Donor Cytomegalovirus Transmission Patterns in Solid Organ Transplant Recipients With Primary Infection

2020 ◽  
Author(s):  
Maria E Hasing ◽  
Xiaoli L Pang ◽  
Curtis Mabilangan ◽  
Jutta K Preiksaitis
Keyword(s):  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Donor Group ◽  
Or Groups ◽  
Group A ◽  
Group B ◽  
Multiple Strains ◽  
Group Sharing ◽  
Cmv Dnaemia

Abstract Background The epidemiology of single versus multiple cytomegalovirus (CMV) strain transmission from donor (D+) to seronegative solid organ transplant (SOT) recipients (R−) is uncertain, as is whether “relapsing” recipient infection represents changing strain predominance when multiple strains are transmitted. Here we characterized CMV strain transmission patterns in D+/R− SOT recipients. Methods We studied pairs or groups of D+/R− SOT recipients who received organs from a common donor (group A) and recipients who experienced ≥2 waves of CMV DNAemia (group B). CMV in plasma was characterized by genotype-specific real-time PCR for genes gB and gH. Results Single concordant genotypes were identified in 12 of 18 recipient pairs/group sharing a common donor (group A); at least 6 of 18 (33%) donors transmitted > 1 strain. A single CMV strain was detected in 14 of 15 recipients in group B; only 1 recipient had coinfection. A shift in CMV strain predominance occurred after the first posttransplant year in at least 4 recipients with coinfection. Conclusions Using a common donor approach, we confirmed that multiple CMV strain transmission from donors to R− SOT recipients is not uncommon. D+/R− SOT recipients with CMV coinfection can undergo changes in strain predominance in late waves of CMV DNAemia.

scholarly journals Contribution of Population Pharmacokinetics to Dose Optimization of Ganciclovir-Valganciclovir in Solid-Organ Transplant Patients

2016 ◽  
Vol 60 (4) ◽  
pp. 1992-2002 ◽  
Author(s):  
A. Padullés ◽  
H. Colom ◽  
O. Bestard ◽  
E. Melilli ◽  
N. Sabé ◽  
...  
Keyword(s):  
Prediction Model ◽  
Population Pharmacokinetics ◽  
Late Onset ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Bayesian Prediction ◽  
Solid Organ ◽  
Infection Group ◽  
Group A ◽  
Group B

ABSTRACTTreatment of solid-organ transplant (SOT) patients with ganciclovir (GCV)-valganciclovir (VGCV) according to the manufacturer's recommendations may result in over- or underexposure. Bayesian prediction based on a population pharmacokinetics model may optimize GCV-VGCV dosing, achieving the area under the curve (AUC) therapeutic target. We conducted a two-arm, randomized, open-label, 40% superiority trial in adult SOT patients receiving GCV-VGCV as prophylaxis or treatment of cytomegalovirus infection. Group A was treated according to the manufacturer's recommendations. For group B, the dosing was adjusted based on target exposures using a Bayesian prediction model (NONMEM). Fifty-three patients were recruited (27 in group A and 26 in group B). About 88.6% of patients in group B and 22.2% in group A reached target AUC, achieving the 40% superiority margin (P< 0.001; 95% confidence interval [CI] difference, 47 to 86%). The time to reach target AUC was significantly longer in group A than in group B (55.9 ± 8.2 versus 15.8 ± 2.3 days,P< 0.001). A shorter time to viral clearance was observed in group B than in group A (12.5 versus 17.6 days;P= 0.125). The incidences of relapse (group A, 66.67%, and group B, 9.01%) and late-onset infection (group A, 36.7%, and group B, 7.7%) were higher in group A. Neutropenia and anemia were related to GCV overexposure. GCV-VCGV dose adjustment based on a population pharmacokinetics Bayesian prediction model optimizes GCV-VGCV exposure. (This study has been registered at ClinicalTrials.gov under registration no. NCT01446445.)

scholarly journals 686. Elevations in TNFα and IL-18 are Associated with Increased Risk of Probable Cytomegalovirus Tissue Invasive Disease in Solid Organ Transplant Recipients

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S396-S397
Author(s):  
Andrew H Karaba ◽  
Alexis Figueroa ◽  
Stuart C Ray ◽  
Robin K Avery ◽  
Robin K Avery ◽  
...  
Keyword(s):  
Viral Load ◽  
Research Study ◽  
Organ Transplant ◽  
Scientific Research ◽  
Principal Component ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Study Investigator ◽  
Cmv Disease ◽  
Cmv Dnaemia

Abstract Background Human cytomegalovirus (CMV) continues to cause significant morbidity and mortality in solid organ transplant (SOT) recipients despite prophylaxis. Tissue invasive CMV disease (TI-CMV) can lead to end-organ damage and graft loss. Diagnosing TI-CMV can be challenging as CMV viral load in the blood does not always correlate with episodes of TI-CMV and therefore definitive diagnosis often requires an invasive procedure such as bronchoscopy or colonoscopy. The purpose of this study was to determine if proinflammatory cytokines, including IL-18, are elevated in SOT recipients with probably TI-CMV as a way to identify patients at risk for this severe form of CMV disease. Methods The electronic medical record was searched for adult SOT recipients who were tested for CMV via blood qPCR during an 11-month period.Twenty-nine SOT recipients were identified that had episodes of CMV DNAemia without other concomitant infections during this time period. Patients were divided into those that had probable TI-CMV and those with CMV DNAemia alone, by chart review. Inflammatory cytokines (IFNγ, TNFα, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-18, and IL-1RA) were measured in residual plasma from these patients using a commercially available multiplex assay for at least two time points during the study period. Wilcoxon-Rank-Sum, logistic regression, and principal component analysis was performed comparing patients with and without probable TI-CMV. Results Patients with probable TI-CMV had significantly higher IL-18, TNFα, and IL-1β than patients with CMV DNAemia alone (p &lt; 0.001, &lt; 0.001, and &lt; 0.05 respectively). When adjusting for transplant type and CMV recipient serostatus, elevations in TNFα (OR 1.43, 95% CI 1.07-1.92) and IL-18 (OR 2.00, 95% CI 1.06-3.75) were associated with increased odds of having probable TI-CMV. In principal component analysis the combination of CMV viral load, IL-18, TNFa, and IL-1β accounted for 80% of the variance in the data. Conclusion TNFα and IL-18 in combination with CMV viral load may be useful in predicting likelihood of TI-CMV. This is important in situations where tissue biopsies are not feasible, and adds to our diagnostic capability for TI-CMV in SOT recipients. Disclosures Stuart C. Ray, MD, miDiagnostics, Inc. (Board Member, Research Grant or Support) Robin K. Avery, MD, Aicuris (Scientific Research Study Investigator)Astellas (Scientific Research Study Investigator)Chimerix (Scientific Research Study Investigator)Merck (Grant/Research Support, Scientific Research Study Investigator)Oxford Immunotec (Scientific Research Study Investigator)Qiagen (Scientific Research Study Investigator)Takeda/Shire (Scientific Research Study Investigator)

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