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1.
Patients were studied prospectively after marrow transplant to correlate cytomegalovirus (CMV) infection with the in vitro lymphocyte transformation response to CMV antigen. Ninety-two (58%) of 158 patients developed CMV infection. The lymphocyte response to CMV antigen of patients who were seropositive before transplant was significantly suppressed immediately after transplant. Isolation of CMV was associated with further suppression of responses; seroconversion to CMV was associated with a significant increase. The lymphocyte response of 73 long-term survivors was similar to that of normal persons. The presence of antibody to CMV in the donor before transplant had little effect on the lymphocyte response of patients after transplant even though the patients' lymphocyte s were of donor origin. As in previously reported studies of immunity to other herpesviruses after marrow transplant, it was concluded that recovery of the response to CMV antigen is related primarily to active virus infection and not to patient or donor pretransplant immunity.  相似文献   

2.
Immune responses and infections with herpes viruses were studied prospectively in 36 cardiac transplant reclpients. Specific lymphocyte transformation and interferon production in response to viral antigens, viral culture results, antibody levels, responses to phytohemagglutinin, and T-cell numbers were determined. Responses to phytohemagglutinin and T-cell numbers were depressed for six to 12 weeks. Cytomegalovirus infection occurred in 100 percent of seropositive patients and in 62 percent of seronegative patients. Primary infection was more frequently symptomatic. Heart implantation from a seropositive patient was significantly correlated with subsequent infection in seronegative patients. Depression of transformation in response to cytomegalovirus correlated with prolonged shedding. Herpes simplex infection occurred in 95 percent of seropositive patients but decreased after 12 weeks. Asymptomatic shedding was rare, and primary infection did not occur. Return of transformation in response to herpes simplex was associated with decreased Infection. Herpes zoster occurred in 22 percent during the first year, and transformation responses to varicella-zoster returned thereafter. Depression of interferon production in response to viruses did not correlate with infection as well as did lymphocyte transformation.  相似文献   

3.
Thirty-two CMV seronegative heart transplant patients received prophylactic anti-CMV immunoglobulin during the first three posttransplant months. One of the 16 recipients of a heart from a seronegative donor acquired CMV infection and developed CMV disease. In eight of the 16 recipients of a heart from a seropositive donor, CMV infection was observed. Viremia was diagnosed in seven of them, but only two of these patients developed CMV disease. The incidence of CMV infection and of CMV disease in the globulin-treated CMV seronegative recipients of a heart from a seropositive donor was comparable to the incidence of CMV infection and of CMV disease in 31 nonglobulin-treated CMV seropositive recipients. This was significantly lower (percentage difference 69 percent, 95 percent CI 42-97 percent, p less than 0.001) than expected on the basis of the data from the literature and indicates that passive immunization with anti-CMV immunoglobulins induces the same protection against CMV disease as natural acquired anti-CMV resistance. This protective effect was temporary, as one patient developed symptomatic CMV infection four months after transplantation at a time when the anti-CMV immunoglobulin levels had decreased to pretransplantation values.  相似文献   

4.
Risk factors for cytomegalovirus infection after human marrow transplantation   总被引:49,自引:0,他引:49  
The records of 545 patients were reviewed for risk factors associated with cytomegalovirus (CMV) infection after marrow transplant. CMV infection occurred among 36% of seronegative patients and 69% of seropositive patients. Among seronegative patients, significant risk factors for CMV infection included positive serology of the marrow donor (relative rate, 2.3) and the use of granulocyte transfusions from seropositive donors (relative rate, 2.5). Among both seronegative and seropositive patients, the occurrence of acute graft-versus-host disease (GVHD) significantly increased the risk of CMV infection (average relative rate, 1.8) and of subsequent CMV pneumonia (average relative rate, 2.6). CMV excretion and viremia were each associated with subsequent pneumonia, but the positive predictive values were low. One-third of long-term survivors excreted CMV at greater than 250 days after transplantation. The only risk factor for late excretion was CMV infection that occurred in the first 150 days after transplantation. In contrast to the effect of acute GVHD on CMV infection, CMV infection did not increase the risk of either acute or chronic GVHD.  相似文献   

5.
The morbidity of cytomegalovirus (CMV) infection and toxoplasmosis was evaluated in 75 heart transplant recipients. Among the 73 patients who survived more than one week after transplantation, 16 (22%) acquired primary CMV infection and 30 (41%) had evidence of secondary infection. All CMV seronegative recipients receiving hearts from seropositive donors developed CMV infection. The majority of infections (42/46) occurred during the first 4 months after transplantation. Overall, the incidence of symptomatic CMV disease was 44%. The infections were generally mild and only 1 death was attributed to primary CMV disease complicated by bacterial septicaemia and multiple organ failure. The severity of CMV disease was greatest among those with primary infection. There were 3 cases of toxoplasmosis. Two patients were toxoplasma seronegative before transplantation and developed clinical and serological signs of infection 2-3 months after transplantation despite receiving organs from seronegative donors. Of toxoplasma seronegative recipients receiving allografts from seropositive donors 3/4 were prophylactically treated with pyrimethamine for 6 weeks. None developed clinical or serological signs of toxoplasmosis while one patient who received trimethoprim-sulfamethoxazole had a subclinical infection.  相似文献   

6.
The relationship between herpes simplex virus (HSV) infection and specific cell-mediated immunity was investigated in 141 patients before and for the first four months after marrow transplant. Sixty-two (82%) of 76 seropositive patients but only one of 65 seronegative patients developed HSV infection. Lymphocyte responses to HSV antigen were suppressed immediately after transplant and subsequently became reactive in those patients with HSV infection. The presence or absence of antibody to HSV in the donor before transplant did not influence the response. Seventy long-term survivors of marrow transplant were also studied. Among 60 patients who had pretransplant serum available for study, 26 (68%) of 38 who had been seropositive before transplant had positive responses compared with none of 22 who had been seronegative. Recovery of responsiveness to HSV antigen after marrow transplant is primarily related to recurrent virus infection and not to the pretransplant immune status of the donor.  相似文献   

7.
Among 181 patients undergoing allogeneic bone marrow transplantation over a five-year period (1978 through 1982), cytomegalovirus (CMV) infection was a frequent and often lethal complication. Recipient pretransplant serology was the most important predictor of posttransplant CMV infection. CMV infection occurred in 26/137 seronegative recipients and in 28/44 seropositive recipients (P less than .001). Among patients who developed CMV infection, the time to infection was identical in seronegative and seropositive patients (median, 71 days post transplant). Bone marrow donor CMV serology did not significantly influence CMV infection rate. CMV infection was strongly associated with acute graft-v-host disease (AGVHD), occurring in 34/81 patients with AGVHD and 20/100 without GVHD (P less than .001). AGVHD preceded CMV infection by 33.7 days (mean) in patients developing both complications. Patients who developed CMV infections had also received more cellular blood products post transplant. These data suggest that CMV infection may occur through reactivation of latent virus (in seropositive recipients) or through exogenous exposure, possibly through transfused blood products, but that duration of immunoincompetence may be more critical than route of exposure in timing of clinically evident CMV infection. Prophylaxis tailored to the likely infectious source and more effective GVHD prevention both may be critical in preventing CMV infection after bone marrow transplantation.  相似文献   

8.
Epidemiologic and clinical characteristics of cytomegalovirus (CMV) infection and disease were analyzed retrospectively in 159 autologous marrow transplant recipients. The probability of CMV infection by day 100 after transplant was 22.5% in patients seronegative to CMV before transplant versus 61.1% in seropositive patients (P less than .0001 by logrank test). Multivariate analysis identified positive pretransplant CMV serology as the only definable risk factor for CMV infection (relative risk 1.4, P less than .0001). CMV pneumonia developed in 11 patients at a median time of 100 days after transplant and was fatal in nine cases. CMV pneumonia was associated with significantly decreased probability of survival by day 100 after transplant (relative risk of death of 16.7, P less than .0001). In contrast to earlier reports, CMV infection had no significant effect on the rapidity of platelet or neutrophil recovery after transplant as assessed by time-dependent multivariate analysis. Because the incidence of severe CMV disease is not negligible after autologous marrow transplantation, preventive measures against CMV infection are warranted, as in allogeneic marrow transplantation.  相似文献   

9.
The influence of the cytomegalovirus (CMV) serostatus of blood and kidney donors on patient and graft survival was studied prospectively in 73 cadaveric renal graft recipients. Six out of 12 (50%) CMV seronegative recipients receiving a kidney from a CMV seropositive donor developed CMV disease, in contrast to none of 7 CMV seronegative donor/recipient combinations. Transmission of CMV with blood products to seronegative recipients was not observed in this study. A poor graft survival of 41% 3 years after transplantation was found in CMV seronegative recipients with CMV seropositive allograft donors, compared with an actuarial 3 year graft survival of 72% in the 7 CMV seronegative donor/recipient combinations. Six patients with graft failure had a CMV infection. This study, in accordance with other studies, suggests that selection of CMV seronegative renal allograft donors for CMV seronegative recipients will improve graft survival.  相似文献   

10.
Cell-mediated immunity was assessed in 38 seropositive recipients of renal transplants by measuring the in vitro lymphocyte transformation response (LTR) to cytomegalovirus (CMV) and to phytohemagglutinin; results were correlated with clinical course, viral excretion, and immunosuppressive treatment. Thirteen seropositive controls all responded to CMV with a mean stimulation index of 31 +/- 6; 14 seronegative controls all had stimulation indices of less than 3. LTR to CMV was found to require both thymus-derived lymphocytes and macrophages. Before immunosuppression, responses of patients were similar to those of controls. After renal transplantation mean LTRs to CMV were dramatically reduced up to 18 months postoperatively, especially in patients treated with antithymocyte globulin. Viremia and CMV-related illness were significantly more frequent in recipients of antithymocyte globulin. Although there was only a rough correlation between clinical events and LTR to CMV, five deaths were noted among seven patients (all treated with antithymocyte globulin) who failed to respond to phytohemagglutinin on two consecutive tests.  相似文献   

11.
Cell-mediated immunity to cytomegalovirus (CMV) was determined in congenitally infected children and their mothers by use of assays for CMV-specific lymphocyte blastogenesis and interferon production. Six viruric children responded poorly in both assays. Two older nonviruric children responded in the blastogenesis assay, and lymphocytes from one of them produced interferon. Mothers of older children usually responded in the blastogenesis assay, but only one of them produced interferon. Mothers whose infected infants were younger than nine months of age responded poorly in both assays, while control seropositive postpartum women generally responded normally. The cell-mediated immune defects detected in this study may play a role in the pathogenesis of congenital CMV infection.  相似文献   

12.
We have retrospectively analyzed the incidence of cytomegalovirus (CMV) infection in 250 consecutive renal allograft transplants performed in 244 recipients. The mean follow-up was 35.1+/-25.4 months. Immunosuppression was cyclosporine- or tacrolimus-based triple therapy. CMV infection prophylaxis with ganciclovir for 3 months post transplant was prescribed in CMV-seronegative recipients of allografts from seropositive donors (D+R-) and in all recipients treated with OKT3. CMV antigenemia was monitored by the pp65-antigen assay. Thirteen of 57 D+R- recipients (22.8%) developed CMV antigenemia. One recipient had a breakthrough of CMV antigenemia during ganciclovir prophylaxis; 12 D+R- recipients developed CMV antigenemia 147.5+/-173.8 days after transplantation. Four of 13 (30.7%) D+R- recipients had asymptomatic CMV infection, 8 (61.6%) had CMV infection with non-specific symptoms including fever, and 1 (7.7%) developed CMV pneumonia. Six of 13 (46.1%) D+R- patients had been treated with intensified immunosuppressive therapy before CMV infection. In the low-risk CMV groups (D+R+; D-R+; D-R-), 28 recipients (14.5%) developed CMV antigenemia 42.5+/-15.2 days post transplantation. Ten of the 28 (35.7%) recipients had asymptomatic CMV infection, 17 (60.7%) developed CMV infection with non-specific symptoms, and 1 (3.6%) developed CMV pneumonia. Twenty-one of 28 (75.0%) had intensified immunosuppressive therapy before CMV infection. In conclusion, ganciclovir prophylaxis diminished and delayed the onset of CMV infection but did not totally prevent it from occurring in D+R- renal transplant recipients. Clinicians should be vigilant to the possibility of CMV infection in both seronegative and seropositive recipients, especially after anti-rejection therapy.  相似文献   

13.
In immunocompetent persons, cytomegalovirus (CMV) is thought to persist primarily in monocytes and myeloid progenitor cells, establishing a chronic infection. In older adults, chronic CMV infection is typically diagnosed by a positive IgG serology. While many studies have shown CMV-specific T-cell expansion in CMV seropositive older individuals, significant heterogeneity has also been observed in this elderly population. In a study of 71 community-dwelling older adults, we assessed CMV viral DNA in peripheral monocytes by nested PCR and compared the relationships of detectable CMV DNA and IgG serology with serum levels of neopterin, a marker for monocyte/macrophage-mediated immune activation. The results showed that 52 (73.2%) participants were CMV seropositive, of whom 30 (57.5%) had detectable CMV DNA. CMV seropositive and seronegative participants did not differ in their neopterin levels, but individuals with detectable CMV DNA had higher neopterin than those without (10.6 ± 4.4 vs 8.0 ± 1.9 nM, respectively, p < .0001) adjusting for demographic and clinical covariates and interferon (IFN)-γ levels. In addition, there was no association between IgG titers and neopterin. These findings suggest that detection of CMV viral DNA in monocytes may be an informative tool to evaluate chronic CMV infection and its potential role in monocyte/macrophage-mediated immune activation in the elderly.  相似文献   

14.
Background: Although the primary treatment of symptomatic cytomegalovirus (CMV) disease in organ transplant recipients is successful in >90% of individuals, relapsing disease, particularly in those with primary infection, remains an important problem. Previously, we had observed that the rate of symptomatic recurrence was >60% in those with primary disease (seronegative for CMV prior to transplant), and approximately 20% in those who were seropositive prior to transplant. The present study was undertaken to determine whether a maintenance regimen of oral ganciclovir for 2–3 months added to the routine 14–21 days of intravenous ganciclovir would further prevent symptomatic CMV recurrence. Methods: From May 1995 until June 1998, all kidney and liver transplant recipients with confirmed tissue‐invasive CMV disease or CMV syndrome were treated with 14–21 days of intravenous ganciclovir (5 mg/kg b.i.d. with dose adjusted for renal dysfunction) followed by 2–3 months of oral ganciclovir (2 g daily). The incidence of recurrence of CMV disease and/or viremia during and after oral therapy was then determined over a mean follow‐up of 530.6 days. Results: Thirty‐seven patients, 19 kidney and 18 liver transplant recipients, were studied; 5 had biopsy‐proven tissue‐invasive disease (13.5) and 32 suffered a CMV syndrome (86.5). Twenty‐one of these patients (58.6) were seronegative for CMV prior to transplant and received an allograft from a seropositive donor (D+/R?). Overall, 10 patients (27.0) developed CMV recurrence. Eight of 21 patients who were D+/R? for CMV (38.1) developed recurrence as opposed to 2 of 16 patients with other serologic status (12.5) (P=0.14). Patients with recurrent CMV disease and/or viremia had a peak antigenemia assay titer during their initial CMV event of 319.2 positive cells/2 slides compared with 109.8 positive cells/2 slides for patients without recurrent CMV infection (P=0.14); the trend of having a higher peak antigenemia assay titer among patients who recurred occurred both in patients who were at risk of primary CMV infection (D+/R? for CMV) and in those who were not. Two patients developed recurrent infection with strains of CMV that were resistant to ganciclovir. Conclusions: This new therapeutic regimen of oral ganciclovir following intravenous ganciclovir slightly reduced the overall rate of recurrent CMV disease and/or viremia, but it still did not adequately prevent CMV recurrence in patients who are at risk of primary infection prior to transplant. Of particular concern, 2 patients with primary infection treated with this regimen developed ganciclovir‐resistant recurrent disease ( Note Presented in part at the American Society of Transplant Physicians Meeting, May 1999, Chicago, Illinois.
).  相似文献   

15.
Cytomegalovirus (CMV) DNA load was analyzed as a marker for relapse of CMV infection in 24 solid organ transplant patients with CMV infection or disease who received a fixed 14-day course of intravenous ganciclovir. Viral load was measured in blood samples obtained before and at the completion of treatment. Eight (33%) of 24 patients developed relapsing CMV infection. Median pretreatment viral loads were higher in the relapsing group (80,150 copies/106 leukocytes) than in the nonrelapsing group (5500 copies/106 leukocytes; P=.007). The relapsing group also had persistent detectable viral DNA (median, 5810 copies/106 leukocytes) after treatment, whereas it was undetectable in the nonrelapsing group (P<. 0001). Primary CMV infection (seronegative recipients of seropositive organs, D+R-) was an independent marker for CMV relapse (P=.03), and these patients had higher pre- and posttreatment viral loads than did non-D+/R- patients (P<.0001 and P=.0014, respectively). CMV DNA load is a useful marker for individualizing antiviral treatment of CMV infection in solid organ transplant recipients.  相似文献   

16.
Abstract: The incidence of cytomegalovirus (CMV) infection after liver transplantation (LT) has decreased in recent years. Advances in immunosuppression and CMV prophylaxis have improved the management of CMV disease. Organ involvement is infrequent and gastrointestinal CMV disease is quite rare. Few cases of an antral mass due to CMV infection have been described; those reported to date have mostly been in patients with acquired immunodeficiency syndrome. We describe a case of a CMV‐seronegative liver transplant patient who received a seropositive liver graft. Owing to gastrointestinal complaints, CMV prophylaxis was stopped one month after LT. The patient developed an antral mass due to CMV infection and an anastomotic biliary stricture. Antigenemia became negative with ganciclovir, but this treatment did not eliminate the mass. Ganciclovir resistance was ruled out as well as other causes of antral mass, especially malignancy. The patient finally required gastrectomy and hepaticojejunostomy. We conclude that CMV disease is less common today but should be included in the diagnosis of gastrointestinal mass after transplantation.  相似文献   

17.
Cytomegalovirus (CMV) remains a cause of significant morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Ganciclovir prophylaxis, or preemptive treatment based on detection of antigenemia or CMV DNA by PCR, effectively prevents CMV disease during the first 100 days after transplant in allograft recipients. In recipients of T-cell depleted transplant or if severe acute graft-versus-host disease is present, ganciclovir prophylaxis or preemptive treatment should be started with an induction course of ganciclovir (5 mg/kg BID) and given at least 5 days per week and continued until day 100 after transplant. Although prevention of CMV disease before day 100 is highly effective, there is a continued risk of late-onset CMV disease after day 100. In CMV-seropositive recipients, the incidence of late CMV disease may be as high as 17%. Strategies to prevent late CMV infection and disease are needed. In seronegative recipients, seronegative or leukocyte-reduced blood products are effective in preventing acquisition of CMV through blood products. Controversy exists about the optimal strategy of preventing CMV disease in seropositive autologous HSCT recipients. The outcome of CMV pneumonia remains poor despite treatment with ganciclovir in combination with CMV hyperimmune globulin or intravenous immunoglobulin. Owing to continued clinical significance of CMV in the HSCT setting, new and more effective anti-CMV drugs with improved pharmacokinetic properties are urgently needed.  相似文献   

18.
Cytomegalovirus (CMV) is a pathogen, commonly found in the donors and recipients of solid organ transplantation. CMV is one of the major causes of morbidity and mortality in these patients. Relapsing episodes of CMV infection occur in 23-33% of transplant patients which is likely a reflection of incomplete suppression of viral replication following antiviral treatment with intravenous ganciclovir. We have studied CMV DNA load and antigenemia as markers for relapse of CMV infection in 49 renal transplant patients out of 68 with CMV infection who received a course of intravenous ganciclovir among 300 transplants carried out between January of 2001 and June of 2005. Viral load and antigenemia were measured in blood samples obtained before, during and at the completion of treatment. We also studied different viral load as predictors of relapse CMV infection. Twelve (24.5%) of 49 recipients developed relapsing CMV infection. The relapsing group had higher viral loads after treatment than the no relapsing group. There was no difference in antigenemia level between both groups. The viral loads before and during the treatment, the age and sex of donors and recipients, inmunosupresión, percentage of seronegative recipients with seropositive donors, duration of the therapy and the percentage of patients with heavy immunosuppression were similar in the two groups, but the incidence of acute rejection was higher in the relapsing group. We also evaluated the range of viral load after treatment which is able to trigger the relapse of CMV infection. We conclude that CMV DNA load after treatment is a useful marker for individualizing antiviral treatment of CMV infection in renal transplant recipients. Acute rejection is a risk factor to the relapsing CMV infection.  相似文献   

19.
The impact of transfusion of leucodepleted platelet concentrates (PCs) on cytomegalovirus (CMV) disease was assessed in 215 allogeneic (145 unrelated and 70 related donor) transplants over 3 years. In 43%, both donor and patient were CMV seronegative (CMV-/-). All received CMV-seronegative red cells and random leucodepleted PCs. No CMV disease occurred in any CMV-/- (low risk) transplant. CMV infection occurred in 31 seropositive patients (26%); 13 died and five deaths were attributable to CMV disease. When compared with historical controls, who received CMV-seronegative PCs, we found no difference in transfusion-acquired CMV in the current cohort.  相似文献   

20.
The most common organ-specific manifestation of cytomegalovirus (CMV) infection after liver transplantation is hepatitis. Here we retrospectively describe the detailed virological, histological, immunological, and clinical findings associated with CMV infection in 229 consecutive adult liver transplantation patients. CMV infection was diagnosed by pp65 antigenemia. From 439 liver biopsies, CMV antigens were demonstrated by immunohistochemistry and CMV DNA by hybridization. The Banff criteria were used for histology. The expression of various adhesion molecules (intercellular adhesion molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1], endothelial leukocyte adhesion molecule-1 [ELAM-1]), their ligands (leukocyte function antigen-1 [LFA-1], very late antigen-4 [VLA-4], Sialyl-LewisX-molecule [SLeX]), and lymphoid activation markers (major histocompatibility complex [MHC] Class II, interleukin-2-receptor [IL-2R]) was demonstrated by immunohistochemistry. CMV infection of the transplant occurred in 26 patients (11% of all 229 patients and 17% of the 151 patients with liver biopsy). The incidence was higher among seronegative (26%) than in seropositive recipients (9%), but most cases 18/26 (70%) were reactivations. The CMV pp65 antigenemia levels were usually high in primary infections (893+/-1069, range 50-3000 pp65+cells), but varied widely in reactivations (388+/-740, range 3-3000). The histological Banff score was slightly increased (2.3+/-0.9). Microabscesses, lymphocytic infiltration, Kupffer cell reaction, and parenchymal alterations were common but viral inclusions rare. CMV significantly (P<0.05) increased ICAM-1 and VCAM-1 expression and the number of LFA-1, VLA-4, and Class II-positive lymphocytes in the graft. All CMV infections were successfully treated with antivirals. Intragraft CMV infection had no influence on the long-term outcome, but biliary complications were common. In conclusion, CMV infection of the liver transplant occurred both in primary infection and in reactivation, and also in the cases with low pp65 antigenemia levels. Microabscesses and other histological alterations were common but viral inclusions rare. Increased adhesion molecule expression was associated with lymphocyte infiltration. Successfully treated CMV hepatitis had no influence on the long-term clinical outcome.  相似文献   

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