Enterocolic fistula: A rare presentation of cytomegalovirus infection

In the present report, the first reported case of cytomegalovirus (CMV)-associated enterocolic fistula in an HIV/AIDS patient is described. CMV colitis is the second most common presentation of CMV infection in immunocompromised patients. CMV-associated enteric fistulae are an exceedingly rare complication, with only four previous cases described: a gastrocolic, an enterocutaneous, a rectovaginal and a colocutaneous fistula. Management of these patient demonstrates the importance of treating the precipitating viral infection before considering surgical intervention of the enterocolic fistula.     

Relapsing cytomegalovirus infection in solid organ transplant recipients

Abstract:: Efforts to prevent relapsed cytomegalovirus (CMV) disease among solid organ transplant (SOT) recipients present clinical challenges. Historically, SOT recipients treated with short courses of ganciclovir, without documented clearance of viremia, had relapse rates of 23–33%. Current treatment often includes much longer courses of valganciclovir, and persistence of viremia at the end of treatment is rare. We sought to determine the rate and risk factors for relapse under those treatment conditions. Records of 1760 SOT recipients from January 2003 to June 2007 were reviewed; 105 cases of CMV viremia were identified. Relapse occurred in 20/105 (19%); 50% had end‐organ disease at the time of relapse. Most patients received approximately 3 months of valganciclovir. Clearance of viremia was documented in 19/20 patients with relapse. Multivariable analysis identified receipt of a thoracic organ and diabetes mellitus as risk factors for relapse. Despite long treatment courses with valganciclovir and documented clearance of viremia, CMV relapse remains common among SOT recipients. Better understanding of the epidemiology of CMV among SOT recipients and validation of risk factors for disease relapse should be the focus of future prospective trials. Such trials should include different treatment durations and extended monitoring for relapse.     

Elucidation of cytomegalovirus disease recurrence in an HIV-1-positive patient

Background. Cytomegalovirus (CMV) is responsible for the most common opportunistic viral infection in patients with acquired immunodeficiency syndrome (AIDS). The colon is a common site for CMV infection in patients positive for the human immunodeficiency virus (HIV). The clinical diagnosis of CMV infection is based on the characteristic endoscopic appearance of extensive ulceration of the gastric mucosa. Methods. A 54-year-old HIV-positive man visited our hospital because of high fever. The patient presented with diarrhea, and colonoscopy was performed. Ganciclovir was administered, with a good clinical response. However, the patient complained of the same symptoms again 6 months later. Nested polymerase chain reaction (PCR) was performed on all the patient's samples to detect CMV, followed by sequencing of the UL97 gene for CMV resistance detection. Results. The PCR tests for Legionella, Chlamydia pneumoniae, Pneumocystis carinii, and Aspergillus were negative. DNA preparations from biopsy specimens of areas of colon ulceration were positive for CMV. Six months after treating the colon ulcerations, the PCR for CMV was positive, and the possible emergence of CMV mutants conferring ganciclovir resistance was examined. Direct sequencing of the PCR products revealed the known V594 mutation in the UL97 gene predisposing for ganciclovir resistance as well as the polymorphisms (579, GGCGGT) and (598, GGTGGC) in all samples tested. Conclusions. In summary, molecular biology methods can be used for early detection of CMV in characteristic colonic lesions in HIV-1-positive patients. Furthermore, detection of mutant strains resistant to antiviral drugs as well as polymorphisms elucidate the natural history of the infection.     

Gastroduodenal cytomegalovirus infection is common in kidney transplantation patients

Objective Cytomegalovirus (CMV) infection is known to cause ulcerations, erosion and mucosal haemorrhage in the gastrointestinal tract. The aim of this study was to report the CMV findings in the gastroduodenal mucosa of kidney transplantation patients and immunocompetent controls.

Material and methods Forty-six kidney transplant patients with upper gastrointestinal symptoms and 43 immunocompetent, dyspeptic patients (controls) prospectively underwent oesophagogastroduodenoscopies (OEGDs), with biopsies from the duodenum and stomach. CMV was demonstrated by immunohistochemistry, both in frozen sections using a monoclonal antibody against CMV-specific antigens (pp65 matrix protein) and in paraffin sections by means of a monoclonal antibody against the delayed early protein (p52).

Results CMV was detected in the gastric mucosa in 30% of the kidney transplant patients and in 9% of the controls (p<0.05) and in the duodenal mucosa in 70% and 35%, respectively (p<0.01). The total frequency of CMV findings was similar in patients who underwent OEGDs <1 year and >1 year after transplantation. CMV inclusions were found only in transplantation patients <1 year after transplantation (n=9). CMV findings, especially inclusions, in the gastric biopsies were associated with nausea and upper gastric pain. Histopathological findings in CMV-positive samples were non-specific, focal inflammation in haematoxylin-eosin-stained preparations, while CMV p52 staining showed inclusions in either the epithelial or endothelial cells.

Conclusions CMV could be detected in the gastroduodenal mucosa in 74% of kidney transplantation patients and in 40% of immunocompetent controls (p<0.01). CMV diagnostics are always recommended when gastroduodenal biopsies of kidney transplantation patients are performed.     

Clostridium difficile and cytomegalovirus colitis co‐infection: search for the hidden ‘bug’

D.F. Florescu, C. Mindru, H.E. Chambers, A.C. Kalil. Clostridium difficile and cytomegalovirus colitis co‐infection: search for the hidden ‘bug’.
Transpl Infect Dis 2011: 13: 411–415. All rights reserved Abstract: Few cases of co‐infection with cytomegalovirus (CMV) and Clostridium difficile colitis have been reported previously. We describe 2 cases of CMV and C. difficile colitis, and review 7 previously published reports. We aim to raise awareness of possible CMV–C. difficile co‐infection, especially in refractory cases of C. difficile colitis.     

Predictors for persistent cytomegalovirus reactivation after T-cell-depleted allogeneic hematopoietic stem cell transplantation

Cytomegalovirus (CMV) reactivation occurs in up to 60% of CMV-seropositive recipients after allogeneic hematopoietic stem cell transplantation (HSCT). The incidence of CMV disease among T-cell-depleted HSCT patients has been reported from 5-15%. The incidence of reactivation refractory to antivirals in this population is not well studied. METHODS: In this retrospective study we characterized the outcome of CMV reactivation in a cohort of 255 adult and pediatric patients who underwent T-cell-depleted HSCT at Memorial Sloan-Kettering Cancer Center from September 1999 through August 2004. CMV infection was monitored by the pp65 antigenemia assay (CMV Ag). Persistent reactivation was defined as antigenemia positivity >21 days on antiviral therapy. RESULTS: Of 118 CMV-seropositive recipients, 69 (58.4%) had reactivated CMV. Twenty of 69 (29%) developed persistent reactivation at first episode of reactivation, and 7 (10%) in subsequent episode. All patients with persistent reactivation received >/=2 antivirals and CMV hyperimmune globulin; 45% received combination antiviral therapy. The median duration of persistent reactivation was 98 days, range 31-256 days. In multivariate analysis, maximum CMV Ag >25 cells/slide was associated with persistent reactivation (odds ratio 16.2%, 95% confidence interval 4-64, P<0.0001). CMV disease occurred in 6/27 (22%) patients with persistent reactivation. Patients with persistent reactivation had lower CD4(+) and CD8(+) lymphocyte counts compared with those with non-persistent reactivation at day +90 post HSCT (P=0.01 and 0.02, respectively). CONCLUSIONS: Persistent reactivation occurred in 39% of T-cell-depleted HSCT despite treatment with currently available antivirals. Maximum CMV Ag >25 cells/slide was associated with persistent CMV reactivation. More effective treatment modalities are needed for this high-risk population to reduce CMV-associated morbidity and mortality.     

Rhabdomyolysis associated with cytomegalovirus infection in kidney transplant recipients

Rhabdomyolysis is a pathological syndrome caused by skeletal muscle cell damage that affects the integrity of the cellular membrane and leads to the release of toxic intracellular constituents into the bloodstream. Although cytomegalovirus (CMV) has rarely been reported as a cause of rhabdomyolysis, CMV infection could be considered as a possible cause because of its clinical significance in kidney transplant recipients (KTRs). We report 2 cases of rhabdomyolysis associated with CMV infection in KTRs. A 64‐year‐old woman (Case 1) and a 65‐year‐old man (Case 2), who had each received a kidney from a living unrelated donor, were admitted with complaints of weakness in both legs and myalgia. Laboratory findings revealed highly increased creatine phosphokinase and myoglobinuria. In both cases, no recent alterations of medications had occurred, and other causes of rhabdomyolysis—such as trauma, alcohol, drugs, and electrolyte abnormalities – were excluded. CMV pp65 antigen was positive, and patients were diagnosed with rhabdomyolysis associated with CMV infection. Both patients recovered without complications after ganciclovir treatment. In conclusion, CMV infection should be considered as a possible cause of rhabdomyolysis in KTRs.     

Continuous cytomegalovirus seroconversion in a large group of healthy blood donors

BACKGROUND AND OBJECTIVES: Transmission of cytomegalovirus (CMV) to seronegative, immunocompromised recipients can cause serious and fatal complications. Although the seroprevalence of CMV is high, the risk of primary CMV infection among healthy blood donors has not yet been analysed in a large population. MATERIALS AND METHODS: We developed an algorithm to determine the rate of CMV seroconversion in an overall cohort of 24,260 subjects who donated 176,474 blood units during an 11-year observation period. RESULTS: We detected CMV seroconversion in all relevant age groups (18-60 years) with an overall seroconversion rate of 0.55% per year. Both CMV seroconversion and seroprevalence occurred more frequently in female donors (P = 0.02 and P < 0.001, respectively). We identified 30-35-year-old blood donors as the group with the highest rate of CMV seroconversion per year (1.33% vs. 0.46%; P < 0.0001). CONCLUSIONS: We conclude that the risk of primary CMV infection is a continuous lifelong event and correlates with age and female gender.     

Clinico-pathological study of cytomegalovirus (CMV) in AIDS autopsies: under-recognition of CMV pneumonitis and CMV adrenalitis

Abstract Background: Cytomegalovirus (CMV) is a common cause of morbidity in human immunodeficiency virus (HIV) infected patients, predominantly when severe immunosuppression has occurred. Although CMV infection of the retina and gastrointestinal tract is well recognised as causing substantial morbidity, the significance of infection at other sites, in particular the lungs and adrenal glands is unclear. Aims: To assess the extent of CMV infection in postmortem examinations performed on HIV-infected patients. To estimate the degree of concordance between clinical and postmortem findings and the effect of prior diagnosis and/or treatment of CMV infection. Methods: The postmortem examination findings and clinical records of 25 consecutive HIV-infected patients who underwent a complete autopsy were examined. Results: CMV infection was demonstrated in 19 patients (76%) at postmortem examination, with the most common sites of infection being the adrenal glands (56%) and lungs (44%). Concordance between clinical diagnosis of CMV infection and postmortem findings was low with only five of 19 patients (26%) having an antemortem diagnosis. No patient with CMV infection of the lungs or adrenal glands had a clinical diagnosis made, despite four patients having florid CMV pneumonitis at postmortem examination; in three the probable cause of death. Conclusion: CMV infection is a common postmortem finding in HIV-infected patients but the concordance between clinical diagnosis and autopsy findings is low. CMV appears to be a significant pathogen in HIV-related respiratory disease. (Aust NZ J Med 1995; 25: 503–506.)     

Association of detectable cytomegalovirus (CMV) DNA in monocytes rather than positive CMV IgG serology with elevated neopterin levels in community-dwelling older adults

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

Treatment of multidrug-resistant cytomegalovirus retinitis with systemically administered leflunomide

Multiresistant cytomegalovirus (CMV) infection is increasingly recognized in solid organ transplant recipients. Leflunomide is a novel drug with both immunosuppressive and anti-CMV properties. Herein we report a case of a renal transplant recipient treated with leflunomide for multiresistant CMV retinitis, and provide correlation between serum and vitreous levels of leflunomide. She had stabilization of her retinitis and measurable levels of drug in her vitreous fluid and serum. These initial findings suggest that leflunomide may be useful in the treatment of CMV disease, including retinitis in patients after solid organ transplantation.     

Low‐dose valganciclovir prophylaxis for cytomegalovirus in intermediate‐risk (R+) renal transplant recipients: Single‐center experience

Renal transplant recipients (RTR) who are seropositive for CMV (R+) are considered to be at intermediate risk for CMV disease. Current guidelines recommend high‐dose valganciclovir (VGCV) prophylaxis because of limited data on the efficacy of low‐dose VGCV. We describe our experience with using low‐dose VGCV in R+ RTR. We retrospectively reviewed a cohort of 316 R+ RTR at our institution between 2002 and 2006. The primary endpoint was CMV disease at 1 year post transplant. The incidence of CMV disease at 12 months after transplantation was only 3% (6/221) in the D+R+ and 4% (4/95) in the D?R+ RTR. Low‐dose VGCV was effective at preventing CMV disease in intermediate‐risk (R+) RTR.