimed to evaluate and compare HCV screening programs after implementing a universal population-level pilot program among prenatal patients in Alberta, Canada. METHODS: The Alberta Prenatal Screening Program for Select Communicable Diseases was amended to include universal HCV antibody screening. Cohorts of pregnant individuals screened for HCV through risk-based or universal programs were generated over 1-year periods. HCV screening rates and prevalence were analyzed and compared between cohorts to evaluate the effectiveness of screening methods. Social and demographic risk factors for HCV-positive individuals were compared between screening cohorts to identify which populations may be overlooked with risk-based guidelines. RESULTS: HCV antibody screening rates were 11.9% and 99.9% among pregnant individuals in the risk-based and universal cohorts, respectively. HCV prevalence among the cohorts was 0.07% and 0.11% (difference = 0.04%, p = 0.032), with an average of 21 additional HCV-positive pregnant individuals identified annually with universal screening. HCV-positive pregnant patients diagnosed through universal screening were more likely to engage in high-risk sexual behaviours/sex work compared to those diagnosed through risk-based screening (47.6% vs. 12.5%, respectively p = 0.035), suggesting that these high-risk cases are being missed by risk-based screening. CONCLUSIONS: Universal HCV screening diagnoses significantly higher numbers of pregnant individuals infected with HCV compared to risk-based screening. Universal HCV screening or amending risk-based guidelines to incorporate more proxy variables for risk factors should be considered to improve prenatal HCV screening guidelines in Canada and help achieve HCV elimination in the next decade. IMPACT AND IMPLICATIONS: HCV is a bloodborne pathogen that can cause severe liver disease and be vertically transmitted from a mother to her baby during pregnancy. Pregnant individuals in Alberta are currently only tested for HCV if they disclose engaging in activities that put them at risk of acquiring the infection (risk-based screening). Using a population-wide universal prenatal HCV screening program, our work shows that testing based on patient disclosed risk alone leads to the significant underdiagnosis of HCV in pregnant individuals and suggests individuals engaging in sex work or risky sexual behaviours are being overlooked by the current risk-based program. Our outcomes represent the first province-wide study to evaluate and compare prenatal HCV risk-based and universal screening programs in Canada and provide evidence to support the update of prenatal HCV screening policies across the country and in similar jurisdictions.

7.
Clin Transplant ; 37(2): e14896, 2023 02.
Article in English | MEDLINE | ID: mdl-36583465

ABSTRACT

The increased procurement of organs from donors with risk factors for blood-borne diseases and the expanding syphilis epidemic have resulted in a growing number of organs transplanted from donors with reactive syphilis serology in our center. Based on guidelines, recipients typically receive therapy shortly after the transplant, but data on outcomes are limited. The primary objective of this study was to determine syphilis seroconversion rates at three months post-transplant in recipients of solid organs procured from donors with reactive syphilis serology. Organ donors and recipients were tested for syphilis antibody; positive results were confirmed with Treponema pallidum Particle Agglutination (TPPA). Eleven donors with reactive syphilis antibody donated organs to 25 syphilis negative recipients. Three recipients seroconverted at post-transplant month 3. All of them had received therapy shortly after transplant. TPPA was negative in all 3. Despite post-transplant treatment, 3 of 25 (12%) syphilis negative recipients of organs from syphilis positive donors seroconverted at 3 months. All remained TPPA negative possibly reflecting passive antibody transfer or differing test sensitivity to low level treponemal antibodies. Further studies are needed to assess optimal syphilis transmission prevention strategies and follow up recipient testing in organ transplantation.


Subject(s)
Organ Transplantation , Syphilis , Humans , Syphilis/diagnosis , Syphilis/epidemiology , Retrospective Studies , Follow-Up Studies , Treponema pallidum , Tissue Donors , Organ Transplantation/adverse effects , Organ Transplantation/methods , Transplant Recipients , Antibodies
8.
Transpl Infect Dis ; 25(6): e14181, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37922374

ABSTRACT

INTRODUCTION: Respiratory viral infections (RVI) in lung transplant recipients (LTR) have variably been associated with rejection and chronic lung allograft dysfunction. Our center has used systemic corticosteroids to treat outpatient RVI in some cases, but evidence is limited. We reviewed all adult LTR diagnosed with outpatient RVI January 2017 to December 2019. The primary outcome was recovery of lung function (forced expiratory volume in 1 s [FEV1]) at next stable visit between 1 and 12 months postinfection, expressed as a ratio over stable preinfection FEV1 (FEV1 recovery ratio). METHODS: We identified 100 adult LTR with outpatient RVI diagnoses eligible for study, 36% of whom received corticosteroids. We modelled the adjusted association between corticosteroid use and FEV1 recovery ratio using linear regression. RESULTS: Steroid-treated patients had a lower FEV1 presentation ratio (0.92 vs. 1.04, p = .0070) and were more likely to have chronic lung allograft dysfunction at time of infection (25% vs. 5%, p = .0077). Mean FEV1 recovery ratio was 1.02 (SD 0.19) with no association with corticosteroid therapy via multivariable linear regression (p = .5888). CONCLUSIONS: Steroid treatment was not associated with FEV1 recovery. This suggests corticosteroids may not have a role in the management of RVI in this population.


Subject(s)
Lung Transplantation , Virus Diseases , Adult , Humans , Lung Transplantation/adverse effects , Transplant Recipients , Outpatients , Lung , Adrenal Cortex Hormones/therapeutic use , Virus Diseases/drug therapy , Virus Diseases/epidemiology , Virus Diseases/diagnosis , Steroids , Forced Expiratory Volume
9.
Am J Transplant ; 21(12): 3958-3970, 2021 12.
Article in English | MEDLINE | ID: mdl-34174153

ABSTRACT

Although antiviral prophylaxis has reduced cytomegalovirus (CMV) DNAemia and disease in seronegative solid organ transplant (SOT) recipients (R-) receiving seropositive donor organs (D+), its impact on CMV transmission is uncertain. Transmission, defined as CMV antigenemia/CMV DNAemia and/or seroconversion by year 2, and associated demographic risk factors were studied retrospectively in 428 D+/R- and 429 D-/R- patients receiving a SOT at our center. The cumulative transmission incidence was higher for lung (90.5%) and liver recipients (85.1%) than heart (72.7%), kidney (63.9%), and pancreas (56.2%) recipients (p < .001) and was significantly lower in living (50.1%) versus deceased donor (77.4%, p < .001) kidney recipients despite identical antiviral prophylaxis. In multivariate analysis, only allograft type predicted transmission risk (HR [CI] lung 1.609 [1.159, 2.234] and liver 1.644 [1.209, 2.234] vs kidney). For 53 D+ donating to >1 R- with adequate follow-up, 43 transmitted to all, three transmitted to none, and seven transmitted inconsistently with lungs and livers always transmitting but donor-matched heart, kidney or kidney-pancreas allografts sometimes not. Kidney pairs transmitted concordantly. CMV transmission risk is allograft-specific and unchanged despite antiviral prophylaxis. Tracking transmission and defining donor factors associated with transmission escape may provide novel opportunities for more targeted CMV prevention and improve outcome analysis in antiviral and vaccine trials.


Subject(s)
Cytomegalovirus Infections , Organ Transplantation , Antiviral Agents/therapeutic use , Cytomegalovirus , Cytomegalovirus Infections/drug therapy , Cytomegalovirus Infections/etiology , Cytomegalovirus Infections/prevention & control , Ganciclovir/therapeutic use , Humans , Organ Transplantation/adverse effects , Retrospective Studies , Risk Factors , Transplant Recipients
10.
J Viral Hepat ; 28(6): 942-950, 2021 06.
Article in English | MEDLINE | ID: mdl-33749086

ABSTRACT

Tenofovir alafenamide fumarate (TAF) has high plasma stability resulting in fewer renal adverse events compared to tenofovir disoproxil fumarate (TDF) in chronic hepatitis B (CHB) patients. We aimed to study the effectiveness and renal safety of TAF in a real-world setting, in patients with or without compromised kidney function. CHB patients (Nucleos(t)ide Analogue [NA]-naïve or experienced) who received TAF >1 year from 11 academic institutions as part of the Canadian Hepatitis B Network (CanHepB) were included. Kidney function was measured by estimated glomerular filtration rate (eGFR) as per Cockcroft-Gault. Patients were followed for up to 160 weeks. Of 176 patients receiving TAF, 143 switched from NA (88% TDF), and 33(19%) were NA naïve. Majority of NA-naïve patients (75%) achieved undetectable HBV DNA after one year of TAF treatment. Majority of patients with eGFR <60 mL/min who had renal deterioration during TDF (76%) reversed to eGFR increase after one year of TAF (p=0.009). Among patients with stage 2 chronic kidney disease (CKD) (eGFR 60-89), the estimated eGFR decline during TDF was halted after switching to TAF (p=0.09). NA-experienced patients with abnormal ALT before TAF showed a significant decline after switching to TAF: -0.005 [-0.006 - -0.004] log10 ULN U/L/month, p<0.001). In CHB patients, TAF was safe, well-tolerated and effective in this real-world cohort. Switching to TAF led to improved kidney function, particularly in those with stage 2 CKD, which suggests that the indication for TAF in the guidelines could be extended to patients with an eGFR higher than 60 mL/min.


Subject(s)
Hepatitis B, Chronic , Alanine , Canada , Fumarates , Hepatitis B, Chronic/drug therapy , Humans , Kidney , Tenofovir/analogs & derivatives
11.
J Viral Hepat ; 28(3): 517-527, 2021 03.
Article in English | MEDLINE | ID: mdl-33306853

ABSTRACT

Due to shared modes of exposure, HIV-HBV co-infection is common worldwide. Increased knowledge of the demographic and clinical characteristics of the co-infected population will allow us to optimize our approach to management of both infections in clinical practice. The Canadian Hepatitis B Network Cohort was utilized to conduct a cross-sectional evaluation of the demographic, biochemical, fibrotic and treatment characteristics of HIV-HBV patients and a comparator HBV group. From a total of 5996 HBV-infected patients, 335 HIV-HBV patients were identified. HIV-HBV patients were characterized by older median age, higher male and lower Asian proportion, more advanced fibrosis and higher anti-HBV therapy use (91% vs. 30%) than the HBV-positive / HIV seronegative comparator group. A history of reported high-risk exposure activities (drug use, high-risk sexual contact) was more common in HIV-HBV patients. HIV-HBV patients with reported high-risk exposure activities had higher male proportion, more Caucasian ethnicity and higher prevalence of cirrhosis than HIV-HBV patients born in an endemic country. In the main cohort, age ≥60 years, male sex, elevated ALT, the presence of comorbidity and HCV seropositivity were independent predictors of significant fibrosis. HIV seropositivity was not an independent predictor of advanced fibrosis (adj OR 0.75 [95%CI: 0.34-1.67]). In conclusion, Canadian co-infected patients differed considerably from those with mono-infection. Furthermore, HIV-HBV-infected patients who report high-risk behaviours and those born in endemic countries represent two distinct subpopulations, which should be considered when engaging these patients in care.


Subject(s)
Coinfection , HIV Infections , Hepatitis B , Canada/epidemiology , Coinfection/epidemiology , Cross-Sectional Studies , HIV Infections/complications , HIV Infections/epidemiology , Hepatitis B/complications , Hepatitis B/epidemiology , Hepatitis B virus , Humans , Infant, Newborn , Male , Prevalence
12.
Clin Transplant ; 35(7): e14315, 2021 07.
Article in English | MEDLINE | ID: mdl-33848359

ABSTRACT

BACKGROUND: Primary graft dysfunction (PGD) is an important contributor to early mortality in lung transplant recipients and is associated with impaired lung function. The radiographic sequelae of PGD on computed tomography (CT) have not been characterized. METHODS: We studied adult double lung transplant recipients from 2010 to 2016 for whom protocol 3-month post-transplant CT scans were available. We assessed CTs for changes including pleural effusions, ground glass opacification, atelectasis, centrilobular nodularity, consolidation, interlobular septal thickening, air trapping and fibrosis, and their relationship to prior post-transplant PGD, future lung function, post-transplant baseline lung allograft dysfunction (BLAD), and chronic lung allograft dysfunction (CLAD). RESULTS: Of 237 patients studied, 50 (21%) developed grade 3 PGD (PGD3) at 48 or 72 h. PGD3 was associated with increased interlobular septal thickening (p = .0389) and atelectasis (p = .0001) at 3 months, but only atelectasis remained associated after correction for multiple testing. Atelectasis severity was associated with lower peak forced expiratory volume in 1 s (FEV1) and increased risk of BLAD (p = .0014) but not with future CLAD onset (p = .7789). CONCLUSIONS: Severe PGD was associated with atelectasis on 3-month post-transplant CT in our cohort. Atelectasis on routine CT may be an intermediary identifiable stage between PGD and future poor lung function.


Subject(s)
Lung Transplantation , Primary Graft Dysfunction , Pulmonary Atelectasis , Adult , Humans , Lung , Lung Transplantation/adverse effects , Primary Graft Dysfunction/diagnosis , Primary Graft Dysfunction/etiology , Pulmonary Atelectasis/diagnostic imaging , Pulmonary Atelectasis/etiology , Retrospective Studies , Survivors
13.
Semin Respir Crit Care Med ; 42(3): 460-470, 2021 06.
Article in English | MEDLINE | ID: mdl-34030207

ABSTRACT

Mycobacterium is a large, clinically relevant bacterial genus made up of the agents of tuberculosis and leprosy and hundreds of species of saprophytic nontuberculous mycobacteria (NTM). Pathogenicity, clinical presentation, epidemiology, and antimicrobial susceptibilities are exceptionally diverse between species. Patients with end-stage lung disease and recipients of lung transplants are at a higher risk of developing NTM colonization and disease and of severe manifestations and outcomes of tuberculosis. Data from the past three decades have increased our knowledge of these infections in lung transplant recipients. Still, there are knowledge gaps to be addressed to further our understanding of risk factors and optimal treatments for mycobacterial infections in this population.


Subject(s)
Lung Transplantation , Mycobacterium Infections, Nontuberculous , Tuberculosis , Humans , Lung Transplantation/adverse effects , Mycobacterium , Mycobacterium Infections, Nontuberculous/drug therapy , Mycobacterium Infections, Nontuberculous/epidemiology , Nontuberculous Mycobacteria
14.
Clin Infect Dis ; 70(2): 181-190, 2020 01 02.
Article in English | MEDLINE | ID: mdl-30843046

ABSTRACT

BACKGROUND: The incidence of herpes zoster is up to 9 times higher in immunosuppressed solid organ transplant recipients than in the general population. We investigated the immunogenicity and safety of an adjuvanted recombinant zoster vaccine (RZV) in renal transplant (RT) recipients ≥18 years of age receiving daily immunosuppressive therapy. METHODS: In this phase 3, randomized (1:1), observer-blind, multicenter trial, RT recipients were enrolled and received 2 doses of RZV or placebo 1-2 months (M) apart 4-18M posttransplant. Anti-glycoprotein E (gE) antibody concentrations, gE-specific CD4 T-cell frequencies, and vaccine response rates were assessed at 1M post-dose 1, and 1M and 12M post-dose 2. Solicited and unsolicited adverse events (AEs) were recorded for 7 and 30 days after each dose, respectively. Solicited general symptoms and unsolicited AEs were also collected 7 days before first vaccination. Serious AEs (including biopsy-proven allograft rejections) and potential immune-mediated diseases (pIMDs) were recorded up to 12M post-dose 2. RESULTS: Two hundred sixty-four participants (RZV: 132; placebo: 132) were enrolled between March 2014 and April 2017. gE-specific humoral and cell-mediated immune responses were higher in RZV than placebo recipients across postvaccination time points and persisted above prevaccination baseline 12M post-dose 2. Local AEs were reported more frequently by RZV than placebo recipients. Overall occurrences of renal function changes, rejections, unsolicited AEs, serious AEs, and pIMDs were similar between groups. CONCLUSIONS: RZV was immunogenic in chronically immunosuppressed RT recipients. Immunogenicity persisted through 12M postvaccination. No safety concerns arose. CLINICAL TRIALS REGISTRATION: NCT02058589.


Subject(s)
Herpes Zoster Vaccine , Herpes Zoster , Immunogenicity, Vaccine , Kidney Transplantation , Adult , Antibodies, Viral , Herpes Zoster/prevention & control , Herpesvirus 3, Human , Humans , Vaccines, Synthetic/adverse effects
15.
Liver Int ; 40(8): 1841-1852, 2020 08.
Article in English | MEDLINE | ID: mdl-32449966

ABSTRACT

BACKGROUND AND AIMS: Achieving sustained virological response (SVR; cure) in hepatitis C patients using a simple regimen is key to making elimination by 2030 possible. In the largest real-world analysis to date, the effectiveness of pangenotypic, panfibrotic, single-tablet, sofosbuvir/velpatasvir (SOF/VEL) once-daily for 12 weeks was assessed in 12 clinical real-world cohorts from various geographical areas, settings and treatment practices. Factors affecting risk of not achieving SVR were assessed. METHODS: Adults treated with SOF/VEL 400/100 mg, without ribavirin, were included. All HCV patients reaching Week 12 or 24 post-treatment were assessed for SVR12/24. Factors associated with not achieving SVR12/24 for virological reasons were evaluated using logistic regression analysis. RESULTS: Overall, 5552 patients were included: 13.3% treatment-experienced; 20.7% compensated cirrhotic; 30.2% genotype 1; 29.5% genotype 2; 32.9% genotype 3; 4.7% genotype 4; 3.7% HIV coinfection; 13.4% current/former intravenous drug use. Of the 5196 patients evaluated for effectiveness, 98.9% achieved SVR12/24. High SVR12/24 rates occurred in all genotypes including genotype 3 (98.3%; 1649/1677) and in those with compensated cirrhosis (97.9; 1055/1078). Only 55 patients did not achieve SVR12/24 due to a virological reason; the only factor statistically significantly associated with an increased risk of not achieving SVR12/24 was compensated cirrhosis (P = .002). Overall, 6% (332/5552) of patients did not achieve SVR12/24 for non-virological reasons (67% lost to follow-up; 26.5% early treatment discontinuation). CONCLUSIONS: In this large cohort, representative of clinical practice, a simple 12-week regimen of SOF/VEL without ribavirin resulted in high SVR12/24 rates in diverse patient populations, even among those with compensated cirrhosis.


Subject(s)
Hepatitis C, Chronic , Hepatitis C , Adult , Antiviral Agents/therapeutic use , Carbamates , Drug Therapy, Combination , Genotype , Hepacivirus/genetics , Hepatitis C/drug therapy , Hepatitis C, Chronic/drug therapy , Heterocyclic Compounds, 4 or More Rings , Humans , Ribavirin/therapeutic use , Sofosbuvir/therapeutic use , Sustained Virologic Response , Treatment Outcome
16.
Transpl Infect Dis ; 22(2): e13229, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31794120

ABSTRACT

BACKGROUND: Non-tuberculous mycobacteria (NTM) are environmental organisms that colonize or infect lung transplant recipients. Because of differences in populations studied and geographical diversity of species, risk factors for infection and its impact on patient outcomes post transplant are conflicting in the literature. METHODS: We reviewed the charts of 375 lung transplant recipients at the University of Alberta Hospital (Edmonton, Canada) between 2005 and 2014 to assess NTM epidemiology and risk factors. NTM positivity was determined from a laboratory database. The impact of NTM on patient and graft survival was tested by multivariate Cox regression analysis. RESULTS: Non-tuberculous mycobacteria were cultured from 26 patients before and 17 patients after transplant. The most commonly isolated species were Mycobacterium avium complex (55%) and Mycobacterium abscessus (20%). Five-year mortality was significantly higher in those infected with NTM after transplant (P = .016), but there was no difference in chronic lung allograft dysfunction (CLAD) at 5 years (P = .999). Cystic fibrosis and lower body mass index were associated with pre-transplant but not post-transplant NTM. CONCLUSIONS: Isolation of NTM occurred in 7% of patients before and 4.5% of patients after transplant. In this cohort, NTM isolation was associated with increased risk of death but not CLAD onset at 5 years.


Subject(s)
Lung/pathology , Mycobacterium Infections, Nontuberculous/epidemiology , Mycobacterium Infections, Nontuberculous/microbiology , Nontuberculous Mycobacteria/isolation & purification , Primary Graft Dysfunction/microbiology , Transplant Recipients/statistics & numerical data , Adolescent , Adult , Aged , Allografts , Canada/epidemiology , Chronic Disease/epidemiology , Female , Humans , Lung/microbiology , Lung Transplantation/statistics & numerical data , Male , Middle Aged , Nontuberculous Mycobacteria/classification , Prevalence , Regression Analysis , Retrospective Studies , Risk Factors , Young Adult
17.
Clin Transplant ; 33(9): e13514, 2019 09.
Article in English | MEDLINE | ID: mdl-30817047

ABSTRACT

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of viral hepatitis in the pre- and post-transplant period. The current guidelines reflect the declining need for hepatitis B immunoglobulin following liver transplant, now replaced with nucleos(t)ide analogues that effectively suppress viral replication for the long term with minimal risk for drug resistance. It describes the limitations of pegylated interferon alpha in the treatment for chronic hepatitis D. The guidelines feature the paradigm shift in the treatment arena of chronic hepatitis C, now consisting of highly effective direct-acting antiviral (DAA) medications that effect a cure almost universally. Its safety profile and easy tolerance have permitted its use in patients with decompensated cirrhosis and/or end-stage renal disease. The high potency of the DAA's has fueled the rapidly expanding utilization of hepatitis C-exposed grafts in non-hepatitis C-infected liver, heart, or kidney recipients within structured protocols, followed by viral eradication with DAA therapy in the peri- or post-transplant period. Chronic hepatitis E has become more recognized in the solid-organ transplant recipients, and the therapeutic approach has been streamlined to start with reduction of immunosuppression, and if indicated afterward, ribavirin monotherapy.


Subject(s)
Antiviral Agents/therapeutic use , Hepacivirus/drug effects , Hepatitis C, Chronic/drug therapy , Organ Transplantation/methods , Practice Guidelines as Topic/standards , Tissue Donors/supply & distribution , Viral Load/drug effects , Hepatitis C, Chronic/diagnosis , Hepatitis C, Chronic/virology , Humans , Societies, Medical , Transplant Recipients
20.
Can J Surg ; 59(2): 83-6, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26820317

ABSTRACT

SUMMARY: The potential for transmission of hematogenously transmitted pathogens during exposure-prone procedures is a clinically important concern to both patients and surgeons. There is inconsistency among regulatory bodies in Canada regarding the management of infection risk among surgeons, particularly with regard to screening and the postexposure management of infected surgeons. The Canadian Association of General Surgeons commissioned a task force to review the evidence regarding the management of blood-borne pathogens and transmission risk during surgical procedures. The results of this review indicate a need for several jurisdictions to update their guidelines to reflect current evidence-based practices.


Subject(s)
Blood-Borne Pathogens , Communicable Diseases/transmission , General Surgery , Health Policy , Infection Control/standards , Societies, Medical , Canada , Humans
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