Cytomegalovirus Infection In Patients Research Articles

Evaluation of a Non-invasive Method to Detect Cytomegalovirus (CMV)-DNA in Stool Samples of Patients with Inflammatory Bowel Disease (IBD): A Pilot Study

A severe flare of colitis in patients with IBD treated with immunosuppressive therapy may be complicated by an underlying CMV infection. The aim of this pilot study was to investigate the diagnostic efficacy of quantitative polymerase chain reaction (PCR) to detect CMV DNA in stool samples of IBD patients. Twenty-one patients with a severe flare of IBD, incompletely responding or refractory to either steroids or immunosuppressive agents, were included in the study. Nineteen patients completed the study according to the protocol undergoing an endoscopy with biopsies and collection of stool samples. Biopsy and stool samples were qualitatively and quantitatively analyzed for CMV DNA using real-time PCR. Thirty-two percent (6/19) of the patients had detectable CMV DNA in colonic biopsies and in five (83%) of those patients CMV DNA was detected in the stool. Thirteen patients had negative findings for CMV DNA in biopsy and stool samples. The sensitivity, specificity, and accuracy of the PCR-based stool test for detection of CMV DNA compared to PCR-based detection of CMV in mucosal biopsies were 83, 93, and 90%, respectively. The pilot study suggests a high accuracy of this non-invasive testing method to detect CMV DNA in stool samples as compared to mucosal biopsies. This approach may offer a non-endoscopic testing modality for underlying CMV infection in patients with a severe flare of IBD, which could also be applied more broadly to determine the prevalence of CMV infections in patients with IBD.

Cytomegalovirus Infection in Patients with Active Inflammatory Bowel Disease

The reported prevalence of cytomegalovirus (CMV) infection with active inflammatory bowel disease (IBD) is highly variable, and whether CMV negatively impacts the clinical course is controversial. The aim of this study was to determine the prevalence of CMV in patients with active ulcerative colitis (UC) or Crohn's disease (CD) and compare the course of disease in patients with and without CMV. Consecutive patients with acute exacerbations of active IBD colitis had immunohistochemistry staining for CMV antigen performed on archived specimens. Clinical features were retrospectively reviewed. Twelve (10%) of 122 UC patients had CMV, and 0/20 patients with CD had CMV. Of 12 UC patients with CMV infection, seven were not taking steroids or immunosuppressives at their index flare. UC patients with CMV were more likely to have leukocytosis (OR = 5.3, 95% CI 1.5-18.2), require hospitalization (OR = 4.9, 95% CI 1.2-19.0), and be hospitalized > or =7 days (OR = 5.0, 95% CI 1.6-21.3) compared to patients without CMV. Of 12 UC patients with CMV, ten (83%) were treated for their index flare with steroids or 6-mercaptopurine. Only one patient (8%) was treated for CMV infection which occurred 14 months after index endoscopy. Over the 6 months after the index flare, UC patients with CMV had a higher frequency of IBD-related hospitalizations compared to patients without CMV (50 vs. 24%, P = 0.021), but none required surgery or died. The prevalence of CMV with active UC was 10%. Although CMV infection may be a marker of disease severity, our results suggest it does not cause severe morbidity or mortality in a general population of patients with a UC flare.

Intragraft Cytomegalovirus Infection: A Randomized Trial of Valacyclovir Prophylaxis versus Pre-Emptive Therapy in Renal Transplant Recipients

In a randomized study, we observed a higher incidence of biopsy-proven acute rejection with pre-emptive valganciclovir therapy as compared with valacyclovir prophylaxis for prevention of cytomegalovirus (CMV) disease after renal transplantation (RTx). Persistence of the virus within the allograft could stimulate the alloimmune response. The aim of our study was to evaluate intragraft CMV infection in patients randomized to the trial. RTx recipients at risk of CMV were randomized to pre-emptive therapy with valganciclovir (n=36) for significant CMV viraemia (> or =2,000 copies/ml by quantitative PCR in whole blood samples) or 3-month prophylaxis with valacyclovir (n=34). Renal biopsies performed during 12 months post-RTx were analysed for the presence of CMV by real-time PCR and immunohistochemical staining. A total of 35 patients (59 biopsies) in the pre-emptive group and 31 patients (57 biopsies) with valacyclovir prophylaxis had > or =1 biopsy specimen with sufficient material for intragraft CMV determination. Cumulative incidence of intragraft CMV infection was 14% and 7% (P=0.315) with pre-emptive therapy and prophylaxis, respectively. Patients at risk for primary CMV infection (CMV serological donor-positive and recipient-negative) were at higher risk for intragraft CMV infection (40% versus 5%; P=0.008). CMV viraemia at the time of biopsy was associated with the presence of CMV within the allograft (P<0.001). During the first year after RTx, the incidence of intragraft CMV infection was relatively low with comparable rates in patients managed by pre-emptive valganciclovir therapy and valacyclovir prophylaxis.

The role of cytomegalovirus infection in refractory ulcerative colitis: A case report

Cytomegalovirus (CMV) has been identified as a pathogen that contributes to flares of colitis and as a potential cause of steroid-refractory ulcerative colitis. However, clinically relevant patterns of CMV infection in IBD have yet to be identified. We present a case of a 70-year-old male with ulcerative colitis (UC), diagnosed 10 years prior, who presented with acute onset of bloody diarrhea. The patient's disease has been well-controlled for the past 5 years on Imuran and infliximab 5mg/kg every 8weeks. His last colonoscopy was two years prior and showed inactive colitis. Stool studies were obtained and an infectious cause of his diarrhea was negative. He underwent a flexible sigmoidoscopy which showed friable and granular mucosa in the rectum. Biopsies for pathology and viral cultures were taken. The viral culture was positive. However, an extensive histological examination of the tissue did not identify inclusion bodies. Furthermore, the immunohistochemistry (IHC) staining was also negative. After discussion with the infectious disease specialist, it was decided that this most likely did not represent an active infection. The patient had continued symptoms and was started on prednisone with slight improvement in his symptoms. A colonoscopy showed active colitis with diffuse involvement of the rectum and sigmoid. Biopsies were again taken and revealed similar results as above. At this time, we planned a dose intensification of his infliximab to 10mg/kg. However, despite the steroids and dose intensification the patient continued to have severe symptoms and was admitted to the hospital for intravenous steroids and monitoring. A repeat colonoscopy was done at this time, which showed active colitis that had now extended to the mid-transverse colon. Biopsies done during this colonoscopy showed active CMV colitis as evidenced by inclusion bodies and positive IHC stain. The patient was started on a three week course of intravenous ganciclovir. His symptoms resolved after completion of treatment. A follow-up colonoscopy showed improvement in his colitis. Biopsies did not reveal any active inflammation or inclusion bodies. The case presented raises questions regarding the identification, diagnosis and management of CMV colitis in patients with ulcerative colitis. There are conflicting data regarding these issues. In this era of increased use of biologic therapy it is possible that CMV infection may become more prevalent and therefore further studies are needed to identify the prevalence and role of CMV infection in patients with UC. Also, further investigations are needed to identify the most useful techniques for diagnosing active CMV colitis. These have important implications in regards to management and prognosis of refractory disease.

Cytomegalovirus Infection in Patients with Acute Leukemia and MDS.

Abstract 4167 [Background]It is important for the progress of the support treatment for AML. It is possible for more than seventy years old patients to cure AML actively. [Purpose]We examined the CMV reactivation after chemotherapy of AML, MDS, and ALL. [Methods]The study design planned to enroll 195 patients. Diagnoses included AML (121), MDS (56), ALL (18). Patients received induction chemotherapy. Induction regimens consisted of IDA (12 mg/m2 per day, day 1, 3, 5 and 8) and BHAC (350 mg/ m2 per day, day 1-10)(= Ara-C 200 mg/ m2 per day, day 1-10). Patients received consolidation chemotherapy. Consolidation chemotherapy comprised of High-dose Ara-C Therapy-containing regimens. We examined the CMV reactivation when patients have fever but they were recovered from the leukocyte decrease term after chemotherapy. [Results]About 10% of patients experienced CMV reactivation. Thirteen of 121 AML patients experienced CMV reactivation. Three of 56 MDS patients experienced CMV reactivation. Four of 18 ALL patients experienced CMV reactivation. [Conclusion]It is important to be careful for CMV reactivation in patients receiving High-dose Ara-C Therapy. Disclosures:No relevant conflicts of interest to declare.

Acute Cytomegalovirus Infection Is a Risk Factor in Refractory and Complicated Inflammatory Bowel Disease

The role of cytomegalovirus (CMV) infection in patients with inflammatory bowel disease (IBD) is controversial. Although CMV has been specifically associated with refractory disease, the strength and nature of this association have been a subject of debate. The aim of this study was to evaluate the prevalence and outcome of acute cytomegalovirus infection in patients with severe refractory and complicated inflammatory bowel disease. Seventy-two patients with active IBD (both ulcerative colitis [UC] and Crohn's diseases [CD]) were included in this study. Thorough history taking and physical examination of all patients was made with special emphasis on symptoms and signs of CMV disease. Colonoscopic assessment was made for the extent and activity of IBD and collection of specimen. Prevalence of CMV infection was estimated by serology; anti-CMV IgM and IgG antibodies, and pathologic studies of colonic biopsies used conventional haematoxylin and eosin (H & E) and immunohistochemistry (IHC) with monoclonal antibodies. Complete blood count and liver function tests were done for all patients. Among 72 patients with active inflammatory bowel disease, 23 (31.9%) were resistant to intravenous steroids. CMV was detected in eight (six with UC and two with CD) of the 23 (34.8%) steroid-resistant patients and in only one (3.2%) patient in the remaining 31 patients under steroid treatment and was not detected in 18 IBD patients not using steroids. Among nine CMV-positive IBD patients, six (66.6%) were female and six had fever; cervical lymphadenopathy was found in five patients and splenomegaly in two, compared to no patients in the CMV-negative group (P = 0.01 and 0.03, respectively). Leucopenia and thrombocytopenia were predominantly seen in the CMV-positive versus CMV-negative patients (2.1+/-0.3 vs. 5.9+/-3.4 and 98+/-34 vs. 165+/-101, respectively). Pancolitis was found in five of nine CMV-positive IBD patients whereas in only two patients out of 63 in the CMV-negative group (P = 0.005). Acute CMV infection in patients with IBD is not rare and is often underestimated. CMV infection in patients with refractory or complicated IBD should be ruled out before aggressive immunosuppressive therapy. High clinical index of suspicion for the association of CMV infection with IBD should be directed towards female IBD patients presenting with fever, lymphadenopathy, splenomegaly, leucopenia, and mild hepatitis. CMV IHC is significantly more sensitive than routine H & E stain and should be considered as part of the routine evaluation of IBD patients with severe exacerbation or steroid-refractory disease before proceeding with other medical or surgical therapy that may not be necessary once the CMV is treated.

Increased mortality in long-term intensive care patients with active cytomegalovirus infection*

To determine the prevalence and impact on patient outcome of active human cytomegalovirus infections in patients with prolonged treatment in an intensive care unit. Retrospective analysis of stored plasma samples. Anesthesiological intensive care unit of a university hospital. All 138 patients treated for at least 14 days (of a total of 4940 patients admitted during the study period). Immunocompromised patients and patients with inconclusive results for cytomegalovirus DNA were excluded. None. Stored plasma samples of patients with prolonged intensive care unit stay were tested for cytomegalovirus DNA. Sixty-four of 255 evaluable samples from 99 immunocompetent patients tested cytomegalovirus DNA-positive with a mean DNA concentration of 8,600 genome equivalents per milliliter. Active cytomegalovirus infection was diagnosed by reproducibly positive results in 35 patients (35%). Only one case had been diagnosed clinically. Patients with and without active cytomegalovirus infection were not significantly different in parameters, such as age, sex, admission category, source of admission, or comorbidities. Even review of specific surgical procedures or the use of a heart-lung-machine showed no significant differences between the groups. The mortality rate in patients with cytomegalovirus infection was significantly increased (28.6% vs. 10.9%, p = 0.048), and surviving patients had a longer intensive care unit stay (32.6 vs. 22.1 days, p <0.001). Active cytomegalovirus infection is a frequent but seldom diagnosed finding in surgical patients with prolonged intensive care unit stay, which is associated with increased mortality and prolonged intensive care unit stay of surviving patients.

Markers of Chlamydia pneumoniae and human cytomegalovirus infection in patients with chronic peripheral vascular disease and their relation to inflammation, endothelial dysfunction and changes in lipid metabolism

Our aim was to detect markers of Chlamydia pneumoniae (CPN) and human cytomegalovirus (HCMV) infection in patients with peripheral vascular occlusive disease and to follow markers of inflammation, endothelial dysfunction and lipid metabolism alteration in patients with active infection. CPN genome was detected in 9 (47.4 %) patients by at least one PCR method. Serological markers of acute CPN infection were found in 5 (26.3 %) subjects; each of them showed also positivity in at least one of the PCR methods. HCMV DNA were detected in 2 (10.5 %) patients; HCMV-specific antibodies were detected in 14 (73.7 %) subjects, however only in IgG subclass. Subjects with HCMV PCR positivity thus showed no serological markers of active HCMV infection. Laboratory findings of acute CPN infection were associated with increased plasma levels of Lp(a), triacylglycerols, atherogenic index of plasma and E-selectin (p < 0.05). No significant differences were found in the other markers, including plasma levels of total cholesterol, ferritin, homocysteine, oxidized LDL, IL-6, IL-8, IL-18, TNF-alpha, soluble forms of VCAM-1 and ICAM-1, von Willebrand factor, C-reactive protein, and plasma nitrites & nitrates. Frequent presence of chlamydial DNA in atheromatous plaques from patients with peripheral vascular disease was confirmed. HCMV DNA was detected only sporadically and with positivity in anamnestic anti-HCMV antibodies (IgG) only, indicating a rare presence of latent virus rather than active replication. Patients with laboratory markers of acute CPN infection exhibited more pronounced alterations in lipid metabolism and endothelial dysfunction.

Hyaluronan-Mediated Leukocyte Adhesion and Dextran Sulfate Sodium-Induced Colitis Are Attenuated in the Absence of Signal Transducer and Activator of Transcription 1

Inflammatory bowel disease is a chronic inflammatory condition of the intestinal mucosa whose etiology is unclear but is likely to be multifactorial. We have shown previously that an increased amount of hyaluronan (HA) is present both in the inflamed mucosa of inflammatory bowel disease patients and in isolated human cells after polyI:C treatment. The signal transducer and activator of transcription (STAT)1 protein plays an important role in many signaling pathways that are associated with inflammation. We therefore investigated the role of STAT1 in adhesive interactions that occur between leukocytes and polyI:C-induced mucosal smooth muscle cells (M-SMCs). Activation of STAT1 was observed after the polyI:C treatment of M-SMCs. Specific phosphorylation of tyrosine and serine residues of STAT1 was observed in polyI:C-treated, but not untreated, M-SMC cultures. To evaluate further the role of STAT1, a corresponding STAT-1-null mouse was used. PolyI:C-induced, HA-mediated leukocyte adhesion to colon SMCs from STAT1-null mice was significantly decreased compared with that from wild-type control mice. In vivo, using the dextran sulfate sodium-induced model of colon inflammation, both tissue damage and HA deposition were attenuated in STAT1-null mice compared with that in wild-type control mice. Additionally, the inter-alpha-trypsin inhibitor (IalphaI), a proteoglycan essential for facilitating leukocyte binding to the HA matrix, was reduced in STAT1-null mice. Together, these results demonstrate that STAT1 plays an important role in HA-mediated inflammatory processes.

Outcomes of the First 2 American Hand Transplants at 8 and 6 Years Posttransplant

The feasibility of hand allotransplantation has been demonstrated. The purpose of the article is to report the (1) functional return, (2) psychosocial outcomes, (3) clinical and histological assessment for rejection, (4) complications, and (5) graft survival in the 2 American hand transplant recipients. We present 2 patients 106 and 81 months, respectively, after unilateral transplantation of an allogeneic hand and forearm. We analyzed clinical course, number of rejection episodes, adverse events, function of the allograft, and quality of life. Clinical laboratory results, biopsy histology, and patient clinical examinations were used to compare the clinical course. Standard hand function tests were used to evaluate function. Psychological interviews were used to assess acceptance and quality of life. Our patients have allograft survival with improvements in intrinsic muscle activity, total active motion and return of functional grip, pinch strength, and sensibility. Rejection episodes were restricted primarily to the first 6 months after transplantation, and all responded to treatment. The major posttransplantation complications were a cytomegalovirus infection in patient 1 and osteonecrosis of the hip requiring both hips to be replaced, 1 at year 4 and the other at year 6, as well as transient immunosuppression-related diabetes in patient 2. Recently we have weaned both patients off maintenance steroids. Current Carroll scores are fair for patient 1 (72/99) and fair for patient 2 (55/99), although patient 2 has not had good recovery of intrinsic function. Both patients are back at work and report an excellent quality of life at nearly 9 and 7 years, respectively, after transplantation. Our intermediate long-term results of hand transplants have demonstrated functional return similar to that of replants. Graft survival and quality of life after hand transplantation has far exceeded initial expectations. We conclude that allogeneic hand transplant is feasible and holds promise as a treatment modality for catastrophic upper extremity loss. Therapeutic IV.

Cutaneous cytomegalovirus infection in a patient with acquired immunodeficiency syndrome

Abstract Cytomegalovirus (CMV) infection in immunocompromised patients is a common opportunistic systemic infection which can lead to death, and usually presents with visceral manifestations, especially of the lung, brain, eye, and gastrointestinal tract. Cutaneous CMV infection is, however, relatively rare in immunocompromised patients. Cutaneous CMV infection can have variable clinical and histologic manifestations, and thus can be easily missed. We report a case of cutaneous CMV infection in a patient with acquired immunodeficiency syndrome, presenting as a generalized, pruritic, erythematous, maculopapular eruption.

Importance of diagnosis of concomitant cytomegalovirus infection in patients with intestinal Behçetʼs disease

Importance of diagnosis of concomitant cytomegalovirus infection in patients with intestinal Behçetʼs disease

Cytomegalovirus Infection in Patient with Refractory Ulcerative Colitis: Prevalence, Outcome and Therapeutic Effect of Antiviral Treatment

Background & Aim: Cytomegalovirus (CMV) infection has been reported as a cause of refractory ulcerative colitis (UC), but the natural history of CMV infection related to the development and treatment of UC has not been clarified. In some cases, CMV infection is associated with a poor outcome but it is not clear which patients are more likely to be affected and in which stage of the disease. The aim of this study was to evaluate the prevalence, outcome and therapeutic effect of antiviral treatment of CMV infection in a consecutive series of patients with severe steroid refractory UC. Methods: The subjects were a total of 78 patients with severe UC at our Hospital between 1990 and 2006 in the study. Forty-six patients were identified with refractory UC, defined as poor response to high-dose systemic steroids (refractory UC). Patients were evaluated for CMV by using serology (antigenemia), and histopathological assessment of hematoxylin-eosin (HE) and immunohistchemical (CMV IgG antibodies)-stained colonic biopsies. Positive result in any test was considered as CMV infection. We studied refractory UC with CMV for frequency, clinical characteristic, outcome of medical treatment, and therapeutic effect of antiviral treatment (Ganciclovir; GCV). Results: The prevalence of CMV infection in the steroid-refractory UC was 39.1% (18/46). There was no difference in the CMV infection rate between males and females (males, 9/24; 37.5% and females, 9/22; 40.9%). In case of UC with refractory lesion, there is a high possibility that treatment is ineffective (73.0%). In endoscopic finding, longitudinal ulcer (65.9%) and extensive mucosal abrasion (61.0%) were found with high frequency, and there were refractory lesion significantly in depths of the colon. Of 18 refractory UC with CMV detected, 13 (72.2%) were refractory to steroids and other immunosuppressive drugs, and had undergone. Of 13 refractory UC with CMV treated with GCV, 9 (71.5%) temporally obtained remission by first anti-virus medication, otherwise 5 of 9 patients responded by GCV were fared up and was operated on. Only 5 patients went into remission after antiviral treatment (10.8 ± 7.2 month). Conclusions: CMV infection is a frequent cause of severe refractory UC. The findings of this study suggest that it is very important to decide on a patient's medication by relying on exact diagnosis concerning the condition of UC by endoscopy. Further, GCV is useful for treatment of CMV-associated UC after immunosuppressive therapy. UC patients with CMV infection more often required surgical treatment (13/18, 72.2%) and is associated with poor outcome.

Cytomegalovirus infection following lung transplantation

The significance of cytomegalovirus (CMV) infection after lung transplantation was investigated in 20 patients (ten women and ten men; mean age 46 [21-67] years). Indications for transplantation were emphysema (n = 6), cystic fibrosis (n = 2), primary pulmonary hypertension (n = 2), pulmonary fibrosis (n = 5), obliterating bronchiolitis (n = 2), cystic lung (n = 2) and bronchiectasis (n = 1). Incidence, diagnostic parameters (serology, virus isolation and histology) and efficacy of prophylactic and therapeutic measures were recorded. 16 of the 20 patients developed a CMV infection, which in 12 was clinically significant. CMV pneumonia developed in two patients, proving fatal in one. The infection occurred a median of 47 (17-200) days after the transplantation. Administration of Ganciclovir (5 mg/kg twice daily intravenously) brought about remission of symptoms in all but one of the patients and improved the clinical parameters.--This experience demonstrates that regular monitoring of the patients for possible CMV infection and its early therapy can achieve a low death rate.

Severe systemic cytomegalovirus infections in patients with steroid-refractory ulcerative colitis treated by an oral microemulsion form of cyclosporine: Report of two cases

CMV reactivation is frequently observed in acute flares of ulcerative colitis (UC), particularly those which do not respond to intravenous steroids. Several recent series have suggested that, in most cases, CMV reactivation does not lead to severe complications and resolves spontaneously with the UC flare and discontinuation of immunosuppression. In the present paper, we describe two patients with active UC who developed a severe systemic CMV infection during a treatment with an oral microemulsion form of cyclosporine. This is of concern, particularly in a context of increasing use of immunosuppressive drugs in UC. We propose a prophylactic and curative approach to decrease morbidity related to CMV infection in active UC.

Cytomegalovirus Complicating Biological Immunosuppressive Therapy in Two Patients with Psoriasis Receiving Treatment with Etanercept or Efalizumab

Cytomegalovirus (CMV) is a herpes virus with life-long persistence following primary infection. Forty percent of the population carry the virus by the age of 20 years and sixty percent by the age of 60 years. CMV infections are usually asymptomatic, but in the immuno-compro-mised patient reactivation or a primary infection may cause severe disease, with retinitis, colitis, hepatitis or pneumonia. TNF-α mediates host-resistance against micro-organisms and inhibits CMV replication and serum TNF-α is elevated during acute CMV-infections (1). TNF-α blocking agents (infliximab, etanercept and adalimumab) block the pivotal role of TNF-α in the inflammatory response. Efalizumab is a monoclonal antibody directed against the CD11a subunit of LFA 1 on lymphocytes, thereby blocking lymphocyte to antigen-presenting cells interaction and diapedesis. We describe here 2 cases of CMV infection in patients receiving biological treatment. CASE REPORTS

HLA-DRB1*09 Is Associated with Increased Incidence of Cytomegalovirus Infection and Disease after Allogeneic Hematopoietic Stem Cell Transplantation

Cytomegalovirus (CMV) infection is a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT); however, we have little information on the clinical association of various human leukocyte antigen (HLA) alleles with CMV infection. We reviewed medical records of 60 patients who underwent allo-HSCT. The effect of the 7 most frequent HLA alleles on the incidence of CMV infection and disease was analyzed, including HLA-A*02, A*11, A*24, B*13, B*40(60), DRB1*15, and DRB1*09. All the patients were monitored for CMV infection at least once weekly within 3 months. CMV infection was found in 38 (63.3%) patients on a median of day 36 (range: 16-89). Diagnosis of CMV disease was established in 6 (10.0%) patients, comprising pneumonia (n = 2), enterocolitis (n = 2), and hemorrhagic cystitis (n = 2). CMV disease was successfully treated using ganciclovir or foscarnet combined with immune globulins in 4 patients. The other 2 patients died without improvement of CMV disease. In multivariate analysis, grade II-IV acute graft-versus-host disease (aGVHD), CMV seronegative donors, and HLA-DRB1*09 were associated with increased incidence of CMV infection and disease after allo-HSCT. We suggest that more cautions should be taken to prevent CMV infection in patients with HLA-DRB1*09 after allo-HSCT.

Comparison of Serology Assays and Polymerase Chain Reaction for the Monitoring of Active Cytomegalovirus Infection in Renal Transplant Recipients

Background Cytomegalovirus (CMV) infection is a common complication of renal transplantation. It can be diagnosed serologically, mainly based on seroconversion or by the detection of viral antigen via CMV-DNA amplification (polymerase chain reaction [PCR]). Aim We sought diagnosis of an active CMV infection in renal transplant patients comparing serologic assays of CMV-IgM antibodies with CMV-DNA amplification. Methods We retrospectively studied renal transplant recipients 26 (including 15 women) hospitalized with clinical suspicion of CMV disease. The diagnosis of CMV infection was suspected on the basis of nonspecific symptoms, including fever, leukopenia, hyperbilirubinemia, and alanine aminotransferase elevation, alone or in combination. At the time of admission, all patients were screened for CMV-IgM antibody (immunoassays AxSYM/IMx) and CMV-DNA (qualitative PCR). Results The confirmation of CMV infection by the two methods (immunoassay and PCR) was obtained in only three patients (11.5%), its unambiguous exclusion—in four cases (15.4%). Nineteen patients (73.1%) were positive for CMV-IgM and negative for CMV-DNA. Conclusion Detection of CMV-IgM antibodies by various immunoassays is not sensitive enough for diagnosis and cannot be used for monitoring during the active period in renal transplant recipients. This observation supported the prolonged presence of IgM antibodies after recent CMV infection in this patient group.

Cellular Immunity and Active Human Cytomegalovirus Infection in Patients with Septic Shock

Human cytomegalovirus (CMV) is an important opportunistic pathogen after transplantations. In the present study, monitoring of CMV in patients with septic shock was used to discover whether T helper cell type 1 (Th1) cell and natural killer (NK) cell functions interact with CMV reactivation in patients not undergoing immunosuppressive therapy. Thirty-eight patients with septic shock were monitored, and the 23 CMV-seropositive patients were included in this prospective study. Seven patients (30.4%) developed an active CMV infection despite the detection of CMV-reactive Th1 cells. After active CMV infection, the frequency of CMV-reactive Th1 cells increased from a median of 0.52% to 5.04% (P=.009). Active CMV infections were terminated without antiviral therapy within 2 weeks. In parallel, the frequency of staphylococcal enterotoxin B (SEB; superantigen)-reactive Th1 cells increased from a median of 1.11% to 8.48% (P=.027). In patients without active CMV infection, the frequency of CMV-reactive (median, 0.39%) and SEB-reactive (median, 1.11%) Th1 cells did not increase. Cytotoxic NK cell activity was persistently suppressed despite the presence of CD56(+)CD16(+) NK cells. Moreover, interleukin-2 application in vitro did not restore NK cell activity. A proinflammatory immune response may contribute to CMV reactivation in patients with septic shock. Adaptive T cell immunity, more likely than NK cell immunity, may contribute to termination of active CMV infection without antiviral therapy in these patients.

Usefulness of quantitative real-time PCR assay for early detection of cytomegalovirus infection in patients with ulcerative colitis refractory to immunosuppressive therapies

Studies suggest that cytomegalovirus (CMV) infection exacerbates ulcerative colitis (UC) refractory to immunosuppressive therapies. Early and accurate diagnosis of CMV infection is important for the treatment of UC. We evaluated the usefulness of quantitative real-time polymerase chain reaction (PCR) for detecting CMV infection in inflamed colonic mucosa of patients with UC refractory to immunosuppressive therapies. From 2003 to 2006, 30 patients (mean age: 41 +/- 18 years; 14 men, 16 women) with UC refractory to immunosuppressive therapies were enrolled in the study. We evaluated CMV infection by CMV antigenemia, histologic examination, and quantitative real-time PCR for CMV using colonic mucosa and investigated the clinical outcomes of antiviral therapy. CMV-DNA was detected only in the inflamed colonic mucosa in 17 (56.7%) of 30 patients. Of the 17 CMV-DNA-positive patients, 4 were positive for CMV antigenemia or inclusion bodies on histologic examination; of the 13 CMV-DNA-negative patients none was positive for CMV antigenemia or inclusion bodies. Of the 17 CMV-DNA-positive patients, 12 (70.6%) were treated with ganciclovir for 2 weeks and 10 patients went into remission. Two other patients required colectomy after antiviral therapy. In contrast, of the 13 CMV-DNA-negative patients 12 (92.3%) achieved remission after intensifying their immunosuppressive therapies. Quantitative real-time PCR assay for detecting CMV-DNA is useful for early, accurate diagnosis of CMV infection in patients with UC refractory to immunosuppressive therapies, enabling prompt and appropriate treatment.