An assessment of donor-to-recipient transmission patterns of human cytomegalovirus by analysis of viral genomic variants.

BACKGROUND: We studied human cytomegalovirus (CMV) donor-to-recipient transmission patterns in organ transplantation by analyzing genomic variants on the basis of CMV glycoprotein B (gB) genotyping. METHODS: Organ transplant recipients were included in the study if they had CMV viremia, if they had received an organ from a CMV-seropositive donor, and if there was at least 1 other recipient of an organ from the same donor who developed CMV viremia. Genotypes (gB1-4) were determined by real-time polymerase chain reaction. RESULTS: Forty-seven recipients of organs from 21 donors developed CMV viremia. Twenty-three recipients had a pretransplant donor/recipient (D/R) CMV serostatus of D(+)/R(+), and 24 had a serostatus of D(+)/R(-). The prevalences of genotypes in recipients were as follows: for gB1, 51% (n = 24); for gB2, 19% (n = 9); for gB3, 9% (n = 4); for gB4, 0% (n = 0); and for mixed infection, 21% (n = 10). Recipients of an organ from a common donor had infection with CMV of the same gB genotype in 12 (57%) of 21 instances. Concordance between genotypes was higher among seronegative (i.e., D(+)/R(-)) recipients than among seropositive (D(+)/R(+)) recipients, although discordances resulting from the transmission of multiple strains were seen. In seropositive recipients, transmission of multiple strains from the donor could not be differentiated from reactivation of a recipient's own strains. CONCLUSION: Our analysis of strain concordance among recipients of organs from common donors showed that transmission of CMV has complex dynamic patterns. In seropositive recipients, transmission or reactivation of multiple CMV strains is possible

An assessment of donor-to-recipient transmission patterns of human cytomegalovirus by analysis of viral genomic variants.

BACKGROUND: We studied human cytomegalovirus (CMV) donor-to-recipient transmission patterns in organ transplantation by analyzing genomic variants on the basis of CMV glycoprotein B (gB) genotyping. METHODS: Organ transplant recipients were included in the study if they had CMV viremia, if they had received an organ from a CMV-seropositive donor, and if there was at least 1 other recipient of an organ from the same donor who developed CMV viremia. Genotypes (gB1-4) were determined by real-time polymerase chain reaction. RESULTS: Forty-seven recipients of organs from 21 donors developed CMV viremia. Twenty-three recipients had a pretransplant donor/recipient (D/R) CMV serostatus of D(+)/R(+), and 24 had a serostatus of D(+)/R(-). The prevalences of genotypes in recipients were as follows: for gB1, 51% (n = 24); for gB2, 19% (n = 9); for gB3, 9% (n = 4); for gB4, 0% (n = 0); and for mixed infection, 21% (n = 10). Recipients of an organ from a common donor had infection with CMV of the same gB genotype in 12 (57%) of 21 instances. Concordance between genotypes was higher among seronegative (i.e., D(+)/R(-)) recipients than among seropositive (D(+)/R(+)) recipients, although discordances resulting from the transmission of multiple strains were seen. In seropositive recipients, transmission of multiple strains from the donor could not be differentiated from reactivation of a recipient's own strains. CONCLUSION: Our analysis of strain concordance among recipients of organs from common donors showed that transmission of CMV has complex dynamic patterns. In seropositive recipients, transmission or reactivation of multiple CMV strains is possible

The Clinical Utility of Whole Blood Versus Plasma Cytomegalovirus Viral Load Assays for Monitoring Therapeutic Response

Background. In patients with cytomegalovirus (CMV) disease, regular monitoring of viral loads and treatment until negative are recommended. However, with more sensitive polymerase chain reaction (PCR) assays and cellular peripheral sample types, detection of low-level viremia is achievable. We compared a whole blood real-time PCR with a plasma PCR assay for monitoring therapeutic response. Methods. Patients enrolled in a trial to treat CMV disease for 21 days had regular viral load monitoring. The results of a plasma-based PCR assay were compared with a real-time PCR assay of whole blood and assessed for their ability to predict recurrence. Results. In 219 evaluable patients, viral loads in plasma versus whole blood demonstrated good correlation but significant difference in absolute value and clearance kinetics. Virus was still detectable by day 21 in 154 of 219 (70.3%) patients with the whole blood versus 105 of 219 (52.1%; P<0.001) patients with the plasma assay. The positive predictive value of persistent plasma viremia at day 21 for virologic recurrence was 41.9% vs. 36.3% for the whole blood assay. In the subset of patients with a negative plasma but positive whole blood at day 21 (n=49), the incidence of virologic recurrence was similar to that of all patients with a negative plasma assay (23.1% vs. 23.6%). Conclusions. When treating CMV disease, enhanced detection of residual viremia using a whole blood real-time PCR does not seem to offer significant clinical advantages nor allows for better prediction of recurrence of CMV viremia or disease. The treat-to-negative paradigm may not hold true when such assays are used

Cytomegalovirus and other herpesviruses infections in heart and bone marrow transplant recipients Infecções causadas por citomegalovírus e outros vírus do grupo herpes em transplantados cardíacos e de medula óssea

From January 1988 to January 1989 all the heart transplant and bone marrow recipients at the Instituto do Coração of the Hospital das Clínicas of the University of São Paulo Medical School were studied for the incidence and morbidity associated with herpesviruses infections after transplantation. Five bone marrow and 5 heart transplant recipients were followed for a mean of 4.2 months post-transplantation. All the patients were seropositive for cytomegalovirus (CMV) before admission and 80% experienced one or more recurrences during the observation period. Of the 12 episodes of CMV infection, that were identified in this study, 83% were accompanied by clinical or laboratory abnormalities. However, there was only one case of severe disease. The overall incidence of infection for herpes simplex (HSV) was 50%. Although most of HSV reactivations were oral or genital, one case of HSV hepatitis occurred. One of the 6 episodes of HSV infections that were treated with acyclovir showed an unsatisfactory response and was successfully managed with ganciclovir. All the individuals had anti-varicella zoster virus antibodies, but none of them developed infection. The study emphasizes the importance of active diagnostic surveillance of herpesvirus infections in transplant patients. Both CMV and HSV reactivations showed high incidence and important morbidity and thus, deserve prophylactic therapy.<br>De janeiro de 1988 a janeiro de 1989 todos os pacientes submetidos a transplante de coração ou de medula óssea no Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo foram estudados quanto à incidência e morbidade das infecções pós-transplante causadas por vírus do grupo herpes. Cinco recipientes de medula óssea e 5 transplantados cardíacos foram observados por um período médio de 4.2 meses após o transplante. Todos os pacientes tinham sorologia positiva para citomegalovírus (CMV) antes do transplante e 80% desenvolveram uma ou mais recorrências durante o período de observação. Dos 12 episódios de infecão por CMV detectados neste estudo, 83% foram acompanhados por alterações clínicas ou laboratoriais. Apenas um caso apresentou doença grave. A incidência de infecções causadas por vírus Herpes simplex (HSV), foi de 50%. Apesar da maioria das reativações do HSV fossem representadas por lesões orais ou genitais, houve também um caso de hepatite por HSV. Um dos 6 episódios de infecção, por HSV que foram tratados com aciclovir não respondeu ao tratamento. Posteriormente, o paciente se beneficiou com o uso de ganciclovir. Todos os indivíduos apresentavam antes do transplante anticorpos anti-vírus da varicela zoster. Porém, não houve nenhum caso de reativação. Este estudo realça a importância do controle diagnóstico ativo das infecções por herpes-vírus em pacientes transplantados. Tanto as infecções causadas por CMV como por HSV mostraram alta incidência e grande morbidade indicando a necessidade de quimioprofilaxia