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Burden and Timeline of Infectious Diseases in the First Year After Solid Organ Transplantation in the Swiss Transplant Cohort Study

van Delden, Christian ; Stampf, Susanne ; Hirsch, Hans H ; [et al.]

Oxford University Press (OUP) ; 2020

In: Clinical Infectious Diseases Vol. 71, No. 7 ( 2020-10-23), p. e159-e169

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In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 71, No. 7 ( 2020-10-23), p. e159-e169

Abstract: The burden and timeline of posttransplant infections are not comprehensively documented in the current era of immunosuppression and prophylaxis. Methods In this prospective study nested within the Swiss Transplant Cohort Study (STCS), all clinically relevant infections were identified by transplant–infectious diseases physicians in persons receiving solid organ transplant (SOT) between May 2008 and December 2014 with ≥12 months of follow-up. Results Among 3541 SOT recipients, 2761 (1612 kidney, 577 liver, 286 lung, 213 heart, and 73 kidney-pancreas) had ≥12 months of follow-up; 1520 patients (55%) suffered 3520 infections during the first year posttransplantation. Burden and timelines of clinically relevant infections differed between transplantations. Bacteria were responsible for 2202 infections (63%) prevailing throughout the year, with a predominance of Enterobacteriaceae (54%) as urinary pathogens in heart, lung, and kidney transplant recipients, and as digestive tract pathogens in liver transplant recipients. Enterococcus spp (20%) occurred as urinary tract pathogens in kidney transplant recipients and as digestive tract pathogens in liver transplant recipients, and Pseudomonas aeruginosa (9%) in lung transplant recipients. Among 1039 viral infections, herpesviruses predominated (51%) in kidney, liver, and heart transplant recipients. Among 263 fungal infections, Candida spp (60%) prevailed as digestive tract pathogens in liver transplant recipients. Opportunistic pathogens, including Aspergillus fumigatus (1.4%) and cytomegalovirus (6%), were rare, scattering over 12 months across all SOT recipients. Conclusions In the current era of immunosuppression and prophylaxis, SOT recipients experience a high burden of infections throughout the first year posttransplantation, with rare opportunistic pathogens and a predominance of bacteria.

Type of Medium: Online Resource

ISSN: 1058-4838 , 1537-6591

URL: Article

DOI: 10.1093/cid/ciz1113

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Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2020

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Immune monitoring-guided vs fixed duration of antiviral prophylaxis against cytomegalovirus in solid-organ transplant recipients. A Multicenter, Randomized Clinical Trial

Manuel, Oriol ; Laager, Mirjam ; Hirzel, Cédric ; [et al.]

Oxford University Press (OUP) ; 2023

In: Clinical Infectious Diseases ( 2023-09-22)

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In: Clinical Infectious Diseases, Oxford University Press (OUP), ( 2023-09-22)

Abstract: The use of assays detecting cytomegalovirus (CMV)-specific T-cell-mediated immunity may individualize the duration of antiviral prophylaxis in transplant recipients. Methods In this open-label randomized trial, adult kidney and liver transplant recipients from six centers in Switzerland were enrolled if they were CMV-seronegative with seropositive donors or CMV-seropositive receiving anti-thymocyte globulins. Patients were randomized to a duration of antiviral prophylaxis based on immune-monitoring (intervention) or a fixed duration (control). Patients in the control group were planned to receive 180 days (CMV-seronegative) or 90 days (CMV-seropositive) of valganciclovir. Patients were assessed monthly with a CMV-specific interferon gamma release assay (T-Track® CMV); prophylaxis in the intervention group was stopped if the assay was positive. The primary outcomes were the proportion of patients with clinically significant CMV infection and reduction in days of prophylaxis. Between-group differences were adjusted for CMV serostatus. Results Overall, 193 patients were randomized (92 in the immune-monitoring and 101 in the control group) of which 185 had evaluation of the primary endpoint (87 and 98 patients, respectively). Clinically significant CMV infection occurred in 26/87 (adjusted percentage, 30.9%) in the immune-monitoring group and in 32/98 (adjusted percentage, 31.1%) in the control group (adjusted risk difference -0.1, 95%CI -13.0%, 12.7%; p = 0.064). The duration of antiviral prophylaxis was shorter in the immune-monitoring group (adjusted difference -26.0 days, 95%-CI -41.1 to -10.8 days, p & lt; 0.001). Conclusions Immune monitoring resulted in a significant reduction of antiviral prophylaxis, but we were unable to establish noninferiority of this approach on the co-primary endpoint of CMV infection.

Type of Medium: Online Resource

ISSN: 1058-4838 , 1537-6591

URL: Article

DOI: 10.1093/cid/ciad575

RVK:

XA 10000

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2023

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Antibody Response in Immunocompromised Patients After the Administration of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccine BNT162b2 or mRNA-1273: A Randomized Controlled Trial

Speich, Benjamin ; Chammartin, Frédérique ; Abela, Irene A ; [et al.]

Oxford University Press (OUP) ; 2022

In: Clinical Infectious Diseases Vol. 75, No. 1 ( 2022-08-24), p. e585-e593

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In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 75, No. 1 ( 2022-08-24), p. e585-e593

Abstract: BNT162b2 by Pfizer-BioNTech and mRNA-1273 by Moderna are the most commonly used vaccines to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Head-to-head comparison of the efficacy of these vaccines in immunocompromised patients is lacking. Methods Parallel, 2-arm (allocation 1:1), open-label, noninferiority randomized clinical trial nested into the Swiss HIV Cohort Study and the Swiss Transplant Cohort Study. People living with human immunodeficiency virus (PLWH) or solid organ transplant recipients (SOTR; ie, lung and kidney) from these cohorts were randomized to mRNA-1273 or BNT162b2. The primary endpoint was antibody response to SARS-CoV-2 spike (S1) protein receptor binding domain (Elecsys Anti-SARS-CoV-2 immunoassay, Roche; cutoff ≥0.8 units/mL) 12 weeks after first vaccination (ie, 8 weeks after second vaccination). In addition, antibody response was measured with the Antibody Coronavirus Assay 2 (ABCORA 2). Results A total of 430 patients were randomized and 412 were included in the intention-to-treat analysis (341 PLWH and 71 SOTR). The percentage of patients showing an immune response was 92.1% (95% confidence interval [CI]: 88.4–95.8; 186/202) for mRNA-1273 and 94.3% (95% CI: 91.2–97.4; 198/210) for BNT162b2 (difference: -2.2%; 95% CI: -7.1 to 2.7), fulfilling noninferiority of mRNA-1273. With the ABCORA 2 test, 89.1% had an immune response to mRNA-1273 (95% CI: 84.8–93.4; 180/202) and 89.5% to BNT162b2 (95% CI: 85.4–93.7; 188/210). Based on the Elecsys test, all PLWH had an antibody response (100.0%; 341/341), whereas for SOTR, only 60.6% (95% CI: 49.2–71.9; 43/71) had titers above the cutoff level. Conclusions In immunocompromised patients, the antibody response of mRNA-1273 was noninferior to BNT162b2. PLWH had in general an antibody response, whereas a high proportion of SOTR had no antibody response.

Type of Medium: Online Resource

ISSN: 1058-4838 , 1537-6591

URL: Article

DOI: 10.1093/cid/ciac169

RVK:

XA 10000

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2022

detail.hit.zdb_id: 2002229-3

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Immunogenicity of High-Dose Versus MF59-Adjuvanted Versus Standard Influenza Vaccine in Solid Organ Transplant Recipients: The Swiss/Spanish Trial in Solid Organ Transplantation on Prevention of Influenza (STOP-FLU Trial)

Mombelli, Matteo ; Neofytos, Dionysios ; Huynh-Do, Uyen ; [et al.]

Oxford University Press (OUP) ; 2023

In: Clinical Infectious Diseases ( 2023-08-16)

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In: Clinical Infectious Diseases, Oxford University Press (OUP), ( 2023-08-16)

Abstract: The immunogenicity of the standard influenza vaccine is reduced in solid-organ transplant (SOT) recipients, so new vaccination strategies are needed in this population. Methods Adult SOT recipients from 9 transplant clinics in Switzerland and Spain were enrolled if they were & gt;3 months after transplantation. Patients were randomized (1:1:1) to a MF59-adjuvanted or a high-dose vaccine (intervention), or a standard vaccine (control), with stratification by organ and time from transplant. The primary outcome was vaccine response rate, defined as a ≥4-fold increase of hemagglutination-inhibition titers to at least 1 vaccine strain at 28 days postvaccination. Secondary outcomes included polymerase chain reaction–confirmed influenza and vaccine reactogenicity. Results A total of 619 patients were randomized, 616 received the assigned vaccines, and 598 had serum available for analysis of the primary endpoint (standard, n = 198; MF59-adjuvanted, n = 205; high-dose, n = 195 patients). Vaccine response rates were 42% (84/198) in the standard vaccine group, 60% (122/205) in the MF59-adjuvanted vaccine group, and 66% (129/195) in the high-dose vaccine group (difference in intervention vaccines vs standard vaccine, 0.20; 97.5% confidence interval [CI], .12–1); P & lt; .001; difference in high-dose vs standard vaccine, 0.24 [95% CI, .16–1]; P & lt; .001; difference in MF59-adjuvanted vs standard vaccine, 0.17 [97.5% CI, .08–1]; P & lt; .001). Influenza occurred in 6% of the standard, 5% in the MF59-adjuvanted, and 7% in the high-dose vaccine groups. Vaccine-related adverse events occurred more frequently in the intervention vaccine groups, but most of the events were mild. Conclusions In SOT recipients, use of an MF59-adjuvanted or a high-dose influenza vaccine was safe and resulted in a higher vaccine response rate. Clinical Trials Registration. Clinicaltrials.gov NCT03699839.

Type of Medium: Online Resource

ISSN: 1058-4838 , 1537-6591

URL: Article

DOI: 10.1093/cid/ciad477

RVK:

XA 10000

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2023

detail.hit.zdb_id: 2002229-3

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