Active Cytomegalovirus Disease Research Articles

Significant Increase in Cytomegalovirus (CMV) Infection in Solid Organ Transplants Associated With Increased Use of Thymoglobulin as Induction Therapy?

Cytomegalovirus (CMV) infection remains one of the most common viral pathogens affecting solid organ transplants (SOT). In 10 years of following the outcome of transplants, we noticed an increased incidence of CMV infection, along with increased use of rabbit anti-thymocyte globulin (rATG). The study aims to assess the incidence of active CMV infection and disease, response to treatment, and recurrence in a cohort of SOT. Furthermore, we look for correlating the CMV incidence with the type of induction therapy: r-ATG or interleukin 2 receptor-blocking antibody (basiliximab). This was a single-center, retrospective 10-year study in patients submitted to kidney, kidney-liver, and kidney-pancreas transplants who used a preemptive therapy protocol for CMV. Among the 476 enrolled transplant recipients, 306 (64.2 %) had at least one episode of CMV infection (replication), and 71/306 patients (23.2 %) presented CMV-related disease. The most frequent clinical conditions associated with CMV disease were gastrointestinal. Among the 476 transplant patients, 333 received immunosuppressive induction with rATG (69.9 %); 140 (29.4 %) received induction with interleukin 2 receptor-blocking antibody (basiliximab). The initial maintenance immunosuppressive therapy in the patients who presented CMV infection was primarily performed with prednisone, tacrolimus, and sodium mycophenolate (91.7 %). The induction with rATG increased from 35.2%-94.6% in 10 years. The incidence of CMV infection was 20.7 % in the first year of observation and gradually increased to 87.3 % in the last year. The data suggest that the increase in the use of rATG in recent years could be responsible for the very expressive increase in the incidence of CMV infection/disease.

Cytomegalovirus reactivation after bortezomib treatment for multiple myeloma and light chain amyloidosis

Cytomegalovirus (CMV) is an opportunistic herpesvirus, and reactivation of infection is possible in immunocompromised patients. Historically, the risk for haematology patients is restricted to those treated with an allogeneic transplant or T-cell depleting agents. Bortezomib is a highly efficacious proteasome inhibitor widely used to treat multiple myeloma and light chain (AL) amyloidosis patients. The objective of this small prospective study was to quantify the risk of CMV reactivation associated with bortezomib treatment. Fifty-seven consecutive multiple myeloma or AL amyloidosis patients commencing bortezomib-based therapy were included. Viral copy numbers were established at baseline and then at fortnightly intervals during treatment. Pre-emptive anti-viral treatment was initiated in patients with a viral load >7500copies/mL. Reactivation of CMV was detected in 39% (n=12/31) of seropositive bortezomib treated patients compared with 0% of CMV seronegative patients. Detectable DNAemia developed during the first two cycles of treatment in 83% (n=10/12) patients. Anti-viral treatment was initiated in 42% (n=5/12), but no cases of active CMV disease were seen. This study suggests that there is a substantial risk of CMV reactivation in CMV-seropositive plasma cell dyscrasia patients treated with bortezomib.

Cytomegalovirus co-infection with HIV in children and adolescents on antiretroviral therapy in Abuja, Nigeria

Background: Cytomegalovirus (CMV) co-infection with human immunodeficiency virus (HIV) is known to accelerate HIV disease progression. It has the potential of being a killer disease or a silent lifetime companion in HIV patients. There is dearth of information on CMV prevalence among HIV infected children and adolescents in our environment. We therefore conducted this study to determine its sero-prevalence, and risk factors for co-infection among HIV infected children and adolescents on highly active antiretroviral therapy (HAART) in our center. Method: A descriptive cross sectional study of HIV-infected children and adolescents aged 2 months to 18 years on HAART was conducted over a 6 month period between October 2017 and March 2018 in our health facility. Blood samples of subjects were screened for CMV IgM using commercial test kits. Biodata of subjects, CD4 cell count, and viral load were collected into a designed proforma, and statistical analysis was done with SPSS version 22.0.Result: A total of 161 HIV-infected children and adolescents were recruited, 103 (64.0%) were males, 83 (51.6%) were between the ages of 5 and 0.05). Multivariate analysis however did not show any significant difference in age, weight, length/height, and systolic blood pressure. Conclusion: The prevalence of active CMV infections among HIV infected children and adolescents on HAART in our centre is high. Low CD4 cell count and high viral load were not associated with active CMV disease, and no risk factor for co-infection was also identified. Identifying those with primary/active infection will be necessary for possible treatment with anti-herpes drugs before development of reactivated CMV disease. Keywords: CMV; HIV; co-infection; anti-retroviral; children; adolescents

Cytomegalovirus Disease in HIV-infected Children-A Single-Centre Clinical Experience over 23 Years.

Cytomegalovirus (CMV) results in significant morbidity and mortality in Human Immunodeficiency Virus (HIV)-infected individuals. There is paucity of literature on paediatric CMV disease, especially from developing countries. A retrospective review of records of all HIV-infected children with evidence of CMV disease was done. A total of 15 children were found to have CMV disease (retinitis in all, pneumonia in two and invasive gastrointestinal disease in one). Median CD4+ T cell count and percentage at diagnosis of CMV disease was 64.5 cells/µl and 3.6%, respectively. Intravenous ganciclovir was used in patients with active CMV disease. Of the 15 children, three died while two were lost to follow-up. Symptomatic patients had poor visual outcome and almost all children who were diagnosed on active screening attained normal vision. Retinitis is the most common CMV disease in HIV-infected children. Early detection by active screening and initiation of systemic ganciclovir reduces the morbidity.

Accuracy of Inpatient International Classification of Diseases, Ninth Revision, Clinical Modification Coding for Cytomegalovirus After Kidney Transplantation

BackgroundInternational Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) coding for cytomegalovirus (CMV) has been used as a proxy for active CMV infection or disease occurring in the inpatient setting in retrospective studies of kidney transplant recipients using large amounts of administrative data. However, the accuracy of inpatient CMV coding has not been determined. MethodsWe identified 393 kidney transplant recipients who were readmitted to Barnes-Jewish Hospital in St. Louis, Missouri from January 1, 2007 to December 31, 2011 to determine the accuracy of the ICD-9-CM diagnosis code for CMV (078.5) in identifying active CMV infection or disease (asymptomatic viremia, CMV syndrome, or tissue-invasive CMV disease) in the inpatient setting, using microbiological, histopathologic, or ophthalmologic evidence for CMV as the gold standard. ResultsThe sensitivity and positive predictive value of CMV coding in identifying active CMV infection or disease were 0.77 and 0.71, respectively. The specificity and negative predictive value were both 0.98. The sensitivity of CMV coding in identifying CMV syndrome or tissue-invasive CMV disease was 0.93. ConclusionsCMV coding had good accuracy in identifying active CMV infection or disease among readmitted kidney transplant recipients in our hospital. Further validation studies of CMV coding in other hospitals are needed to obtain more generalizable estimates of the accuracy of CMV coding.

Betaherpesvirus (Cmv, Hhv-6 and Hhv-7) Active Infections in Brazilian Hematopoietic Stem Cell Transplant Patients

Cytomegalovirus (CMV) is one of the most prevalent infectious pathogen in transplant recipients, including those receiving bone marrow or stem cell grafts. Rapid diagnostic tests to identify active CMV infection and preemptive treatment are significant improvements in the management of CMV. Two newly identified beta herpesviruses, hu - man herpesvirus-6 (HHV-6) and human betaherpesvirus-7 (HHV-7), are genetically more closely related to each other than to CMV and have been frequently detected in the blood of allogeneic HSCT. HHV-6 reactivation has been associated with fever, rash, delayed engraftment and encephalitis. Also, HHV-7 has been reported as a cause of severe central nervous system disease and with severe GVHD and sepsis secondary to immune suppression. Nested polymerase chain reaction in blood samples (serum or leukocytes) was used to monitor active CMV, HHV-6 and HHV-7 infections and disease in forty-three HSCT patients for up to 150 days after transplant. All adult recipients with a risk for CMV disease (D+/R+; D+/R-) were enrolled in this study. Acyclovir was used at low doses prior to the transplant as herpes virus prophylactic therapy. Patients who were at least 2 consecutive N-PCR positive for CMV received preemptive therapy with ganciclovir. The prevalence’s of positive active CMV, HHV-6 and HHV-7 infec- tions were 72%, 4.6% and 13.9%, respectively. Thirteen patients died (30.2%). Biopsies confirmed CMV disease occurred in 8 out of 43 patients (18.6%), in the gastrointestinal tract. All of them presented active CMV infection and one presented active CMV+HHV-6 infection. None of these patients presented active HHV-7 infection. One patient with CMV disease died by disseminated CMV. Detection of active HHV-6 and HHV-7 infections was low and clini cally significant complications were rare. CMV disease remains the most prominent disease associated with HSCT. Results show that surveillance with N-PCR a sensitive, non-invasive and low-cost technique for detection of active beta herpesvirus infections can be used when antigenemia or DNA quantitative methods are unavailable, because patients with a propensity for developing CMV disease can be readily identified and pre-emptive therapy started.

Cytomegalovirus DNA Measurement in Blood and Plasma Using Roche LightCycler CMV Quantification Reagents

Cytomegalovirus (CMV) is a common cause of morbidity and mortality in immunosuppressed patients. Newly available commercial systems facilitate the measurement of CMV DNA in whole blood or plasma, as a means of detecting and monitoring active disease. We evaluated the performance characteristics of a quantitative polymerase chain reaction that relies on analyte-specific reagents and instruments from Roche Diagnostics. DNA was extracted using a MagNaPure instrument from blood and matched plasma specimens of patients with active CMV disease (defined by another molecular assay) and from controls. Viral load was measured against Roche's standards on a LightCycler instrument, followed by melt curve analysis to confirm product specificity. Dual hybridization probes targeted the CMV UL54 gene and a control sequence that was spiked before extraction. Accuracy and linearity were established using spiked DNA from the Towne-strain CMV. The assay was linear across 6 logs, and it detected CMV DNA in 67/70 blood samples (96%) from patients who were considered to have an active CMV infection, including all 67 viral loads above 208 CMV copies/mL, suggesting that it was sensitive enough to detect clinically significant infections in immunosuppressed patients. Virus levels in plasma correlated reasonably well with the levels in whole blood (r=0.5756), suggesting that levels in either plasma or blood level were indicative of active infection. It was important to verify the calculated values by visualizing the amplification plot and using the melt curve analysis to resolve discrepancies. The LightCycler CMV assay is rapid, sensitive, and linear for quantifying CMV viral load, and it seems to be useful in the diagnosis and monitoring of affected patients.

Enumeration of cytomegalovirus-specific interferon CD8+ and CD4+ T cells early after allogeneic stem cell transplantation may identify patients at risk of active cytomegalovirus infection

Recovery of functional cytomegalovirus (CMV)-specific T lymphocytes is critical for protection from active CMV infection and disease in allogeneic stem cell transplant recipients (Allo-SCT).[1][1]–[6][2] To date, assessment of CMV-specific T-cell immunity has not had a major impact on the clinical

Factors influencing the occurrence of active cytomegalovirus (CMV) infections after organ transplantation.

In this study, several factors influencing the occurrence of active CMV infection after organ transplantation (Tx) are analysed. For this purpose, 105 heart, kidney and lung transplant recipients who were CMV-positive or had a CMV-positive donor, were closely monitored for active CMV infection by antigenaemia, cultures, CMV serology and lymphocyte proliferation (LP) to CMV. Univariate and multivariate regression analysis were performed. As pretransplant risk factors the HLA-type and numbers of HLA mismatches between recipients and their donors, and the CMV serology of the recipient and donor were analysed. A new finding was that recipients of donors positive for HLA-B7 were especially at risk for developing active CMV infection (P = 0.03) and CMV disease (P = 0.03). This was not due to increased rejection treatment in these patients. Post-transplant risk factors for development of active CMV infection were absence of detectable cellular immunity to CMV (lymphocyte proliferation) after Tx (P < 0.01) and rejection treatment with OKT3 or ATG (P = 0.05). High levels of IgG anti-CMV did not prevent occurrence of active CMV infection or CMV disease in the CMV+ recipients.

Ganciclovir/Valganciclovir Prophylaxis Decreases Cytomegalovirus-Related Events and Bronchiolitis Obliterans Syndrome after Lung Transplantation

Until recently, cytomegalovirus (CMV) infection represented a major threat to lung transplant recipients. Preliminary studies have shown that antiviral prophylaxis might improve the outcome for these patients. We extended our initial pilot trial of prolonged prophylaxis with either oral ganciclovir (1 g 3 times per day) or valganciclovir (450 mg twice per day). The trial included 96 patients who were at risk for CMV-related events. CMV prophylaxis resulted in a significant decrease in CMV-related events (i.e., active infection and disease), from 75% in a control group and for 274 cases from the literature who did not receive prophylaxis to a cumulative incidence of 27% (P < .001). Only 11% of the prophylaxis recipients experienced CMV disease (P = .002). Moreover, at 5 years, there was a significant decrease in the rate of bronchiolitis obliterans syndrome, from 60% to 43% (P = .002), and an improved rate of survival, from 47% to 73% (P= .036), irrespective of the immunosuppressive regimen received. CMV strains with UL97 mutations were recovered from 7 of 12 analyzed cases, but the presence of this mutation had no impact on the severity of CMV disease. A regimen of prolonged ganciclovir or valganciclovir prophylaxis decreased the rate of active CMV infection and disease, reduced the incidence of bronchiolitis obliterans syndrome, and improved the survival rate. Drug-resistant CMV strains may occur, but such strains appeared to have no impact on the outcome of CMV-related events.

Active CMV disease does not always correlate with viral load detection

The use of quantitative cytomegalovirus (CMV) real-time polymerase chain reaction (RT-PCR) and preemptive ganciclovir therapy is replacing prophylaxis as the management of choice in high-risk patients undergoing stem cell transplantation (SCT). However, there are limited data defining its role in this setting. In the current retrospective single-centre study, quantitative RT-PCR was used to determine CMV in 577 consecutive patients undergoing SCT (172 allogeneic and 405 autologous) over a 5-year period. CMV RT-PCR was performed weekly until cessation of immunosuppression (allogeneic) or for 30 days post-SCT (autologous). Treatment was commenced after two consecutive positive results or a high copy on the first occasion (> 1000 copies/ml, > 3 log). The overall CMV reactivation rate in patients undergoing allogeneic SCT was 30%, with reactivation observed in 72% of high-risk patients (recipient positive patients). CMV end-organ disease was observed in eight patients (1%); of these, four were CMV RT-PCR negative at the time of diagnosis of end-organ CMV disease, with three remaining negative throughout the course of the disease. CMV-related mortality was recorded in three patients. The current data support a preemptive treatment strategy-based CMV RT-PCR, but indicate that in symptomatic patients, a negative CMV PCR result does not exclude CMV end-organ disease.

Cytomegalovirus Co-infection in AIDS-associated Oral Kaposi’s Sarcoma

The increasing appearance of AIDS-associated oral Kaposi's sarcoma (KS) in South Africa may be ascribed to the later start of the HIV epidemic, more patients reaching stages III and IV, and the inaccessibility of most patients to anti-retroviral therapy. The objective of this study was to demonstrate cytomegalovirus (CMV) co-infection in oral KS and to consider its possible significance. We reviewed 20 cases of oral KS in known HIV-positive patients without active CMV disease. HHV8 PCR and CMV immunohistochemistry were performed. HHV8 DNA was present in all cases. CMV inclusions were detected in five cases. The significance of CMV co-infection in oral KS is unclear. The inclusions suggest active infection, although there is no evidence to support CMV in the pathogenesis of KS. Nonetheless, it is vital that physicians be alerted to active CMV infection, so that timely intervention and careful observation can be instituted, ensuring early diagnosis and treatment.

Detection of Cytomegalovirus (CMV) DNA by Polymerase Chain Reaction Is Associated with Hearing Loss in Newborns with Symptomatic Congenital CMV Infection Involving the Central Nervous System

The study sought to determine the relationship between cytomegalovirus (CMV) viremia during early infancy and clinical and laboratory outcome events, particularly hearing loss in infants with symptomatic congenital CMV infection involving the central nervous system (CNS). A total of 147 infant patients were enrolled prospectively in 2 clinical trials evaluating ganciclovir for the treatment of symptomatic congenital CMV infection involving the CNS. Aliquots of serum collected at enrollment in either of the 2 trials were available from 50 of the infants, and the degree of viremia was determined by real-time quantitative polymerase chain reaction. Of the 50 infants from whom serum samples were available, 37 had detectable CMV DNA in the serum sample collected at enrollment and were classified as viremic. Viremic infants were more likely to have (1) hearing loss both at enrollment (P = .045) and at the 6-month follow-up testing (P = .035) and (2) other indicators of active CMV disease, including elevated levels of alanine aminotransferase, petechial rash, and organomegaly. In children with symptomatic congenital CMV infection involving the CNS, viremia during early infancy is associated with hearing loss and systemic CMV disease.

Pharmacokinetics of Ganciclovir Following Oral Valganciclovir Versus Intravenous Ganciclovir in Allogeneic Hematopoietic Stem-Cell Transplant Patients with Stable Graft-Versus-Host Disease of the Gastrointestinal Tract.

Cytomegalovirus (CMV) disease can be effectively prevented in allogeneic hematopoietic stem cell transplant (HSCT) patients by ganciclovir (GCV) given as prophylaxis or preemptive therapy. Due to the low bioavailability of oral GCV capsules, GCV is usually administered intravenously (IV) to HSCT patients. Valganciclovir (VGCV) is the valine ester prodrug of ganciclovir. In healthy subjects, HIV-infected patients, and solid-organ transplants, the oral bioavailability of VGCV is about 60%, or 10-fold higher than oral GCV capsules. The bioavailability and total GCV exposure provided by oral VGCV relative to IV GCV in HSCT patients with gastrointestinal (GI) GHVD has not been established.METHODS: HSCT patients were eligible for the study if the following criteria were satisfied: 1) ≥16 years of age; 2) biopsy-proven GHVD of GI tract with nausea and/or diarrhea (300–1500 ml/day) or proven GVHD of skin or liver plus diarrhea with no other explanation; 3) no active CMV infection or disease; 4) neutrophil count ≥1000/μL; 5)creatinine clearance >60 ml/min. Following a standardized breakfast, eligible patients were randomized to receive a single dose of open-label study drug (900 mg of oral VGCV or 5 mg/kg of IV GCV). After a minimum 48 hr. washout period, patients were crossovered to alternate study drug. Blood for levels of GCV and VGCV were obtained predose and then over the 24 hours after dosing. Pharmacokinetic (PK) parameters were derived by noncompartmental methods.RESULTS: Data from 16 patients are currently available. Patient demographics include mean age 45 yrs (range 23 to 58 yrs); males 13, females 3; mean weight 80kg (range 52 to 107 kg); mean creatinine clearance 96 ml/min (range 62 to 184 ml/min). Median time after transplant for study was 303 days (range 102 to 988 days). Mean GCV PK parameters are summarized in the following table.Mean GCV Value (Coefficient of variation in %)Oral VGCV-900 mgIV GCV-5mg/kgParameterN = 16N = 16AUC o -τ (μg•hr/mL)43.58 (37)46.74 (40)AUC o-∞ (μg•hr/mL)46.03 (41)48.89 (43)C(max) μg/mL) (6.45 (30)12.53 (30)T max (hr)3.13 (22)0.97 (8)T½ (hr)4.97 (31)5.09 (29)GCV AUC values were similar, although maximum GCV concentrations were higher and acheived earlier with IV GCV. Terminal elimination half-life of GCV with oral VGCV and IV GCV were similar. After 900 mg of oral VGCV, mean plasma Cmax for VGCV was low (0.22 μg/mL), which is consistent with rapid and almost complete metabolism of VGCV to GCV.CONCLUSION: These preliminary results suggest that systemic exposure to GCV after 900 mg of oral VGCV is comparable to that achieved with IV GCV in HSCT patients with stable GI GVHD. Oral VGCV could be a useful alternative to IV GCV in certain HSCT patients requiring prophylaxis or preemptive therapy for CMV.

The pp67 mRNA assay in treatment and monitoring of cytomegalovirus disease in renal transplant patients in India

The present report describes use of nucleic acid sequence-based amplification (NASBA) technology to detect pp67 mRNA of cytomegalovirus (CMV) in transplant patients in India. In our experience, pp67 mRNA assay was an accurate, rapid, and effective diagnostic tool to detect active CMV disease in 40.7% (50/123) of symptomatic transplant cases. This assay also allowed us to monitor CMV therapy. As part of the immunosuppressive regimen mycophenolate mofetil was found to increase the risk of developing CMV disease. All positive cases with this assay were subjected to antiviral therapy, with complete remission of the disease. At our center CMV NASBA assay has become the gold standard for the diagnosis of CMV disease in transplant patients.

Eficacia del tratamiento anticipado con ganciclovir en la prevención de la enfermedad por citomegalovirus en receptores de un trasplante de hígado

In liver transplant recipients the most frequent infection is that produced by cytomegalovirus (CMV). One of the methods to reduce the incidence of that infection is the CMV pp65 antigenemia-guided preemptive therapy with intravenous ganciclovir. Liver transplant recipients were tested for CMV antigenemia at days 14, 28, 45, 60, 90 and 180 postransplantation and when clinically indicated. Patients showing > 50/200.000 leukocytes received ganciclovir 5 mg/kg/12 h for 14 days. Risk factors for active CMV disease where studied. 182 CMV seropositive patients where included in the study. 16 patients with > 50/200.000 leukocytes received ganciclovir as preemptive therapy. CMV disease appeared in 9/182 patients (4.9%): 2/16 who received PT and 7/166 among those who did not receive preemptive therapy. The only factor associated with increased incidence of CMV disease was to have missing samples for CMV antigenemia during the follow up (p < 0.0042; OR = 8,17; 95% CI, 1.94-34.36). Ganciclovir antigenemia-guided preemptive therapy is associated with a low incidence of CMV disease. Bad adherence to the protocol of antigenemia samples increases the risk for CMV disease.

Study of cytomegalovirus infection in renal transplant recipients

Background: The purpose of the study was to detect the incidence of active cytomegalovirus (CMV) infection in the population of different immune status and to observe the effect of prophylactic usage of the anti-CMV drug acyclovir. Methods: All patients were divided into post-renal transplantation group (P), fever group (F) and normal group (N). The P group was subdivided into P1 group (less than 6 months) and P2 group (more than 6 months). Results: The incidence of P group was higher than that of N group ( p<0.01), and no significant difference was noted between the incidence of N group and F group ( p>0.05). The average antigen-positive (Ag+) cell number per 5×10 4 leukocytes was 13.5, and 55 in active CMV infection and CMV disease. Conclusions: The result of the study reveals that the incidence of active CMV infection correlates with the population immune status, the small dose of acyclovir in the first 3 months following renal transplantation has prophylactic effect, LSAB method can make rapid and early diagnosis of active CMV infection and CMV disease, the Ag+ number correlates with the severity of infection.

Treatment of Active Cytomegalovirus Disease with Oral Ganciclovir in Renal Allograft Recipients: Monitoring Efficacy with Quantitative Cytomegalovirus Polymerase Chain Reaction

Treatment regimens of patients with active cytomegalovirus (CMV) disease require 2-3 weeks of intravenous ganciclovir (GCV) with/without CMV hyperimmune globulin. Oral GCV is effective as a prophylactic agent in prevention of CMV disease. Here we explored the utility of oral GCV as a treatment of active CMV disease. Fifteen renal allograft recipients (CMV donor+/recipient- [53%], CMV donor+/recipient+ [40%] or CMV donor-/recipient+ [7%]) developed active CMV disease. Cytomegalovirus polymerase chain reaction (CMV-PCR) tests were performed at the time of presentation and patients were treated with oral ganciclovir 1 g tid (adjusted for renal function). Patients were monitored for efficacy of treatment by assessment of clinical symptoms and CMV-PCR. Treatment was continued until the CMV-PCR copy number was negative and symptoms resolved. The mean CMV-PCR copy number at the time of diagnosis was 580 copies/microg DNA (nl: < 5 copies/microg DNA). After 5-7 days of treatment, the mean copy number was 65 copies/microg DNA. Fourteen of 15 patients responded well to oral ganciclovir, with complete resolution of clinical symptoms and eradication of CMV-PCR positivity. One patient did not respond to oral ganciclovir therapy due to probable noncompliance. Our data suggest that oral ganciclovir treatment, coupled with careful CMV-PCR monitoring, may be a reasonable alternative to long-term intravenous ganciclovir.

Cytomegalovirus (CMV)-specific CD4+ T lymphocyte immune function in long-term survivors of AIDS-related CMV end-organ disease who are receiving potent antiretroviral therapy.

To better understand the relation of cytomegalovirus (CMV)-specific CD4+ T lymphocyte immunity and clinical outcome in AIDS-related CMV end-organ disease, 2 patient groups were prospectively studied: patients recently diagnosed with active CMV end-organ disease and survivors of CMV retinitis who had responded to highly active antiretroviral therapy and had quiescent retinitis when anti-CMV therapy was discontinued. Most patients with active CMV disease had negative CMV-specific CD4+ T lymphocyte responses at diagnosis, as measured by lymphoproliferation (7/7) or cytokine flow cytometry (3/5) assays. In contrast, all 10 subjects with quiescent retinitis and >150 absolute CD4+ T lymphocytes/microL whose anti-CMV therapy was discontinued during 6 months of follow-up had positive CMV-specific immune responses at least once by each assay. However, 6 of these 10 subjects also had negative CMV-specific immune responses > or =1 time. Such patients may be at risk for future CMV disease progression and should be closely monitored.

Kidney Transplantation in Infants

After completing this article, readers should be able to: 1. Compare and contrast end-stage renal disease in children and adults. 2. Describe the anomalies that may accompany congenital urologic abnormalities. 3. List the primary causes of kidney graft losses in infants. 4. List the common infections encountered posttransplant. Kidney transplantation is the preferred mode of treatment for most children who have end-stage renal disease (ESRD). Despite advances in dialysis management, children who undergo this treatment modality experience stunting in growth and development,1 and mortality rates are higher for children on dialysis compared with those who receive transplants for all age groups.2 In the past, results of kidney transplantation in infants had made the procedure prohibitive, and success rates were extremely low. Compared with adults and larger pediatric patients, infants who have ESRD are at the highest risk for early graft loss and consistently have had the highest mortality rates. Recent advances in the medical and surgical management of these infants have led to improved results in survival and long-term renal transplant function. However, survival rates vary among transplant centers, and the infant subgroup remains the most challenging of any age group receiving transplantation. According to analyses of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) and the United Network of Organ Sharing (UNOS) data, 15% of living donor grafts and 35% of cadaver grafts in infants are lost in the early posttransplant period due to technical complications, vascular thrombosis, or irreversible acute rejection.33,4 Graft survival at 7 years for infants receiving transplantation from living donors (those in whom the best possible outcome is expected) is approximately 71% nationally,4 although results vary. This long-term graft survival is surprisingly high, considering that graft survival at 1 year was only 80% nationally. In our experience with 45 consecutive kidney transplants …