Prevention of cytomegalovirus infection in the pediatric renal transplant recipient

Cytomegalovirus (CMV) infection is the most important single infectious complication of organ transplantation, affecting more than 70% of transplant recipients. Its emergence as a major pathogen has coincided with the use of cytotoxic therapy. Manifestations of serious CMV disease include: pneumonia, hepatitis, gastrointestinal disease, leukopenia and chorioretinitis. CMV is associated with superinfection with opportinistic organisms, graft failure and increased mortality. Serious infection most frequently occurs with primary CMV infection in which latently infected cells from CMV-positive donors are given to seronegative recipients. Pediatric patients who have a lower pre-transplant rate of CMV seropositivity are at particularly high risk of developing serious CMV disease. Preventative efforts range from the ideal but impractical use of only CMV-negative donors (organ and blood products), to the use of CMV hyperimmune globulin and antiviral chemotherapy. Data support the use of prophylactic hyperimmune globulin and preliminary information supports the use of prophylactic high-dose acyclovir in renal transplant patients. Prophylactic gancyclovir alone or with hyperimmune globulin and pre-transplant vaccination with live-attenuated Towne strain CMV vaccine remain investigational.     

High-dose acyclovir and intravenous immune globulin reduce the incidence of CMV disease after liver transplantation

We attempted to prevent cytomegalovirus (CMV) disease in liver transplant (LTx) recipients by means of a combined prophylaxis regimen consisting of high-dose acyclovir (HDA) and immune globulin (IVIG). In 259 consecutive patients, HDA was given for 3 months post-LTx; recipients seronegative for CMV also received IVIG. The previous 94 patients comprised our control group; in this group, low dose acyclovir was given to prevent herpes, and prophylaxis of CMV consisted of IVIG given only to seronegative recipients of seropositive donors. The overall incidence of CMV disease was lower in the HDA group (10.8%) than in the control group (27.6%); (P<0.001). The CMV disease rate associated with primary exposure was 26.3% in the HDA group and 83.3% in the control group (P<0.001). The incidence of CMV disease occurring after acute rejection was 9.5% in HDA patients and 24.6% in controls (P<0.005) The HDA protocol was associated with a trend toward a lower incidence of CMV in patients requiring OKT3 therapy (16.7% vs 29%). High-dose acyclovir/IVIG thus reduces the incidence of CMV disease in seronegative recipients after LTx and lowers the risk of CMV disease associated with therapy for rejection.     

Acyclovir plus CMV immunoglobulin prophylaxis and early therapy with ganciclovir are effective and safe in CMV high-risk renal transplant pediatric recipients

Abstract Cytomegalovirus (CMV) infection is still a major cause of morbidity in high-risk renal transplant recipients. In the present report, we have reviewed our records of renal transplant pediatric recipients (RTPR; mean age 14.1 ± 4.9 years) since 1991, when we started a policy of CMV prophylaxis constituting high-dose oral acyclovir plus CMV hyperimmune immunoglobulins (Hlg) followed by early i.v. ganciclovir therapy in high-risk patients (i.e., CMV donor +/ recipient -). Four patients received a kidney from a living relative (LR), 2 patients had one previous transplant, and 1 had a combined liver -kidney transplant. Thirty-three patients who were negative for CMV antibodies (ab) before transplantation received a kidney from CMV ab positive donors. The immunosuppressive regimen included cyclosporin A and steroids, with the addition of azathioprine in the 4 patients who received an LR kidney. Serial assessments for CMV antigenemia (pp 65) were routinely performed for 6 months after transplantation to define CMV infection. Among the 33 CMV seronegative recipients (R -) who received the graft from a CMV seropositive donor (D +), 18 (54.5 %) experienced CMV infection, whereas among the 28 CMV R +, who received a graft from a CMV D +, 11 (39.3 %) experienced CMV infection. With regard to CMV - related symptoms, only 2 patients suffered from a CMV syndrome (fever and leukopenia in 1 patient, fever and arthralgia in the other). In no case did the spectrum of CMV disease occur; only minor symptoms were present in 7 of the remaining CMV-infected patients (fever in 6 and leukopenia in 1). Rejection episodes and renal function did not differ between CMV-infected and non-CMV-infected patients. Our experiences support the use of prophylactic acyclovir plus CMV HIg followed by early therapy with i.v. ganciclovir to combat the risk of increased morbidity in high risk RTPR.     

Increased intestinal permeability during cytomegalovirus infection in renal transplant recipients

Cytomegalovirus (CMV) infections in renal transplant recipients can affect the gastrointestinal tract, but significant clinical manifestations are seldom seen. We hypothesize that subclinical involvement of the gastrointestinal tract may be quite frequent during CMV infection. In order to study this, we measured intestinal permeability by calculating the urinary lactulose mannitol (LM) excretion ratio after oral administration of lactulose and mannitol (normal<0.030) in patients with symptomatic and asymptomatic CMV infection. A total of 111 patients were enrolled in the study, 104 of whom were tested on postoperative day (POD) 10. Twenty-nine patients developed CMV infection, 12 of whom could be studied with the permeability test (median POD 40). Another nine patients without CMV infection were also studied at day 40 and served as controls. The LM ratio increased significantly during CMV infection compared to measurements before active infection (median 0.060 vs. 0.030, P<0.01) and was significantly higher during the infection than in the control group (median 0.007, P<0.01). No correlation could be found between the LM ratio and viral load, humoral response to the virus, or symptomatology of infection. We conclude that an increased intestinal permeability is found in a substantial number of patients with an active, albeit asymptomatic, CMV infection after renal transplantation. Pathophysiological mechanisms and clinical implications remain speculative but will be subject to further study.     

Antigenemia,immunoblotting, and enzyme immunoassay for early diagnosis of cytomegalovirus infection in renal transplant patients

Timely and rapid diagnosis of cytomegalovirus (CMV) infection is important for the management of transplant patients. We compared three serological assays, IgM immunoblot and IgG/IgM enzyme immunoassay (EIA), as well as the detection of CMV antigens in polymorphonuclear blood leukocytes (antigenemia), for their value in the early diagnosis of CMV infection. Thirty-one patients were monitored longitudinally for 3 months after renal transplantation. Laboratory documented CMV infection occurred in 20 patients. All of these cases showed a positive IgM immunoblot result that was confirmed by at least one of the other test assays (IgG EIA 19/20, antigenemia assay 13/20, and IgM EIA 12/20). All of the ten patients whose clinical picture was compatible with symptomatic CMV disease were positive for CMV infection according to IgM immunoblot and IgG EIA, nine were positive according to the antigenemia assay, and seven were positive according to IgM EIA. With reference to the temporal pattern, the antigenemia assay indicated CMV infection significantly earlier than the serological tests (P0.05). In symptomatic patients CMV antigen-positive leukocytes were, on the average, detected on the day of onset of symptoms, whereas detection by IgM immunoblot, IgG EIA, and IgM EIA followed 8, 13, and 14 days later, respectively. These results show that: (1) the CMV antigenemia assay is very useful for the early diagnosis of symptomatic CMV infections; (2) CMV antibodies, as an indicator of CMV infection, are detectable earlier and more frequently by IgM immunoblot than by IgG/IgM EIA; (3) compared to CMV anti-genemia, the IgM immunoblot indicated CMV infection more often but significantly later; and (4) only a combination of several diagnostic methods allows optimal detection of CMV infections in renal transplant patients.     

Two grams daily of oral acyclovir reduces the incidence of cytomegalovirus disease in CMV-seropositive liver transplant recipients

Our objective in this study was to determine the efficacy of 2 grams a day of oral acyclovir administered for 16 weeks after transplantation for the prevention of cytomegalovirus (CMV) infection and disease in CMV-seropositive liver transplant recipients. Seventy-three adult liver transplant recipients, seropositive for CMV, were randomized to receive either 2 grams a day of oral acyclovir for 16 weeks after transplantation or no prophylaxis. The incidence of CMV disease was significantly lower in the acyclovir group (5 %) than in the control group (27 %; P < 0.05). By log-rank analysis, the differences in the probability of presenting CMV disease over the first 16 weeks and over the 1st year were also significant (P < 0.05). We conclude that 2 grams a day of oral acyclovir provides effective prophylaxis against CMV disease in CMV-seropositive liver transplant recipients. Received: 14 March 1997 Received after revision: 30 May 1997 Accepted: 9 June 1997     

Randomized controlled trial of oral ganciclovir versus oral acyclovir after induction with intravenous ganciclovir for long-term prophylaxis of cytomegalovirus disease in cytomegalovirus-seropositive liver transplant recipients

BACKGROUND: Without effective antiviral prophylaxis, cytomegalovirus (CMV) disease is a common cause of morbidity and mortality after liver transplantation. In this randomized, controlled trial, we compared the efficacy and safety of oral ganciclovir with oral acyclovir after induction with intravenous (IV) ganciclovir for long-term prophylaxis of CMV disease in CMV-seropositive liver transplant recipients. METHODS: Patients were initially administered IV ganciclovir at a dose of 6 mg/kg per day from day 1 to day 14 after transplantation followed by either oral ganciclovir (1 g every 8 hr) or oral acyclovir (800 mg every 6 hr) from day 15 to day 100 after transplantation. RESULTS: CMV disease occurred in only 1 of 110 patients (0.9%) receiving ganciclovir compared with 8 of 109 patients (7.3%) receiving acyclovir within the first year after transplantation (P =0.019). There was one case of CMV colitis in the ganciclovir group, whereas four cases of CMV syndrome, three cases of CMV pneumonia, and one case of CMV hepatitis developed in the acyclovir group. The only death from CMV disease occurred in an acyclovir-treated patient with CMV pneumonia. Both oral ganciclovir and oral acyclovir were generally well tolerated. Reversible leukopenia (decline in white blood cell count to <3.0 x 10(9)/L) was more common with oral ganciclovir (38/110 patients, 35%) than with oral acyclovir (20/109 patients, 18%) (P =0.009). The emergence of ganciclovir-resistant strains of CMV was not found during the study. CONCLUSIONS: A prophylactic regimen of 2 weeks of IV ganciclovir followed by an additional 12 weeks of oral ganciclovir is superior to a similar regimen of IV ganciclovir followed by oral acyclovir and almost completely eliminates CMV disease after liver transplantation. This superior protection against CMV disease extends up to 1 year after transplantation and is not associated with ganciclovir resistance.     

Comparative study of prophylactic oral ganciclovir and valacyclovir in high-risk kidney transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) is a major pathogen in renal transplant patients causing significant post-transplant morbidity and mortality. Prophylactic antiviral therapy, currently implemented in most kidney transplant centres, has significantly reduced the incidence of CMV infection after transplantation. Oral ganciclovir has been shown to be an effective prophylactic agent in preventing CMV disease and infection with a demonstrated superior efficacy over oral acyclovir. Valacyclovir, a prodrug of acyclovir with a higher level of bioavailability than acyclovir, has also been shown to be effective in preventing CMV disease when given as prophylactic treatment. METHODS: In a retrospective analysis of 150 renal transplant recipients in our centre, we compared the efficacy of oral ganciclovir with valacyclovir in preventing CMV infection. Seventy-seven consecutive renal transplant recipients prophylactically treated with oral ganciclovir for 12 weeks after transplant were compared with 73 consecutive recipients treated with oral valacylovir for an equal length of time. RESULTS: No difference was noted in the incidence of CMV infection between the two treatment groups (5.1 vs 5.4%) after a 6 month follow-up. Likewise, the incidence of acute rejection was similar in both groups (11.6 vs 6.8%). All cases of CMV infection occurred in high-risk patients (donor positive/recipient negative). CONCLUSION: The prophylactic use of oral valacylovir is as effective as oral ganciclovir in reducing CMV infection and disease after kidney transplantation.     

A longitudinal prospective study of cytomegalovirus pp65 antigenemia in renal transplant recipients

Cytomegalovirus (CMV)-encoded pp65 antigen in peripheral blood leukocytes (CMV antigenemia) was investigated in 1017 serial samples from 64 patients for 16 weeks after renal transplantation in a prospective study. In 110 samples from 24 patients, at least one antigen-positive leukocyte was identified. The median number of stained cells was 4 (range 1–1000) per 4×10⁵ leukocytes. Twenty-one of 24 patients with serological signs of an active CMV infection were antigen-positive (sensitivity 87.5%), whereas 3 patients with antigenemia did not show serological signs of infection during the observation period (specificity 92.5%). Positive results were obtained 19 days (median) before serological response and 9 days (median) before the onset of CMV syndrome. The sensitivity in defining a CMV syndrome was 100% (n=8). In all patients who presented with CMV syndrome, antigenemia was present prior to the onset of symptoms or on the same day. In contrast, serological monitoring rendered the diagnosis of CMV infection possible at the onset of clinical symptoms in only two of eight patients. We conclude that (1) insufficient results obtained with the CMV antigenemia assay by other investigators are mainly due to technical problems that can easily be overcome by the protocol presented and (2) the detection of CMV pp65 antigen in peripheral blood leukocytes is an excellent tool for rapid and early diagnosis of CMV infection.     

Evaluation of a Cytomegalovirus Prophylaxis Protocol in Cytomegalovirus-IgG Positive Renal Transplant Recipients (R+)

BackgroundThe aim of the study was to evaluate the efficacy of a unique cytomegalovirus- (CMV) prophylaxis protocol in terms of CMV infection and disease progression in CMV IgG positive kidney transplant recipients.MethodsAchievement of negative CMV load, using concurrent prophylactic intravenous ganciclovir therapy during induction immunosuppression, combined with a 6-month prophylactic course of acyclovir, would yield a reduced incidence of early CMV infection and disease. CMV DNA was tested for at discharge, at the third, and sixth post-op months, and at the occurrence of any event that could be associated with CMV infection. CMV DNA positive patients received ganciclovir treatment until the viral load became negative. CMV replication was monitored using a quantitative PCR method capable of detecting as few as 42.5 copies/mL. All patients were given a maintenance dose of acyclovir.ResultThe file data of 267 patients who had undergone kidney transplantation between 2007 to 2016 were examined. Thirty-four patients were excluded from the study for various reasons, unrelated to the protocol. Of the remaining 233 patients, 42 (18%) had CMV DNA infection. Three patients had CMV disease (1.3%), 1of whom died of pneumonia. Diabetes mellitus (DM) was a risk factor for CMV DNA positivity (P < .004).ConclusionThe incidence of CMV infection and disease is low in renal transplant recipients whose CMV viral load is eliminated after concurrent ganciclovir administration with induction immunosuppression.     

Serum neopterin/creatinine values correlate with severity of symptoms caused by cytomegalovirus infection in renal transplant recipients

Serum neopterin/creatinine ratios were longitudinally measured in 86 renal transplant recipients from the day before transplantation until 4 months after transplantation, and the relationship to the clinical symptoms of cytomegalovirus (CMV) infection was studied. Infection with cytomegalovirus occurred in 23 patients, 11 cases of which were due to primary infection. Symptoms caused by CMV infection were more severe in male patients, in patients who had received prior antirejection treatment, and in patients with primary CMV infection. The measurement of serum neopterin/creatinine ratios proved to be a marker for the severity of symptoms caused by CMV infection, as peak values were significantly higher in eight patients with CMV disease than in patients with no or only mild symptoms of CMV infection (P<0.05). Moreover, in seven out of eight cases of CMV disease, serum neopterin/creatinine ratios started to rise up to 2 weeks before CMV infection was proven by serology.     

Opportunistic infections in children following renal transplantation

Opportunistic infections following renal transplantation in children are a major cause of severe morbidity and mortality. These infections account for the majority of early post renal-transplant deaths in children. General risk factors which affect the incidence and severity of these infections include: transmission of the infectious agent by the donor organ; history of immunity in the recipient prior to transplantation; type and amount of immunosuppression including treatment for rejection episodes; availability of specific treatment for the infection. Children are at particular risk because of the lack of exposure to certain pathogens prior to transplantation. There have been recent advances in the prevention and treatment of important infections which occur in children following transplantation, including varicella,Pneumocystis carinii pneumonia (PCP) and cytomegalovirus (CMV) disease. Varicella is treatable with acyclovir, often without decreasing immunosuppression and placing the graft at risk. Prophylaxis against PCP may be achieved by provision of alternate-day trimethoprim sulpha, but clear guidelines for determining who should be treated are lacking. Treatment of this disease with high-dose trimethoprim sulfa or pentamidine is usually successful. CMV disease is frequently severe, especially when the donor is seropositive and the recipient seronegative. In these situations, prophylactic CMV immunoglobulin reduces the morbidity and the mortality of the disease and prophylactic oral acyclovir may decrease its incidence. Treatment of severe CMV disease with gancyclovir is promising.     

CMV‐specific T‐cell immunity,viral load,and clinical outcome in seropositive renal transplant recipients: a pilot study

Sund F, Lidehäll A‐K, Claesson K, Foss A, Tötterman TH, Korsgren O, Eriksson B‐M. CMV‐specific T‐cell immunity, viral load, and clinical outcome in seropositive renal transplant recipients: a pilot study.
Clin Transplant 2010: 24: 401–409. © 2009 Wiley Periodicals, Inc. Abstract: Background: Cytomegalovirus (CMV) infection is still the leading opportunistic infection following solid organ transplantation. The aim of this prospective study of renal transplant recipients was to evaluate the dynamics of CMV‐specific T‐cells, viral load, and clinical symptoms of CMV infection. Methods: Levels of tetramer‐selected CD8⁺ T‐cells (TetraCD8), CMV‐specific interferon‐γ producing CD8⁺ T‐cells (IFNγCD8), and CD4⁺ T‐cells (IFNγCD4), measured using major histocompatibility complex‐tetramer and cytokine flow cytometry techniques, and CMV DNA were monitored monthly in 17 CMV‐seropositive patients up to one yr (median 12 months, range 3–12) after transplantation and correlated to clinical outcome. Results: CMV DNAemia was detected in 94% of the patients, but only one patient developed CMV disease. CMV DNAemia >1 million copies/mL was seen in asymptomatic patients. CMV‐specific T‐cells decreased rapidly after transplantation. TetraCD8 and IFNγCD8 regenerated within three months, whereas IFNγCD4 recovery was impaired up to one yr after transplantation. The proportion of IFNγCD4 at two months post‐transplantation as compared with baseline, correlated strongly with the magnitude of the CMV DNAemia. Conclusions: Monitoring the reduction of IFNγCD4 compared with baseline during the first months after transplantation could be considered in predicting risk for high‐grade CMV DNAemia and in deciding strategic approaches for pre‐emptive and prophylactic therapy.     

Cytomegalovirus prophylaxis using oral ganciclovir or valganciclovir in kidney and pancreas-kidney transplantation under antibody preconditioning

We investigated retrospectively the risk factors for cytomegalovirus (CMV) infection under ganciclovir or valganciclovir prophylaxis (oral ganciclovir 1 g tid, valganciclovir 450 mg/d) in our kidney and simultaneous pancreas-kidney (SPK) transplant patients undergoing transplantation between July 1, 2001 and February 28, 2003. Two hundred eleven patients receiving prophylactic oral ganciclovir or valganciclovir were included in the study. All patients were given antibody preconditioning (thymoglobulin 178, alemtuzumab 33). Duration of prophylactic treatment was between 3 and 8 months. Fifteen (7.1%) patients developed a positive CMV antigenemia in the first 6 months after transplantation, and 18 of 176 (10.2%) patients developed a positive CMV antigenemia during the first year. No patient developed tissue invasive CMV disease. At 6 months after transplantation, valganciclovir was slightly more effective than ganciclovir prophylaxis (P=.052). Positive donor CMV serology significantly increased the risk of CMV infection compared to CMV-negative donors (P=.014 and P=.003 at 6 and 12 months, respectively). Duration of CMV prophylaxis for more than 3 months decreased the risk of CMV infection (P=.04 and P=.009 at 6 and 12 months, respectively). Either valganciclovir prophylaxis (450 mg/d) or high-dose oral ganciclovir (1 g tid) is effective in preventing tissue-invasive CMV disease, and results in a low incidence of CMV antigenemia in patients undergoing kidney and SPK transplantation.     

The prevention of cytomegalovirus disease in renal transplantation.

Primary cytomegalovirus (CMV) disease can be prevented in renal transplant recipients with the use of either CMV hyperimmune globulin (CMVIg) or acyclovir. Started within 72 hours of transplantation and continued for 16 weeks posttransplant, CMVIg decreases the incidence of primary CMV disease from 60% to 21%. Acyclovir administered preoperatively and for 3 months thereafter decreases the incidence of CMV disease from 29% to 8% and is the most cost-effective therapy. The effectiveness of these preparations in preventing CMV reinfection or reactivation has not been established. The utility of therapies other than CMVIg or acyclovir for the prevention of CMV disease has not been proven; CMV vaccination is ineffective, polyvalent immunoglobulins require further study, and interferon alpha (IFN-alpha) has been associated with frequent irreversible rejection reactions and therefore should not be used for CMV prophylaxis. Although further investigation is necessary, patients at risk for primary CMV disease should receive prophylactic therapy with either CMVIg or acyclovir.     

Acute Cytomegalovirus Cholecystitis Following Renal Transplantation

Solid organ transplant recipients are at risk of infection from cytomegalovirus (CMV). A wide range of disease is associated with CMV infection and we report two cases of CMV cholecystitis in patients following renal transplantation. Both patients presented with severe hemorrhagic cholecystitis, which required immediate resuscitation and emergency cholecystectomy. The diagnosis of CMV infection was confirmed in both cases using CMV-specific staining of the gallbladder. The diagnosis of CMV cholecystitis must be considered in all patients with upper abdominal pain after renal transplantation.     

Risk factors for cytomegalovirus infection and disease in renal transplant recipients: HLA-DR7 and triple therapy

In a prospective study, an analysis of risk factors for the development of cytomegalovirus (CMV) infection and disease was performed on 77 renal allograft recipients. Twenty-five out of the 77 recipients (32%) had a CMV infection. Twenty-two of the recipients received triple immunosuppressive therapy (cyclosporin A, prednisolone, and azathioprine) while the remaining 55 received standard therapy (cyclosporin A and prednisolone). In 23 recipients (30%) acute rejection was diagnosed and the first positive parameter of infection occurred 22 days after rejection therapy. Infection occurred in 10 out of 18 HLA-DR7-positive recipients (56%) and in 15 out of 59 HLA-DR7-negative recipients (25%; P< 0.02). In multiple regression analysis, HLA-DR7 was found to be a significant predictor of CMV infection (P< 0.005). CMV disease was diagnosed in only 9 out of 25 recipients with an acute infection. Six recipients (67%) with CMV disease received triple therapy for maintenance immuuosuppression; this was significantly correlated to CMV disease (P< 0.05) as compared to three recipients (33%) with CMV disease maintained with standard therapy. Our data suggest that HLA-DR7-positive recipients are more susceptible to CMV infection and that CMV disease is associated with triple immunosuppressive therapy.     

Incidence of cytomegalovirus disease in cyclosporine-treated renal transplant recipients based on donor/recipient pretransplant immunity

We retrospectively reviewed the clinical data of all renal transplant patients treated with cyclosporine as their main chronic immunosuppressive agent between 12/83 and 11/85 to identify cytomegalovirus-negative patients at our institutions who received cytomegalovirus (CMV)-positive kidneys. Using a latex agglutination test, twenty-two such patients were identified, of whom 2 were excluded due to early death and lack of posttransplant follow-up serology. Of the remaining 20 patients, 12 developed CMV antibody in the first 4 months posttransplant, and of these, 11 were hospitalized with complications related to primary CMV disease. Two of these seroconverting patients eventually died, and one lost her kidney. Of the 8 persistantly CMV-negative patients, 1 lost his kidney soon after transplantation, and one had a febrile illness 4 months posttransplant caused by a bacterial pneumonia. Concomitantly, 145 renal transplants (CMV-negative recipient receiving a CMV-negative kidney or CMV-positive recipient receiving either positive or negative kidneys) given to 142 patients functioned for at least 4 weeks. Only 3 cases of CMV reactivation disease occurred in previously antibody-positive patients. We conclude that the transplantation of a cytomegalovirus-positive kidney into a CMV-negative recipient carries a high risk of mortality/morbidity from primary cytomegalovirus disease. On the other hand, reactivation of CMV disease was uncommon early in the posttransplant course of cyclosporine-treated patients.     

Early detection of primary cytomegalovirus infection after heart and kidney transplantation and the influence of hyperimmune globulin prophylaxis

A randomized study of prophylaxis with hyper-immune globulin (HIg) was performed in 28 cytomegalovirus (CMV)-seronegative heart and kidney recipients with CMV-seropositive donors who were extensively monitored for active CMV infection and CMV disease. Detection of CMV antigen in peripheral blood granulocytes (antigenemia) was the first sign of primary CMV infection, generally occurring several weeks before IgM or IgG anti-CMV antibodies were detected and before positive cultures appeared. A correlation was found between rejection treatment with OKT3 or ATG, severity of CMV disease, and graft loss. Rejection treatment had no influence on incidence of CMV transmission. Primary CMV infection occurred most often in older patients with older donors. No beneficial effects were seen with HIg prophylaxis, which was administered from week 1 until week 7 after transplantation. Incidence of primary CMV infection was equal in both groups (50%) and no influence on the severity of primary CMV infection was seen. The only effect that was seen was on the time from transplantation to detection of active CMV infection, which was prolonged by HIg prophylaxis.     

Cytomegalovirus infection and colonic perforation in renal transplant patients

Cytomegalovirus (CMV) infection in immunocompromised patients is a major cause of morbidity and mortality. A well-documented manifestation of gastrointestinal CMV infection is gastrointestinal haemorrhage. In contrast, CMV-associated intestinal perforation has rarely been reported after transplantation, although it is well documented in AIDS patients. Three patients are reported who received their first cadaveric renal transplant in 1994 and subsequently developed CMV disease. During the course of their CMV illness, which was treated with ganciclovir, each presented with clinical suspicion of peritonitis and proceeded to laparotomy. All three were found to have sigmoid colon perforations with histological evidence of CMV infection. Following bowel resection and defunctioning, two patients made an uneventful recovery and have had the continuity of their bowel restored, but one died of overwhelming sepsis within hours of surgery. The explanation for the apparent clustering of this rare condition in transplant patients is uncertain.