Application of quantitative detection of multiple-source cytomegalovirus DNA in diagnosis of cytomegalovirus pneumonia after allogeneic hematopoietic stem cell transplantation / 器官移植

Objective To evaluate the diagnostic value of quantitative detection of cytomegalovirus (CMV) DNA from different sources [plasma, sputum and bronchoalveolar lavage fluid(BALF)] for CMV pneumonia after allogeneic hematopoietic stem cell transplantation. Methods Clinical data of 405 recipients undergoing allogeneic hematopoietic stem cell transplantation were retrospectively analyzed. Among them, 19 recipients diagnosed with CMV pneumonia were assigned into the CMV pneumonia group, and 229 recipients with CMV viremia alone, 11 recipients without CMV pneumonia who received fiberoptic bronchoscopy and 16 recipients diagnosed with bacterial or fungal pneumonia based on pathogenic evidence receiving sputum culture were assigned into the control A, B and C groups, respectively. The incidence of CMV pneumonia was summarized. The CMV DNA load of specimens from different sources (plasma, sputum and BALF) of recipients with CMV pneumonia was analyzed. The clinical prognosis of recipients with CMV pneumonia was evaluated. Results Among 405 recipients undergoing allogeneic hematopoietic stem cell transplantation, 19 cases developed CMV pneumonia, and the overall incidence of CMV pneumonia was 4.7%(19/405). The CMV DNA load in the plasma, sputum and BALF of recipients with CMV pneumonia was higher than those in the control A, B and C groups (all P < 0.05). In the 19 recipients, 12 cases were cured after antiviral treatment and 7 died from treatment failure(3 cases abandoned treatment). The fatality was 37%(7/19). Conclusions Quantitative detection of CMV DNA in the plasma, sputum and BALF may increase the diagnostic rate of CMV pneumonia, thereby improving clinical prognosis of recipients undergoing allogeneic hematopoietic stem cell transplantation.

SOCS1 and SOCS3 are expressed in mononuclear cells in human cytomegalovirus viremia after allogeneic hematopoietic stem cell transplantation

BACKGROUND: The expression of the SOCS genes in cytomegalovirus (CMV) viremia after hematopoietic stem cell transplantation (HSCT) remains largely unexplored. METHODS: Using quantitative RT-PCR of mononuclear cells, we conducted pairwise comparison of SOCS1 and SOCS3 expression levels among a healthy donor group (N=55), a pre-HSCT group (N=17), and the recipient subgroup (N=107), which were divided according to the occurrence of CMV viremia and acute graft-versus-host disease (aGVHD). RESULTS: Compared to that in the healthy donor group, SOCS1 expression was higher in the CMV+ subgroup, especially in the CMV+GVHD- group, but decreased in the other subgroups. When compared to the expression in the pre-HSCT group, SOCS1 expression was significantly higher in the CMV+ subgroup, especially in the CMV+GVHD+ subgroup. Meanwhile, compared to that in the healthy donor group, SOCS3 expression was significantly lower in all other groups. The CMV-GVHD- subgroup showed significantly lower SOCS3 expression compared to the CMV+ subgroup, the CMV+GVHD+ subgroup, and the CMV+GVHD- subgroup. CONCLUSION: We report differential expression of SOCS genes according to CMV viremia with acute GVHD occurrence after HSCT, suggesting that regulation of SOCS expression is associated with CMV viremia.

Comparison Cytomegalovirus Qualitative Assay Using Real-Time PCR and Conventional PCR / 대한임상미생물학회지

BACKGROUND: Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality in immunocompromised patients. We compared the abilities of the recently developed Real-Q Cytomegalovirus Kit (Biosewoom Inc., Korea) and the previously used PANA mPCR CMV Detection Kit (Panagene Inc., Korea) to detect CMV. METHODS: We analyzed 300 samples (whole blood: 262, urine: 37, CSF: 1) submitted for qualitative CMV PCR testing during October 2011 at Yonsei University College of Medicine Severance Hospital. Real-time PCR was performed with a Real-Q Cytomegalovirus Kit and conventional PCR was conducted with a PANAmPCR CMV Detection Kit. RESULTS: The positive rates of both Real-time PCR and conventional PCR were 25.3% (76/300), and the kappa coefficient (K) was 0.96 (95% confidence interval (CI), 0.93-1.00). The concordance rate of the Real-Q Cytomegalovirus Kit and the PANAmPCR CMV Detection Kit was 98.7% (296/300), and four out of 300 samples showed discordant results. If the concordant results of 296 samples and the four results confirmed by direct sequencing were assumed to be true, the sensitivity and specificity of the Real-Q Cytomegalovirus Kit were 97.4% (95% CI, 93.8-100.0%) and 99.1% (95% CI, 97.9-100.0%), respectively. CONCLUSION: The recently developed Real-Q Cytomegalovirus Kit showed excellent sensitivity and specificity, and had a high concordance rate with the previously established PANAmPCR CMV Detection Kit, which uses conventional PCR. Furthermore, Real-time PCR could decrease the test time, as the electrophoresis step required for conventional PCR is not required for Real-time PCR.

Infección y enfermedad por citomegalovirus en niños sometidos a trasplante de órgano sólido: experiencia en un centro de referencia chileno / Cytomegalovirus infection and disease in pediatric solid organ transplarntation: experience in a Chilean multiorganic transplantation center

Cytomegalovirus (CMV) infection and disease in transplant (Tx) recipients may severely complícate the patients outcome. Aim: To determine the incidence, clinical characteristics and risk factors for CMV infection and disease in liver and kidney transplant recipients in a tertiary care children's hospital. Method: A clinical and laboratory evaluation was prospectively performed in 44 and 20 children receiving a renal and liver Tx respectively in the Hospital Luis Calvo Mackenna between 2004 and 2006. Results: At the time of the organ Tx 20.3 percent (13/64) children were seronegative for CMV. Thirty six per cent (23/64) patients were infected with CMV, of whom 32 percent (14/44) received kidney Tx and 9/20 (45 percent) received liver Tx. CMV disease occurred in 52 percent (12/23) of infected patients. CMV disease was characterized by fever (100 percent), anemia (50 percent), leucopenia (16.6 percent) and specific organ involvement (renal graft 60 percent liver graft 57.1 percent, lung 25 percent, intestine 16.6 percent). Variables significantly associated with infection were a CMV seronegative status (p = 0.035) and lower age 5.5 + 3.7 years oíd vs 8.3 + 4.4 years oíd (p = 0.01). Conclusions: Incidence of CMV infection was high in children receiving a solid organ transplant in our institution and near half of infected children developed CMV-associated disease.

La infección y enfermedad por citomegalovirus (CMV) en pacientes sometidos a trasplantes (Tx) es una complicación que condiciona la evolución del injerto y la sobrevida del paciente. Objetivos: Determinar la incidencia de infección y enfermedad por CMV durante los primeros seis meses de efectuados Tx hepático y renal. Caracterizar la enfermedad, e identificar factores de riesgo asociados a infección. Metodología: Análisis prospectivo en 64 pacientes pediátricos sometidos a Tx renal (n: 44) o hepático (n: 20) en el Hospital Luis Calvo Mackenna entre 2004 y 2006. Resultados: Al trasplante, 23,1 por ciento (13/64) eran receptores IgG CMV (-). Cumplieron criterio de infección 36 por cientoo (23/64) de los pacientes, con Tx renal 32 por ciento (14/44) y con Tx hepático 45 por ciento (9/20). Desarrolló enfermedad el 52 por ciento) (12/23) la que se caracterizó porfiebre (100 por cientoo), anemia (50 por cientoo), leucopenia (16,6 por cientoo), disfunción del órgano trasplantado 60 por cientoo en Tx renal, hepático 57, l por cientoo, compromiso pulmonar en 25 por cientoo e intestinal en 16,6 por cientoo del total de pacientes. Variables asociadas a infección fueron: ser receptor IgG CMV (-)pre-Tx (p=0,035) y una menor edad del paciente 5,5 +3,7 vs 8,3 + 4,4 (p= 0,01). Conclusiones: Hay una elevada tasa de infección por CMV en la población de pacientes con Tx renal y hepática en nuestro medio, la mitad de ellos desarrolló enfermedad amenazando la función del injerto.

Cytomegalovirus Induced Gastric Ulcer as a Principal Manifestation in the Initial Stage of Hodgkin's Disease / 대한소화기학회지

Cytomegalovirus (CMV) is an important cause of opportunistic infection in immunocompromised patients. CMV infection occurs as a result of the cell-mediated immunity change in lymphoma patients. Although CMV can cause ulceration anywhere in the gastrointestinal (GI) tract in immunocompromised patients, only a few case reports about CMV GI infection in malignant lymphoma have been documented in literature. Furthermore, it was rare that CMV gastric ulcer with massive bleeding presented as an initial manifestation in a patient who has been not diagnosed lymphoma. We report a case of CMV induced gastric ulcer as an initial manifestation in patient with Hodgkin's disease.

A case of cytomegalovirus esophagitis associated with upper gastrointestinal bleeding / 대한내과학회지

Cytomegalovirus (CMV) infections are common in immunocompromised patients, although they may occur occasionally in immunocompetent patients. The majority of CMV infections in immunocompetent adults are asymptomatic or associated with mild mononucleosis-like syndrome. CMV involvement of the colon is the most common site of infection in the gastrointestinal tract and is more commonly a cause of massive gastrointestinal bleeding compared to CMV involvement of the upper gastrointestinal tract and small intestine. However, although rarely, CMV esophagitis can be the source of upper gastrointestinal bleeding. We report an immunocompetent patient with cytomegalovirus esophagitis and massive upper gastrointestinal bleeding who had undergone left lobectomy and cholecystectomy for intrahepatic duct stones and gallstones.

The role of glucocorticoid in treating cytomegalovirus pneumonia following renal transplantation / 中华器官移植杂志

Objective To study the role of glucocorticoid (GC) in treating patients with cyto- megalovirus (CMV) pneumonia following renal transplantation.Methods There were 75 cases CMV pneumonia following renal transplantation during one month (3 cases),2-6 months (64 cases) and more than 6 months (8 cases).All patients were subjected to the comprehensive treatments including anti-virus therapy.In 47 cases,GC was given (GC group),and in the rest 28 cases,GC was not administered (non-GC group).Results In GC group,40 cases (85.1%) were cured and there were 7 deaths (14.9%).In non-GC group,17 cases (60.7%) were cured and there were 11 deaths (39.3%).There was significant difference between two groups (P

Prevalence of IgM Antibodies to Toxoplasma, Rubella and Cytomegalovirus Infections During Pregnancy

The present study was conducted to find out the prevalence of IgM antibodies to Toxoplasma, Rubella and Cytomegalovirus in women with Bad Obstetric History (BOH) in and around Amritsar. Over a period of one year, 200 serum samples were collected from pregnant women having BOH and 100 serum samples were collected from pregnant women without BOH. Out of 200 sera, from women with BOH 137 (68.5%) were positive for Toxoplasma, Rubella and CMV alone or in combination. IgM seropositivity to Toxoplasma was 42.5%, Rubella was 17.5% and CMV was 29.5%. The highest percentage of these antibodies to Toxoplasma, Rubella and CMV was in cases of abortions i.e. 71.8%, 59.9% and 61% respectively. The study shows that there is a strong association of these agents with BOH. Thus, screening and early diagnosis for these agents in women can help in proper management of these cases.

Segmental Ischemia of the Small Bowel Caused by Cytomegalovirus Infection in a Patient with Multiple Injuries after a Traffic Accident

Cytomegalovirus infections (CMV) of the gastrointestinal tract (GI) are common, and most often seen in patients with acquired immunodeficiency syndrome (AIDS), inflammatory bowel disease, or those receiving immunosuppressive therapy. CMV enteritis is uncommon in an immunocompetent individual. A CMV infection of the small bowel accounts for 4.3% of all CMV infections of the GI tract. The GI manifestations of CMV include: diarrhea, bleeding, obstruction and perforation, all of which are usually secondary to discrete erosions or ulceration. High mortality rates have been reported for CMV enteritis. Here, a rare case of CMV enteritis, resulting in segmental ileal ischemia, is reported in a 47-year old man following a traffic accident. On the 17th hospital day, he developed melena, watery diarrhea, fever and abdominal pain. An abdominal computed tomography (CT) on the 23rd hospital day showed an enlarged appendix with mild periappendiceal infiltration and segmental wall thickening in the terminal ileum. An ileocecal resection was performed. Pathological evaluation of the operative specimen revealed CMV inclusion bodies, with ulcerations. The patient was treated with ganciclovir therapy for 3 weeks after which his symptoms improved. If a CMV infection is highly suspected in multiply injured trauma victims, the earlier recognition of potential small bowel involvement can hopefully decrease the incidence of bleeding, ischemic demage to the bowel and perforation, which are usually fatal events.

A Case of Cytomegalovirus (CMV) Colitis in a Patient after Splenectomy / 대한소화기내시경학회지

Cytomegalovirus (CMV) is the most common cause of life-threatening opportunistic viral infection in patients with acquired immunodeficiency syndrome (AIDS). However, CMV infection may occur in the immunocompetent individuals. CMV colitis has not been reported in a patient with splenectomy in Korea. Recently, we experienced a case of fatal CMV colitis in a patient with splenectomy. A 69-year-old man complained of bloody mucoid diarrhea and abdominal pain for 2 months. He had the splenectomy 6 months ago. CMV colitis was diagnosed by colonoscopy and pathologic examination. He died of sepsis in spite of antiviral ganciclovir therapy.

A Case of Congenital Cytomegalovirus Encephalopathy with Patchy, Nodular Lesion of Periventricular area on Brain Magnetic Resonance Imaging / 대한소아신경학회지

Cytomegalovirus(CMV) is the most common cause of congenital viral infections. CMV infection occurs in 0.4% to 2.4% of all live births. CMV causes thin cerebral cortices, diminished volume of white matter, and delayed myelination, bringing on encephalopathy, which may be manifested as seizures in some cases. CT findings in CMV encephalopathy present as irregular intracranial calcifications of the periventricular area. Recently, there are increasingly more reports about MRI findings in CMV encephalopathy and common findings of the encephalopathy are periventricular cysts and dilated lateral ventricles. We experienced a case of congenital CMV encephalopathy with patchy, nodular lesions of the periventricular area on magnetic resonance imaging(MRI). We report this case with a review of associated literature.

Successful treatment with ganciclovir for cytomegalovirus duodenitis following allogenic bone marrow transplantation

Cytomegalovirus(CMV) disease is a major cause of morbidity and mortality in immunocompromised patients. CMV enteritis should be considered when nausea and vomiting continue 3 to 4 weeks after bone marrow transplantation(BMT). The treatment of CMV enteritis is not well established. We report a CMV duodenitis patient following allogenic bone marrow transplantation. The patient had prolonged nausea and vomiting for 5 weeks after bone marrow transplantation and CMV duodenitis was diagnosed by the gastroduodenoscopic mucosal biopsy which showed cytomegalic cells. Ganciclovir treatment for 3 weeks resulted in the resolution of symptoms and promoted healing of the lesion. The patient was free of CMV infection until 288 days after allogenic BMT without maintenance ganciclovir treatment.

THE STRATEGIES FOR PREVENTING AND TREATING INFECTION OF CYTOMEGALOVIRUS IN BONE MARROW TRANSPLANTATION / 药物分析学报

In bone marrow transplantation (BMT), cytomegalovirus (CMV) interstitial pneumonitis (IP) is one of the most dangerous complications, which has been the first important cause to lead the failure of BMT. At present, there is no effective and specific therapy for CMV-IP, therefore how to prevent CMV infection effectively is a top task. From 1991 to 1996, we used comprehensive steps to prevent CMV-IP in BMT, and none of 14 patients developed CMV-IP. The preventing results that we achieved by using the steps were quite satisfied.

The Usefulness of PCR and Early Antigen Immunostaining as a Rapid Identification Method of Cytomegalovirus Infection / 대한임상병리학회지

BACKGROUND: Cytomegalovirus infection is an important cause of morbidity and mortality after organ transplantation. Thus, rapid, sensitive and specific laboratory test, such as CMV antigenemia assay and polymerase chain reaction (PCR) is necessary to determine a patient's risk of CMV disease and to monitor the effectiveness of antiviral therapy. We compared the results of CMV-PCR and CMV early antigen immunostaining (CMV-EA) with CMV-specific IgM antibody to evalutate clinical usefulness for the early diagnosis of CMV infection and monitoring of antiviral therapy. METHODS: We analyzed 170 samples submitted for CMV tests between September 1995 and April 1996 in Yonsei University College of Medicine Severance Hospital. CMV-PCR and CMV-EA were performed with buffy coat cells and detection of CMV-specific IgM antibody was performed by enzyme-linked fluorescent assay (ELFA). RESULTS: One hundred and seventy samples of 159 patients were tested and analyzed. The concordance rate of CMV-PCR, CMV-EA and CMV-specific IgM in the same blood sample was 75.3%. The total incidence of CMV disease was 2.5%. The sensitivity and specificity based on the patients' clinical status of PCR were 100% and 91.6% respectively. In CMV-EA immunostaining method, they were 75.0% and 100% respectively. And, for CMV-specific IgM antibody ELFA, the sensitivity was only 50.0% and the specificity was 96.4%. CONCLUSIONS: CMV-PCR and CMV-EA immunostaining are reliable methods as rapid early detection of CMV infection. The sensitivity and specificity are very high comparing to CMV- specific IgM antibody. It could also be concluded that they have advantages not only for early diagnosis but also monitoring or follow-up of a therapeutic course as quantitative assays.

Diffuse Pulmonary Infiltration Rapidly Progressed after the Chemotherapy of a Patient with Malignant Lymphoma / 결핵

Acute respiratory failure with diffuse pulmonary infiltration was occurred in a patient with malignant lymphoma 1month after the 8th CHOP chemotherapy. The ground glass and consolidation appearances on chest C-T in this immunodeficient patient could be presented in many clinical situations such as pneumonia by opportunistic infections(fungal, parasites, viral, and usual bacterial pathogens), anti-tumor drug's pulmonary toxicity and tumor invasion. And the other diseases of acute interstitial pneumonitis, alveolar proteinosis, BOOP, pulmonary edema and alveolar hemorrhage, which could present the same radiological findings, should included in differential diagnosis. This patient was diagnosed as the opportunistic pneumonia by Pneumocystis carinii and probably Cytomegalovirus through bronchoalveolar lavage and transbronchial lung biopsy.

Cytomegalovirus Infection in Idiopathic Inflammatory Bowel Disease: Clinicopathologic Analysis of 6 Cases

Cytomegalovirus (CMV) infection is an uncommon association with idiopathic inflammatory bowel disease (IBD) often leading to a variety of serious complications. A total of 41 resected cases of IBD were examined to elucidate the pathologic features of intestinal CMV infection which was assessed by histologic examination and confirmed by immunohistochemistry with CMV antibody. Six cases were positve for CMV antibody; five cases in 19 ulcerative colitis (UC, 26.3%) and one case in 22 Crohn's disease (CD, 4.5%). Of 7 cases of the steroid-treated UC group, five cases were superinfected with CMV (71.4%) but none in 12 cases of the steroid-untreated UC group. All of the five CMV-positive cases in UC showed deep ulceration and transmural inflammation, while none of 10 UC cases without above features were CMV positive. Fibrinoid necrosis and thrombi were found in 83.3% of the CMV infected group, while none in the CMV-negative group of UC cases (p=0.01). We conclude that IBD, particularly UC, is susceptible to the CMV infection when steroid hormone is administered, and that deep colonic ulceration, transmural inflammation and fibrinoid necrosis of vasculature may suggest superinfection of CMV in UC patients. It seems that deep colonic ulceration may be the consequence of an ischemic change following vascular luminal occlusion or vasculitis by CMV infection.

Study of Cytomegalovirus Infection in Renal Transplant Recipients Who had IgG CMV Antibody in the Pretransplantation Period / 대한신장학회잡지

Cytomegalovirus(CMV) infection occurs more frequently in renal transplant recipients than in the normal population. But the incidence and severity of CMV infection and antibody positivity are different between countries. We studied the incidence of CMV infection with a long term follow up in renal transplant recipients who were IgG CMV positive and whose donors were also IgG CMV positive preoperatively. We studied the difference and usefulness of various detection methods including IgM CMV antibody by ELISA, shell vial culture, and quantitative dual polymerase chain reaction(PCR). We also studied possible factors that may affect CMV infection and the function of the grafted kidney in CMV infected patients. This study included 36 patients, 20 males and 16 females, who received renal transplantation at Hanyang University Hospital between July, 1994 and March, 1995. IgG and IgM CMV antibodies were detected and shell vial cultures were performed in recipient candidates and donor candidates preoperatively. Postoperatively, we checked IgM CMV and performed shell vial cultures in renal transplant recipients every month after the operation and when CMV infections were suspected. We also performed dual PCR with endpoint titration to quantify the amount of CMV DNA. The total incidence of CMV infection was 30.6% (11 patients among 36 patients). Three patients had CMV disease, and only one patient was severe enough to need gancyclovir therapy. The average onset of infection was 12.9 weeks after the operation(earliest 5weeks-latest 33weeks). In all patients with CMV disease, CMV positivity appeared by all three detection methods. But detection time and duration of positivity were different. The amount of CMV DNA in patients with active CMV disease was higher than those of asymptomatic patients and one patient following antiviral therapy. Age, sex, donor type, HLA matching and rejection did not affect CMV infection. Incidence of CMV infection was higher in patients who were transfused within 3 weeks before the operation(6/8 vs 5/28, p=0.048). Changes of creatinine level from initial outpatient department(OPD) visit to last OPD visit which were corrected by OPD follow up time showed no significant difference between CMV infected and non-infected patients In conclusion, the incidence of CMV infection and disease was relatively low, and the degree of disease severity was mild. In our renal transplant recipients, CMV infection may not be a serious problem. Quantitative dual PCR using end-point titration is a good method to detect CMV infections and monitor the clinical course. Because it is easy to use, detect disease earlier and can quantify the amount of CMV DNA. Among various factors, transfusion affected CMV infection significantly in our patients. In an average of 231 days of OPD follow up time, CMV infected patients showed no impairment of grafted kidney function, but a more long term follow up is needed.

A case of CMV Gastrointestinal Disease / 대한소화기내시경학회지

Cytomegalovirus(CMV) commonly infects immunocompromised patient, including those with malignant disease, immunosuppression (particularly that induced by steroid therapy), organ transplantation AIDS. Involvement of the gastrointestinal tract is often associated with disseminated infection. Enteric involvement is expressed by inflammation, hemorhage, and ulceration. CMV is postulated to cause submucosal capillary and arteriolor vasculitis that can result in ischemic injury. CMV induced gastritic and colonic ulcers have not previously been reported in Korea. We report a patient of malignancy who had gastric and colonic ulcers assoicated with CMV infection whieh showed chracteristic histological finding of CMV infection in biopsed specimen.

Ultrastructural Observation on Maturation Process of Cytomegalovirus in Human Cells

Cytomegalovirus(CMV) infection can be diagnosed by finding characteristic intranuclear inclusion body and enlargement of the cell size congenital CMV infection can be associated with various types of anomalies seen in different gestational age. These anomalies are probable due to direct virus infection of the parenchymal cell m early gestation. Based on four autopsy cases of congenital CMV infection we have studied maturation process of virus particles in parenchymal cells, with special reference to me mode of replication and transmission. Virus particles in CMV-infected cells in brain and kidney showed nucleocapsids with characteristic concentric core, that were enclosed around fibrillar network in nucleus. During replication process virions showed various morphogenic mutation that was rather consistent in different tissues and individuals. There were virions without core or with eccentric core. Occasional cores were divided into 2~5 fragments. The virus particles reached the cytoplasm through the nuclear membrane, and here the virions increased twice in size. After virions were fully matured in the cytop1asm. they showed exocytosis phenomenon through the cellular membrane to reach extracellular portion.