Comparison of the Commercial QuantiFERON-CMV and Overlapping Peptide-based ELISPOT Assays for Predicting CMV Infection in Kidney Transplant Recipients

PubMed Central

Kwon, Ji-Soo; Kim, Taeeun; Kim, Sun-Mi; Sung, Heungsup; Shin, Sung; Kim, Young Hoon; Han, Duck Jong

2017-01-01

Cytomegalovirus (CMV) is one of the most important opportunistic infections in transplant recipients. Tests for CMV-specific T cell responses have been proposed to change the current risk stratification strategy using CMV assays. We evaluated the usefulness of pre-transplant CMV-specific T cell assays in kidney transplant (KT) candidates for predicting the development of CMV infection after transplantation comparing the results of the overlapping peptides (OLPs)-based enzyme-linked immunospot (ELISPOT) assay and the commercial QuantiFERON-CMV assay. We prospectively enrolled all cases of KT over a 5-month period, except donor CMV-seropositive and recipient seronegative transplants that are at highest risk of CMV infection. All the patients underwent QuantiFERON-CMV, CMV OLPs-based pp65, and immediate-early 1 (IE-1)-specific ELISPOT assays before transplantation. The primary outcome was the incidence of CMV infection at 6 months after transplant. The total of 47 KT recipients consisted of 45 living-donor KTs and 2 deceased-donor KTs. There was no association between positive QuantiFERON-CMV results and CMV infection. However, 10 of 34 patients with phosphoprotein 65 (pp65)- or IE-1-specific ELISPOT results higher than cut-off value developed CMV infections compared with none of 13 patients with results lower than cut-off value developed CMV. The OLPs-based ELISPOT assays are more useful than the QuantiFERON-CMV assay for predicting CMV infection. Patients with higher CMV-specific T cell immunity at baseline appear to be more likely to develop CMV infections after KT, suggesting that the abrupt decline in CMV-specific T cell responses after immunosuppression, or high CMV-specific T cell responses due to frequent CMV activation before KT, may promote CMV infection. PMID:29093653

Analysis of spontaneous resolution of cytomegalovirus replication after transplantation in CMV-seropositive patients with pretransplant CD8+IFNG+ response.

PubMed

Páez-Vega, Aurora; Poyato, Antonio; Rodriguez-Benot, Alberto; Guirado, Lluis; Fortún, Jesús; Len, Oscar; Abdala, Edson; Fariñas, María C; Cordero, Elisa; de Gracia, Carmen; Hernández, Domingo; González, Rafael; Torre-Cisneros, Julián; Cantisán, Sara

2018-05-18

This prospective study evaluates whether CMV-seropositive (R+) transplant patients with pretransplant CD8+IFNG+ T-cell response to cytomegalovirus (CMV) (CD8+IFNG+ response) can spontaneously clear the CMV viral load without requiring treatment. A total of 104 transplant patients (kidney/liver) with pretransplant CD8+IFNG+ response were evaluable. This response was determined using QuantiFERON-CMV assay. The incidence of CMV replication and disease was 45.2% (47/104) and 6.7% (7/104), respectively. Of the total patients, 77.9% (81/104) did not require antiviral treatment, either because they did not have CMV replication (n = 57) or because they had asymptomatic CMV replication that could be spontaneously cleared (n = 24). Both situations are likely related to the presence of CD8+IFNG+ response to CMV, which has a key role in controlling CMV infection. However, 22.1% of the patients (23/104) received antiviral treatment, although only 7 of them did so because they had symptomatic CMV replication. These patients developed symptoms in spite of having pretransplant CD8+IFNG+ response, thus suggesting that other immunological parameters might be involved, such as a dysfunctional CD4 + response or that they might have become QFNon-reactive due to the immunosuppression. In conclusion, around 80% of R+ patients with pretransplant CD8+IFNG+ response to CMV did not require antiviral treatment, although this percentage might be underestimated. Nevertheless, other strategies such as performing an additional CD8+IFNG+ response determination at posttransplant time might provide more reliable information regarding the patients who will be able to spontaneously clear the viremia. Copyright © 2018 Elsevier B.V. All rights reserved.

Traceability Assessment and Performance Evaluation of Results for Measurement of Abbott Clinical Chemistry Assays on 4 Chemistry Analyzers.

PubMed

Lim, Jinsook; Song, Kyung Eun; Song, Sang Hoon; Choi, Hyun-Jung; Koo, Sun Hoe; Kwon, Gye Choel

2016-05-01

-The traceability of clinical results to internationally recognized and accepted reference materials and reference measurement procedures has become increasingly important. Therefore, the establishment of traceability has become a mandatory requirement for all in vitro diagnostics devices. -To evaluate the traceability of the Abbott Architect c8000 system (Abbott Laboratories, Abbott Park, Illinois), consisting of calibrators and reagents, across 4 different chemistry analyzers, and to evaluate its general performance on the Toshiba 2000FR NEO (Toshiba Medical Systems Corporation, Otawara-shi, Tochigi-ken, Japan). -For assessment of traceability, secondary reference materials were evaluated 5 times, and then bias was calculated. Precision, linearity, and carryover were determined according to the guidelines of the Clinical and Laboratory Standards Institute (Wayne, Pennsylvania). -The biases from 4 different analyzers ranged from -2.33% to 2.70% on the Toshiba 2000FR NEO, -2.33% to 5.12% on the Roche Hitachi 7600 (Roche Diagnostics International, Basel, Switzerland), -0.93% to 2.87% on the Roche Modular, and -2.16% to 2.86% on the Abbott Architect c16000. The total coefficients of variance of all analytes were less than 5%. The coefficients of determination (R(2)) were more than 0.9900. The carryover rate ranged from -0.54% to 0.17%. -Abbott clinical chemistry assays met the performance criteria based on desirable biological variation for precision, bias, and total error. They also showed excellent linearity and carryover. Therefore, these clinical chemistry assays were found to be accurate and reliable and are readily applicable on the various platforms used in this study.

Prevalence and clinical characteristics of CMV coinfection among HIV infected individuals in Guinea-Bissau: A cross-sectional study.

PubMed

Grønborg, Helene L; Jespersen, Sanne; Egedal, Johanne H; Correia, Faustino G; Medina, Candida; Krarup, Henrik; Hønge, Bo L; Wejse, Christian

2018-05-31

To describe the prevalence of CMV in a cohort of HIV infected individuals in Guinea-Bissau, West Africa and to evaluate differences in patients' clinical characteristics associated with their CMV status. Newly diagnosed HIV infected adults were invited to participate in this cross-sectional study, from May until December 2015. Enrolled patients were interviewed and underwent a full physical examination focusing on CMV disease manifestations. Blood samples were analyzed for CMV serology, QuantiFERON-CMV response and CMV DNA. Mortality follow-up were registered for one year after inclusion. In total, 180 patients were enrolled. Anti-CMV IgG positivity was found in 138/138 (100%) and 4/138 (2.8%) were anti-CMV IgM positive. A positive QuantiFERON-CMV response was found in 60/70 (85.7%) of the patients and 83/137 (60.6%) had CMV viremia. QuantiFERON-CMV response and detectable CMV DNA were associated with lower CD4 cell count, older age, and upper gastrointestinal complaints. During one year of follow-up, the IRR for death among CMV DNA positive patients was 1.5 (p=0.5). CMV coinfection was detected among all enrolled patients and CMV viremia was highly prevalent. Only age and upper gastrointestinal complaints were associated with the patients' CMV status. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Cytomegalovirus (CMV) immune monitoring with ELISPOT and QuantiFERON-CMV assay in seropositive kidney transplant recipients

PubMed Central

Ryu, Ji Hyeong; Choi, Ae-Ran; Yu, Ji Hyun; Lim, Jihyang; Han, Kyungja; Kim, Sang Il; Yang, Chul Woo; Chung, Byung Ha

2017-01-01

Although cytomegalovirus (CMV) specific cell-mediated immunity (CMI) has been suggested as a predictive marker for CMV infection, proper CMI monitoring strategy in CMV-seropositive recipients and optimal method are not defined. The aim of this study was to evaluate two interferon gamma release assays during early post-transplant period as a predictor of the development of CMV infection in CMV-seropositive patients. A total of 124 CMV-seropositive recipients who received kidney transplantation from CMV-seropositive donor were prospectively examined. At pre-transplant and post-transplant 1 and 3 months, CMV-CMIs were tested using QuantiFERON-CMV assay (QF-CMV) and CMV specific T cell ELISPOT against CMV pp65 and IE-1 antigens (pp65-ELISPOT, IE-1-ELISPOT). CMV DNAemia occurred in 16 (12.9%) patients within 3 months after transplant. Post-transplant pp65 or IE-1 ELISPOT response, but not QF-CMV, was significantly associated with CMV DNAemia. The pp65 ELISPOT (cut-off; 30 spots/200,000 cells) and IE-1 ELISPOT (10 spots/200,000 cells) at post-transplant 1 month predicted the risk of post-transplant CMV DNAemia (P = 0.019). Negative predictive values (NPV) for protection from CMV DNAemia in case of positive ELISPOT results were 94.5% (95% CI: 86.9–97.8%) and 97.6% (95% CI: 86.3–99.6%) in pp65-ELISPOT and IE-1-ELISPOT assays, respectively. These results suggest that the variability may exist between CMV ELISPOT assays and QF-CMV, and CMV ELISPOT at post-transplant 1 month can identify the risk of CMV DNAemia in seropositive kidney transplant recipients. PMID:29232714

Cytomegalovirus (CMV) immune monitoring with ELISPOT and QuantiFERON-CMV assay in seropositive kidney transplant recipients.

PubMed

Lee, Hyeyoung; Park, Ki Hyun; Ryu, Ji Hyeong; Choi, Ae-Ran; Yu, Ji Hyun; Lim, Jihyang; Han, Kyungja; Kim, Sang Il; Yang, Chul Woo; Chung, Byung Ha; Oh, Eun-Jee

2017-01-01

Although cytomegalovirus (CMV) specific cell-mediated immunity (CMI) has been suggested as a predictive marker for CMV infection, proper CMI monitoring strategy in CMV-seropositive recipients and optimal method are not defined. The aim of this study was to evaluate two interferon gamma release assays during early post-transplant period as a predictor of the development of CMV infection in CMV-seropositive patients. A total of 124 CMV-seropositive recipients who received kidney transplantation from CMV-seropositive donor were prospectively examined. At pre-transplant and post-transplant 1 and 3 months, CMV-CMIs were tested using QuantiFERON-CMV assay (QF-CMV) and CMV specific T cell ELISPOT against CMV pp65 and IE-1 antigens (pp65-ELISPOT, IE-1-ELISPOT). CMV DNAemia occurred in 16 (12.9%) patients within 3 months after transplant. Post-transplant pp65 or IE-1 ELISPOT response, but not QF-CMV, was significantly associated with CMV DNAemia. The pp65 ELISPOT (cut-off; 30 spots/200,000 cells) and IE-1 ELISPOT (10 spots/200,000 cells) at post-transplant 1 month predicted the risk of post-transplant CMV DNAemia (P = 0.019). Negative predictive values (NPV) for protection from CMV DNAemia in case of positive ELISPOT results were 94.5% (95% CI: 86.9-97.8%) and 97.6% (95% CI: 86.3-99.6%) in pp65-ELISPOT and IE-1-ELISPOT assays, respectively. These results suggest that the variability may exist between CMV ELISPOT assays and QF-CMV, and CMV ELISPOT at post-transplant 1 month can identify the risk of CMV DNAemia in seropositive kidney transplant recipients.

Comparison of Abbott RealTime High-Risk HPV and Hybrid Capture 2 Assays for Detection of HPV Infection.

PubMed

Ko, Kiwoong; Yu, Shinae; Lee, Eun Hee; Park, Hyosoon; Woo, Hee-Yeon; Kwon, Min-Jung

2016-09-01

Various assays for detecting high-risk human papillomavirus (HR HPV) have been introduced recently, including the Abbott RealTime High-Risk HPV assay. We sought to compare the performance of Abbott PCR to Hybrid Capture 2 for the detection of HR HPV. A total of 941 cervical swab specimens were obtained. We submitted all specimens for HR HPV detection with HC2 and Abbott PCR, and then additionally analyzed discordant and concordant positive results using restriction fragment mass polymorphism (RFMP) genotyping analysis. HC2 detected one of 13 HR HPV types in 12.3% (116/941) of cases, while Abbott PCR detected one of 14 detectable HR HPV types in 12.9% (121/941) of cases. The overall agreement rate was 97.3% with a kappa coefficient of 0.879. Discordant results between these two assays were observed in 25 cases. HC2 showed a sensitivity of 90.0% and specificity of 95.9%, while Abbott PCR showed a sensitivity of 98.0% and specificity of 96.8% when using RFMP results as the gold standard. For HPV 16/18 detection, Abbott PCR showed 95.8%/88.9% sensitivity and 99.2%/99.8% specificity, respectively. The overall coinfection rate between HPV 16, 18 and non-16/18 was 9.9% (12/121) in Abbott PCR analysis. Considering its high agreement rate with HC2, higher sensitivity/specificity compared to HC2, and ability to differentiate HPV 16/18 from other HPV types, Abbott PCR could be a reliable laboratory testing method for the screening of HPV infections. © 2016 by the Association of Clinical Scientists, Inc.

Excluding Anti-cytomegalovirus Immunoglobulin M-Positive Cord Blood Units Has a Minimal Impact on the Korean Public Cord Blood Bank Inventory

PubMed Central

Shin, Sue; Roh, Eun Youn; Oh, Sohee; Song, Eun Young; Kim, Eui Chong; Yoon, Jong Hyun

2017-01-01

Cord blood units (CBUs) for transplantation should be free of communicable disease and must contain a specific amount of total nucleated cells and CD34+ cells. Although posttransplantation cytomegalovirus (CMV) infections are from latent infection in patients, ensuring CMV-free CBUs by performing CMV-specific IgM and nucleic acid amplification testing (NAT) is one of the mandatory procedures for the safety of CBUs. However, the exclusion policies (based on these test results) vary among nations and institutions. We tested 28,000 processed CBUs between May 2006 and June 2014. The cord blood leukocytes from CMV IgM-positive samples were then subjected to NAT. The total nucleated cell and CD34+ cell counts were measured for each CBU, and the results were compared to the CMV IgM and IgG results. The seroprevalence of CMV among pregnant women was 98.1% (18,459/18,818) for IgG and 1.7% (441/25,293) for IgM. The concentration and the total number of CD34+ cells were significantly higher in CBUs from IgM-negative mothers compared to those from IgM-positive mothers (72.4/μl vs. 57.2/μl, respectively, p < 0.0001; 1.45 × 106/unit vs. 1.15 × 106/unit, respectively, p < 0.0001). Among CBUs with positive CMV IgM in their mothers' plasma or cord blood plasma, only 0.58% of the samples (3/517) had a positive NAT. The number of excluded CBUs from inventory due to positive CMV IgM in the cord blood was 54 of 18,326 (0.3%). For inventory purposes, it is appropriate to remove CBUs with positive cord blood CMV IgM findings irrespective of the NAT status as well as positive maternal CMV IgM in South Korea. PMID:27524276

Excluding Anti-cytomegalovirus Immunoglobulin M-Positive Cord Blood Units Has a Minimal Impact on the Korean Public Cord Blood Bank Inventory.

PubMed

Shin, Sue; Roh, Eun Youn; Oh, Sohee; Song, Eun Young; Kim, Eui Chong; Yoon, Jong Hyun

2017-01-24

Cord blood units (CBUs) for transplantation should be free of communicable disease and must contain a specific amount of total nucleated cells and CD34+ cells. Although posttransplantation cytomegalovirus (CMV) infections are from latent infection in patients, ensuring CMV-free CBUs by performing CMV-specific IgM and nucleic acid amplification testing (NAT) is one of the mandatory procedures for the safety of CBUs. However, the exclusion policies (based on these test results) vary among nations and institutions. We tested 28,000 processed CBUs between May 2006 and June 2014. The cord blood leukocytes from CMV IgM-positive samples were then subjected to NAT. The total nucleated cell and CD34+ cell counts were measured for each CBU, and the results were compared to the CMV IgM and IgG results. The seroprevalence of CMV among pregnant women was 98.1% (18,459/18,818) for IgG and 1.7% (441/25,293) for IgM. The concentration and the total number of CD34+ cells were significantly higher in CBUs from IgM-negative mothers compared to those from IgM-positive mothers (72.4/μl vs. 57.2/μl, respectively, p < 0.0001; 1.45 × 106/unit vs. 1.15 × 106/unit, respectively, p < 0.0001). Among CBUs with positive CMV IgM in their mothers' plasma or cord blood plasma, only 0.58% of the samples (3/517) had a positive NAT. The number of excluded CBUs from inventory due to positive CMV IgM in the cord blood was 54 of 18,326 (0.3%). For inventory purposes, it is appropriate to remove CBUs with positive cord blood CMV IgM findings irrespective of the NAT status as well as positive maternal CMV IgM in South Korea.

Assessment of cytomegalovirus and cell-mediated immunity for predicting outcomes in non-HIV-infected patients with Pneumocystis jirovecii pneumonia.

PubMed

Kim, Taeeun; Park, Se Yoon; Lee, Hyun-Jung; Kim, Sun-Mi; Sung, Heungsup; Chong, Yong Pil; Lee, Sang-Oh; Choi, Sang-Ho; Kim, Yang Soo; Woo, Jun Hee; Kim, Sung-Han

2017-07-01

The clinical importance of pulmonary cytomegalovirus (CMV) co-infection in patients with Pneumocystis jirovecii pneumonia (PCP) is uncertain. We therefore determined the association of CMV infection with outcomes in non-HIV-infected patients with PCP by assessing CMV viral load and CMV-specific T-cell response.We prospectively enrolled all non-HIV-infected patients with confirmed PCP, over a 2-year period. Real-time polymerase chain reaction from bronchoalveolar lavage was performed to measure CMV viral load, and CMV enzyme-linked immunospot assays of peripheral blood were used to measure CMV-specific T-cell responses. The primary outcome was 30-day mortality.A total of 76 patients were finally analyzed. The mortality in patients with high BAL CMV viral load (>2.52 log copies/mL, 6/32 [18%]) showed a nonsignificant trend to be higher than in those with low CMV viral load (2/44 [5%], P = .13). However, the mortality in patients with low CMV-specific T-cell responses (<5 spots/2.0 × 10 PBMC, 6/29 [21%]) was significantly higher than in patients with high CMV-specific T-cell response (2/47 [4%], P = .048). Moreover, the 2 strata with high CMV viral load and low CMV-specific T-cell responses (4/14 [29%]) and low CMV viral load and low CMV-specific T-cell responses (2/15 [13%]) had poorer outcomes than the 2 strata with high CMV viral load and high CMV-specific T-cell responses (2/18 [11%]) and low CMV viral load and high CMV-specific T-cell responses (0/29 [0%]).These data suggest that the CMV replication and impaired CMV-specific T-cell responses adversely affect the outcomes in non-HIV-infected patients with PCP.

49 CFR 350.105 - What definitions are used in this part?

Code of Federal Regulations, 2011 CFR

2011-10-01

... governments, and other persons carrying out programs, activities, and projects relating to CMV safety and... percent of total MCSAP funds are available for these activities. Commercial motor vehicle (CMV) means a... vehicle safety plan (CVSP) means the document outlining the State's CMV safety objectives, strategies...

CMV Infection in Pediatric Severe Ulcerative Colitis - A Multicenter Study from the Pediatric IBD Porto Group of ESPGHAN.

PubMed

Cohen, Shlomi; Martinez-Vinson, Christine; Aloi, Marina; Turner, Dan; Assa, Amit; de Ridder, Lissy; Wolters, Victorien M; de Meij, Tim; Alvisi, Patrizia; Bronsky, Jiri; Kopylov, Uri

2017-07-31

Data on the clinical course and outcomes of pediatric patients with cytomegalovirus (CMV) infection complicating acute severe ulcerative colitis (ASC) are very limited. The aim of our study was to compare outcomes of children with ASC who were CMV-positive or CMV-negative. This was a multicenter retrospective case-controlled study, from centers affiliated with the Pediatric IBD Porto Group of ESPGHAN. We included CMV -positive children hospitalized for ASC and compared their colectomy rate during hospitalization and up to 1 year thereafter, matched with CMV-negative controls. A total of 56 children were included; 15 CMV-positive and 41 CMV-negative. More CMV-positive patients were resistant to intravenous corticosteroids as compare to CMV negative (93% and 56% respectively, p=0.009). Fourteen of the CMV-positive children (93%) were treated with ganciclovir (5/14 (36%) with 5mg/kg and 9/14 (64%) with 10mg/kg). During hospitalization, 3 (20%) CMV-positive and 3 (7.8%) CMV-negative patients required colectomy (p=0.17). By 12 months, 5 (33%) and 5 (13%) CMV-positive and negative patients required colectomy, respectively (p=0.049); the significance was not retained on multivariate analysis. A higher prevalence of CMV-positivity was found in pediatric UC patients who required colectomy within 12 months of hospitalization for ASC. Further studies are needed to clarify the impact of CMV infection on the outcome of acute severe colitis in pediatric patients.

Hyperimmunoglobulin prophylaxis, monitoring and preemptive ganciclovir treatment eliminate the risk of CMV infection to improve patient and renal allograft survival.

PubMed

Schneeberger, H; Aydemir, S; Müller, R; Illner, W D; Pfeiffer, M; Theodorakis, J; Zanker, B; Land, W

2000-01-01

This study was designed to investigate whether the introduction of ganciclovir to clinical use for anti-CMV treatment changes the risk of CMV infection in renal transplant patients. A total of 1545 cases who had received cadaveric renal transplants were divided into two groups: group 1 (n = 721) was made up of patients who received their transplants within 6 years before the introduction (1991) of ganciclovir and group 2 (n = 824), of individuals transplanted thereafter. Patient and graft survival of CMV D+/R- patients was uni- and multivariately compared with non-CMV D+/R- patients. In CMV D+/R- patients in group 1, survival was significantly lower, and their relative risk for graft loss was 1.32-fold (P = 0.0483) that of non-CMV D+/R- patients. In group 2 patient and graft survival was identical regardless of whether the patients were at risk for CMV infection or not. The risk of CMV infection can be eliminated by hyperimmunoglobulin prophylaxis, CMV monitoring and preemptive ganciclovir treatment in renal transplant patients.

Cytomegalovirus Infection among Infants in California Neonatal Intensive Care Units, 2005–2010

PubMed Central

Lanzieri, Tatiana M.; Bialek, Stephanie R.; Bennett, Mihoko V.; Gould, Jeffrey B.

2016-01-01

Aim Assess the burden of congenital and perinatal cytomegalovirus (CMV) disease among infants hospitalized in neonatal intensive care units (NICUs). Methods CMV infection was defined as a report of positive CMV viral culture or PCR at any time since birth in an infant hospitalized in a NICU reporting to California Perinatal Quality Care Collaborative during 2005–2010. Results 156 (1.7 per 1000) infants were reported with CMV infection, representing an estimated 5% of the expected number of live births with symptomatic CMV disease. Prevalence was higher among infants with younger gestational ages and lower birth weights. Infants with CMV infection had significantly longer hospital stays; 14 (9%) died. Conclusions Reported prevalence of CMV infection in NICUs represents a fraction of total expected disease burden from CMV in the newborn period, likely resulting from underdiagnosis and milder symptomatic cases that do not require NICU care. More complete ascertainment of infants with congenital CMV infection that would benefit from antiviral treatment may reduce the burden of CMV disease in this population. PMID:24334425

Cytomegalovirus persistence and T-cell immunosenescence in people aged fifty and older: A systematic review.

PubMed

Weltevrede, Marlies; Eilers, Renske; de Melker, Hester E; van Baarle, Debbie

2016-05-01

Immunosenescence is the age-related deterioration of immunocompetence which is reflected in a poorer response to new antigens. This process is characterized by decreases in naïve T cells and increases in memory T cells. The highly prevalent β-herpesvirus cytomegalovirus (CMV) is thought to enhance T-cell immunosenescence. The aim of this study was to perform a systematic review on the current evidence regarding the relation between CMV-infection and immunosenescence in Western people aged fifty years and older. Studies that investigated the relation between CMV infection and immune parameters in Western people aged 50 years and older were eligible for inclusion. No restrictions were placed on study type. This article focuses on the relation between CMV infections as measured by serology and T cell subsets. A narrative approach to data synthesis was applied. In the majority of included studies higher levels of Effector Memory (EM) and TEMRA (Effector Memory T cells re-expressing CD45RA) cells were found in the CD4+ and the CD8+ T cell pools in CMV-seropositive elderly compared to CMV-seronegative elderly. No clear evidence was found for lower levels of naïve T cells in CMV-seropositive elderly compared to CMV-seronegative elderly. The total CD8+ T cell pool appeared to be larger in CMV-seropositive elderly in three out of four studies, while the total CD4+ T cell pool appeared to be smaller in CMV-seropositive elderly in two out of four studies. CMV seems to enhance immunosenescence based on the high levels of the highly differentiated EM and TEMRA cells in the CD8+ and CD4+ T cell pools. The relation of the shifts within the T cell compartments in CMV-seropositive elderly in relation to susceptibility to infectious diseases remains to be investigated. Copyright © 2016 Elsevier Inc. All rights reserved.

Differences in cognitive functions between cytomegalovirus-infected and cytomegalovirus-free university students: a case control study.

PubMed

Chvátalová, Veronika; Šebánková, Blanka; Hrbáčková, Hana; Tureček, Petr; Flegr, Jaroslav

2018-03-28

Cytomegalovirus (CMV) is the herpetic virus, which infects 45-100% people worldwide. Many reports suggest that CMV could impair cognitive functions of infected subjects. Here we searched for indices of effects of CMV on infected subjects' intelligence and knowledge. The Intelligence Structure Test I-S-T 2000 R was used to compare IQ of 148 CMV-infected and 135 CMV-free university students. Infected students expressed higher intelligence. Paradoxically, their IQ decreased with decreasing concentration of anti-CMV antibodies, which can be used, statistically, as a proxy of the time passed from the moment of infection in young subjects when the age of subjects is statistically controlled. The paradox of seemingly higher intelligence of CMV infected subjects could be explained by the presence of the subpopulation of about 5-10% CMV-positive individuals in the population of "CMV-negative students". These false negative subjects had probably not only the oldest infections and therefore the lowest concentration of anamnestic antibodies, but also the lowest intelligence among the infected students. Prevalence of CMV infection in all countries is very high, approaching sometimes 90%. Therefore, the total impact of CMV on human intelligence may be large.

Evaluation of the Abbott RealTime HCV assay for quantitative detection of hepatitis C virus RNA.

PubMed

Michelin, Birgit D A; Muller, Zsofia; Stelzl, Evelyn; Marth, Egon; Kessler, Harald H

2007-02-01

The Abbott RealTime HCV assay for quantitative detection of HCV RNA has recently been introduced. In this study, the performance of the Abbott RealTime HCV assay was evaluated and compared to the COBAS AmpliPrep/COBAS TaqMan HCV test. Accuracy, linearity, interassay and intra-assay variations were determined, and a total of 243 routine clinical samples were investigated. When accuracy of the new assay was tested, the majority of results were found to be within +/-0.5 log(10) unit of the results obtained by reference laboratories. Determination of linearity resulted in a quasilinear curve up to 1.0 x 10(6)IU/ml. The interassay variation ranged from 15% to 32%, and the intra-assay variation ranged from 5% to 8%. When clinical samples were tested by the Abbott RealTime HCV assay and the results were compared with those obtained by the COBAS AmpliPrep/COBAS TaqMan HCV test, the results for 93% of all samples with positive results by both tests were found to be within +/-1.0 log(10) unit. The viral loads for all patients measured by the Abbott and Roche assays showed a high correlation (R(2)=0.93); quantitative results obtained by the Abbott assay were found to be lower than those obtained by the Roche assay. The Abbott RealTime HCV assay proved to be suitable for use in the routine diagnostic laboratory. The time to results was similar for both of the assays.

Cochlear implant performance in children deafened by congenital cytomegalovirus-A systematic review.

PubMed

Kraaijenga, V J C; Van Houwelingen, F; Van der Horst, S F; Visscher, J; Huisman, J M L; Hollman, E J; Stegeman, I; Smit, A L

2018-05-16

Congenital cytomegalovirus (cCMV) infection is a major cause of sensorineural hearing loss in children. The objective of this systematic review was to compare performance in paediatric cochlear implant users with SNHL caused by cCMV compared to non-cCMV implantees. Systematic review SEARCH STRATEGY: PubMed, EMBASE and the Cochrane databases were searched from inception up to 15 May 2017 for children, cochlear implant, performance and their synonyms. Titles, abstracts and full texts were screened for eligibility. Directness of evidence and risk of bias were assessed. From the included studies, study characteristics and outcome data (speech perception, speech production, receptive language and auditory performance of cCMV groups and non-cCMV groups) were extracted. A total of 5280 unique articles were screened of which 28 were eligible for critical appraisal. After critical appraisal, 12 studies remained for data extraction. Seven of 12 studies showed worse performance after cochlear implantation in cCMV children compared to non-cCMV children. Worse performance in cCMV children was attributed to cCMV-related comorbidities in six of these studies. Available data on asymptomatic cCMV children compared to non-cCMV children did not reveal an unfavourable effect on cochlear implant performance. The available evidence reveals that cCMV children often have worse cochlear implant performance compared to non-cCMV children, which can be attributed to cCMV related comorbidities. We urge physicians to take into account the cCMV related comorbidities in the counselling of paediatric CI users deafened by cCMV. © 2018 The Authors. Clinical Otolaryngology Published by John Wiley & Sons Ltd.

Early CMV Viremia Is Associated with Impaired Viral Control following Nonmyeloablative Hematopoietic Cell Transplantation with a Total Lymphoid Irradiation and Antithymocyte Globulin Preparative Regimen

PubMed Central

Schaenman, Joanna M.; Shashidhar, Sumana; Rhee, Chanu; Wong, Jonathan; Navato, Shelly; Wong, Ruby M.; Ho, Dora Y.; Arai, Sally; Johnston, Laura; Brown, Janice M.

2017-01-01

The reconstitution of immune function after hematopoietic cell transplant (HCT) plays an important role in the control of viral infections. Both donor and recipient cytomegalovirus (CMV) serostatus has been shown to contribute to effective immune function; however, the influence of a nonmyeloablative preparative (NMA) regimen using total lymphoid irradiation (TLI) and antithymocyte globulin (ATG) on antiviral immune reconstitution has not yet been described. In 117 recipients of NMA HCT patients following ATG and TLI, not unexpectedly, CMV viremia was seen in approximately 60% of the seropositive patients regardless of donor serostatus, and recipient seropositivity significantly increased the odds of CMV viremia after transplant in a multivariate analysis. The administration of ATG and TLI resulted in a strikingly earlier viremia in the posttransplant period when compared to the previously reported timing of viremia following myeloablative preparative regimens, especially for transplant recipients who were seropositive for CMV with seronegative donors. Furthermore, early viremia in the setting of a CMV naïve donor was associated with a delay in functional antiviral control. These observations demonstrate the dynamic nature of immunity in relation to CMV antigen exposure in the complex environment resulting from NMA conditions where both donor and residual recipient immune response affect viral control. PMID:20736077

Kinetic of the CMV-specific T-cell immune response and CMV infection in CMV-seropositive kidney transplant recipients receiving rabbit anti-thymocyte globulin induction therapy: A pilot study.

PubMed

Martín-Gandul, Cecilia; Pérez-Romero, Pilar; Mena-Romo, Damián; Molina-Ortega, Alejandro; González-Roncero, Francisco M; Suñer, Marta; Bernal, Gabriel; Cordero, Elisa

2018-03-23

Some studies have suggested that rATG treatment may be associated with an increased incidence of CMV infection and delayed CMV immune response. However, the evidences supporting this matter are scarce. This study aims to characterize the kinetic of the CMV-specific T-cell immune response before and after rATG induction therapy and the relationship with the development of CMV infection in CMV-seropositive kidney transplant recipients. An observational prospective study of CMV-seropositive kidney transplant patients that received rATG induction therapy was performed. A pretransplant sample was obtained before the surgery to determine the CMV-specific immunity. CMV viral load (by PCR) and CMV-specific T-cell immune response (by flow cytometry) were determined during the follow-up at 0.5, 1, 2, 3, 6, and 12 months post transplantation. A total of 23 patients were included in the study. CMV prophylaxis was administrated for a media of 90 days after transplantation. At the end of follow-up, 18 (78.3%) patients had CMV-specific immunity with a median value of 0.31% CD8 + CD69 + INF-γ + T cells at a median of 16 weeks post transplantation. Five patients never acquired CMV-specific immunity. No statistically significant association between CMV infection and CMV-specific T-cell immune response (P = .086) was observed. However, patients with positive pretransplant CMV-specific immunity developed earlier immunity and achieved higher levels of CD8 + CD69 + INF-γ+ T-cell post-transplantation than patients with negative pretransplant immunity. CMV-specific immune monitoring in addition to CMV-serology may be useful to stratify patient's risk of CMV infection before transplantation. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Role of antigenemia assay in the early diagnosis and treatment of CMV infection in renal transplant patients.

PubMed

Chiaramonte, S; Pellizzer, G; Rassu, M; Dissegna, D; Bragantiini, L; Zuccarotto, D; La Greca, G

2000-04-01

CMV antigenemia by direct pp65 antigen detection and quantification was monitored on a weekly basis during the first 3 months after kidney transplantation. Preemptive therapy with ganciclovir was started according to the following criteria: any positive antigemia in CMV-NEG subjects, a single determination > or = 30 cell or a two fold increase of positive cells in two consecutive specimens in CMV-POS and continued until pp65 was cleared. Overall, 109 patients were monitored. Among the 24 CMV-NEG patients, 13 (54%) developed a pp65 positive assay without symptoms and were treated. Ten patients remained CMV-infection free and one patient developed late onset (7 months) CMV disease (hepatitis). Among the 85 POS patients 15 (17%) developed a pp65 positive assay and were treated. Two of them developed CMV disease within 7 days of the onset of positive antigenemia and 13 were asymptomatic. The other 70 patients remained CMV-infection free. The interval between transplant and the onset of CMV infection was 39 +/- 13 days in the CMV-NEG group and 64 +/- 20 days in the CMV-POS group (p < 0.001). The peak antigenemia level was 193 +/- 175 cells in the CMV-NEG group and 55+/- 78 cells in the CMV-POS group (p < 0.001). The duration of treatment did not differ in the two groups (22 +/- 7days). A second course of therapy, due to a relapse of asymptomatic infection was performed in 11/13 (85%) treated CMV-NEG patients and in 2/15 (13%) treated CMV-POS patients. Among the total 28 treated patients, we observed only 6 episodes of mild creatinine increase and 9 episodes of mild neutropenia. In the overall population, we observed 8 systemic infections not related to CMV.

The effect of different immunoprophylaxis regimens on post-transplant cytomegalovirus (CMV) infection in CMV-seropositive liver transplant recipients.

PubMed

Low, Chian Yong; Hosseini-Moghaddam, Seyed Mohammadmehdi; Rotstein, Coleman; Renner, Eberhard L; Husain, Shahid

2017-10-01

The effects of different immunoprophylaxis regimens on cytomegalovirus (CMV) infection in liver transplant recipients (LTRs) have not been compared. In a cohort, we studied 343 CMV-seropositive recipient (R+) and 83 seronegative donor/recipient (D-/R-) consecutive LTRs from 2004 to 2007. Immunoprophylaxis regimens included steroid-only, steroids plus rabbit anti-thymocyte globulin (rATG), and steroids plus basiliximab. Logistic regression analysis, Cox proportional hazards regression model, and log-rank test were performed for multivariate analysis as appropriate. In total, 164 (39%), 69 (16%), and 193 (45%) patients received steroid-only, basiliximab, and rATG immunoprophylaxis, respectively. CMV infection rates were 15.7% (54/343) in CMV R+ LTRs and 2.4% (2/83) in CMV R- LTRs. Among CMV R+ LTRs who received rATG, the use of at least 6 weeks of CMV prophylaxis reduced the rate of CMV infection from 24.4% (19/78) to 11.7% (9/77). In multivariate analysis, CMV R+ vs D-/R- (odds ratio [OR]=13.1, 95% confidence interval [CI]: 1.8-97.2), rATG >3 mg/kg vs steroid-only induction (OR=1.6, 95% CI: 1.1-2.3), and CMV prophylaxis <6 weeks vs ≥6 weeks (OR=2.7, 95% CI: 1.2-6.4) were independently associated with CMV infection. Subgroup analysis in CMV D-/R+ group who received rATG showed that ≥6 weeks of CMV prophylaxis significantly decreased the risk of CMV infection (OR=1.9, 95% CI: 1.1-3.9; P=.03). The use of rATG immunoprophylaxis increases the risk of CMV infection in CMV-seropositive LTRs, specifically in the CMV D-/R+ group. Prophylaxis with valganciclovir in this group for at least 6 weeks decreases the risk of CMV infection. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cytomegalovirus infection in seropositive unrelated cord blood recipients: a study of 349 Korean patients.

PubMed

Park, Meerim; Lee, Young Ho; Lee, Soo Hyun; Yoo, Keon Hee; Sung, Ki Woong; Koo, Hong Hoe; Lee, Ji Won; Kang, Hyoung Jin; Park, Kyung Duk; Shin, Hee Young; Ahn, Hyo Seop; Lee, Jae Wook; Chung, Nack-Gyun; Cho, Bin; Kim, Hack-Ki; Koh, Kyung-Nam; Im, Ho Joon; Seo, Jong Jin; Baek, Hee Jo; Kook, Hoon; Hwang, Tai Ju; Lee, Jae Min; Hah, Jeong Ok; Lim, Yeon Jung; Park, Jun Eun; Lyu, Chuhl Joo; Lim, Young Tak; Chong, So Young; Oh, Doyeun

2015-03-01

To gain insight into the natural history of cytomegalovirus (CMV) infection following unrelated cord blood transplantation (UCBT) in seropositive patients, we analyzed the data of 349 seropositive patients who received UCBT in Korea between 2000 and 2011. CMV reactivation occurred in 49 % (171/349) of the CMV-seropositive transplant recipients at a median of 31 days post UCBT. One hundred sixty-four out of 171 patients (96 %) received preemptive therapy. The median duration of CMV reactivation was 29 days. In multivariate analysis, weight >22 kg, use of total body irradiation, use of pre-transplant antithymocyte globulin, graft-versus-host disease (GVHD) prophylaxis with mycophenolate mofetil, and presence of grade II-IV acute GVHD were independent predictors of CMV reactivation. CMV reactivation did not impact transplantation-related mortality (TRM), leukemia relapse, or survival. CMV disease was diagnosed in 62 patients (17.8 %) at a median 55 days after UCBT. Longer duration of CMV reactivation was the only risk factor for progression to CMV disease (p = 0.01). CMV disease resulted in higher TRM (56.0 vs. 31.4 %, p < 0.01) and lower survival (36.1 vs. 55.1 %, p = 0.02).

Primary Cytomegalovirus Infection in Pregnant Egyptian Women Confirmed by Cytomegalovirus IgG Avidity Testing

PubMed Central

Kamel, N.; Metwally, L.; Gomaa, N.; Sayed Ahmed, W.A.; Lotfi, M.; Younis, S.

2013-01-01

Objective To determine the frequency of primary cytomegalovirus (CMV) infection in pregnant Egyptian women using CMV IgG avidity testing. Subjects and Methods A cross-sectional study was conducted at Suez Canal University Hospital, Ismailia, Egypt. A total of 546 pregnant women, presenting for routine antenatal screening, were tested for CMV IgG and IgM using a commercially available enzyme-linked immunosorbent assay (ELISA). Sera from CMV IgM-positive women were tested by CMV IgG avidity assay. Results All the 546 pregnant women were seropositive for anti-CMV IgG. Of the 546 women, 40 (7.3%) were positive or equivocal for IgM antibodies. All sera from the 40 women (IgG+/IgM+) showed a high or intermediate CMV IgG avidity index. Of the 40 women, 23 (57.5%) were in the second or third trimesters of pregnancy and had their first-trimester blood retrieved, and the tested CMV IgG avidity assay showed a high avidity index. Conclusion Women who were IgM positive had no primary CMV infection in the index pregnancy as evidenced by the high CMV IgG avidity testing. PMID:24052007

Primary cytomegalovirus infection in pregnant Egyptian women confirmed by cytomegalovirus IgG avidity testing.

PubMed

Kamel, N; Metwally, L; Gomaa, N; Sayed Ahmed, W A; Lotfi, M; Younis, S

2014-01-01

To determine the frequency of primary cytomegalovirus (CMV) infection in pregnant Egyptian women using CMV IgG avidity testing. A cross-sectional study was conducted at Suez Canal University Hospital, Ismailia, Egypt. A total of 546 pregnant women, presenting for routine antenatal screening, were tested for CMV IgG and IgM using a commercially available enzyme-linked immunosorbent assay (ELISA). Sera from CMV IgM-positive women were tested by CMV IgG avidity assay. All the 546 pregnant women were seropositive for anti-CMV IgG. Of the 546 women, 40 (7.3%) were positive or equivocal for IgM antibodies. All sera from the 40 women (IgG+/IgM+) showed a high or intermediate CMV IgG avidity index. Of the 40 women, 23 (57.5%) were in the second or third trimesters of pregnancy and had their first-trimester blood retrieved, and the tested CMV IgG avidity assay showed a high avidity index. Women who were IgM positive had no primary CMV infection in the index pregnancy as evidenced by the high CMV IgG avidity testing. © 2013 S. Karger AG, Basel.

Incidence and Risk Factors for Cytomegalovirus Infection in Patients With Kidney Transplantation: A Single-Center Experience.

PubMed

Feng, S; Yang, J; Wang, W; Hu, X; Liu, H; Qian, X; Feng, D; Zhang, X

2016-10-01

Cytomegalovirus (CMV) infection is deemed to be a major cause of morbidity and mortality in patients after kidney transplantation. The purpose of this study was to analyze the incidence of CMV infection and risk factors for CMV infection in our center, to help in determination of its impact on the kidney function in this patient population, and to provide new ideas for the prevention and treatment of CMV infection. A total of 319 kidney transplant recipients from our center were studied between January 2000 and December 2015. The CMV viral load in each kidney transplant patients was monitored with the use of CMV quantitative nucleic acid testing (CMV-QNAT). Laboratory data and other medical records were also collected. The incidence of CMV infection was 8.8% in our studied patients. The patients within 3 to 6 months and 5 to 10 years after transplantation had a higher risk of CMV infection. CMV infection was probably correlated with lower white blood cell counts but elevated hemoglobin, serum creatinine, blood urea nitrogen, potassium, and estimated glomerular filtration rate (eGFR). Anti-CMV immunoglobulin (Ig)G and history of allograft rejection were also associated with CMV infection. In multivariate regression analysis, white blood cells, eGFR, anti-CMV IgG, and history of allograft rejection were the independent risk factors associated with CMV infection in kidney transplantation patients. CMV infection was an important complication after kidney transplantation, particularly in these patients with allograft impairment. Copyright © 2016 Elsevier Inc. All rights reserved.

The Association Between CMV Viremia or Endoscopic Features and Histopathological Characteristics of CMV Colitis in Patients with Underlying Ulcerative Colitis.

PubMed

Yang, Hong; Zhou, Weixun; Lv, Hong; Wu, Dongsheng; Feng, Yunlu; Shu, Huijun; Jin, Meng; Hu, Lingling; Wang, Qiang; Wu, Dong; Chen, Jie; Qian, Jiaming

2017-05-01

Cytomegalovirus (CMV) infection has been shown to be related to severe or steroid-refractory ulcerative colitis (UC) flare-ups. The aim of this study was to evaluate the endoscopic and pathological characteristics of CMV colitis in patients with UC and to assess the predictive value of the endoscopic and pathological features of CMV colitis. A total of 50 consecutive UC patients with CMV infection who were admitted to Peking Union Medical College Hospital from 2010 to 2015 were enrolled in this study. Twenty-five UC patients with CMV infection (50.0%) had concurrent CMV colitis. When the cutoff value was set at 1150 copies, the sensitivity and specificity of blood CMV DNAq polymerase chain reaction for predicting CMV colitis were 44.4% and 78.9%, respectively. A higher proportion of endoscopic punched-out ulcers, irregular ulcers, and cobblestone-like appearance were observed among the patients in the CMV colitis group than those in the non-CMV colitis group (52.0% versus 20.0%, 60.0% versus 16.0%, and 20.0% versus 0%, respectively, P < 0.05). The number of CMV inclusion bodies per high-power field was significantly higher in those with punch-out ulcerations (25.7% versus 60.0%, P < 0.05). A higher grade of pathological inflammation was observed in the CMV colitis group than in the control group (68.0% versus 44.0%). Characteristic endoscopic features with punch-out ulcers and high CMV viremia load may be useful for predicting the presence of CMV colitis in histology. Punch-out ulcers were found to be associated with a higher number of inclusion bodies on histology, suggesting a role of targeted biopsy for endoscopist.

Detection of CMV pneumonitis after lung transplantation using PCR of DNA from bronchoalveolar lavage cells.

PubMed

Bewig, B; Haacke, T C; Tiroke, A; Bastian, A; Böttcher, H; Hirt, S W; Rautenberg, P; Haverich, A

2000-01-01

Cytomegalovirus (CMV) is known as a common pathogen causing infections after lung transplantation. Rapid diagnosis of CMV infection is important for the initiation of a specific treatment. Evaluation of methods for the rapid diagnosis of CMV pneumonitis. The detection rates of CMV DNA in bronchoalveolar lavage (BAL) and bronchial brushes by polymerase chain reaction (PCR), of viral antigens (p52 and IE1) in BAL and of pp65 antigen in peripheral blood leukocytes were compared to the clinical status after lung transplantation. In 28 patients, 105 BAL, 96 blood samples and 14 brushes were analyzed. In 6 patients, a total of eight episodes of CMV pneumonitis occurred. Five of the 6 with positive CMV antigens in BAL (p52 or IE1) showed signs of CMV pneumonitis. All episodes of CMV pneumonitis were detected by the PCR of BAL cells. Fourteen samples positive for CMV pp65 antigen in blood were negative in BAL PCR. In these cases, no clinical signs of pulmonary CMV infection occurred. Overall sensitivity, specificity, and positive and negative predictive values for the detection of CMV pneumonitis by PCR of BAL cells were 100, 98.9, 88.9 and 100%, respectively. In brush samples, PCR did not provide additional information to the results of the PCR of BAL cells. PCR of DNA from BAL cells is suitable for reliable and rapid detection of CMV pneumonitis. Copyright 2000 S. Karger AG, Basel.

[Cytomegalovirus (CMV) infection in infants may result intractable stridor].

PubMed

Kashiwagi, Y; Kawashima, H; Takekuma, K; Hoshika, A; Nozaki-Renaud, J

2000-08-01

We found ten cases of human cytomegalovirus (CMV) infection who were intractable stridor. Their symptoms were not improved by the treatment with aminophyllin nor beta stimulants. They were admitted repeatedly complaining of stridor, fever and diarrhea. In two cases, the immunological findings showed a decrease of bacterial sterilizing activity of the neutrophils. Additionally, blood count showed leukocytosis more than 15,000/ul in all cases. Total serum IgE and specific IgE antibodies to many antigens were not elevated. Transaminase was elevated. Chest X-p findings of interstitial pneumonia or atelectasis continued for a long time in some cases. Virological examinations revealed high concentrations of specific IgM or CF antibodies against CMV in all cases. CMV DNA in saliva were examined by polymerase chain reaction (PCR) with primer sets for the immediate early (IE) region of CMV and showed positive in seven cases. CMV in bronchoalveolar lavage (BAL) was isolated in two cases, and CMV PCR in BAL was positive in three cases. The sequence of the CMV-PCR products showed almost same sequence except one point mutation in bp 1203. We considered that CMV infections in infants may induce stridor for a long period.

Evaluation of the COBAS AMPLICOR CMV MONITOR test for detection of viral DNA in specimens taken from patients after liver transplantation.

PubMed

Sia, I G; Wilson, J A; Espy, M J; Paya, C V; Smith, T F

2000-02-01

Detection of cytomegalovirus (CMV) DNA in blood by PCR is a sensitive method for the detection of infection in patients posttransplantation. The test, however, has low specificity for the identification of overt CMV disease. Quantitative CMV PCR has been shown to overcome this shortcoming. The COBAS AMPLICOR CMV MONITOR test was evaluated by using consecutive serum and peripheral blood mononuclear cell (PBMN) samples from liver transplant patients. Twenty-five patients had CMV viremia (by shell vial cell culture assay) and/or tissue-invasive disease (by biopsy); 20 had no active infection. A total of 262 serum and 62 PBMN specimens were tested. Of 159 serum specimens from patients with overt CMV infection, the COBAS assay detected CMV DNA in 21 patients (sensitivity, 84%). Only 1 of 103 samples from patients with no evidence of active infection had detectable CMV DNA (341 copies/ml). By comparison of 62 matching serum and PBMN samples by the same assay, 12 PBMN samples were exclusively positive, whereas only 2 serum samples were exclusively positive (P < 0.05). At the time of clinical CMV infection, viral copy numbers were higher in PBMNs than serum from four of five patients. The COBAS AMPLICOR CMV MONITOR test is a sensitive and specific test for the quantitative detection of CMV DNA in blood. Clinical applications of the assay will require further validation with samples from a larger population of transplant patients.

Evaluation of the COBAS AMPLICOR CMV MONITOR Test for Detection of Viral DNA in Specimens Taken from Patients after Liver Transplantation

PubMed Central

Sia, Irene G.; Wilson, Jennie A.; Espy, Mark J.; Paya, Carlos V.; Smith, Thomas F.

2000-01-01

Detection of cytomegalovirus (CMV) DNA in blood by PCR is a sensitive method for the detection of infection in patients posttransplantation. The test, however, has low specificity for the identification of overt CMV disease. Quantitative CMV PCR has been shown to overcome this shortcoming. The COBAS AMPLICOR CMV MONITOR test was evaluated by using consecutive serum and peripheral blood mononuclear cell (PBMN) samples from liver transplant patients. Twenty-five patients had CMV viremia (by shell vial cell culture assay) and/or tissue-invasive disease (by biopsy); 20 had no active infection. A total of 262 serum and 62 PBMN specimens were tested. Of 159 serum specimens from patients with overt CMV infection, the COBAS assay detected CMV DNA in 21 patients (sensitivity, 84%). Only 1 of 103 samples from patients with no evidence of active infection had detectable CMV DNA (341 copies/ml). By comparison of 62 matching serum and PBMN samples by the same assay, 12 PBMN samples were exclusively positive, whereas only 2 serum samples were exclusively positive (P < 0.05). At the time of clinical CMV infection, viral copy numbers were higher in PBMNs than serum from four of five patients. The COBAS AMPLICOR CMV MONITOR test is a sensitive and specific test for the quantitative detection of CMV DNA in blood. Clinical applications of the assay will require further validation with samples from a larger population of transplant patients. PMID:10655353

Comparative analysis of cytomegalovirus retinitis and microvascular retinopathy in patients with acquired immunodeficiency syndrome

PubMed Central

Chen, Chao; Guo, Chun-Gang; Meng, Li; Yu, Jing; Xie, Lian-Yong; Dong, Hong-Wei; Wei, Wen-Bin

2017-01-01

AIM To compare the clinical manifestation of cytomegalovirus (CMV) retinitis and microvascular retinopathy (MVR) in patients with acquired immunodeficiency syndrome (AIDS) in China. METHODS A total of 93 consecutive patients with AIDS, including 41 cases of CMV retinitis and 52 cases of MVR were retrospectively reviewed. Highly active antiretroviral therapy (HAART) status was recorded. HIV and CMV immunoassay were also tested. CD4+ T-lymphocyte count and blood CMV-DNA test were performed in all patients. Aqueous humor CMV-DNA test was completed in 39 patients. Ophthalmological examinations including best corrected visual acuity (BCVA, by International Standard Vision Chart), intraocular pressure (IOP), slit-lamp biomicroscopy, indirect ophthalmoscopy were performed. RESULTS In MVR group, the anterior segment examination was normal in all patients with a mean BCVA of 0.93±0.13. Blood CMV-DNA was 0 (0, 269 000) and 42 patients (80.77%) did not receive HAART. In CMV retinitis group, 13 patients (31.71%) had anterior segment abnormality. The mean BCVA was 0.64±0.35 and blood CMV-DNA was 3470 (0, 1 450 000). Nineteen patients (46.34%) had not received HAART. MVR group and CMV retinitis group the positive rates of aqueous CMV-DNA were 0 and 50%, respectively. Two patients with MVR progressed to CMV retinitis during the follow-up period. CONCLUSION In comparison of CMV, patients with MVR have relatively mild visual function impairment. Careful ophthalmological examination and close follow-up are mandatory, especially for patients who have systemic complications, positive CMV-DNA test and without received HAART. PMID:28944199

Our experience of treatment of cribriform morular variant of papillary thyroid carcinoma; difference in clinicopathological features of FAP-associated and sporadic patients.

PubMed

Ito, Yasuhiro; Miyauchi, Akira; Ishikawa, Hideki; Hirokawa, Mitsuhiro; Kudo, Takumi; Tomoda, Chisato; Miya, Akihiro

2011-01-01

Cribriform-morular variant (CMV) is a comparably rare histological subtype of papillary thyroid carcinoma (PTC). This can be associated with familial adenomatous polyposis (FAP) due to APC gene mutations. In this study, we investigated the difference in the biological characteristics between FAP-associated and sporadic CMV. Between 1991 and 2010, 32 patients with CMV were treated in Kuma Hospital. Thirty-one of these underwent initial surgery for CMV in Kuma Hospital. Twelve patients were FAP-associated and the remaining 19 were sporadic CMV. All patients were female. Tumors of FAP-associated CMV were more frequently multiple than those of sporadic CMV. Patient age and tumor size did not differ between the two groups. Of 12 FAP-associated CMV, 5 were detected by thyroid nodule (thyroid precedent group) and 7 were detected by FAP (polyposis precedent group) as an initial manifestation. Patient age was younger and tumor size was smaller in the polyposis group than in the thyroid nodule group. All patients lacked extrathyroid extension on intraoperative finding and were node-negative on pathological examination. To date, two patients with FAP-associated CMV who initially underwent hemithyroidectomy (one in Kuma Hospital and one in another hospital) showed recurrence to the remnant thyroid during follow-up. None of the patients showed recurrence to other regions or died of carcinoma. Taken together, CMV is considered an indolent disease in our series. FAP-associated CMV showed multiple tumors more frequently than sporadic CMV. Total thyroidectomy is recommended for FAP-associated CMV, but extensive lymph node dissection is not necessary.

Economic burden of preemptive treatment of CMV infection after allogeneic stem cell transplantation: a retrospective study of 208 consecutive patients.

PubMed

Robin, Christine; Hémery, François; Dindorf, Christel; Thillard, Julien; Cabanne, Ludovic; Redjoul, Rabah; Beckerich, Florence; Rodriguez, Christophe; Pautas, Cécile; Toma, Andrea; Maury, Sébastien; Durand-Zaleski, Isabelle; Cordonnier, Catherine

2017-12-05

Cytomegalovirus (CMV) infection and disease (CMV episodes) are global concerns after allogeneic hematopoietic stem cell transplantation (HSCT). They affect survival, both by direct and indirect effects. Due to safety issues of current anti-CMV antivirals, long-term CMV prophylaxis is poorly tolerated and the most common strategy to decrease the incidence of CMV disease is preemptive. New, less toxic, molecules are currently being assessed for CMV prophylaxis which should replace or considerably decrease the preemptive approach. The aim of this study was to assess the economic burden of CMV episodes after HSCT with a preemptive approach. We analyzed data from 208 consecutive adults transplanted in our institution, between 2008 and 2013. Hospital resource utilization was retrieved via the linked hospital admissions and Diagnostic Related Groups for the period of conditioning to 12 months after transplant. CMV episodes occurred in 70 patients (34%) over the first 12 months following HSCT, after a mean of 75 days (median: 46 (7-334)). The mean total length of stay was significantly associated with the occurrence of a CMV episode (113.9 vs. 87.5 days, p = 0.0002) but was associated neither with the pre-transplant CMV serology of donors/recipients nor with survival. The mean cost of transplant was €104,016 (SD = €37,281) after 12 months. Bivariate and multivariate analyses indicated that the occurrence of >1 CMV episode increased the costs of allogeneic HSCT by 25-30% (p < 0.0001). Our study, which is the largest, single-institution cost study of allogeneic HSCT in Europe, shows that two or more CMV episodes significantly increased the transplant cost. New prophylactic strategies to prevent CMV infection and disease should decrease transplant costs.

[Cytomegalovirus infection after heart transplantation. Retrospective analysis of an antiviral CMV prevention].

PubMed

Antretter, H; Höfer, D; Klaus, A; Larcher, C; Margreiter, J; Margreiter, R

2000-04-14

Cytomegalovirus (CMV) infection is the most common viral infection in the early period after heart transplantation (HTX) and causes a significant morbidity and mortality. Although controversial, CMV is related to acute and chronic allograft rejection and to the development of graft vascular disease. It therefore plays an important role in the long-time outcome after solid organ transplantation. 45 patients received a new heart between 1.1.97 and 31.12.1998. All of them were enrolled postoperatively in three-month antiviral prophylaxis (Cymevene). Only those patients were excluded from prophylaxis who were seronegative for CMV and received hearts from seronegative donors (n = 6). The pp65 antigenaemia assay and the murex hybrid capture CMV DNA assay on peripheral blood as well as the early antigen detection in the urine were used for CMV detection and also for monitoring. A total number of 580 assays were analysed (12.9 assays/patient). 561 tests (96.7%) were negative, 19 (3.3%) were positive. For CMV testing the pp65 antigenemia assay was used in 64.1%, the murex hybrid capture CMV DNA assay in 18.4% and the urine early antigen detection in 17.4%. Three patients (6.7%) developed viraemia during the first 3 postoperative months. Two patients (4.4%) suffered from CMV infection 8 and 9 months after heart transplantation and had to be treated with antiviral agents. Three patients (6.7%) died early after transplantation, but none had a CMV infection. Prevention of CMV disease was successful with three months of antiviral CMV prophylaxis after HTX. Asymptomatic viraemia during the prophylaxis period did not lead to tissue invasive disease. It is possible to carry out rapid CMV detection and CMV monitoring with the commercially available antigenaemia assays.

The use of reference change values in clinical laboratories.

PubMed

Bugdayci, Guler; Oguzman, Hamdi; Arattan, Havva Yasemin; Sasmaz, Guler

2015-01-01

The use of Reference Change Values (RCV) has been advocated as very useful for monitoring individuals. Most of these are performed for monitoring individuals in acute situations and for following up the improvement or deterioration of chronic diseases. In our study, we aimed at evaluating the RCV calculation for 24 clinical chemistry analytes widely used in clinical laboratories and the utilization of this data. Twenty-four serum samples were analyzed with Abbott kits (Abbott Laboratories, Abbott Park, IL, USA), manufactured for use with the Architect c8000 (Abbott Laboratories, Abbott Park, IL, USA) auto-analyzer. We calculated RCV using the following formula: RCV = Z x 2 1/2x (CVA2 + CVw2)1/2. Four reference change values (RCV) were calculated for each analyte using four statistical probabilities (0.95, and 0.99, unidirectional and bidirectional). Moreover, by providing an interval after identifying upper and lower limits with the Reference Change Factor (RCF), serially measured tests were calculated by using two formulas: exp (Z x 2 1/2 x (CV(A)2 + CVw2)½/100) for RCF(UP) and (1/RCF(UP)) for RCF(DOWN). RCVs of these analytes were calculated as 14.63% for glucose, 29.88% for urea, 17.75% for ALP, 53.39% for CK, 46.98% for CK-MB, 21.00% amylase, 8.00% for total protein, 8.70% for albumin, 51.08% for total bilirubin, 86.34% for direct bilirubin, 6.40% for calcium, 15.03% for creatinine, 21.47% for urate, 14.19% for total cholesterol, 46.62% for triglyceride, 20.51% for HDL-cholesterol, 29.59% for AST, 46.31% for ALT, 31.54% for GGT, 20.92% for LDH, 19.75% for inorganic phosphate, 3.05% for sodium, 11.75% for potassium, 4.44% for chloride (RCV, p < 0.05, unidirectionally). We suggest using RCV as well as using population-based reference intervals in clinical laboratories. RCV could be available as a tool for making clinical decision, especially when monitoring individuals.

Comparison of Abbott and Da-an real-time PCR for quantitating serum HBV DNA.

PubMed

Qiu, Ning; Li, Rui; Yu, Jian-Guo; Yang, Wen; Zhang, Wei; An, Yong; Li, Tong; Liu, Xue-En; Zhuang, Hui

2014-09-07

To compare the performance of the Da-an real-time hepatitis B virus (HBV) DNA assay and Abbott RealTime HBV assay. HBV DNA standards as well as a total of 180 clinical serum samples from patients with chronic hepatitis B were measured using the Abbott and Da-an real-time polymerase chain reaction (PCR) assays. Correlation and Bland-Altman plot analysis was used to compare the performance of the Abbott and Da-an assays. The HBV DNA levels were logarithmically transformed for analysis. All statistical analyses were performed using SPSS for Windows version 18.0. The correlation between the two assays was analyzed by Pearson's correlation and linear regression. The Bland-Altman plots were used for the analysis of agreement between the two assays. A P value of < 0.05 was considered statistically significant. The HBV DNA values measured by the Abbott or Da-an assay were significantly correlated with the expected values of HBV DNA standards (r = 0.999, for Abbott; r = 0.987, for Da-an, P < 0.001). A Bland-Altman plot showed good agreement between these two assays in detecting HBV DNA standards. Among the 180 clinical serum samples, 126 were quantifiable by both assays. Fifty-two samples were detectable by the Abbott assay but below the detection limit of the Da-an assay. Moreover, HBV DNA levels measured by the Abbott assay were significantly higher than those of the Da-an assay (6.23 ± 1.76 log IU/mL vs 5.46 ± 1.55 log IU/mL, P < 0.001). A positive correlation was observed between HBV DNA concentrations determined by the two assays in 126 paired samples (r = 0.648, P < 0.001). One hundred and fifteen of 126 (91.3%) specimens tested with both assays were within mean difference ± 1.96 SD of HBV DNA levels. The Da-an assay presented lower sensitivity and a narrower linear range as compared to the Abbott assay, suggesting the need to be improved.

High-resolution linkage map in the proximity of the host resistance locus Cmv1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Depatie, C.; Muise, E.; Gros, P.

1997-01-15

The mouse chromosome 6 locus Cmv1 controls replication of mouse Cytomegalovirus (MCMV) in the spleen of the infected host. In our effort to clone Cmv1, we have constructed a high-resolution genetic linkage map in the proximity of the gene. For this, a total of 45 DNA markers corresponding to either cloned genes or microsatellites were mapped within a 7.9-cM interval overlapping the Cmv1 region. We have followed the cosegregation of these markers with respect to Cmv1 in a total of 2248 backcross mice from a preexisting interspecific backcross panel of 281 (Mus spretus X C57BL/6J)F1 X C57BL/6J and 2 novelmore » panels of 989 (A/J X C57BL6)F1 X A/J and 978 (BALB/c X C57BL/6J)F1 X BALB/c segregating Cmv1. Combined pedigree analysis allowed us to determine the following gene order and intergene distances (in cM) on the distal region of mouse chromosome 6: D6Mit216-(1.9)-D6Mit336-(2.2)-D6Mit218-(1.0)-D6Mit52-(0.5)-D6Mit194-(0.2)-Nkrp1/D6Mit61/135/257/289/338-(0.4)-Cmv1/Ly49A/D6Mit370-(0.3)-Prp/Kap/D6Mit13/111/219-(0.3)-Tel/D6Mit374/290/220/196/195/110-(1.1)-D6Mit25. Therefore, the minimal genetic interval for Cmv1 of 0.7 cM is defined by 13 tightly linked markers including 2 markers, Ly49A and D6Mit370, that did not show recombination with Cmv1 in 1967 meioses analyzed; the proximal limit of the Cmv1 domain was defined by 8 crossovers between Nkrp1/D6Mit61/135/257/289/338 and Cmv1/Ly49A/D6Mit370, and the distal limit was defined by 5 crossovers between Cmv1/Ly49A/D6Mit370 and Prp/Kap/D6Mit13/111/219. This work demonstrates tight linkage between Cmv1 and genes from the natural killer complex (NKC), such as Nkrp1 and Ly49A suggesting that Cmv1 may represent an NK cell recognition structure encoded in the NKC region. 54 refs., 4 figs., 2 tabs.« less

Cribriform-Morular Variant of Papillary Thyroid Carcinoma: Clinical and Pathological Features of 30 Cases.

PubMed

Akaishi, Junko; Kondo, Tetsuo; Sugino, Kiminori; Ogimi, Yuna; Masaki, Chie; Hames, Kiyomi Y; Yabuta, Tomonori; Tomoda, Chisato; Suzuki, Akifumi; Matsuzu, Kenichi; Uruno, Takashi; Ohkuwa, Keiko; Kitagawa, Wataru; Nagahama, Mitsuji; Katoh, Ryohei; Ito, Koichi

2018-04-25

Cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC) is rare; it may occur in cases of familial adenomatous polyposis (FAP) or be sporadic. To clarify the clinicopathological features of CMV-PTC, the medical records of these patients were investigated retrospectively. Between 1979 and 2016, a total of 17,062 cases with PTC underwent initial surgery at Ito Hospital. Of these, 30 (0.2%) cases histologically diagnosed with CMV-PTC were reviewed. The patients were all women, with a mean age at the time of surgery of 24 years. Seven (23%) cases were thought to have FAP because they had colonic polyposis or a family history of FAP or APC gene mutation. The remaining 23 (77%) were thought to be sporadic. Multiple tumors were detected in 6 cases, with a solitary tumor in 24. One patient had lung metastasis at diagnosis. Eleven patients underwent total thyroidectomy or subtotal thyroidectomy, and 19 underwent lobectomy. Twenty-six (87%) patients underwent neck lymph node dissection. Three patients had tumor metastasis in central lymph nodes, but these were incidentally detected metastatic classical PTC (cPTC) based on histological examination. In this series, there were no cases of LN metastases of CMV-PTC. During a mean follow-up of 15 years, one patient had new cPTC in the remnant thyroid after initial surgery, and the other patients showed no signs of recurrence. CMV-PTC occurred in young women, their long-term prognosis was excellent. Total thyroidectomy is recommended for FAP-associated CMV-PTC, but modified neck lymph node dissection is not necessary.

Cytomegalovirus infections in lung and hematopoietic cell transplant recipients in the Organ Transplant Infection Prevention and Detection Study: A multi-year, multicenter prospective cohort study.

PubMed

Avery, Robin K; Silveira, Fernanda P; Benedict, Kaitlin; Cleveland, Angela A; Kauffman, Carol A; Schuster, Mindy G; Dubberke, Erik R; Husain, Shahid; Paterson, David L; Chiller, Tom; Pappas, Peter

2018-03-07

Most studies of post-transplant CMV infection have focused on either solid organ or hematopoietic cell transplant (HCT) recipients. A large prospective cohort study involving both lung and HCT recipients provided an opportunity to compare the epidemiology and outcomes of CMV infections in these 2 groups. Patients were followed up for 30 months in a 6-center prospective cohort study. Data on demographics, CMV infections, tissue-invasive disease, recurrences, rejection, and immunosuppression were recorded. The overall incidence of CMV infection was 83/293 (28.3%) in the lung transplant group and 154/444 (34.7%) in the HCT group (P = .0706). Tissue-invasive CMV disease occurred in 8/83 (9.6%) of lung and 6/154 (3.9%) of HCT recipients with CMV infection, respectively (P = .087). Median time to CMV infection was longer in the lung transplant group (236 vs 40 days, P < .0001), likely reflecting the effects of prophylaxis vs preemptive therapy. Total IgG levels of < 350 mg/dL in lung recipients and graft vs host disease (GvHD) in HCT recipients were associated with increased CMV risk. HCT recipients had a higher mean number of CMV episodes (P = .008), although duration of viremia was not significantly different between the 2 groups. CMV infection was not associated with reduced overall survival in either group. Current CMV prevention strategies have resulted in a low incidence of tissue-invasive disease in both lung transplant and HCT, although CMV viremia is still relatively common. Differences between the lung and HCT groups in terms of time to CMV and recurrences of CMV viremia likely reflect differences in underlying host immunobiology and in CMV prevention strategies in the modern era. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

An analysis on the fate of a selection of blood products derived from cytomegalovirus-seronegative donors at three tertiary referral hospitals in Australia.

PubMed

Hirani, Rena; Tohidi-Esfahani, Ibrahim; Mondy, Phillip; Irving, David O

2018-03-01

Supply of cytomegalovirus (CMV)-seronegative blood products in Australia is an ongoing challenge. Requests for CMV-negative products are increasing with prediction that the demand will exceed supply by 2019. Clinical information evaluating how these products are being utilized by health providers within Australia is limited. This study aimed to identify indications for use of CMV-negative blood products and gather data to support possible practice change. All CMV-negative products issued to three tertiary Australian hospitals from May 1, 2016, to May 31, 2016, were identified (n = 1219). This equated to 1044 red blood cell units and 175 platelet units. Data were collected on the fate of each unit. Information collected included the indication and urgency of transfusion, reason for discard, product age, and recipient CMV immunoglobulin G status. Of the units issued during the audit period, 32 (2.6%) were discarded by the hospitals. Transfusion data were collected on 411 units. Of these, 136 (33.1%) were transfused to CMV-positive recipients, in most cases for hematology indications, and 67 units (16.3%) were transfused to CMV-negative requiring recipients. A total of 144 (35%) CMV-negative units were selected based on their irradiation status. Other reasons for the selection of CMV-negative units included product close to expiry (n = 134, 32.6%) or specific patient phenotype requirements (n = 31, 7.5%). In this study, the majority of CMV-negative blood products were not used for CMV-negative requiring recipients. Alterations to inventory management would be advantageous to ensure continued supply for CMV-negative requiring recipients. © 2017 AABB.

Diagnosis of cytomegalovirus pneumonia by quantitative polymerase chain reaction using bronchial washing fluid from patients with hematologic malignancies

PubMed Central

Choi, Joon Young; Lee, Hea Yon; Lee, Jong Wook; Lee, Dong Gun

2017-01-01

Background The incidence of cytomegalovirus (CMV) pneumonia is increasing in patients diagnosed with hematologic malignancies. The utility of CMV-DNA viral load measurement has not been standardized, and viral cut-off values have not been established. This study was designed to investigate the utility of CMV quantitative real-time PCR (qRT-PCR) using bronchial washing fluid. Methods We retrospectively reviewed the microbiologic and pathologic results of bronchial washing fluid and biopsy specimens in addition to the patients' clinical characteristics. Results A total of 565 CMV qRT-PCR assays were performed using bronchial washing fluid from patients with hematologic malignancies. Among them, 101 were positive for CMV by qRT-PCR; of these, 24 were diagnosed with CMV pneumonia and 70 with CMV infection, and 7 were excluded due to a diagnosis of invasive pulmonary aspergillosis rather than viral pneumonia. The median CMV load determined by qPCR was 1.8 × 105 copies/mL (3.6 103-1.5 × 108) in CMV pneumonia patients and 3.0 × 103 copies/mL (5.0 × 102-1.1 × 105) in those diagnosed with CMV infection (P < 0.01). Using the ROC curve, the optimal inflection points were 18,900 copies/mL (137,970 IU/mL) in post-bone marrow transplantation (BMT) patients, 316,415 copies/mL (2,309,825 IU/mL) in no-BMT patients and 28,774 copies/mL (210,054 IU/mL) in all patients. Conclusions The CMV titers in bronchial washing fluid determined by qRT-PCR differed significantly between patients diagnosed with CMV pneumonia and those with CMV infection. The viral cut-off values in bronchial washing fluid were suggested for the diagnosis of CMV pneumonia, which were different depending on the BMT status. PMID:28061469

Diagnosis of cytomegalovirus pneumonia by quantitative polymerase chain reaction using bronchial washing fluid from patients with hematologic malignancies.

PubMed

Lee, Hwa Young; Rhee, Chin Kook; Choi, Joon Young; Lee, Hea Yon; Lee, Jong Wook; Lee, Dong Gun

2017-06-13

The incidence of cytomegalovirus (CMV) pneumonia is increasing in patients diagnosed with hematologic malignancies. The utility of CMV-DNA viral load measurement has not been standardized, and viral cut-off values have not been established. This study was designed to investigate the utility of CMV quantitative real-time PCR (qRT-PCR) using bronchial washing fluid. We retrospectively reviewed the microbiologic and pathologic results of bronchial washing fluid and biopsy specimens in addition to the patients' clinical characteristics. A total of 565 CMV qRT-PCR assays were performed using bronchial washing fluid from patients with hematologic malignancies. Among them, 101 were positive for CMV by qRT-PCR; of these, 24 were diagnosed with CMV pneumonia and 70 with CMV infection, and 7 were excluded due to a diagnosis of invasive pulmonary aspergillosis rather than viral pneumonia. The median CMV load determined by qPCR was 1.8 × 105 copies/mL (3.6 103-1.5 × 108) in CMV pneumonia patients and 3.0 × 103 copies/mL (5.0 × 102-1.1 × 105) in those diagnosed with CMV infection (P < 0.01). Using the ROC curve, the optimal inflection points were 18,900 copies/mL (137,970 IU/mL) in post-bone marrow transplantation (BMT) patients, 316,415 copies/mL (2,309,825 IU/mL) in no-BMT patients and 28,774 copies/mL (210,054 IU/mL) in all patients. The CMV titers in bronchial washing fluid determined by qRT-PCR differed significantly between patients diagnosed with CMV pneumonia and those with CMV infection. The viral cut-off values in bronchial washing fluid were suggested for the diagnosis of CMV pneumonia, which were different depending on the BMT status.

Transcriptome profiling using Illumina- and SMRT-based RNA-seq of hot pepper for in-depth understanding of genes involved in CMV infection.

PubMed

Zhu, Chunhui; Li, Xuefeng; Zheng, Jingyuan

2018-05-03

Hot pepper (Capsicum annuum L.), which is a member of the Solanaceae family, is becoming an increasingly important vegetable crop worldwide. Cucumber mosaic virus (CMV) is a destructive virus that can cause leaf distortion and fruit lesions, affecting pepper production. However, studies on the responses to CMV infection in pepper at the transcriptional level are limited. In this study, the transcript profiles of pepper leaves after CMV infection were investigated using Illumina and single-molecule real-time (SMRT) RNA-sequencing (RNA-seq). A total of 2143 differentially expressed genes (DEGs) were identified at five different stages. Gene ontology (GO) and KEGG analysis revealed that these DEGs were involved in the response to stress, defense response and plant-pathogen interaction pathways. Among these DEGs, several key genes that consistently appeared in studies of plant-pathogen interactions had increased transcript abundance after inoculation, including chitinase, pathogenesis-related (PR) protein, TMV resistance protein, WRKY transcription factor and jasmonate ZIM-domain protein. Nine of these DEGs were further validated by quantitative real-time-PCR (qRT-PCR). Furthermore, a total of 73, 597 alternate splicing (AS) events were identified in the pepper leaves after CMV infection, distributed in 12, 615 genes. The intron retention of WRKY33 (Capana09g001251) might be involved in the regulation of CMV infection. Taken together, our study provides a transcriptome-wide insight into the molecular basis of resistance to CMV infection in pepper leaves and potential candidate genes for improving resistance cultivars. Copyright © 2017. Published by Elsevier B.V.

Lack of evidence of association between IFNG and IL28B polymorphisms and QuantiFERON-CMV test results in seropositive transplant patients.

PubMed

Aguado, Rocío; Páez-Vega, Aurora; Agüera, María L; Montejo, Miguel; Guirado, Lluis; Fortún, Jesús; Suárez-Benjumea, Alejandro; Len, Oscar; Fariñas, María C; de Gracia, Carmen; Hernández, Domingo; Cobos-Ceballos, María J; Torre-Cisneros, Julián; Cantisán, Sara

2018-06-01

The aim of this study was to analyze the relationship between the IFNG +874 T/A and IL28B (rs12979860) C/T polymorphisms and the secretion of IFNG by CD8+ T cells after stimulation with cytomegalovirus (CMV) peptides, measured using QuantiFERON-CMV (QF-CMV) assay. A total of 184 CMV-seropositive solid organ transplant patients (108 kidney, 68 liver and 8 lung) were recruited. Of them, 151 patients were QF-CMV Reactive (IFNG ≥ 0.2 UI/mL) and 33 were Non-reactive. Genotype frequencies in the study population were TT (26.6%), AT (50.0%) and AA (23.4%) for IFNG +874 and CC (52.7%), CT (39.1%) and TT (8.2%) for IL28B (rs12979860). These frequencies did not significantly differ between QF-CMV Reactive and Non-reactive patients. Nor were any significant differences observed in the quantitative IFNG level among the genotypes in either the IFNG or the IL28 genes. When we analyzed whether these polymorphisms had any impact on the risk of CMV replication after transplantation, the adjusted analysis showed no association. In summary, our results showed that IFNG +874 T/A and IL28B (rs12979860) C/T polymorphisms are not associated with the IFNG response to CMV measured by the QuantiFERON-CMV assay, although these results should be confirmed with a higher number of patients. Copyright © 2018. Published by Elsevier Inc.

Evaluation of a new automated Abbott RealTime MTB RIF/INH assay for qualitative detection of rifampicin/isoniazid resistance in pulmonary and extra-pulmonary clinical samples of Mycobacterium tuberculosis.

PubMed

Ruiz, Pilar; Causse, Manuel; Vaquero, Manuel; Gutierrez, Juan Bautista; Casal, Manuel

2017-01-01

A new automated real-time PCR assay for the detection of rifampicin (RIF) and isoniazid (INH) resistance in Mycobacterium tuberculosis (MTB) was evaluated. A total of 163 clinical samples (128 pulmonary and 35 extra-pulmonary) were processed using four PCR assay kits: Abbott RealTime MTB RIF/INH, Genotype MTBDRplus, Xpert/MTB RIF, and Anyplex MTB/MDR. The results of phenotypic drug-susceptibility testing using BACTECMGIT 960 were used as reference. The sensitivity and specificity of the new Abbott RealTime MTB RIF/INH assay in comparison with phenotypic testing was 96.3% (95%CI 87.32%-100%) for RIF and 100% (95%CI 99.3%-100%) for INH; the sensitivity was 78.8% (95%CI 66.8%-90.9%) and the specificity was 100% (95%CI 98.9%-100%). The Abbott RealTime MTB RIF/INH test could be a valid method for detecting the most common mutations in strains resistant to RIF and INH.

Preemptive treatment approach to cytomegalovirus (CMV) infection in solid organ transplant patients: relationship between compliance with the guidelines and prevention of CMV morbidity.

PubMed

Künzle, N; Petignat, C; Francioli, P; Vogel, G; Seydoux, C; Corpataux, J M; Sahli, R; Meylan, P R

2000-09-01

Cytomegalovirus (CMV) remains a major cause of morbidity in solid organ transplant patients. In order to reduce CMV morbidity, we designed a program of routine virological monitoring that included throat and urine CMV shell vial culture, along with peripheral blood leukocyte (PBL) shell vial quantitative culture for 12 weeks post-transplantation, as well as 8 weeks after treatment for acute rejection. The program also included preemptive ganciclovir treatment for those patients with the highest risk of developing CMV disease, i.e., with either high-level viremia (>10 infectious units [IU]/106 PBL) or low-level viremia (<10 IU/106 PBL) and either D+/R- CMV serostatus or treatment for graft rejection. During 1995-96, 90 solid organ transplant recipients (39 kidneys, 28 livers, and 23 hearts) were followed up. A total of 60 CMV infection episodes occurred in 45 patients. Seventeen episodes were symptomatic. Of 26 episodes managed according to the program, only 4 presented with CMV disease and none died. No patient treated preemptively for asymptomatic infection developed disease. In contrast, among 21 episodes managed in non-compliance with the program (i.e., the monitoring was not performed or preemptive treatment was not initiated despite a high risk of developing CMV disease), 12 episodes turned into symptomatic infection (P=0.0048 compared to patients treated preemptively), and 2 deaths possibly related to CMV were recorded. This difference could not be explained by an increased proportion of D+/R- patients or an increased incidence of rejection among patients with episodes treated in non-compliance with the program. Our data identify compliance with guidelines as an important factor in effectively reducing CMV morbidity through preemptive treatment, and suggest that the complexity of the preemptive approach may represent an important obstacle to the successful prevention of CMV morbidity by this approach in the regular healthcare setting.

Cytomegalovirus Retinitis in Pediatric Stem Cell Transplants: Report of a Recent Cluster and the Development of a Screening Protocol.

PubMed

Larochelle, Marissa B; Phan, Ryan; Craddock, John; Abzug, Mark J; Curtis, Donna; Robinson, Christine C; Giller, Roger H; Cosgrove, Shaun; Siringo, Frank; McCourt, Emily; Palestine, Alan G

2017-03-01

The incidence of cytomegalovirus (CMV) retinitis in the pediatric allogeneic hematopoietic stem cell transplant (HSCT) population is unknown. We report a cluster of 5 pediatric patients with CMV retinitis diagnosed in a 12-month period and compare this to the rate of CMV viremia and retinitis in the 4 years prior. Presented is the ophthalmic screening protocol developed in response to this experience. Retrospective cross-sectional study. A retrospective chart review was performed on patients at Children's Hospital of Colorado (CHCO) who received allogeneic HSCT between January 2010 and December 2014. Fisher exact test was used to compare the proportion of CMV viremia and CMV retinitis in patients transplanted between January 2010 and December 2013 with those transplanted in 2014. A total of 101 patients underwent allogeneic HSCT from January 2010 to December 2013; 32 (32%) tested positive for CMV viremia. No cases of CMV retinitis were identified. From January 2014 to December 2014, 28 patients underwent allogeneic HSCT; 13 patients (46%) had CMV viremia, not a statistically significant increase (P = .18). There were 5 cases of CMV retinitis diagnosed in those transplanted in 2014, a statistically significant increase compared with those transplanted in 2010-2013 (P = .0004). A multidisciplinary team was formed to review the literature and an ophthalmic screening protocol was developed. Our recent cluster of CMV retinitis in pediatric allogeneic HSCT patients may suggest a rise in incidence of CMV retinitis. We propose an ophthalmic screening protocol to diagnose retinitis in pediatric HSCT patients in the early, often asymptomatic stage. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparison of cytomegalovirus (CMV)-specific neutralization capacity of hyperimmunoglobulin (HIG) versus standard intravenous immunoglobulin (IVIG) preparations: Impact of CMV IgG normalization.

PubMed

Schampera, Matthias Stefan; Schweinzer, Katrin; Abele, Harald; Kagan, Karl Oliver; Klein, Reinhild; Rettig, Ingo; Jahn, Gerhard; Hamprecht, Klaus

2017-05-01

Based on a non-randomized study of Nigro et al. (2005) the intravenous administration of hyperimmunoglobulins (HIGs) is applied frequently to women with primary CMV-infection as "off-label use" in Germany. In order to describe their CMV-specific neutralization-capacity in vitro, we analyzed the HIG preparations Cytotect ® , and Cytogam ® as well as the standard intravenous immunoglobulins (IVIG) Octagam ® , Gamunex ® , Kiovig ® . We performed short-term cell-free CMV neutralization assays (CFNT) and long-term cell-adapted neutralization-plaque-reduction assays (PRANT). Human retinal epithelial cells (ARPE-19) were used as target cells. A clinical CMV primary-isolate from amnion fluid propagated in epithelial cells without any initial fibroblast adaption was used. For calibration we previously generated serum-pools (N=100) from two cohorts of mothers at birth: seronegative and latently CMV-infected mothers. Biochemical analysis included total protein, albumin, Ig-class, and IgG-subclasses. Additionally, CMV antibody-reactivity was checked using recombinant immunoblotting. HIG and IVIG preparations showed differences in levels and patterns of protein, Ig-class and CMV-specific antibody concentrations. All IgG-preparations showed high in vitro NT-capacity and high IgG-avidity. The NT 90 -values for HIGs and IVIGs and our seropositive reference-pool showed similar NT-capacity at a dilution of (1:100) which corresponded well to 4.1 PEI-Units/ml. All HIG- and IVIG-preparations showed similar NT-capacity following CMV IgG-normalization. Our in vitro results are in strong contrast to former findings suggesting higher functional CMV NT titers in IVIG-preparations compared to HIGs. Copyright © 2017 Elsevier B.V. All rights reserved.

The impact of viral load and time to onset of cytomegalovirus replication on long-term graft survival after kidney transplantation.

PubMed

Reischig, Tomas; Kacer, Martin; Hruba, Petra; Jindra, Pavel; Hes, Ondrej; Lysak, Daniel; Bouda, Mirko; Viklicky, Ondrej

2017-01-01

Asymptomatic cytomegalovirus (CMV) infection is associated with graft dysfunction and failure. However, no study assessed CMV viral load in terms of the risk for graft failure. In a prospective cohort of kidney transplant recipients, we assessed the impact of CMV DNAemia on the overall graft survival and the incidence of moderate-to-severe interstitial fibrosis and tubular atrophy (IF/TA) in protocol biopsy at 36 months. CMV DNAemia was stratified by viral load in whole blood. A total of 180 patients transplanted from October 2003 through January 2011 were included and followed for 4 years; 87 (48%) patients received 3-month prophylaxis with valacyclovir and 45 (25%) with valganciclovir; 48 (27%) were managed by pre-emptive therapy. Within 12 months of transplantation, CMV DNAemia developed in 102 (57%) patients with 36 (20%) having a viral load of ≥2,000 copies/ml. Multivariate Cox analysis identified CMV DNAemia as an independent risk factor for graft loss (hazard ratio 3.42; P=0.020); however, after stratification by viral load, only CMV DNAemia ≥2,000 copies/ml (hazard ratio 7.62; P<0.001) remained significant. Both early-onset (<3 months; P=0.048) and late-onset (>3 months; P<0.001) CMV DNAemia ≥2,000 copies/ml were risk factors for graft loss. The incidence of moderate-to-severe IF/TA was not significantly influenced by CMV DNAemia. Kidney transplant recipients having CMV DNAemia with a higher viral load irrespective of the time to onset are at increased risk for graft loss.

Determination of the Biological Form of Human Cytomegalovirus DNA in the Plasma of Solid-Organ Transplant Recipients.

PubMed

Tong, Yupin; Pang, Xiaoli L; Mabilangan, Curtis; Preiksaitis, Jutta K

2017-04-01

Whether cytomegalovirus (CMV) DNA exists in plasma as virion-associated or free DNA is uncertain. An assay combining DNase I digestion and CMV quantitative polymerase chain reaction (DNase-CMV-qPCR) was developed to differentiate free naked DNA from virion DNA. One hundred three frozen and 10 fresh CMV DNA-positive plasma samples from solid-organ transplant recipients (SOTRs) were tested. Three sets of paired qPCR (P-qPCR) assays with amplicons of variable length were used to study CMV DNA fragmentation in 20 SOTR plasma samples, viral stocks (Towne, Merlin, AD169) and the first World Health Organization (WHO) international standard (IS) for CMV DNA. In all plasma samples, 98.8%-100% of CMV DNA was free DNA; this was the only form in 93 of 103 (90.3%) frozen and all 10 fresh samples tested using DNase-CMV-qPCR. Low levels of virion CMV DNA were found in 10 of 103 (9.7%) samples with higher total DNA load. Cytomegalovirus DNA results were highly reproducible for 3 CMV virus stocks and WHO IS (P > .80), tested by three sets of paired q-PCR. However, for the 20 SOTR plasma samples, the smaller amplicon assay result was 2.6-fold, 3.4-fold, and 6.5-fold higher than the longer amplicion result (P < .001). Cytomegalovirus DNA in SOTR plasma is almost exclusively free DNA, highly fragmented, and not virion associated. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Sensorineural hearing loss in a pediatric population: association of congenital cytomegalovirus infection with intracranial abnormalities.

PubMed

Kimani, Jane W; Buchman, Craig A; Booker, Jessica K; Huang, Benjamin Y; Castillo, Mauricio; Powell, Cynthia M; Weck, Karen E

2010-10-01

To examine the incidence of congenital cytomegalovirus (CMV) infection relative to common genetic etiologies of hearing loss in a pediatric population with sensorineural hearing loss (SNHL), and to characterize intracranial radiological abnormalities in patients with CMV-associated hearing loss. Retrospective study. Academic tertiary care center. A total of 112 pediatric patients with confirmed SNHL. The association of congenital CMV infection status with abnormal brain magnetic resonance imaging (MRI) scans and the frequencies of congenital CMV infection, gap junction β-2 (GJB2) mutations, and the mitochondrial DNA (mtDNA) 1555A>G mutation in children with SNHL. Of 109 patients, 11 (10%) had positive results for CMV DNA; 10 of the 11 had normal GJB2 sequence and had negative test results for the mtDNA 1555A>G mutation. Brain MRI scans for 97 patients demonstrated a higher proportion of abnormalities in patients with positive CMV test results (80%) compared with those with no detectable CMV DNA (33%) (P = .006). GJB2 mutations and the mtDNA 1555A>G mutation were seen in 10 of 88 patients (11%) and 1 of 97 patients (1%) with SNHL, respectively. The presence of brain abnormalities in most patients with congenital CMV infection suggests that neurological damage in otherwise asymptomatic patients may not be limited to SNHL. Congenital CMV infection accounted for a significant proportion of patients with SNHL, with an incidence rate comparable with that of GJB2-related SNHL.

Epstein-Barr virus and cytomegalovirus infections and their clinical relevance in Egyptian leukemic pediatric patients.

PubMed

Loutfy, Samah Aly; Abo-Shadi, Maha A; Fawzy, Mohamed; El-Wakil, Mohamed; Metwally, Shimaa A; Moneer, Manar M; Fattah, Nasra F Abdel; Kassem, Sara; Elgebaly, Ahmed

2017-03-06

Epstein-Barr virus (EBV) and human cytomegalovirus (CMV) infections are environmental risk factors affecting the outcome of cancer due to an impairment in the cell-mediated immunity. Therefore, this study aimed to detect the frequency of EBV and CMV DNA and their association with clinical characteristics and outcome of pediatric leukemic patients. Samples of 50 immunocompromised pediatric leukemic patients and 30 apparently healthy children were subjected to the amplification of EBV DNA by one version of PCR targeting the Bam H1 W region of the genomic region of EBV, and the amplification of CMV DNA by targeting the CMV UL97 genomic region by a second round PCR. All investigations were performed on WBCs and sera. Results were correlated with the clinical and laboratory characteristics of the disease, and with overall survival. EBV and CMV DNA were detected in 20 and 54% of leukemic patients, respectively. Nine out of ten patients with EBV DNA (90%) were positive for CMV DNA in their sera. The presence of EBV DNA or CMV DNA was associated with neutropenia and a low total leukocyte count (TLC) (p = 0.02, 0.03, respectively). The presence of severe CMV disease, longer duration of febrile neutropenia, neutropenia, lymphopenia, thrombocytopenia and the presence of EBV DNA in patients' sera were significantly associated with worse overall survival. The detection of CMV disease and EBV DNA is relatively common in leukemic children and is significantly associated with a decline in the overall survival.

Cytomegalovirus reactivation is associated with a lower rate of early relapse in myeloid malignancies independent of in-vivo T cell depletion strategy.

PubMed

Hilal, Talal; Slone, Stacey; Peterson, Shawn; Bodine, Charles; Gul, Zartash

2017-06-01

The association between cytomegalovirus (CMV) reactivation and relapse risk has not been evaluated in relation to T cell depletion strategies. We evaluated 93 patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT) and analyzed the association between T cell depletion strategies with the cumulative incidence of relapse and CMV reactivation. A total of 33% of patients who received ATG vs. 34% who received alemtuzumab developed CMV reactivation. The cumulative incidence of relapse was 3% at 1year and 20% at 3 years in patients with CMV reactivation vs. 30% at 1year and 38% at 3 years in patients without CMV reactivation (p=0.02). When analyzed separately, this effect persisted in the myeloid, but not the lymphoid group. There was a numerical trend towards increased non-relapse mortality (NRM) in patients with CMV reactivation, especially in the myeloid group. The choice of T cell depleting agent and the rate of CMV reactivation were not associated with different overall survival (OS) rates. These results suggest that the choice of T cell depletion strategy may have similar effects on rates of CMV reactivation, disease relapse, and survival. Further studies examining these variables in patients not exposed to in-vivo T cell depleting agents may be of interest. Copyright © 2017 Elsevier Ltd. All rights reserved.

Differential effects of Cytomegalovirus carriage on the immune phenotype of middle-aged males and females

PubMed Central

van der Heiden, Marieke; van Zelm, Menno C.; Bartol, Sophinus J. W.; de Rond, Lia G. H.; Berbers, Guy A. M.; Boots, Annemieke M. H.; Buisman, Anne-Marie

2016-01-01

The elderly population is more susceptible to infections as a result of an altered immune response, commonly referred to as immunosenescence. Cytomegalovirus (CMV)-infection associated changes in blood lymphocytes are known to impact this process, but the interaction with gender remains unclear. Therefore, we analysed the effects and interaction of gender and CMV on the absolute numbers of a comprehensive set of naive and memory T- and B-cell subsets in people between 50 and 65 years of age. Enumeration and characterisation of lymphocyte subsets by flow cytometry was performed on fresh whole blood samples from 255 middle-aged persons. CMV-IgG serostatus was determined by ELISA. Gender was a major factor affecting immune cell numbers. CMV infection was mainly associated with an expansion of late-differentiated T-cell subsets. CMV+ males carried lower numbers of total CD4+, CD4+ central memory (CM) and follicular helper T-cells than females and CMV− males. Moreover, CMV+ males had significantly lower numbers of regulatory T (Treg)-cells and memory B-cells than CMV+ females. We here demonstrate an interaction between the effects of CMV infection and gender on T- and B-cells in middle-aged individuals. These differential effects on adaptive immunity between males and females may have implications for vaccination strategies at middle-age. PMID:27243552

Evaluation of Copan FLOQSwab for the molecular detection of Chlamydia trachomatis by Abbott RealTime CT PCR.

PubMed

Coorevits, L; Vanscheeuwijck, C; Traen, A; Bingé, L; Ryckaert, I; Padalko, E

2015-12-01

We evaluated Copan FLOQSwabs next to Abbott swabs for the detection of Chlamydia trachomatis (CT) by Abbott RealTime PCR. We collected 1062 paired swabs from female sex workers. The study was divided in two arms, according to the order of swab collection. If the Abbott swab was collected first, 501 couples were concordant and two discordant (Abbott negative and Copan positive). If the Copan swab was collected first, 537 couples were concordant and 10 discordant (eight Abbott negative and Copan positive and two Abbott positive and Copan negative). All discordant samples contained low levels of C. trachomatis. Technical issues lead to retesting of 64 Copan and 21 Abbott swabs. Our results show that Copan FLOQSwabs can be used interchangeably with Abbott swabs. While appearing to have an advantage in detecting more positive samples, the use of Copan swabs led to a higher retesting rate due to technical errors.

Risk of infectious diseases among first-degree relatives of transplant recipients who develop CMV infection: is the infectious phenotype inheritable?

PubMed

Ekenberg, C; Lodding, I P; Wareham, N E; Sørensen, S S; Sengeløv, H; Gustafsson, F; Rasmussen, A; Perch, M; Lundgren, J D; Helleberg, M

2017-12-01

Transplant recipients are at high risk of cytomegalovirus (CMV) infection. Mechanisms explaining the variation in risk of infections are far from fully elucidated. We hypothesised that host genetics explains part of the variation in risk of infection and examined if relatives of recipients with CMV infection have higher rates of severe infections compared to relatives of recipients without this infectious phenotype. In a register-based study, we included first-degree relatives of transplant recipients and examined the risk of hospitalisation due to overall infection or viral infection and risk of death among relatives of recipients who developed CMV infection within the first year of transplantation compared to relatives of recipients without CMV. Analyses were adjusted for sex, age and calendar year. We included 4470 relatives who were followed for 103,786 person-years, median follow-up 24 years [interquartile range (IQR) 12-36]. There were a total of 1360 infection-related hospitalisations in the follow-up period, incidence rate (IR) 13.1/1000 person-years [95% confidence interval (CI), 12.4; 13.8]. 206 relatives were hospitalised with viral infection, IR 1.8/1000 person-years (95% CI, 1.6; 2.0). There was no increased risk of hospitalisation due to infections, IR ratio (IRR) 0.99 (95% CI, 0.88; 1.12), nor specifically viral infections, IRR 0.87 (95% CI, 0.63; 1.19), in relatives of recipients with CMV compared to relatives of recipients without CMV. Also, no difference was seen in analyses stratified by transplant type, family relation and CMV serostatus. The risk of hospitalisation due to infection is not increased among first-degree relatives of transplant recipients with CMV infection compared to relatives of recipients without CMV.

CMV infection after transplant from cord blood compared to other alternative donors: the importance of donor-negative CMV serostatus.

PubMed

Mikulska, Małgorzata; Raiola, Anna Maria; Bruzzi, Paolo; Varaldo, Riccardo; Annunziata, Silvana; Lamparelli, Teresa; Frassoni, Francesco; Tedone, Elisabetta; Galano, Barbara; Bacigalupo, Andrea; Viscoli, Claudio

2012-01-01

Cytomegalovirus (CMV) infection and disease are important complications after hematopoietic stem cell transplant, particularly after transplant from alternative donors. Allogeneic cord blood transplantation (CBT) is being increasingly used, but immune recovery may be delayed. The aim of this study was to compare CMV infection in CBT with transplants from unrelated or mismatched related donors, from now on defined as alternative donors. A total of 165 consecutive transplants were divided in 2 groups: (1) alternative donors transplants (n = 85) and (2) CBT recipients (n = 80). Donor and recipient (D/R) CMV serostatus were recorded. The incidence of CMV infection, its severity, timing, and outcome were compared. Median follow-up was 257 days (1-1328). CMV infection was monitored by CMV antigenemia and expressed as CMV Ag positive cell/2 × 10(5) polymorphonuclear blood cells. There was a trend toward a higher cumulative incidence of CMV infection among CBT than alternative donor transplant recipients (64% vs 51%, P = .12). The median time to CMV reactivation was 35 days, and was comparable in the 2 groups (P = .8). The maximum number of CMV-positive cells was similar in the 2 groups (11 versus 16, P = .2). The time interval between the first and the last positive CMV antigenemia was almost 4 times longer in CBT compared with alternative donor transplants (109 vs 29 days, respectively, P = .008). The incidence of late CMV infection was also higher in CBT (62% vs 24%, P < .001). The incidence of early and late CMV infection in CBT was similar to D-/R+ alternative transplants, and higher than in D+/R+ alternative transplants: early infection, 72% in CBT versus 69% in D-/R+ alternative versus 55% in D+/R+ alternative (P = .21); and late infection, 67% in CBT versus 60% in D-/R+ alternative versus 7% in D+/R+ alternative (P < .001). Transplant-related mortality and overall survival were similar between the groups: 34% versus 36% (P = .6) and 54% versus 46% (P = .3) for alternative transplant and CBT, respectively. Longer duration and higher incidence of late CMV infection was seen in CBT patients, when compared with alternative donor transplants, whereas no difference in mortality was observed. The duration and incidence of late CMV infection were similar when D-/R+ CBT were compared with D-/R+ alternative donor transplants. Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Performance evaluation of a particle-enhanced turbidimetric cystatin C assay on the Abbott ci8200 analyzer.

PubMed

Flodin, Mats; Larsson, Anders

2009-06-01

Glomerular filtration rate (GFR) is widely accepted as the best overall measure of kidney function. Cystatin C is a novel endogenous GFR marker that has been shown to be superior to creatinine for estimation of GFR in several studies. There is a need for cystatin C assays adapted to routine chemistry instrument to minimize turnaround times and allowing 24 h/day availability. We have evaluated a new cystatin C assay developed for Architect cSystem (Abbott Laboratories, Abbott Park, IL, USA). The cystatin C assay showed good agreement with the corresponding assay from Dade Behring (Deerfield, IL, USA). The assay has a very low total imprecision and a good linearity. The new cystatin C assay is an interesting alternative to current cystatin C assays. On an Architect cSystem the assay can be performed with the same turnaround times and availability as creatinine.

Abundant cytomegalovirus (CMV) reactive clonotypes in the CD8(+) T cell receptor alpha repertoire following allogeneic transplantation.

PubMed

Link, C S; Eugster, A; Heidenreich, F; Rücker-Braun, E; Schmiedgen, M; Oelschlägel, U; Kühn, D; Dietz, S; Fuchs, Y; Dahl, A; Domingues, A M J; Klesse, C; Schmitz, M; Ehninger, G; Bornhäuser, M; Schetelig, J; Bonifacio, E

2016-06-01

Allogeneic stem cell transplantation is potentially curative, but associated with post-transplantation complications, including cytomegalovirus (CMV) infections. An effective immune response requires T cells recognizing CMV epitopes via their T cell receptors (TCRs). Little is known about the TCR repertoire, in particular the TCR-α repertoire and its clinical relevance in patients following stem cell transplantation. Using next-generation sequencing we examined the TCR-α repertoire of CD8(+) T cells and CMV-specific CD8(+) T cells in four patients. Additionally, we performed single-cell TCR-αβ sequencing of CMV-specific CD8(+) T cells. The TCR-α composition of human leucocyte antigen (HLA)-A*0201 CMVpp65- and CMVIE -specific T cells was oligoclonal and defined by few dominant clonotypes. Frequencies of single clonotypes reached up to 11% of all CD8(+) T cells and half of the total CD8(+) T cell repertoire was dominated by few CMV-reactive clonotypes. Some TCR-α clonotypes were shared between patients. Gene expression of the circulating CMV-specific CD8(+) T cells was consistent with chronically activated effector memory T cells. The CD8(+) T cell response to CMV reactivation resulted in an expansion of a few TCR-α clonotypes to dominate the CD8(+) repertoires. These results warrant further larger studies to define the ability of oligoclonally expanded T cell clones to achieve an effective anti-viral T cell response in this setting. © 2016 British Society for Immunology.

Detection of Cytomegalovirus (CMV) Infection in Wheezing Infants by Urine DNA and Serum IgG Testing.

PubMed

Zeng, Zhao-Cheng; Chang, Qing; Sun, Zhi-Wei; Song, Ming-Mei; Jin, Xin-Ling; Jiang, Shu-Ya; Yang, Xia

2017-03-11

BACKGROUND The aim of this study was to investigate the involvement of CMV infection in wheezing infants and the association between CMV-DNA and immunoglobulins (Igs). MATERIAL AND METHODS A total of 243 wheezing infants and 3,000 parturients were enrolled in this study. The infants were randomly grouped to receive blood HCMV-DNA tests (n=46) or urine HCMV-DNA tests (n=197). Furthermore, all participants had serum CMV-specific IgM and IgG testing. Afterwards, 10 HCMV-IgG positive infants were randomly selected for simultaneous blood and urine HCMV-DNA tests, and 25 HCMV-IgG positive puerperants were randomly selected for urine HCMV-DNA tests. RESULTS The detection rate of urine HCMV-DNA was significantly higher than that of blood HCMV-DNA (67.5% vs. 13.0%, p<0.001). Fifteen (6.2%) and 190 (80.0%) infants showed positive CMV-specific IgM and IgG results (p<0.001), respectively. Among the 10 HCMV-IgG positive infants tested further, only two infants had positive HCMV-DNA blood tests, while all of the 10 infants had positive HCMV-DNA urine tests. However, HCMV-DNA was not detected in the urine of the 25 randomly selected parturients positive for HCMV-IgG. CONCLUSIONS CMV infection may be one of the causes of wheezing in infants; CMV infection can be detected by urine-HCMV-DNA and serum HCMV-IgG testing. Infants were more susceptible to CMV infection than parturients.

Cytokine-mediated induction of endothelial adhesion molecule and histocompatibility leukocyte antigen expression by cytomegalovirus-activated T cells.

PubMed Central

Waldman, W. J.; Knight, D. A.

1996-01-01

Cytomegalovirus (CMV) has been associated with allograft rejection and transplantation-associated arteriosclerosis. CMV infects endothelium, the interface between allograft tissue and the host immune system; however, mechanisms by which such interaction might exacerbate the rejection process remain unresolved. Here we test the hypothesis that host immune activity, triggered by CMV-infected graft endothelial cells (ECs), can result in the production of cytokines capable of enhancing the alloimmunogenicity of nearby uninfected endothelia. To model these phenomena in vitro, confluent monolayers of ECs derived from human umbilical vein or adult gonadal vein were incubated 5 days beneath trans-well culture inserts containing CMV-seropositive or CMV-seronegative donor-derived CD3+ or CD4+ T cells alone or in combination with CMV-infected or uninfected allogeneic ECs. The extent of T cell proliferation was determined by [3H]thymidine labeling of trans-well contents after transfer to microtiter plates. Endothelial responses to soluble factors elaborated by CMV-activated T cells were determined by immunohistochemical staining and immunofluorescence flow cytometric analysis of underlying EC monolayers. Results of experiments with CMV-seropositive donor-derived CD4+ T cells demonstrated enhancement of ICAM-1 and histocompatibility leukocyte antigen class I, as well as induction of histocompatibility leukocyte antigen DR on ECs incubated beneath T cell/EC/CMV trans-well co-cultures. Total (CD3+) T cells co-cultured with EC/CMV induced VCAM-1 as well. Furthermore, [3H]thymidine incorporation by these T cells indicated a strong proliferative response. Endothelial responses to T cells alone or in combination with uninfected ECs were minimal, and T cells cultured under these conditions showed little proliferative activity. Similarly, little or no endothelial responses were apparent in monolayers beneath trans-wells containing T cells isolated from CMV-seronegative individuals regardless of the CMV status of stimulator ECs. Finally, experiments employing blocking antibodies identified interferon-gamma and tumor necrosis factor-alpha as inducing agents in this co-culture system. These findings suggest that allograft endothelium harboring CMV has the potential to activate host T cells and that the consequent release of cytokines shows potential to raise surrounding endothelia to a fully activated, highly immunogenic state. Results of these studies thus provide insight into mechanisms that help elucidate the association between CMV and transplantation-associated arteriosclerosis and/or allograft rejection. Images Figure 1 Figure 5 PMID:8546198

An illness in the family: Dr. Maude Abbott and her sister, Alice Abbott.

PubMed

Brookes, Barbara

2011-01-01

This paper explores Maude Abbott's internationally significant career in medicine and her parallel commitment to caring for her sister, Alice Abbott. An examination of Abbott's life reveals the difficulties faced by an ambitious Canadian woman in medicine from the 1890s to the 1920s; difficulties compounded by caring for a sister with a mental illness. The Abbott archive suggests that it was far more difficult for a woman doctor to make the kind of sharp distinction between public and private life that might be expected of professional men.

Trichoderma harzianum T-22 Induces Systemic Resistance in Tomato Infected by Cucumber mosaic virus

PubMed Central

Vitti, Antonella; Pellegrini, Elisa; Nali, Cristina; Lovelli, Stella; Sofo, Adriano; Valerio, Maria; Scopa, Antonio; Nuzzaci, Maria

2016-01-01

Understanding the induction of plant defenses against viruses using biocontrol agents is essential for developing new strategies against these pathogens, given the ineffectiveness of chemical treatments. The ability of Trichoderma harzianum, strain T-22 (T22) to control Cucumber mosaic virus (CMV) in Solanum lycopersicum var. cerasiforme plants and the changes in the physiology of tomato treated/infected with T22/CMV were examined. Plant growth-promoting effects, photosynthetic performance, reactive oxygen species scavenging enzymes, and phytohormones were investigated. T22 improved tomato growth in terms of plant height and improved photosynthesis, total chlorophyll content and plant gas exchange. In contrast, CMV induced a negative effect on dry matter accumulation and inhibited the photosynthetic capacity. The analysis of plant hormones demonstrated that treating with T22 before or simultaneously to CMV infection, led to a systemic resistance by jasmonic acid/ethylene and salicylic acid signaling pathways. Conversely, systemic resistance was abscissic acid-dependent when T22 treatment was administered after the CMV infection. In conclusion, the data reported here indicate that the T22-based strategy may be the most effective measure against CMV. PMID:27777581

CMV retinitis screening and treatment in a resource-poor setting: three-year experience from a primary care HIV/AIDS programme in Myanmar

PubMed Central

2011-01-01

Background Cytomegalovirus retinitis is a neglected disease in resource-poor settings, in part because of the perceived complexity of care and because ophthalmologists are rarely accessible. In this paper, we describe a pilot programme of CMV retinitis management by non-ophthalmologists. The programme consists of systematic screening of all high-risk patients (CD4 <100 cells/mm3) by AIDS clinicians using indirect ophthalmoscopy, and treatment of all patients with active retinitis by intravitreal injection of ganciclovir. Prior to this programme, CMV retinitis was not routinely examined for, or treated, in Myanmar. Methods This is a retrospective descriptive study. Between November 2006 and July 2009, 17 primary care AIDS clinicians were trained in indirect ophthalmoscopy and diagnosis of CMV retinitis; eight were also trained in intravitreal injection. Evaluation of training by a variety of methods documented high clinical competence. Systematic screening of all high-risk patients (CD4 <100 cells/mm3) was carried out at five separate AIDS clinics throughout Myanmar. Results A total of 891 new patients (1782 eyes) were screened in the primary area (Yangon); the majority of patients were male (64.3%), median age was 32 years, and median CD4 cell count was 38 cells/mm3. CMV retinitis was diagnosed in 24% (211/891) of these patients. Bilateral disease was present in 36% of patients. Patients with active retinitis were treated with weekly intravitreal injection of ganciclovir, with patients typically receiving five to seven injections per eye. A total of 1296 injections were administered. Conclusions A strategy of management of CMV retinitis at the primary care level is feasible in resource-poor settings. With appropriate training and support, CMV retinitis can be diagnosed and treated by AIDS clinicians (non-ophthalmologists), just like other major opportunistic infections. PMID:21843351

Incidence of cytomegalovirus retinitis in the era of highly active antiretroviral therapy.

PubMed

Sugar, Elizabeth A; Jabs, Douglas A; Ahuja, Alka; Thorne, Jennifer E; Danis, Ronald P; Meinert, Curtis L

2012-06-01

To estimate the incidence of cytomegalovirus (CMV) retinitis in the era of highly active antiretroviral therapy (HAART) and to characterize the factors associated with increased risk of CMV retinitis. Prospective cohort study. A total of 1600 participants with acquired immunodeficiency syndrome (AIDS) but without CMV retinitis at enrollment who completed at least 1 follow-up visit in the Longitudinal Study of the Ocular Complications of AIDS (LSOCA) were seen every 6 months to obtain disease and treatment history, ophthalmic examination, and laboratory testing. Incidence of CMV retinitis and risk factors for incident CMV retinitis were assessed. The incidence rate of CMV retinitis in individuals with AIDS was 0.36/100 person-years (PY) based upon 29 incident cases during 8134 PY of follow-up. The rate was higher for those with a CD4+ T cell count at the immediately prior visit below 50 cells/μL (3.89/100 PY, P < .01), whereas only 1 individual with a CD4+ T cell count of 50 to 99 cells/μL and 2 individuals with a CD4+ T cell count >100 cells/μL developed CMV retinitis. Having a CD4+ T cell count below 50 cells/μL at the clinical visit prior to CMV retinitis evaluation was the single most important risk factor (HR: 136, 95% CI: 30 to 605, P < .0001) for developing retinitis. Patients with AIDS, especially those with severely compromised immune systems, remain at risk for developing CMV retinitis in the HAART era, although the incidence rate is reduced from that observed in the pre-HAART era. Copyright © 2012 Elsevier Inc. All rights reserved.

Seroepidemiology Study of Cytomegalovirus and Rubella among Pregnant Women at St. Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia.

PubMed

Yeshwondm, Mamuye; Balkachew, Nigatu; Delayehu, Bekele; Mekonen, Getahun

2016-09-01

Maternal cytomegalovirus (CMV) and rubella infections have adverse neonatal outcomes. Both CMV and rubella are more widespread in developing countries and in communities with lower socioeconomic status. The aim of this study was to investigate sero-prevalence of CMV and rubella infection and associated possible risk factors. Using cross sectional study design a total of 200 pregnant women were consecutively recruited starting from June and July 2014. Blood samples were collected, and structured questions were used to gather socio-demographic and risk factor related data. ELISA was used to detect CMV (IgG, IgM) and rubella IgM. SPSS version 20 was used to analyze the data, and regression was also performed. Out of 200 pregnant women, 88.5%, 30(15.5%) and 4(2.0%) were CMV-IgG, CMV-IgM, and rubella-IgM positive, respectively. Women who were immune/positive only for IgG were 73.5%. The second group was those with primary infection [IgG (+) plus IgM (+)] and this consisted of 15.0% participants. Eleven percent of the participants were at high risk for primary infection during their pregnancy. One pregnant woman was identified as having a recent primary infection. In this study, no statistically significant association was detected between CMV infection with idependent factors (p-value>0.05). In addition to detection of high prevalence of CMV, detecting recent infection of rubella worsens the outcome of the disease. Rubella vaccine should be taken into consideration after large scale surveillance. However, screening of all pregnant women for CMV infection may not be cost-effective as in the countries with high seropositivity.

No evidence of obstetrical adverse events after hyperimmune globulin application for primary cytomegalovirus infection in pregnancy: experience from a single centre.

PubMed

Chiaie, Loredana Delle; Neuberger, Patrick; Vochem, Matthias; Lihs, Angela; Karck, Ulrich; Enders, Martin

2018-06-01

To determine the frequency of obstetrical adverse events and clinical outcome in infants following antenatal hyperimmune globulin (HIG) treatment for primary cytomegalovirus (CMV) infection in pregnancy. Data from 50 women including three twin pregnancies were retrospectively evaluated. Primary infection was defined by seroconversion or the presence of CMV-specific IgM and low IgG avidity. All women received two or more infusions of HIG (200 U/kg). Congenital CMV (cCMV) infection was diagnosed by detection of CMV in amniotic fluid and/or neonatal urine. We compared gestational age (GA) at birth, head circumference (HC) and birth weight (BW) of infants in our study cohort with those of live-born infants delivered in our clinic between 2015 and 2016. Median gestational age at time of maternal CMV diagnosis was 13 weeks. One-hundred-forty-one maternal HIG doses were given. No HIG-related severe adverse reactions occurred. Preterm birth rate was 4.2% (2/47) in singleton pregnancies. None of the neonates had birth weight or head circumference < 3rd percentile (< 3P) for gestational age. There was no statistically significant difference regarding GA, BW and HC between our study cohort and the total population of live-born infants. The frequency of CMV-related sequelae in infants with cCMV infection was 10.5% (2/19) (one with bilateral hearing loss and one with mild motoric delay), both cases following first trimester maternal infection. Antenatal HIG treatment was well tolerated and not associated with prematurity or decreased birth weight. HIG application might have a favorable effect on the clinical course of congenital CMV infection.

Soluble donor HLA class I and beta 2m-free heavy chain in serum of lung transplant recipients: steady-state levels and increases in patients with recurrent CMV infection, acute rejection episodes, and poor outcome.

PubMed

DeVito-Haynes, L D; Jankowska-Gan, E; Meyer, K C; Cornwell, R D; Zeevi, A; Griffith, B; Dauber, J; Iacono, A; Burlingham, W J; Love, R B

2000-12-01

We determined the concentration of donor sHLA/beta(2)m and total beta(2)m-free heavy chain (HC) in the serum of lung transplant recipients with ELISA assays. While we were unable to detect specific donor beta(2)m-free HCs due to a lack of available antibodies, we could determine if events that led to an increase in the release of beta(2)m-free HC also led to an increase in the release of donor sHLA/beta(2)m, particularly the 36 kDa, proteolytically cleaved form. We found that lung transplants constituitively release donor sHLA/beta(2)m at ng/ml levels. The levels (both of donor sHLA/beta(2)m and total beta(2)m-free HC) were significantly increased in CMV-sero-negative recipients (but not in CMV-sero-positive recipients) at the onset of post-transplant CMV disease. Acute rejection episodes were also associated with an increased release of donor sHLA/beta(2)m, but not of beta(2)m-free HC. However, in patients with particularly poor outcome (i.e., graft loss within 1 year) there was a significant release of beta(2)m-free HC. Analysis of one such patient showed a predominance of 36 kDa forms of donor-sHLA/beta(2)m. Our data are consistent with the hypothesis that the metalloproteinase that cleaves beta(2)m-free HC is active during uncontrolled CMV infection and acute rejection. However, recall responses to CMV and controlled immune responses to donor may result in little or no activation of sHLA class I release.

78 FR 54487 - Abbott Laboratories; Diagnostic-Hematology; Including On-Site Leased Workers From Manpower...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-04

... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-82,379] Abbott Laboratories... February 22, 2013, applicable to workers of Abbott Laboratories, Diagnostic--Hematology division, including... Clara, California location of Abbott Laboratories, Diagnostic--Hematology Division. The Department has...

Direct detection of Mycobacterium tuberculosis and drug resistance in respiratory specimen using Abbott Realtime MTB detection and RIF/INH resistance assay.

PubMed

Tam, Kingsley King-Gee; Leung, Kenneth Siu-Sing; To, Sabrina Wai-Chi; Siu, Gilman Kit-Hang; Lau, Terrence Chi-Kong; Shek, Victor Chi-Man; Tse, Cindy Wing-Sze; Wong, Samson Sai-Yin; Ho, Pak-Leung; Yam, Wing-Cheong

2017-10-01

Abbott RealTime MTB (Abbott-RT) in conjunction with Abbott RealTime MTB RIF/INH Resistance (Abbott-RIF/INH) is a new, high-throughput automated nucleic acid amplification platform (Abbott-MDR) for detection of Mycobacterium tuberculosis complex (MTBC) and the genotypic markers for rifampicin (RIF) and isoniazid (INH) resistance directly from respiratory specimens. This prospective study evaluated the diagnostic performance of this new platform for MTBC and multidrug-resistant tuberculosis (MDR-TB) using 610 sputum specimens in a tuberculosis high-burden setting. Using conventional culture results and clinical background as reference standards, Abbott-RT exhibited an overall sensitivity and specificity of 95.2% and 99.8%, respectively. Genotypic RIF/INH resistance of 178 "MTB detected" specimens was subsequently analyzed by Abbott-RIF/INH. Compared to phenotypic drug susceptibility test results, Abbott-RIF/INH detected resistance genotypic markers in 84.6% MDR-TB, 80% mono-RIF-resistant and 66.7% mono-INH-resistant specimens. Two of the RIF-resistant specimens carried a novel single, nonsense mutation at rpoB Q513 and in silico simulation demonstrated that the truncated RpoB protein failed to bind with other subunits for transcription. Overall, Abbott-MDR platform provided high throughput and reliable diagnosis of MDR-TB within a TB high-burden region. Copyright © 2017 Elsevier Inc. All rights reserved.

77 FR 4368 - Abbott Laboratories, Diagnostics Division, Including On-Site Leased Workers From Manpower...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-27

... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-75,201] Abbott Laboratories..., applicable to workers of Abbott Laboratories, Diagnostics Division, including on-site leased workers from... (clerical) were employed on-site at the Irving, Texas location of Abbott Laboratories, Diagnostics Division...

76 FR 47143 - Approval for Manufacturing Authority, Foreign-Trade Zone 153; Abbott Cardiovascular Systems, Inc...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-04

... Authority, Foreign-Trade Zone 153; Abbott Cardiovascular Systems, Inc., (Cardiovascular Devices), Riverside... of Abbott Cardiovascular Systems, Inc., within Sites 11-13 of FTZ 153, located in Riverside County... behalf of Abbott Cardiovascular Systems, Inc., as described in the application and Federal Register...

77 FR 13232 - Abbott Laboratories; Filing of Food Additive Petition

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-06

.... FDA-2012-F-0138] Abbott Laboratories; Filing of Food Additive Petition AGENCY: Food and Drug... that Abbott Laboratories has filed a petition proposing that the food additive regulations be amended... given that a food additive petition (FAP 2A4788) has been filed by Abbott Laboratories, 3300 Stelzer Rd...

Prevalence and predictors of cytomegalovirus retinitis in HIV-infected patients with low CD4 lymphocyte counts in Vietnam.

PubMed

Colby, Donn J; Vo, Diem Qh; Teoh, Stephen C; Tam, Nguyen T; Liem, Nguyen T; Lu, Doanh; Nguyen, Thi T; Cosimi, Lisa; Pollack, Todd; Libman, Howard

2014-06-01

We describe the results of a study to determine the prevalence and characteristics of cytomegalovirus (CMV) retinitis among HIV-infected patients in Vietnam. We conducted a cross-sectional prospective study of patients with CD4 lymphocyte count ≤100 cells/mm(3)recruited from public HIV clinics. The diagnosis was made by a trained ophthalmologist using slit lamp biomicroscopy and corroborated on fundus photography. A total of 201 patients were screened. The median age was 32 years, 77% were men, median CD4 count was 47 cells/mm(3), and 62% were on antiretroviral treatment. Prevalence of CMV retinitis was 7% (14/201, 95% CI 4-11%). CMV retinitis was not associated with age, gender, injection drug use, CD4 count, WHO clinical stage, or antiretroviral treatment status. Blurring of vision and reduced visual acuity <20/40 were associated with CMV retinitis, but only 29% of patients with the diagnosis reported blurry vision and only 64% had abnormal vision. On multivariate analysis, the sole predictor for CMV retinitis was decreased visual acuity (OR 22.8,p < 0.001). In Ho Chi Minh City, CMV retinitis was found in 7% of HIV-infected patients with low CD4. HIV-infected patients with a CD4 count <100/mm(3)or who develop blurring of vision in Vietnam should be screened for CMV retinitis. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Cytomegalovirus: pathophysiological mechanisms of the cytomegalovirus-induced cellular responses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nokta, M.A.

1986-01-01

Cytomegalovirus (CMV) infection of fibroblasts of human origin is associated with a cascade of morphologic cellular responses which in other systems have been associated with regulation of intracellular free (IF) (Ca/sup + +/). In the present study, the relationship of specific ion fluxes (Ca/sup + +/, Na/sup +/) to the development of cytomegalovirus (CMV)-induced morphologic cellular responses was investigated. An influx of Ca/sup + +/ was observed by the first hour after CMV infection (PI), and total calcium sequestered by infected cells was enhanced by 5 hr Pl. A gradual rise in intracellular free (IF) (Ca/sup + +/) was observedmore » that continued through 48 hour postinfection (hr Pl). The IF (Ca/sup + +/) response to CMV infection was shown to be multiplicity dependent, require viable virus, and occur under conditions consistent with the expression of immediate early CMV genes. Development and progression of cytomegaly was found to be independent of CMV DNA synthesis and appeared to be dependent on the IF (Ca/sup + +/) response. Ca/sup + +/ influx blockers (e.g. verapamil) and cyclic nucleotide modulators (e.g. papaverine) inhibited both Ca/sup + +/ responses and cytomegaly. Quabain-sensitive /sup 86/Rb uptake and sequestering of Ca/sup + +/ increased in parallel with development of cytomegaly. There may be a relationship between Ca/sup + +/ influx, IF (Ca/sup + +/), activation of the Na/sup +//H/sup +/ exchanger, induction of Na/sup +/, Cl/sup -/, HCO/sub 3/ cotransport, Na/sup +/ entry, Na/sup +//K/sup +/ ATPase activity and development of CMV-induced morphologic cellular responses including cytomegaly.« less

Women in History--Grace Abbott: A Leader in Social Reform

ERIC Educational Resources Information Center

Hoffman, Shari Cole

2006-01-01

This article profiles Grace Abbott, one of the earlier 20th century American women leaders in Progressivism. Abbott's heritage influenced her lifetime commitment to social improvement. She was born on November 17, 1878 in Grand Island, Nebraska into a family of activists. Her Quaker mother, Elizabeth Griffin Abbott, came from an abolitionist…

The Abbott Districts in 2005-06: Progress and Challenges, Spring 2006

ERIC Educational Resources Information Center

Hirsch, Lesley

2006-01-01

New Jersey's urban--or "Abbott"--schools have improved at the preschool and elementary school level, but lag when it comes to middle and high school performance. These are the key findings of an Abbott Indicators Project report entitled, "The Abbott Districts in 2005-06: Progress and Challenges." The report was prepared by…

Donor cytomegalovirus status influences the outcome of allogeneic stem cell transplant: a study by the European group for blood and marrow transplantation.

PubMed

Ljungman, Per; Brand, Ronald; Hoek, Jennifer; de la Camara, Rafael; Cordonnier, Catherine; Einsele, Hermann; Styczynski, Jan; Ward, Katherine N; Cesaro, Simone

2014-08-15

The use of a cytomegalovirus (CMV)-seronegative donor for a CMV-seronegative allogeneic hematopoietic stem cell transplant (HSCT) recipient is generally accepted. However, the importance of donor serostatus in CMV-seropositive patients is controversial. A total of 49 542 HSCT patients, 29 349 seropositive and 20 193 seronegative, were identified from the European Group for Blood and Marrow Transplantation database. Cox multivariate models were fitted to estimate the effect of donor CMV serological status on outcome. Seronegative patients receiving seropositive unrelated-donor grafts had decreased overall survival (hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.06-1.21; P < .0001) compared with seronegative donors, whereas no difference was seen in patients receiving HLA-matched sibling grafts. Seropositive patients receiving grafts from seropositive unrelated donors had improved overall survival (HR, 0.92; 95% CI, .86-.98; P < .01) compared with seronegative donors, if they had received myeloablative conditioning. This effect was absent when they received reduced-intensity conditioning. No effect was seen in patients grafted from HLA-identical sibling donors. The same association was found if the study was limited to patients receiving transplants from the year 2000 onward. We confirm the negative impact on overall survival if a CMV-seropositive unrelated donor is selected for a CMV-seronegative patient. For a CMV-seropositive patient, our data support selecting a CMV-seropositive donor if the patient receives a myeloablative conditioning regimen. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The IFNL3/4 ΔG variant increases susceptibility to cytomegalovirus retinitis among HIV-infected patients.

PubMed

Bibert, Stéphanie; Wojtowicz, Agnieszka; Taffé, Patrick; Manuel, Oriol; Bernasconi, Enos; Furrer, Hansjakob; Günthard, Huldrych F; Hoffmann, Matthias; Kaiser, Laurent; Osthoff, Michael; Cavassini, Matthias; Bochud, Pierre-Yves

2014-08-24

Cytomegalovirus (CMV) retinitis is a major cause of visual impairment and blindness among patients with uncontrolled HIV infections. Whereas polymorphisms in interferon-lambda 3 (IFNL3, previously named IL28B) strongly influence the clinical course of hepatitis C, few studies examined the role of such polymorphisms in infections due to viruses other than hepatitis C virus. To analyze the association of newly identified IFNL3/4 variant rs368234815 with susceptibility to CMV-associated retinitis in a cohort of HIV-infected patients. This retrospective longitudinal study included 4884 white patients from the Swiss HIV Cohort Study, among whom 1134 were at risk to develop CMV retinitis (CD4 nadir < 00 /μl and positive CMV serology). The association of CMV-associated retinitis with rs368234815 was assessed by cumulative incidence curves and multivariate Cox regression models, using the estimated date of HIV infection as a starting point, with censoring at death and/or lost follow-up. A total of 40 individuals among 1134 patients at risk developed CMV retinitis. The minor allele of rs368234815 was associated with a higher risk of CMV retinitis (log-rank test P = 0.007, recessive mode of inheritance). The association was still significant in a multivariate Cox regression model (hazard ratio 2.31, 95% confidence interval 1.09-4.92, P = 0.03), after adjustment for CD4 nadir and slope, HAART and HIV-risk groups. We reported for the first time an association between an IFNL3/4 polymorphism and susceptibility to AIDS-related CMV retinitis. IFNL3/4 may influence immunity against viruses other than HCV.

High CMV IgG antibody levels are associated to a lower CD4+ RESPONSE to antiretroviral therapy in HIV-infected women.

PubMed

Giuliano, Marina; Pirillo, Maria Franca; Liotta, Giuseppe; Andreotti, Mauro; Jere, Haswell; Sagno, Jean-Baptiste; Ciccacci, Fausto; Amici, Roberta; Marazzi, Maria Cristina; Vella, Stefano; Palombi, Leonardo; Mancinelli, Sandro

2017-11-01

Virtually all HIV-infected women in sub-Saharan Africa have evidence of Cytomegalovirus (CMV) infection and levels of specific anti-CMV IgG have been suggested to represent more intense reactivation of subclinical infection. Studies have also shown direct influence of CMV on lymphocytes. The aim of this study was to determine if levels of anti-CMV specific antibodies could impact on the immunological response to antiretroviral treatment (ART) in HIV-infected pregnant women. CMV-specific IgG were measured in HIV-infected pregnant women at 26 weeks of gestation (before ART initiation). Women received ART until 6 months postpartum or indefinitely according to local guidelines at the time of the study. Immunological and virological responses were assessed 6 months and 24 months after delivery. A total of 81 women were studied. At baseline high levels (above the median) of specific IgG were associated to a low CD4+ cell count (P<0.001), a high viral load (P=0.003), and to an older age (P=0.051). In a multivariate model adjusting for baseline CD4+ count, baseline viral load and age, the presence of low levels of CMV IgG was the only independent predictor of a a CD4+ count above 500/mm 3 24 months after delivery among women on continuous therapy. In this cohort, levels of CVM IgG had a significant influence on the immunological response to ART, adding information to the known impact of CMV infection in the HIV-positive population, and underlining the need of new strategies to contain the infection. Copyright © 2017 Elsevier B.V. All rights reserved.

Pre-emptive therapy against cytomegalovirus (CMV) disease guided by CMV antigenemia assay after allogeneic hematopoietic stem cell transplantation: a single-center experience in Japan.

PubMed

Kanda, Y; Mineishi, S; Saito, T; Seo, S; Saito, A; Suenaga, K; Ohnishi, M; Niiya, H; Nakai, K; Takeuchi, T; Kawahigashi, N; Shoji, N; Ogasawara, T; Tanosaki, R; Kobayashi, Y; Tobinai, K; Kami, M; Mori, S; Suzuki, R; Kunitoh, H; Takaue, Y

2001-02-01

From April 1998 to March 2000, a cytomegalovirus (CMV) antigenemia-guided pre-emptive approach for CMV disease was evaluated in 77 adult patients who received allogeneic hematopoietic stem cell transplantation at the National Cancer Center Hospital. A CMV antigenemia assay was performed at least once a week after engraftment. High-level antigenemia was defined as a positive result with 10 or more positive cells per 50 000 cells and low-level antigenemia was defined as less than 10 positive cells. Among the 74 patients with initial engraftment, 51 developed positive antigenemia. Transplantation from alternative donors and the development of grade II-IV GVHD were independent risk factors for positive antigenemia. Ganciclovir was administered as pre-emptive therapy in 39 patients in a risk-adapted manner. None of the nine low-risk patients with low-level antigenemia as their initial positive result developed high-level antigenemia even though ganciclovir was withheld. Only one patient developed early CMV disease (hepatitis) during the study period. CMV antigenemia resolved in all but two cases, in whom ganciclovir was replaced with foscarnet. In eight patients, however, the neutrophil count decreased to 0.5 x 10(9)/l or less after starting ganciclovir, including three with documented infections and two with subsequent secondary graft failure. The total amount of ganciclovir and possibly the duration of high-dose ganciclovir might affect the incidence of neutropenia. We concluded that antigenemia-guided pre-emptive therapy with a decreased dose of ganciclovir and response-oriented dose adjustment might be appropriate to decrease the toxicity of ganciclovir without increasing the risk of CMV disease.

Genotypes of JC virus, DNA of cytomegalovirus, and proviral DNA of human immunodeficiency virus in eyes of acquired immunodeficiency syndrome patients.

PubMed

Eberwein, Philipp; Hansen, Lutz L; Agostini, Hansjürgen T

2005-02-01

JC virus (JCV) is a human polyomavirus that exists in at least eight different genotypes as a result of coevolution with different human populations all over the world. Well adapted to its host, it usually persists in the kidneys and possibly the brain. If the host becomes immunodeficient, JCV can cause the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML). There is increasing evidence that JCV is transactivated by cytomegalovirus (CMV) and the human immunodeficiency virus (HIV). Both CMV and HIV can infect the retina of acquired immunodeficiency syndrome (AIDS) patients, causing severe necrosis in the case of CMV retinitis or a mild HIV-associated vasculopathy, with bleeding and cotton wool spots. The authors therefore investigated by polymerase chain reaction (PCR) whether DNA of these three viruses was detectable in paraffin-embedded eyes of AIDS patients with a clinical history of CMV retinitis. From a total of 65 eyes, JCV was detected in 21 (32%). Thirty-six (55%) were positive for CMV and 6 (9%) for proviral DNA of HIV. JCV and CMV were found in 13 eyes, JCV and HIV in 3 eyes, CMV and HIV in 1 eye, and DNA from all three viruses in 1 eye. The JCV genotypes were types 1A, 2A, 2E, 3, and 4. In 21 eyes of patients without AIDS, only one sample was JCV positive. In conclusion, JCV DNA can be detected in ocular tissue of AIDS patients at a significantly higher level than in eyes of nonimmunosuppressed patients. Further investigations will help to decide if JCV contributes to the retinopathy caused by CMV and HIV.

Analytical and clinical evaluation of the Abbott RealTime hepatitis B sequencing assay.

PubMed

Huh, Hee Jae; Kim, Ji-Youn; Lee, Myoung-Keun; Lee, Nam Yong; Kim, Jong-Won; Ki, Chang-Seok

2016-12-01

Long-term nucleoside analogue (NA) treatment leads to selection for drug-resistant mutations in patients undergoing hepatitis B virus (HBV) therapy. The Abbott RealTime HBV Sequencing assay (Abbott assay; Abbott Molecular Inc., Des Plaines, IL, USA) targets the reverse transcriptase region of the polymerase gene and as such has the ability to detect NA resistance-associated mutations in HBV. We evaluated the analytical performance of the Abbott assay and compared its diagnostic performance to that of a laboratory-developed nested-PCR and sequencing method. The analytical sensitivity of the Abbott assay was determined using a serially-diluted WHO International Standard. To validate the clinical performances of the Abbott assay and the laboratory-developed assay, 89 clinical plasma samples with various levels of HBV DNA were tested using both assays. The limit of detection of the Abbott assay, was 210IU/ml and it successfully detected mutations when the mutant types were present at levels ≥20%. Among 89 clinical specimens, 43 and 42 were amplification positive in the Abbott and laboratory-developed assays, respectively, with 87.6% overall agreement (78/89; 95% confidence interval [CI], 78.6-93.4). The Abbott assay failed to detect the minor mutant populations in two specimens, and therefore overall concordance was 85.3% (76/89), and the kappa value was 0.79 (95% CI, 0.67-0.90). The Abbott assay showed comparable diagnostic performance to laboratory-developed nested PCR followed by direct sequencing, and may be useful as a routine method for detecting HBV NA resistance-associated mutations in clinical laboratory settings. Copyright © 2016 Elsevier B.V. All rights reserved.

Glucose meters: evaluation of the new formulation measuring strips from Roche (Accu-Chek) and Abbott (MediSense).

PubMed

Dimeski, G; Jones, B W; Tilley, V; Greenslade, M N; Russell, A W

2010-07-01

Both Roche and Abbott have released new glucose meter strips. They supply the entire Australian hospital market. The present study compared the performance of the new strips utilizing various specimen types (capillary, venous lithium heparin whole blood, venous lithium heparin plasma and serum) and evaluated how well they comply with the International Standards Organization (ISO) 15197 criteria. The study included imprecision, patient comparison and interference studies. Participants with and without diabetes were recruited to evaluate the performance of various specimen types against the Beckman DxC800 glucose method. The strips were tested for different interferences: galactose, maltose, lactose, Icodextrin, Intragam, paracetamol, sodium, ascorbic acid, variable strip storage temperature, haematocrit, haemolysis and lipaemia. The imprecision of the two strips was approximately 5% or less, except for the Abbott strip at very low values (1.4 mmol/L), approximately 7%. In total, 78% and 84%, respectively, of the results from the finger prick capillary specimens with the Roche (Accu-Chek Performa meter) and Abbott (Optium Xceed meter) strips, not 95% or greater as recommended by the ISO guideline, were within the recommended limits compared with reference plasma estimation on laboratory analysers. Galactose, ascorbic acid, haematocrit and sodium on the Roche and ascorbic acid and haematocrit on the Abbott strip continue to interfere to a variable degree with the glucose measurement. Analytically small differences exist between the glucose meter strips. The most significant analytical difference with the strips was at low glucose levels when compared with laboratory analyses and this may be of clinical importance. The impact of some of the interferences is variable between the two strips. Individuals, health-care professionals and health-care institutions should consider these data when selecting glucose meters for the management of people with diabetes mellitus.

Tracking Progress, Engaging Communities: Abbott Indicators Summary Report--Trenton, New Jersey

ERIC Educational Resources Information Center

Hirsch, Lesley; Applewhite-Coney, Erain

2005-01-01

Trenton is one of 31 urban school districts in New Jersey known as Abbott districts. As an Abbott district, Trenton receives funding to equalize its per student general education budget with the most successful suburban districts in the state. Through a series of indicators, the Trenton Abbott Indicators Report presents the status of educational…

Tracking Progress, Engaging Communities: Abbott Indicators Summary Report-- Newark, New Jersey

ERIC Educational Resources Information Center

Hirsch, Lesley; Applewhite-Coney, Erain

2005-01-01

Newark is one of 31 urban school districts in New Jersey known as Abbott districts. As an Abbott district, Newark receives funding to equalize its per student general education budget with the most successful suburban districts in the state. Through a series of indicators, the Newark Abbott Indicators Report presents the status of educational…

Tracking Progress, Engaging Communities: Abbott Indicators Summary Report--Camden, New Jersey

ERIC Educational Resources Information Center

Hirsch, Lesley; Applewhite-Coney, Erain

2005-01-01

Camden is one of 31 urban school districts in New Jersey known as Abbott districts. As an Abbott district, Camden receives funding to equalize its per student general education budget with the most successful suburban districts in the state. Through a series of indicators, the Camden Abbott Indicators Report presents the status of educational…

Implementing "Abbott v. Burke": A Guide to the 2006 K-12 Abbott Regulations

ERIC Educational Resources Information Center

Education Law Center, 2005

2005-01-01

Except for school construction, there is no legislation to guide implementation of the programs and reforms ordered by the New Jersey Supreme Court in the landmark "Abbott v. Burke" case. Instead, in its 1998 "Abbott V decision," the Supreme Court directed the Commissioner of Education to provide standards and procedures to…

Tracking Progress, Engaging Communities: Abbott Indicators Technical Report--Camden, New Jersey

ERIC Educational Resources Information Center

Hirsch, Lesley; Applewhite-Coney, Erain

2005-01-01

Camden is one of 31 urban school districts in New Jersey known as Abbott districts. As an Abbott district, Camden receives funding to equalize its per student general education budget with the most successful suburban districts in the state. Through a series of indicators, the Camden Abbott Indicators Report presents the status of educational…

Tracking Progress, Engaging Communities: Abbott Indicators Technical Report--Trenton, New Jersey

ERIC Educational Resources Information Center

Hirsch, Lesley; Applewhite-Coney, Erain

2005-01-01

Trenton is one of 31 urban school districts in New Jersey known as Abbott districts. As an Abbott district, Trenton receives funding to equalize its per student general education budget with the most successful suburban districts in the state. Through a series of indicators, the Trenton Abbott Indicators Report presents the status of educational…

Tracking Progress, Engaging Communities: Abbott Indicators Technical Report-- Newark, New Jersey

ERIC Educational Resources Information Center

Hirsch, Lesley; Applewhite-Coney, Erain

2005-01-01

Newark is one of 31 urban school districts in New Jersey known as Abbott districts. As an Abbott district, Newark receives funding to equalize its per student general education budget with the most successful suburban districts in the state. Through a series of indicators, the Newark Abbott Indicators Report presents the status of educational…

Combined evaluation of sexually transmitted infections in HIV-infected pregnant women and infant HIV transmission

PubMed Central

Xu, Jiahong; Yeganeh, Nava; Camarca, Margaret; Morgado, Mariza G.; Watts, D. Heather; Mofenson, Lynne M.; Veloso, Valdilea G.; Pilotto, Jose Henrique; Joao, Esau; Gray, Glenda; Theron, Gerhard; Santos, Breno; Fonseca, Rosana; Kreitchmann, Regis; Pinto, Jorge; Mussi-Pinhata, Marisa M.; Ceriotto, Mariana; Machado, Daisy Maria; Bryson, Yvonne J.; Grinsztejn, Beatriz; Moye, Jack; Klausner, Jeffrey D.; Bristow, Claire C.; Dickover, Ruth; Mirochnick, Mark; Nielsen-Saines, Karin

2018-01-01

Background Sexually transmitted infections (STIs) including Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Treponema pallidum (TP), and cytomegalovirus (CMV) may lead to adverse pregnancy and infant outcomes. The role of combined maternal STIs in HIV mother-to-child transmission (MTCT) was evaluated in mother-infant pairs from NICHD HPTN 040. Methodology Urine samples from HIV-infected pregnant women during labor were tested by polymerase chain reaction (PCR) for CT, NG, and CMV. Infant HIV infection was determined by serial HIV DNA PCR testing. Maternal syphilis was tested by VDRL and confirmatory treponemal antibodies. Results A total of 899 mother-infant pairs were evaluated. Over 30% had at least one of the following infections (TP, CT, NG, and/or CMV) detected at the time of delivery. High rates of TP (8.7%), CT (17.8%), NG (4%), and CMV (6.3%) were observed. HIV MTCT was 9.1% (n = 82 infants). HIV MTCT was 12.5%, 10.3%, 11.1%, and 26.3% among infants born to women with CT, TP, NG or CMV respectively. Forty-two percent of HIV-infected infants were born to women with at least one of these 4 infections. Women with these infections were nearly twice as likely to have an HIV-infected infant (aOR 1.9, 95% CI 1.1–3.0), particularly those with 2 STIs (aOR 3.4, 95% CI 1.5–7.7). Individually, maternal CMV (aOR 4.4 1.5–13.0) and infant congenital CMV (OR 4.1, 95% CI 2.2–7.8) but not other STIs (TP, CT, or NG) were associated with an increased risk of HIV MTCT. Conclusion HIV-infected pregnant women identified during labor are at high risk for STIs. Co-infection with STIs including CMV nearly doubles HIV MTCT risk. CMV infection appears to confer the largest risk of HIV MTCT. Trial registration NCT00099359. PMID:29304083

Association of anti-gangliosides antibodies and anti-CMV antibodies in Guillain-Barré syndrome.

PubMed

Wang, Lijuan; Shao, Chunqing; Yang, Chunjiao; Kang, Xixiong; Zhang, Guojun

2017-05-01

Numerous types of infection were closely related to GBS, mainly including Campylobacter jejuni , Cytomegalovirus, which may lead to the production of anti-gangliosides antibodies (AGA) . Currently, although there are increased studies on the AGA and a few studies of anti-CMV antibodies in GBS, the association between them remains poorly documented. Therefore, our research aims to analyze the correlation of anti-CMV antibodies and AGA in GBS. A total of 29 patients with GBS were enrolled in this study. The CMV antibodies were tested by the electrochemiluminescence immunoassay "ECLIA" (Roche Diagnostics GmbH). The serum gangliosides were determined by The EUROLINE test kit. Of the 29 patients with GBS, 9 (31%) were AGA-seropositive, in which 22 were CMV-IgG positive in CSF at the same time, but all 29 samples were CMV-IgM negative in both serum and CSF. In the AGA-positive group, the rate of both serum and CSF positive was 87.5% (7/8), higher than 50% (7/14) of the negative group, although no statistical significance was found. In addition, we found that there was a trend of higher ratio of men, a younger age onset, less frequent preceding infection, a higher level of CSF proteins, and less frequent cranial nerve deficits, although the data did not reach a statistical significance. In spite of no statistical significance association was found between serum AGA and CMV-IgG in serum and CSF. However, we found that there was a trend of high positive rate of both serum and CSF-CMV-IgG in AGA-positive than the negative group. So we should further expand the sample size to analyze the association between AGA and CMV or other neurotropic virus antibodies in various diseases, to observe whether they could be serological marker of these diseases (especially GBS) or the underlying pathogenesis.

Evaluation of subcutaneous glucose monitoring systems under routine environmental conditions in patients with type 1 diabetes.

PubMed

Aberer, Felix; Hajnsek, Martin; Rumpler, Markus; Zenz, Sabine; Baumann, Petra M; Elsayed, Hesham; Puffing, Adelheid; Treiber, Gerlies; Pieber, Thomas R; Sourij, Harald; Mader, Julia K

2017-07-01

Continuous and flash glucose monitoring (GM) systems have been established in diabetes care. We compared the sensor performance of 3 commercially available GM systems. A total of 12 patients with type 1 diabetes were included in a single-centre, open-label study in which the sensor performance of the Abbott FreeStyle libre (Abbott), Dexcom G4 Platinum (Dexcom) and Medtronic MiniMed 640G (Medtronic) systems over 12 hours was compared during mimicked real-life conditions (meals, exercise, hypo- and hyperglycaemia). Sensor performance was determined by fulfilment of ISO 15197:2013 criteria, calculating mean absolute relative difference (MARD), and was also illustrated using Parkes error grid and Bland-Altman plots. Sensor performance during changes in metabolic variables (lactate, betahydroxybutyrate, glucagon, non-esterified-fatty-acids) was determined by Spearman's rank correlation coefficient testing. The systems fulfilled ISO 15197:2013 criteria by 73.2% (Abbott), 56.1% (Dexcom) and 52.0% (Medtronic). The MARDs ± standard deviation in the entire glycaemic range were 13.2% ± 10.9% (Abbott), 16.8% ± 12.3% (Dexcom) and 21.4% ± 17.6% (Medtronic), respectively. All sensors performed less accurately during hypoglycaemia and best during hyperglycaemia. We did not observe an influence of metabolic variables on sensor performance. © 2017 John Wiley & Sons Ltd.

CHANGES IN EXPRESSION OF PHOSPHORYLATED AND TOTAL ERK 1/2 IN TCDD-EXPOSED EMBRYONIC MOUSE PALATES

EPA Science Inventory

CHANGES IN EXPRESSION OF PHOSPHORYLATED AND TOTAL ERK1/2 IN TCDD-EXPOSED EMBRYONIC MOUSE PALATES.
C Wolf and B Abbott, USEPA, ORD, NHEERL, Reproductive Toxicology Division, Research Triangle Park, NC 27711

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces cleft palate...

Management of the Critically Ill Marrow Transplant Patient

DTIC Science & Technology

1988-01-01

dose-limiting factor diation (TBI) on serum amylase. Total serum amylase (21, 81). In addition, in allogeneic (non-self) was measured on 30 patients...refractory lo other Iherapy. By Polyclonal immune serum globulin (ISC) or nature of the production process, however. antilymphocyte immuioglobulin (ALG) anti...8217 .tients by giving CMV-negative blood products struction of lymphocytes. In severe cases, hy- and by avoiding the use of CMV-positive mar- potension

A double-blinded, prospective study to define antigenemia and quantitative real-time polymerase chain reaction cutoffs to start preemptive therapy in low-risk, seropositive, renal transplanted recipients.

PubMed

David-Neto, Elias; Triboni, Ana H K; Paula, Flavio J; Vilas Boas, Lucy S; Machado, Clarisse M; Agena, Fabiana; Latif, Acram Z A; Alencar, Cecília S; Pierrotti, Ligia C; Nahas, William C; Caiaffa-Filho, Helio H; Pannuti, Claudio S

2014-11-27

Cytomegalovirus (CMV) disease occurs in 16% to 20% of low-risk, CMV-positive renal transplant recipients. The cutoffs for quantitative real-time polymerase chain reaction (qPCR) or phosphoprotein (pp65) antigenemia (pp65emia) for starting preemptive therapy have not been well established. We measured qPCR and pp65emia weekly from day 7 to day 120 after transplantation, in anti-CMV immunoglobulin G–positive donor and recipient pairs. Patients and physicians were blinded to the test results. Suspicion of CMV disease led to the order of new tests. In asymptomatic viremic patients, the highest pp65emia and qPCR values were used, whereas we considered the last value before diagnosis in those with CMV disease. We collected a total of 1,481 blood samples from 102 adult patients. Seventeen patients developed CMV disease, 54 presented at least one episode of viremia that cleared spontaneously, and 31 never presented viremia. Five patients developed CMV disease after the end of the study period. The median (95% confidence interval) pp65emia and qPCR values were higher before CMV disease than during asymptomatic viremia (6 [9–82] vs. 3 [1–14] cells/10(6) cells; P<0.001 and 3,080 [1,263–15,605] vs. 258 [258–1,679] copies/mL; P=0.008, respectively). The receiver operating characteristic curve showed that pp65emia 4 cells/10(6) cells or greater showed a sensitivity and specificity to predict CMV disease of 69% and 81%, respectively (area, 0.769; P=0.001), with a positive predictive value of 37% and a negative predictive value of 93%. For qPCR 2,000 copies/mL or higher, the positive predictive value and negative predictive value were 57% and 91%, respectively (receiver operating characteristic area, 0.782; P=0.000). With these cutoffs, both methods are appropriate for detecting CMV disease.

Tracking Progress, Engaging Communities: Abbott Indicators Summary Report--Union City, New Jersey

ERIC Educational Resources Information Center

Hirsch, Lesley; Applewhite-Coney, Erain

2005-01-01

Union City is one of 31 urban school districts in New Jersey known as Abbott districts. As an Abbott district, Union City receives funding to equalize its per student general education budget with the most successful suburban districts in the state. Through a series of indicators, the Union City Abbott Indicators Report presents the status of…

Tracking Progress, Engaging Communities: Abbott Indicators Technical Report: Union City, New Jersey

ERIC Educational Resources Information Center

Applewhite-Coney, Erain; Hirsch, Lesley

2005-01-01

Union City is one of 31 urban school districts in New Jersey known as Abbott districts. As an Abbott district, Union City receives funding to equalize its per student general education budget with the most successful suburban districts in the state. Through a series of indicators, the Union City Abbott Indicators Report presents the status of…

Chinese Milk Vetch Improves Plant Growth, Development and 15N Recovery in the Rice-Based Rotation System of South China.

PubMed

Xie, Zhijian; He, Yaqin; Tu, Shuxin; Xu, Changxu; Liu, Guangrong; Wang, Huimin; Cao, Weidong; Liu, Hui

2017-06-15

Chinese milk vetch (CMV) is vital for agriculture and environment in China. A pot experiment combined with 15 N labeling (including three treatments: control, no fertilizer N and CMV; 15 N-labeled urea alone, 15 NU; substituting partial 15 NU with CMV, 15 NU-M) was conducted to evaluate the impact of CMV on plant growth, development and 15 NU recovery in rice-based rotation system. The 15 NU-M mitigated oxidative damage by increasing antioxidant enzymes activities and chlorophyll content while decreased malondialdehyde content in rice root and shoot, increased the biomass, total N and 15 N uptake of plant shoots by 8%, 12% and 39% respectively, thus inducing a noticeable increase of annual 15 N recovery by 77% versus 15 NU alone. Remarkable increases in soil NH 4 + and populations of bacteria, actinomycetes and azotobacter were obtained in legume-rice rotation system while an adverse result was observed in soil NO 3 - content versus fallow-rice. CMV as green manure significantly increased the fungal population which was decreased with cultivating CMV as cover crop. Therefore, including legume cover crop in rice-based rotation system improves plant growth and development, annual N conservation and recovery probably by altering soil nitrogen forms plus ameliorating soil microbial communities and antioxidant system which alleviates oxidative damages in plants.

Cytomegalovirus infection of the BS-1 human stroma cell line: effect on murine hemopoiesis.

PubMed

Steinberg, H N; Anderson, J; Lim, B; Chatis, P A

1993-10-01

BS-1, a stromal cell line derived from human bone marrow, can support the growth of murine erythroid (BFU-E), granulocyte-macrophage (CFU-GM), and megakaryocyte (CFU-M) progenitor cells in a short term in vitro coculture system. Exposure of BS-1 cells to cytomegalovirus (CMV) for 3 hr prior to coculture results in a marked reduction in the stroma cell's ability to support murine hemopoiesis. CMV's effect on the BS-1 cell's hematopoietic support function is dependent on the multiplicity of infection with total suppression of BFU-E observed at a 1:1 ratio of virus to bone marrow cells. A 50% loss in the ability of BS-1 cells to support BFU-E is observed at a 0.1:1 ratio. No effect of CMV is observed with further log dilutions of virus. CMV infection of BS-1 cells affects its support of erythroid progenitor cell growth to a greater extent than its influence on the development of granulocyte-macrophage colonies. Antibody to CMV or heat inactivation of the virus reverses the inhibitory affect on BS-1 cells. The results suggest that CMV can infect a cell that constitutes one of the cellular elements of the normal bone marrow microenvironment causing a decrease in the stroma's ability to support the growth and development of normal progenitor cells.

Latency versus persistence or intermittent recurrences: evidence for a latent state of murine cytomegalovirus in the lungs.

PubMed

Kurz, S; Steffens, H P; Mayer, A; Harris, J R; Reddehase, M J

1997-04-01

The state of cytomegalovirus (CMV) after the resolution of acute infection is an unsolved problem in CMV research. While the term "latency" is in general use to indicate the maintenance of the viral genome, a formal exclusion of low-level persistent productive infection depends on the sensitivity of the assay for detecting infectious virus. We have improved the method for detecting infectivity by combining centrifugal infection of permissive indicator cells in culture, expansion to an infectious focus, and sensitive detection of immediate-early RNA in the infected cells by reverse transcriptase PCR. A limiting-dilution approach defined the sensitivity of this assay. Infectivity was thereby found to require as few as 2 to 9 virion DNA molecules of murine CMV, whereas the standard measure of infectivity, the PFU, is the equivalent of ca. 500 viral genomes. Since murine CMV forms multicapsid virions in most infected tissues, the genome-to-infectivity ratio is necessarily >1. This assay thus sets a new standard for investigating CMV latency. In mice in which acute infection was resolved, the viral DNA load in the lungs, a known organ site of CMV latency and recurrence, was found to be 1 genome per 40 lung cells, or a total of ca. 1 million genomes. Despite this high load of CMV DNA, infectious virus was not detected with the improved assay, but recurrence was inducible. These data provide evidence against a low-level persistent productive infection and also imply that intermittent spontaneous recurrence is not a frequent event in latently infected lungs.

Cytomegalovirus (CMV) Enzyme-Linked Immunosorbent Spot Assay but Not CMV QuantiFERON Assay Is a Novel Biomarker To Determine Risk of Congenital CMV Infection in Pregnant Women

PubMed Central

Forner, Gabriella; Saldan, Alda; Mengoli, Carlo; Gussetti, Nadia; Palù, Giorgio

2016-01-01

Cytomegalovirus (CMV) enzyme-linked immunosorbent spot (ELISPOT) and CMV QuantiFERON assays were examined as potential biomarkers predictive of congenital CMV (cCMV) transmission. Fifty-seven pregnant women with primary CMV infection and 23 with nonprimary CMV infection were recruited in the study. Maternal age, CMV IgG avidity, viremia, and viruria were also included among the potential predictors. Spearman's statistical correlation analysis revealed a positive correlation between the CMV ELISPOT and CMV QuantiFERON assay results (P < 0.001), but only the CMV ELISPOT assay correlated with cCMV (P < 0.001). cCMV was positively correlated with maternal viremia and viruria (P < 0.05) and negatively correlated with CMV IgG avidity (P < 0.01). Maternal age and CMV QuantiFERON assay results were not statistically associated with cCMV. CMV-specific cell-mediated immunity detected by the CMV ELISPOT assay plays a critical role in cCMV. PMID:27280418

"A Prairie Childhood" by Edith Abbott: An Excerpt from "The Children's Champion," a Biography of Grace Abbott

ERIC Educational Resources Information Center

Sorensen, John

2003-01-01

Grace Abbott's courageous struggles--to protect the rights of immigrants, to increase the role of women in government, and to improve the lives of all children--are filled with adventurous tales of the remarkable human ability to seek out suffering and to do something about it. "A Prairie Childhood" is an excerpt from the Grace Abbott biography…

Telemedicine screening for cytomegalovirus retinitis at the point of care for human immunodeficiency virus infection.

PubMed

Jirawison, Choeng; Yen, Michael; Leenasirimakul, Prattana; Chen, Jenny; Guadanant, Siripim; Kunavisarut, Paradee; Patikulsila, Direk; Watanachai, Nawat; Ausayakhun, Somsanguan; Heiden, David; Holland, Gary N; Margolis, Todd P; Keenan, Jeremy D

2015-02-01

Cytomegalovirus (CMV) retinitis is a leading cause of blindness in many developing countries, likely the result of inadequate screening. Telemedicine screening for CMV retinitis instituted at the point of care for human immunodeficiency virus (HIV) infection may allow for earlier detection. To determine the diagnostic accuracy of retinal photography in detecting CMV retinitis at the point of HIV care and to characterize the clinical manifestations of CMV retinitis detected through the screening program. We enrolled 103 participants from a population of 258 patients with HIV and a CD4 level of less than 100/μL treated at an HIV clinic in Thailand from June 2010 through June 2012. We captured mosaic fundus photographs through a dilated pupil using a digital fundus camera. An experienced on-site ophthalmologist masked to the results of the fundus images subsequently examined each eye with indirect ophthalmoscopy and recorded the clinical findings on a standardized form. Three remote graders evaluated each image for CMV retinitis. Fundus photography and indirect ophthalmoscopy. Sensitivity and specificity of telemedicine relative to indirect ophthalmoscopy for diagnosis of CMV retinitis and clinical features of CMV retinitis lesions. Sixteen patients (15.5%) were diagnosed as having CMV retinitis, of whom 5 (31%) had bilateral disease. Of the 21 eyes (10.2%) with CMV retinitis, 7 (33%) had visual symptoms. Retinitis lesions occupied less than 10% of the total retinal surface area in 13 of 21 eyes (62%) and did not involve the posterior pole (ie, zone 1) in 15 of 21 eyes (71%). Mean logMAR visual acuity in affected eyes was 0.41 (95% CI, 0.11-0.71; Snellen equivalent, 20/50 [95% CI, 20/25-20/100]). The mean sensitivity for the 3 remote graders in detecting CMV retinitis on fundus photography was 30.2% (95% CI, 10.5%-52.4%), and mean specificity was 99.1% (95% CI, 97.8%-100.0%). The CMV retinitis lesions missed by the remote graders (false-negative findings) were more likely to be small (P = .001) and located in the peripheral retina (P = .04). Patients undergoing screening at a clinic for HIV treatment had less extensive retinitis than patients in recent reports from an ophthalmology clinic. Retinal photography with the camera used in this study was not highly sensitive in detecting CMV retinitis but may identify disease with an immediate threat to vision. Improved accuracy will require a camera that can more easily image the peripheral retina.

CMV-Specific T Cell Monitoring Offers Superior Risk Stratification of CMV-Seronegative Kidney Transplant Recipients of a CMV-Seropositive Donor.

PubMed

Schachtner, Thomas; Stein, Maik; Reinke, Petra

2017-10-01

Detectable cytomegalovirus (CMV)-specific T cells in CMV-seronegative kidney transplant recipients (KTRs) have been attributed to an absence of circulating antibodies despite CMV sensitization. The diagnostic value of CMV-specific T cells, however, needs to be implemented in risk stratification for CMV replication. Three hundred twenty-six KTRs were studied and classified with respect to CMV serostatus and presence of CMV-specific T cells. Samples were collected pretransplantation, at +1, +2, and +3 months posttransplantation. CMV-specific T cells directed to CMV-IE1 and CMV-pp65 were measured by interferon-γ Elispot assay. Nineteen (28%) of 67 D+R- KTRs showed pretransplant CMV-specific T cells. Although no differences were observed for CMV replication, KTRs with CMV-specific T cells presented with lower initial and peak CMV loads (P < 0.05). KTRs with decreasing/undetectable CMV-IE1-specific T cells pretransplantation and posttransplantation were at greatest risk of CMV replication. KTRs with stable/increasing CMV-IE1-specific T cells from pretransplantation to posttransplantation, however, showed low risk of CMV replication (P < 0.001). One hundred sixty-two (80%) of 203 R+ KTRs showed pretransplant CMV-specific T cells. Decreasing/undetectable CMV-IE1-specific T cells from pretransplantation and posttransplantation identified those R+ KTRs at increased risk of CMV replication (65/80 KTRs; 81%; P < 0.001). Despite CMV prophylaxis, D+R- KTRs are at greatest risk of CMV disease. Our data suggest that monitoring CMV-specific T cell kinetics from pretransplantation to posttransplantation, particularly directed to CMV-IE1, offers superior risk stratification compared with CMV serostatus alone.

Clinical laboratory investigation of the Sanofi ACCESS CK-MB procedure and comparison to electrophoresis and Abbott IMx.

PubMed

Mao, G D; Adeli, K; Eisenbrey, A B; Artiss, J D

1996-07-01

This evaluation was undertaken to verify the application protocol for the CK-MB assay on the ACCESS Immunoassay Analyzer (Sanofi Diagnostics Pasteur, Chaska, MN). The results show that the ACCESS CK-MB assay total imprecision was 6.8% to 9.1%. Analytical linearity of the ACCESS CK-MB assay was excellent in the range of < 1-214 micrograms/L. A comparison of the ACCESS CK-MB assay with the IMx (Abbott Laboratories, Abbott Park, IL) method shows good correlation r = 0.990 (n = 108). Linear regression analysis yielded Y = 1.36X-0.3, Sx/y = 7.2. ACCESS CK-MB values also correlated well with CK-MB by electrophoresis with r = 0.968 (n = 132). The linear regression equation for this comparison was Y = 1.08X + 1.4, Sx/y = 14.1. The expected non-myocardial infarction range of CK-MB determined by the ACCESS system was 1.3-9.4 micrograms/L (mean = 4.0, n = 58). The ACCESS CK-MB assay would appear to be rapid, precise and clinically useful.

14 CFR 93.53 - Description of area.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Parkway; thence northerly along Lake Otis Parkway to its intersection with Abbott Road; thence east along Abbott Road to its intersection with Abbott Loop Road; thence north to its intersection with Tudor Road...

Improving clinical laboratory efficiency: a time-motion evaluation of the Abbott m2000 RealTime and Roche COBAS AmpliPrep/COBAS TaqMan PCR systems for the simultaneous quantitation of HIV-1 RNA and HCV RNA.

PubMed

Amendola, Alessandra; Coen, Sabrina; Belladonna, Stefano; Pulvirenti, F Renato; Clemens, John M; Capobianchi, M Rosaria

2011-08-01

Diagnostic laboratories need automation that facilitates efficient processing and workflow management to meet today's challenges for expanding services and reducing cost, yet maintaining the highest levels of quality. Processing efficiency of two commercially available automated systems for quantifying HIV-1 and HCV RNA, Abbott m2000 system and Roche COBAS Ampliprep/COBAS TaqMan 96 (docked) systems (CAP/CTM), was evaluated in a mid/high throughput workflow laboratory using a representative daily workload of 24 HCV and 72 HIV samples. Three test scenarios were evaluated: A) one run with four batches on the CAP/CTM system, B) two runs on the Abbott m2000 and C) one run using the Abbott m2000 maxCycle feature (maxCycle) for co-processing these assays. Cycle times for processing, throughput and hands-on time were evaluated. Overall processing cycle time was 10.3, 9.1 and 7.6 h for Scenarios A), B) and C), respectively. Total hands-on time for each scenario was, in order, 100.0 (A), 90.3 (B) and 61.4 min (C). The interface of an automated analyzer to the laboratory workflow, notably system set up for samples and reagents and clean up functions, are as important as the automation capability of the analyzer for the overall impact to processing efficiency and operator hands-on time.

Expression of a mutation causing hypertrophic cardiomyopathy disrupts sarcomere assembly in adult feline cardiac myocytes.

PubMed

Marian, A J; Yu, Q T; Mann, D L; Graham, F L; Roberts, R

1995-07-01

Mutations in the beta-myosin heavy chain (beta MyHC) induce hypertrophic cardiomyopathy (HCM), cardiac hypertrophy, and sarcomere disarray, with the latter being the characteristic hallmark. Thus, we sought to determine whether expression of mutant beta MyHC in adult feline cardiac myocytes, a species known to develop HCM with a phenotype identical to that in humans, induces sarcomere disarray. A full-length beta MyHC cDNA was cloned from a human heart cDNA library, and an HCM-causing mutation (Arg403Gln) was induced in the beta MyHC cDNA by site-directed mutagenesis using polymerase chain reaction (PCR). The normal and mutant beta MyHC cDNAs were cloned into p delta E1spIB shuttle vector, downstream from a cytomegalovirus (CMV) promoter. Replication-deficient recombinant adenoviral constructs (Ad5/CMV/beta MyHC-N and Ad5/CMV/beta MyHC-403) were generated through homologous recombination of p delta E1spIB/CMV/beta MyHC-N or Ad5/CMV/beta MyHC-403 and pBHG10 after cotransfection in 293 host cells. Infection of COS-1 cells with the beta MyHC construct resulted in the expression of a full-length myosin protein. Efficiency of infection of isolated adult cardiac myocytes was > 95%. Expression of the beta MyHC constructs into mRNA at 48 hours after infection of feline cardiac myocytes was confirmed by reverse transcription-PCR. The net total protein and beta-myosin synthesis were determined by using the amount of incorporation of [3H]phenylalanine into total protein and beta-myosin, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

The Prevalence and Incidence of Epiretinal Membranes in Eyes With Inactive Extramacular CMV Retinitis

PubMed Central

Kozak, Igor; Vaidya, Vijay; Van Natta, Mark L.; Pak, Jeong W.; May, K. Patrick; Thorne, Jennifer E.

2014-01-01

Purpose. To determine the prevalence and incidence of epiretinal membranes (ERM) in eyes with inactive extramacular cytomegalovirus (CMV) retinitis in patients with acquired immune deficiency syndrome (AIDS). Methods. A case–control report from a longitudinal multicenter observational study by the Studies of the Ocular Complications of AIDS (SOCA) Research Group. A total of 357 eyes of 270 patients with inactive CMV retinitis and 1084 eyes of 552 patients with no ocular opportunistic infection (OOI) were studied. Stereoscopic views of the posterior pole from fundus photographs were assessed at baseline and year 5 visits for the presence of macular ERM. Generalized estimating equations (GEE) logistic regression was used to compare the prevalence and 5-year incidence of ERM in eyes with and without CMV retinitis at enrollment. Crude and adjusted logistic regression was performed adjusting for possible confounders. Main outcome measures included the prevalence, incidence, estimated prevalence, and incidence odds ratios. Results. The prevalence of ERM at enrollment was 14.8% (53/357) in eyes with CMV retinitis versus 1.8% (19/1084) in eyes with no OOI. The incidence of ERM at 5 years was 18.6% (16/86) in eyes with CMV retinitis versus 2.4% (6/253) in eyes with no OOI. The crude odds ratio (OR) (95% confidence interval, CI) for prevalence was 9.8 (5.5–17.5) (P < 0.01). The crude OR (95% CI) for incidence was 9.4 (3.2–27.9) (P < 0.01). Conclusions. A history of extramacular CMV retinitis is associated with increased prevalence and incidence of ERM formation compared to what is seen in eyes without ocular opportunistic infections in AIDS patients. PMID:24925880

The prevalence and incidence of epiretinal membranes in eyes with inactive extramacular CMV retinitis.

PubMed

Kozak, Igor; Vaidya, Vijay; Van Natta, Mark L; Pak, Jeong W; May, K Patrick; Thorne, Jennifer E

2014-06-12

To determine the prevalence and incidence of epiretinal membranes (ERM) in eyes with inactive extramacular cytomegalovirus (CMV) retinitis in patients with acquired immune deficiency syndrome (AIDS). A case-control report from a longitudinal multicenter observational study by the Studies of the Ocular Complications of AIDS (SOCA) Research Group. A total of 357 eyes of 270 patients with inactive CMV retinitis and 1084 eyes of 552 patients with no ocular opportunistic infection (OOI) were studied. Stereoscopic views of the posterior pole from fundus photographs were assessed at baseline and year 5 visits for the presence of macular ERM. Generalized estimating equations (GEE) logistic regression was used to compare the prevalence and 5-year incidence of ERM in eyes with and without CMV retinitis at enrollment. Crude and adjusted logistic regression was performed adjusting for possible confounders. Main outcome measures included the prevalence, incidence, estimated prevalence, and incidence odds ratios. The prevalence of ERM at enrollment was 14.8% (53/357) in eyes with CMV retinitis versus 1.8% (19/1084) in eyes with no OOI. The incidence of ERM at 5 years was 18.6% (16/86) in eyes with CMV retinitis versus 2.4% (6/253) in eyes with no OOI. The crude odds ratio (OR) (95% confidence interval, CI) for prevalence was 9.8 (5.5-17.5) (P < 0.01). The crude OR (95% CI) for incidence was 9.4 (3.2-27.9) (P < 0.01). A history of extramacular CMV retinitis is associated with increased prevalence and incidence of ERM formation compared to what is seen in eyes without ocular opportunistic infections in AIDS patients. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Maternal and Congenital cytomegalovirus infection and zero rubella IgM prevalence in newborns in St.Paul's Hospital Millennium Medical College.

PubMed

Mamuye, Yeshwondm; Nigatu, Balkachew; Bekele, Delayehu; Getahun, Mekonen

2016-10-21

Maternal cytomegalovirus (CMV) and Rubella infections result in adverse neonatal outcomes. Both CMV and Rubella are more widespread in developing countries and in communities with lower socioeconomic status. Thus, the aim of this study was to determine IgM specific to CMV and Rubella among newborns and Maternal CMV-seroprevalence and to identify risk factors. Using cross sectional study design a total of 312 (156 newborns and 156 mothers) study participants were recruited by simple random sampling technique from gynecology outpatient department (OPD) and ward, starting from April 1, 2015 to June 30, 2015. Cord and venous blood samples were collected from all participants and structured questionnaire was introduced to gather risk factor related data. ELISA was used to detect CMV and Rubella-IgM. SPSS version 20 was used to analyze the data, and regression analysis was also performed. Out of 156 newborns, 2 [1.3 %; 95 % CI: 0.0-3.8] were positive for CMV-IgM and no single rubella was detected. Association was not computed between risk related variables and cytomegalovirus infected newborns due to the low positivity rate. Multiple independent predictors were found between maternal CMV-IgM and Obstetrical characteristics. Cytomegalovirus-IgM was significantly isolated from mothers with history of transfusion (25.0 %, OR 0.09, 95 % CI 0.0-0.3, P = 0.006), history of abortion (OR 0.02, 95 % CI 0.0-0.6, P = 0.023), HIV sero-status (OR 5.0, 95 % CI 1.5-15.8, P = 0.034), and multi parity (OR 0.08, 95 % CI 0.01-0.7, P = 0.022). Although low congenital CMV and no Rubella are reported among newborns, more effort is needed to screen for congenital infectious viral disease as well as usage of advanced techniques should be taken into consideration.

Detection of Cytomegalovirus (CMV) DNA in EDTA Whole-Blood Samples: Evaluation of the Quantitative artus CMV LightCycler PCR Kit in Conjunction with Automated Sample Preparation▿

PubMed Central

Michelin, Birgit D. A.; Hadžisejdić, Ita; Bozic, Michael; Grahovac, Maja; Hess, Markus; Grahovac, Blaženka; Marth, Egon; Kessler, Harald H.

2008-01-01

Whole blood has been found to be a reliable matrix for the detection and quantitation of cytomegalovirus (CMV) DNA. In this study, the performance of the artus CMV LightCycler (LC) PCR kit in conjunction with automated sample preparation on a BioRobot EZ1 workstation was evaluated. The accuracy, linearity, analytical sensitivity, and inter- and intra-assay variations were determined. A total of 102 clinical EDTA whole-blood samples were investigated, and results were compared with those obtained with the in vitro diagnostics (IVD)/Conformité Européene (CE)-labeled CMV HHV6,7,8 R-gene quantification kit. When the accuracy of the new kit was tested, seven of eight results were found to be within ±0.5 log10 unit of the expected panel results. Determination of linearity resulted in a quasilinear curve over more than 5 log units. The lower limit of detection of the assay was determined to be 139 copies/ml in EDTA whole blood. The interassay variation ranged from 15 to 58%, and the intra-assay variation ranged from 7 to 35%. When clinical samples were tested and the results were compared with those of the routinely used IVD/CE-labeled assay, 53 samples tested positive and 13 samples tested negative by both of the assays. One sample was found to be positive with the artus CMV LC PCR kit only, and 35 samples tested positive with the routinely used assay only. The majority of discrepant results were found with low-titer samples. In conclusion, use of the artus CMV LC PCR kit in conjunction with automated sample preparation on the BioRobot EZ1 workstation may be suitable for the detection and quantitation of CMV DNA in EDTA whole blood in the routine low-throughput laboratory; however, low-positive results may be missed by this assay. PMID:18272703

Detection of cytomegalovirus (CMV) DNA in EDTA whole-blood samples: evaluation of the quantitative artus CMV LightCycler PCR kit in conjunction with automated sample preparation.

PubMed

Michelin, Birgit D A; Hadzisejdic, Ita; Bozic, Michael; Grahovac, Maja; Hess, Markus; Grahovac, Blazenka; Marth, Egon; Kessler, Harald H

2008-04-01

Whole blood has been found to be a reliable matrix for the detection and quantitation of cytomegalovirus (CMV) DNA. In this study, the performance of the artus CMV LightCycler (LC) PCR kit in conjunction with automated sample preparation on a BioRobot EZ1 workstation was evaluated. The accuracy, linearity, analytical sensitivity, and inter- and intra-assay variations were determined. A total of 102 clinical EDTA whole-blood samples were investigated, and results were compared with those obtained with the in vitro diagnostics (IVD)/Conformité Européene (CE)-labeled CMV HHV6,7,8 R-gene quantification kit. When the accuracy of the new kit was tested, seven of eight results were found to be within +/-0.5 log(10) unit of the expected panel results. Determination of linearity resulted in a quasilinear curve over more than 5 log units. The lower limit of detection of the assay was determined to be 139 copies/ml in EDTA whole blood. The interassay variation ranged from 15 to 58%, and the intra-assay variation ranged from 7 to 35%. When clinical samples were tested and the results were compared with those of the routinely used IVD/CE-labeled assay, 53 samples tested positive and 13 samples tested negative by both of the assays. One sample was found to be positive with the artus CMV LC PCR kit only, and 35 samples tested positive with the routinely used assay only. The majority of discrepant results were found with low-titer samples. In conclusion, use of the artus CMV LC PCR kit in conjunction with automated sample preparation on the BioRobot EZ1 workstation may be suitable for the detection and quantitation of CMV DNA in EDTA whole blood in the routine low-throughput laboratory; however, low-positive results may be missed by this assay.

A randomized trial comparing methotrexate and vinblastine (MV) with cisplatin, methotrexate and vinblastine (CMV) in advanced transitional cell carcinoma: results and a report on prognostic factors in a Medical Research Council study. MRC Advanced Bladder Cancer Working Party.

PubMed Central

Mead, G. M.; Russell, M.; Clark, P.; Harland, S. J.; Harper, P. G.; Cowan, R.; Roberts, J. T.; Uscinska, B. M.; Griffiths, G. O.; Parmar, M. K.

1998-01-01

Transitional cell carcinomas may arise at any site within the urinary tract and are a source of considerable morbidity and mortality. In particular, patients with metastatic disease have a poor prognosis, with less than 5% alive at 5 years. A multicentre randomized trial comparing methotrexate and vinblastine (MV) with cisplatin, methotrexate and vinblastine (CMV) in advanced or metastatic transitional cell carcinoma was conducted in the UK. From April 1991 to June 1995, 214 patients were entered by 16 centres, 108 randomized to CMV and 106 to MV. A total of 204 patients have died. The hazard ratio (relative risk of dying) was 0.68 (95% CI 0.51-0.90, P-value = 0.0065) in favour of CMV. This translates to an absolute improvement in 1-year survival of 13%, 16% in MV and 29% in CMV. The median survival for CMV and MV was 7 months and 4.5 months respectively. Two hundred and eight patients objectively progressed or died. The hazard ratio was 0.55 (95% CI 0.41-0.73, P-value = 0.0001) in favour of CMV. Two hundred and nine patients symptomatically progressed or died. The hazard ratio was 0.48 (95% CI 0.36-0.64, P-value = 0.0001) in favour of CMV. The most important pretreatment factors influencing overall survival were WHO performance status and extent of disease. These two factors were used to derive a prognostic index which could be used to categorize patients into three prognostic groups. We conclude that the addition of cisplatin to methotrexate and vinblastine should be considered in patients with transitional cell carcinoma, taking into account the increased toxicity. PMID:9792152

Cytomegalovirus infection management in solid organ transplant recipients across European centers in the time of molecular diagnostics: An ESGICH survey.

PubMed

Navarro, David; San-Juan, Rafael; Manuel, Oriol; Giménez, Estela; Fernández-Ruiz, Mario; Hirsch, Hans H; Grossi, Paolo Antonio; Aguado, José María

2017-12-01

Scant information is available about how transplant centers are managing their use of quantitative molecular testing (QNAT) assays for active cytomegalovirus (CMV) infection monitoring in solid organ transplant (SOT) recipients. The current study was aimed at gathering information on current practices in the management of CMV infection across European centers in the era of molecular testing assays. A questionnaire-based cross-sectional survey study was conducted by the European Study Group of Infections in Immunocompromised Hosts (ESGICH) of the Society of Clinical Microbiology and Infectious Diseases (ESCMID). The invitation and a weekly reminder with a personal link to an Internet service provider (https://es.surveymonkey.com/) was sent to transplant physicians, transplant infectious diseases specialists, and clinical virologists working at 340 European transplant centers. Of the 1181 specialists surveyed, a total of 173 responded (14.8%): 73 transplant physicians, 57 transplant infectious diseases specialists, and 43 virologists from 173 institutions located at 23 different countries. The majority of centers used QNAT assays for active CMV infection monitoring. Most centers preferred commercially available real-time polymerase chain reaction (RT-PCR) assays over laboratory-developed procedures for quantifying CMV DNA load in whole blood or plasma. Use of a wide variety of DNA extraction platforms and RT-PCR assays was reported. All programs used antiviral prophylaxis, preemptive therapy, or both, according to current guidelines. However, the centers used different criteria for starting preemptive antiviral treatment, for monitoring systemic CMV DNA load, and for requesting genotypic assays to detect emerging CMV-resistant variants. Significant variation in CMV infection management in SOT recipients still remains across European centers in the era of molecular testing. International multicenter studies are required to achieve commutability of CMV testing and antiviral management procedures. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Reference ranges for serum total and monomeric prolactin for the current generation Abbott Architect assay.

PubMed

Whitehead, S J; Cornes, M P; Ford, C; Gama, R

2015-01-01

Exclusion of macroprolactinaemia, a well-recognised interference, as the cause of hyperprolactinaemia is essential to avoid potential misdiagnosis and mismanagement of patients. We have derived gender-specific serum total and post-polyethylene glycol (PEG) precipitation monomeric reference ranges for the recently re-standardised Abbott Architect prolactin assay. Prolactin was measured in serum samples obtained from males (n=49) and females (n=52) using the current Abbott Architect immunoassay pre- and post-PEG precipitation. Gender-specific reference ranges were derived for total and monomeric (post-PEG) prolactin. Routine patients' samples (n=175) with a serum total prolactin >700 mIU/L were screened for macroprolactinaemia to assess classification compared with our previous post-PEG precipitation percentage recovery-based approach. Reference ranges for serum total prolactin were 58-419 mIU/L (male) and 63-561 mIU/L (female). Male and female monomeric prolactin reference ranges were 32-309 mIU/L and 39-422 mIU/L, respectively. Mean (SD) post-PEG percentage recovery of the IS 84/500 prolactin standard was 80 (2.3)%. Of 175 patients' samples screened for macroprolactinaemia, 149 had monomeric prolactin concentrations (median monomeric prolactin=1035 mIU/L; median recovery=83%) above the gender-specific reference range. Monomeric prolactin concentrations (median monomeric prolactin=162 mIU/L; median recovery=20%) in the remaining 26 were within the reference ranges. One patient classified as macroprolactin positive and another classified as macroprolactin negative would not have been identified as such using the previous recovery-based approach. The use of post-PEG monomeric reference ranges not only identifies hyperprolactinaemia due solely to macroprolactinaemia but has the added advantage of identifying patients who have simultaneous true monomeric hyperprolactinaemia and elevated concentrations of macroprolactin. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Protective Cytomegalovirus (CMV)-Specific T-Cell Immunity Is Frequent in Kidney Transplant Patients without Serum Anti-CMV Antibodies.

PubMed

Litjens, Nicolle H R; Huang, Ling; Dedeoglu, Burç; Meijers, Ruud W J; Kwekkeboom, Jaap; Betjes, Michiel G H

2017-01-01

The absence of anti-cytomegalovirus (CMV) immunoglobulin G (IgG) is used to classify pretransplant patients as naïve for CMV infection (CMV neg patients). This study assessed whether pretransplant CMV-specific T-cell immunity exists in CMV neg patients and whether it protects against CMV infection after kidney transplantation. The results show that CMV-specific CD137 + IFNγ + CD4 + and CD137 + IFNγ + CD8 + memory T cells were present in 46 and 39% of CMV neg patients ( n  = 28) although at much lower frequencies compared to CMV pos patients (median 0.01 versus 0.58% for CD4 + and 0.05 versus 0.64% for CD8 + T cells) with a less differentiated CD28-expressing phenotype. In line with these data, CMV-specific proliferative CD4 + and CD8 + T cells were observed in CMV neg patients, which significantly correlated with the frequency of CMV-specific T cells. CMV-specific IgG antibody-secreting cells (ASC) could be detected at low frequency in 36% of CMV neg patients (1 versus 45 ASC/10 5 cells in CMV pos patients). CMV neg patients with pretransplant CMV-specific CD137 + IFNγ + CD4 + T cells had a lower risk to develop CMV viremia after transplantation with a CMV pos donor kidney (relative risk: 0.43, P  = 0.03). In conclusion, a solitary CMV-specific T-cell response without detectable anti-CMV antibodies is frequent and clinically relevant as it is associated with protection to CMV infection following transplantation with a kidney from a CMV pos donor.

Association of CMV-Specific T Cell-Mediated Immunity with CMV DNAemia and Development of CMV Disease in HIV-1-Infected Individuals.

PubMed

Aichelburg, Maximilian C; Weseslindtner, Lukas; Mandorfer, Mattias; Strassl, Robert; Rieger, Armin; Reiberger, Thomas; Puchhammer-Stöckl, Elisabeth; Grabmeier-Pfistershammer, Katharina

2015-01-01

Among HIV-1-infected individuals, cytomegalovirus (CMV) reactivation and disease occur in the setting of advanced immunosuppression. The value of a standardized assessment of CMV-specific T-cell mediated immunity by the CMV QuantiFERON assay (CMV-QFT) has not yet been thoroughly investigated in HIV-1-infected subjects. Prospective, longitudinal study in 153 HIV-1-infected subjects with a CD4+ T cell count < 350/μL who simultaneously underwent CMV-QFT, CMV serology testing and CMV-DNA quantification. Factors associated with CMV-QFT were evaluated. Clinical screening for CMV manifestations was then performed every 3 months. Among the 141 CMV IgG-seropositive individuals the CMV-QFT assay yielded reactive results in 84% (118/141), negative results in 15% (21/141) and indeterminate (negative mitogen IFN-gamma response) results in 1% (2/141) of subjects. The mean actual CD4+ T cell count was significantly higher in CMV-QFT reactive subjects, when compared to CMV-QFT non-reactive individuals (183 ± 102 vs. 126 ± 104 cells/μL, P = 0.015). A significantly lower proportion of CMV-QFT reactive vs. non-reactive patients displayed CMV DNAemia > 100 copies/mL (23% (27/118) vs. 48% (11/23), P = 0.02). Furthermore, a statistically significant inverse association between mitogen IFN-gamma response and CMV-DNAemia > 1000 copies/mL was observed (P < 0.001). During the observational period, 5 CMV end-organ manifestations were observed. In three of the CMV cases the CMV-QFT yielded indeterminate results. While CMV-QFT reactivity indicates CMV-specific immunity, indeterminate results due to negative mitogen IFN-gamma response might reflect HIV-1-induced immunodeficiency. Thus, dependency upon CD4+ T cell count should be considered when interpreting CMV-QFT results.

Comparison of the Abbott RealTime High Risk HPV test and the Roche cobas 4800 HPV test using urine samples.

PubMed

Lim, Myong Cheol; Lee, Do-Hoon; Hwang, Sang-Hyun; Hwang, Na Rae; Lee, Bomyee; Shin, Hye Young; Jun, Jae Kwan; Yoo, Chong Woo; Lee, Dong Ock; Seo, Sang-Soo; Park, Sang-Yoon; Joo, Jungnam

2017-05-01

Human papillomavirus (HPV) testing based on cervical samples is important for use in cervical cancer screening. However, cervical sampling is invasive. Therefore, non-invasive methods for detecting HPV, such as urine samples, are needed. For HPV detection in urine samples, two real-time PCR (RQ-PCR) tests, Roche cobas 4800 test (Roche_HPV; Roche Molecular Diagnostics) and Abbott RealTime High Risk HPV test (Abbott_HPV; Abbott Laboratories) were compared to standard cervical samples. The performance of Roche_HPV and Abbott_HPV for HPV detection was evaluated at the National Cancer Center using 100 paired cervical and urine samples. The tests were also compared using urine samples stored at various temperatures and for a range of durations. The overall agreement between the Roche_HPV and Abbott_HPV tests using urine samples for any hrHPV type was substantial (86.0% with a kappa value of 0.7173), and that for HPV 16/18 was nearly perfect (99.0% with a kappa value of 0.9668). The relative sensitivities (based on cervical samples) for HPV 16/18 detection using Roche_HPV and Abbott_HPV with urine samples were 79.2% (95% CI; 57.9-92.9%) and 81.8% (95% CI; 59.7-94.8%), respectively. When the cut-off C T value for Abbott_HPV was extended to 40 for urine samples, the relative sensitivity of Abbott_HPV increased to 91.7% from 81.8% for HPV16/18 detection and to 87.0% from 68.5% for other hrHPV detection. The specificity was not affected by the change in the C T threshold. Roche_HPV and Abbott_HPV showed high concordance. However, HPV DNA detection using urine samples was inferior to HPV DNA detection using cervical samples. Interestingly, when the cut-off C T value was set to 40, Abbott_HPV using urine samples showed high sensitivity and specificity, comparable to those obtained using cervical samples. Fully automated DNA extraction and detection systems, such as Roche_HPV and Abbott_HPV, could reduce the variability in HPV detection and accelerate the standardization of HPV detection in urine. Thus, urine samples may be an effective alternative for HPV detection in women who hesitate to participate in cervical cancer screening programs. Copyright © 2017 Elsevier B.V. All rights reserved.

Validation of T-Track® CMV to assess the functionality of cytomegalovirus-reactive cell-mediated immunity in hemodialysis patients.

PubMed

Banas, Bernhard; Böger, Carsten A; Lückhoff, Gerhard; Krüger, Bernd; Barabas, Sascha; Batzilla, Julia; Schemmerer, Mathias; Köstler, Josef; Bendfeldt, Hanna; Rascle, Anne; Wagner, Ralf; Deml, Ludwig; Leicht, Joachim; Krämer, Bernhard K

2017-03-07

Uncontrolled cytomegalovirus (CMV) replication in immunocompromised solid-organ transplant recipients is a clinically relevant issue and an indication of impaired CMV-specific cell-mediated immunity (CMI). Primary aim of this study was to assess the suitability of the immune monitoring tool T-Track® CMV to determine CMV-reactive CMI in a cohort of hemodialysis patients representative of patients eligible for renal transplantation. Positive and negative agreement of T-Track® CMV with CMV serology was examined in 124 hemodialysis patients, of whom 67 (54%) revealed a positive CMV serostatus. Secondary aim of the study was to evaluate T-Track® CMV performance against two unrelated CMV-specific CMI monitoring assays, QuantiFERON®-CMV and a cocktail of six class I iTAg™ MHC Tetramers. Positive T-Track® CMV results were obtained in 90% (60/67) of CMV-seropositive hemodialysis patients. In comparison, 73% (45/62) and 77% (40/52) positive agreement with CMV serology was achieved using QuantiFERON®-CMV and iTAg™ MHC Tetramer. Positive T-Track® CMV responses in CMV-seropositive patients were dominated by pp65-reactive cells (58/67 [87%]), while IE-1-responsive cells contributed to an improved (87% to 90%) positive agreement of T-Track® CMV with CMV serology. Interestingly, T-Track® CMV, QuantiFERON®-CMV and iTAg™ MHC Tetramers showed 79% (45/57), 87% (48/55) and 93% (42/45) negative agreement with serology, respectively, and a strong inter-assay variability. Notably, T-Track® CMV was able to detect IE-1-reactive cells in blood samples of patients with a negative CMV serology, suggesting either a previous exposure to CMV that yielded a cellular but no humoral immune response, or TCR cross-reactivity with foreign antigens, both suggesting a possible protective immunity against CMV in these patients. T-Track® CMV is a highly sensitive assay, enabling the functional assessment of CMV-responsive cells in hemodialysis patients prior to renal transplantation. T-Track® CMV thus represents a valuable immune monitoring tool to identify candidate transplant recipients potentially at increased risk for CMV-related clinical complications.

Field evaluation of Abbott Real Time HIV-1 Qualitative test for early infant diagnosis using dried blood spots samples in comparison to Roche COBAS Ampliprep/COBAS TaqMan HIV-1 Qual Test in Kenya

PubMed Central

Chang, Joy; Omuomo, Kenneth; Anyango, Emily; Kingwara, Leonard; Basiye, Frank; Morwabe, Alex; Shanmugam, Vedapuri; Nguyen, Shon; Sabatier, Jennifer; Zeh, Clement; Ellenberger, Dennis

2016-01-01

Timely diagnosis and treatment of infants infected with HIV are critical for reducing infant mortality. High-throughput automated diagnostic tests like Roche COBAS AmpliPrep/COBAS TaqMan HIV-1 Qual Test (Roche CAPCTM Qual) and the Abbott Real Time HIV-1 Qualitative (Abbott Qualitative) can be used to rapidly expand early infant diagnosis testing services. In this study, the performance characteristics of the Abbott Qualitative were evaluated using two hundred dried blood spots (DBS) samples (100 HIV-1 positive and 100 HIV-1 negative) collected from infants attending the antenatal facilities in Kisumu, Kenya. The Abbott Qualitative results were compared to the diagnostic testing completed using the Roche CAPCTM Qual in Kenya. The sensitivity and specificity of the Abbott Qualitative were 99.0% (95% CI: 95.0–100.0) and 100.0% (95% CI: 96.0–100.0), respectively, and the overall reproducibility was 98.0% (95% CI: 86.0–100.0). The limits of detection for the Abbott Qualitative and Roche CAPCTM Qual were 56.5 and 6.9 copies/mL at 95% CIs (p = 0.005), respectively. The study findings demonstrate that the Abbott Qualitative test is a practical option for timely diagnosis of HIV in infants. PMID:24726703

Field evaluation of Abbott Real Time HIV-1 Qualitative test for early infant diagnosis using dried blood spots samples in comparison to Roche COBAS Ampliprep/COBAS TaqMan HIV-1 Qual test in Kenya.

PubMed

Chang, Joy; Omuomo, Kenneth; Anyango, Emily; Kingwara, Leonard; Basiye, Frank; Morwabe, Alex; Shanmugam, Vedapuri; Nguyen, Shon; Sabatier, Jennifer; Zeh, Clement; Ellenberger, Dennis

2014-08-01

Timely diagnosis and treatment of infants infected with HIV are critical for reducing infant mortality. High-throughput automated diagnostic tests like Roche COBAS AmpliPrep/COBAS TaqMan HIV-1 Qual Test (Roche CAPCTM Qual) and the Abbott Real Time HIV-1 Qualitative (Abbott Qualitative) can be used to rapidly expand early infant diagnosis testing services. In this study, the performance characteristics of the Abbott Qualitative were evaluated using two hundred dried blood spots (DBS) samples (100 HIV-1 positive and 100 HIV-1 negative) collected from infants attending the antenatal facilities in Kisumu, Kenya. The Abbott Qualitative results were compared to the diagnostic testing completed using the Roche CAPCTM Qual in Kenya. The sensitivity and specificity of the Abbott Qualitative were 99.0% (95% CI: 95.0-100.0) and 100.0% (95% CI: 96.0-100.0), respectively, and the overall reproducibility was 98.0% (95% CI: 86.0-100.0). The limits of detection for the Abbott Qualitative and Roche CAPCTM Qual were 56.5 and 6.9copies/mL at 95% CIs (p=0.005), respectively. The study findings demonstrate that the Abbott Qualitative test is a practical option for timely diagnosis of HIV in infants. Published by Elsevier B.V.

Multicenter comparative study of conventional mechanical gas ventilation to tidal liquid ventilation in oleic acid injured sheep.

PubMed

Wolfson, Marla R; Hirschl, Ronald B; Jackson, J Craig; Gauvin, France; Foley, David S; Lamm, Wayne J E; Gaughan, John; Shaffer, Thomas H

2008-01-01

We performed a multicenter study to test the hypothesis that tidal liquid ventilation (TLV) would improve cardiopulmonary, lung histomorphological, and inflammatory profiles compared with conventional mechanical gas ventilation (CMV). Sheep were studied using the same volume-controlled, pressure-limited ventilator systems, protocols, and treatment strategies in three independent laboratories. Following baseline measurements, oleic acid lung injury was induced and animals were randomized to 4 hours of CMV or TLV targeted to "best PaO2" and PaCO2 35 to 60 mm Hg. The following were significantly higher (p < 0.01) during TLV than CMV: PaO2, venous oxygen saturation, respiratory compliance, cardiac output, stroke volume, oxygen delivery, ventilatory efficiency index; alveolar area, lung % gas exchange space, and expansion index. The following were lower (p < 0.01) during TLV compared with CMV: inspiratory and expiratory pause pressures, mean airway pressure, minute ventilation, physiologic shunt, plasma lactate, lung interleukin-6, interleukin-8, myeloperoxidase, and composite total injury score. No significant laboratories by treatment group interactions were found. In summary, TLV resulted in improved cardiopulmonary physiology at lower ventilatory requirements with more favorable histological and inflammatory profiles than CMV. As such, TLV offers a feasible ventilatory alternative as a lung protective strategy in this model of acute lung injury.

Comparison of Cytomegalovirus (CMV) Enzyme-Linked Immunosorbent Spot and CMV Quantiferon Gamma Interferon-Releasing Assays in Assessing Risk of CMV Infection in Kidney Transplant Recipients

PubMed Central

Saldan, Alda; Mengoli, Carlo; Fiscon, Marta; Silvestre, Cristina; Fallico, Loredana; Peracchi, Marta; Furian, Lucrezia; Cusinato, Riccardo; Bonfante, Luciana; Rossi, Barbara; Marchini, Francesco; Sgarabotto, Dino; Rigotti, Paolo; Palù, Giorgio

2013-01-01

Assessing cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) represents an appealing strategy for identifying transplant recipients at risk of infection. In this study, we compared two gamma interferon-releasing assays (IGRAs), Quantiferon-CMV and CMV enzyme-linked immunosorbent spot (ELISPOT), to determine the ability of each test to predict protective CMV-specific T-cell responses. Two hundred twenty-one Quantiferon-CMV and ELISPOT tests were conducted on 120 adult kidney transplant recipients (KTRs), including 100 CMV-seropositive transplant recipients (R+) and 20 CMV-seronegative transplant recipients of a CMV-positive donor (D+/R−). As a control cohort, 39 healthy adult subjects (including 33 CMV-seropositive and 6 CMV-seronegative subjects) were enrolled. CMV IgG serology was used as a reference for both tests. In the CMV-seropositive individuals, the ELISPOT and Quantiferon-CMV assays provided 46% concordance with the serology, 12% discordance, 18% disagreement between ELISPOT or Quantiferon-CMV and the serology, and 24% gray areas when one or both tests resulted in weak positives. None of the CMV-seronegative subjects showed detectable responses in the ELISPOT or the Quantiferon-CMV test. In transplant recipients, both the ELISPOT and Quantiferon-CMV assays positively correlated with each other and negatively correlated with CMV DNAemia in a significant way (P < 0.05). During the antiviral prophylaxis, all 20 D+/R− KTRs we examined displayed undetectable Quantiferon-CMV and ELISPOT results, and there was no evidence of CMV seroconversion. The receiving operator curve (ROC) statistical analysis revealed similar specificities and sensitivities in predicting detectable viremia (areas under the curve [AUC], 0.66 and 0.62 for Quantiferon-CMV and ELISPOT, respectively). ELISPOT and Quantiferon-CMV values of >150 spots/200,000 peripheral blood mononuclear cells (PBMCs) and >1 to 6 IU gamma interferon (IFN-γ) were associated with protection from CMV infection (odds ratios [OR], 5 and 8.75, respectively). In transplant recipients, the two tests displayed similar abilities for predicting CMV infection. Both the ELISPOT and Quantiferon-CMV assays require several ameliorations to avoid false-negative results. PMID:23678073

Evaluation of the Abbott realtime HCV genotype II RUO (GT II) assay with reference to 5'UTR, core and NS5B sequencing.

PubMed

Mallory, Melanie A; Lucic, Danijela X; Sears, Mitchell T; Cloherty, Gavin A; Hillyard, David R

2014-05-01

HCV genotyping is a critical tool for guiding initiation of therapy and selecting the most appropriate treatment regimen. To evaluate the concordance between the Abbott GT II assay and genotyping by sequencing subregions of the HCV 5'UTR, core and NS5B. The Abbott assay was used to genotype 127 routine patient specimens and 35 patient specimens with unusual subtypes and mixed infection. Abbott results were compared to genotyping by 5'UTR, core and NS5B sequencing. Sequences were genotyped using the NCBI non-redundant database and the online genotyping tool COMET. Among routine specimens, core/NS5B sequencing identified 93 genotype 1s, 13 genotype 2s, 15 genotype 3s, three genotype 4s, two genotype 6s and one recombinant specimen. Genotype calls by 5'UTR, core, NS5B sequencing and the Abbott assay were 97.6% concordant. Core/NS5B sequencing identified two discrepant samples as genotype 6 (subtypes 6l and 6u) while Abbott and 5'UTR sequencing identified these samples as genotype 1 with no subtype. The Abbott assay subtyped 91.4% of genotype 1 specimens. Among the 35 rare specimens, the Abbott assay inaccurately genotyped 3k, 6e, 6o, 6q and one genotype 4 variant; gave indeterminate results for 3g, 3h, 4r, 6m, 6n, and 6q specimens; and agreed with core/NS5B sequencing for mixed specimens. The Abbott assay is an automated HCV genotyping method with improved accuracy over 5'UTR sequencing. Samples identified by the Abbott assay as genotype 1 with no subtype may be rare subtypes of other genotypes and thus require confirmation by another method. Copyright © 2014 Elsevier B.V. All rights reserved.

Clinical Usefulness of Monitoring Cytomegalovirus-Specific Immunity by Quantiferon-CMV in Pediatric Allogeneic Hematopoietic Stem Cell Transplantation Recipients.

PubMed

Lee, Sae Mi; Kim, Yae Jean; Yoo, Keon Hee; Sung, Ki Woong; Koo, Hong Hoe; Kang, Eun Suk

2017-05-01

Cytomegalovirus (CMV) is a well-established cause of morbidity and mortality in pediatric recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). CD8⁺ T-cells are important for controlling CMV infection. We conducted a prospective pilot study to investigate the clinical utility of measuring the CMV-specific T-cell immune response using the QuantiFERON-CMV assay (QF-CMV) in pediatric allo-HSCT recipients. Overall, 16 of 25 (64%) patients developed CMV infection. QF-CMV was evaluated in these 16 patients during the early and late phases of the first CMV infection post allo-HSCT. Whereas the initial QF-CMV results during the early phase of CMV infection did not correlate with the course of the corresponding infection, the QF-CMV results post resolution of the first CMV infection correlated with the recurrence of CMV infection until 12 months post allo-HSCT; no recurrent infections occurred in the four QF-CMV-positive patients, while recurrent infections manifested in five of eight QF-CMV-negative (62.5%) and all three QF-CMV-indeterminate patients (P=0.019). In spite of the small number of patients examined, this study supports the potential application of monitoring CMV-specific T-cell immunity using the QF-CMV assay to predict the recurrence of CMV infection in pediatric allo-HSCT recipients. © The Korean Society for Laboratory Medicine.

CMV seronegative donors: Effect on clinical severity of CMV infection and reconstitution of CMV-specific immunity.

PubMed

van der Heiden, P L J; van Egmond, H M; Veld, S A J; van de Meent, M; Eefting, M; de Wreede, L C; Halkes, C J M; Falkenburg, J H F; Marijt, W A F; Jedema, I

2018-04-18

Cytomegalovirus (CMV)-specific T-cells are crucial to prevent CMV disease. CMV seropositive recipients transplanted with stem cells from a CMV seronegative allogeneic donor (R + D - ) may be at risk for CMV disease due to absence of donor CMV-specific memory T-cells in the graft. We analyzed the duration of CMV reactivations and the incidence of CMV disease in R + D - and R + D + patients after alemtuzumab-based T-cell depleted allogeneic stem cell transplantation (TCD alloSCT). To determine the presence of donor-derived primary CMV-specific T-cell responses we analyzed the origin of CMV-specific T-cells in R + D - patients. The duration of CMV reactivations (54 versus 38 days, respectively, p = 0.048) and the incidence of CMV disease (0.14 versus 0.02, p = 0.003 at 1 year after alloSCT) were higher in R + D - patients compared to R + D + patients. In R + D - patients, CMV-specific CD4 + and CD8 + T-cells were mainly of recipient origin. However, in 53% of R + D - patients donor-derived CMV-specific T-cells were detected within the first year. In R + D - patients, immunity against CMV was predominantly mediated by recipient T-cells. Nevertheless, donor CMV serostatus significantly influenced the clinical severity of CMV reactivations indicating the role of CMV-specific memory T-cells transferred with the graft, despite the ultimate formation of primary donor-derived CMV-specific T-cell responses in R + D - patients. Copyright © 2018 Elsevier B.V. All rights reserved.

Comparison of the Cytomegalovirus (CMV) Enzyme-Linked Immunosorbent Spot and CMV QuantiFERON Cell-Mediated Immune Assays in CMV-Seropositive and -Seronegative Pregnant and Nonpregnant Women

PubMed Central

Saldan, Alda; Forner, Gabriella; Mengoli, Carlo; Tinto, Daniel; Fallico, Loredana; Peracchi, Marta; Gussetti, Nadia

2016-01-01

Human cytomegalovirus (CMV) infection is a major cause of congenital infection leading to birth defects and sensorineural anomalies, including deafness. Recently, cell-mediated immunity (CMI) in pregnant women has been shown to correlate with congenital CMV transmission. In this study, two interferon gamma release assays (IGRA), the CMV enzyme-linked immunosorbent spot (ELISPOT) and CMV QuantiFERON assays, detecting CMV-specific CMI were compared. These assays were performed for 80 CMV-infected (57 primarily and 23 nonprimarily) pregnant women and 115 controls, including 89 healthy CMV-seropositive pregnant women without active CMV infection, 15 CMV-seronegative pregnant women, and 11 seropositive or seronegative nonpregnant women. Statistical tests, including frequency distribution analysis, nonparametric Kruskal-Wallis equality-of-populations rank test, Wilcoxon rank sum test for equality on unmatched data, and lowess smoothing local regression, were employed to determine statistical differences between groups and correlation between the assays. The CMV ELISPOT and CMV QuantiFERON assay data were not normally distributed and did not display equal variance. The CMV ELISPOT but not CMV QuantiFERON assay displayed significant higher values for primarily CMV-infected women than for the healthy seropositive pregnant and nonpregnant groups (P = 0.0057 and 0.0379, respectively) and those with nonprimary infections (P = 0.0104). The lowess local regression model comparing the assays on an individual basis showed a value bandwidth of 0.8. Both assays were highly accurate in discriminating CMV-seronegative pregnant women. The CMV ELISPOT assay was more effective than CMV-QuantiFERON in differentiating primary from the nonprimary infections. A substantial degree of variability exists between CMV ELISPOT and CMV QuantiFERON assay results for CMV-seropositive pregnant women. PMID:26962091

Association of CMV-Specific T Cell-Mediated Immunity with CMV DNAemia and Development of CMV Disease in HIV-1–Infected Individuals

PubMed Central

Aichelburg, Maximilian C.; Weseslindtner, Lukas; Mandorfer, Mattias; Strassl, Robert; Rieger, Armin; Reiberger, Thomas; Puchhammer-Stöckl, Elisabeth; Grabmeier-Pfistershammer, Katharina

2015-01-01

Background Among HIV-1–infected individuals, cytomegalovirus (CMV) reactivation and disease occur in the setting of advanced immunosuppression. The value of a standardized assessment of CMV-specific T-cell mediated immunity by the CMV QuantiFERON assay (CMV-QFT) has not yet been thoroughly investigated in HIV-1–infected subjects. Methods Prospective, longitudinal study in 153 HIV-1–infected subjects with a CD4+ T cell count < 350/μL who simultaneously underwent CMV-QFT, CMV serology testing and CMV-DNA quantification. Factors associated with CMV-QFT were evaluated. Clinical screening for CMV manifestations was then performed every 3 months. Results Among the 141 CMV IgG-seropositive individuals the CMV-QFT assay yielded reactive results in 84% (118/141), negative results in 15% (21/141) and indeterminate (negative mitogen IFN-gamma response) results in 1% (2/141) of subjects. The mean actual CD4+ T cell count was significantly higher in CMV-QFT reactive subjects, when compared to CMV-QFT non-reactive individuals (183 ± 102 vs. 126 ± 104 cells/μL, P = 0.015). A significantly lower proportion of CMV-QFT reactive vs. non-reactive patients displayed CMV DNAemia > 100 copies/mL (23% (27/118) vs. 48% (11/23), P = 0.02). Furthermore, a statistically significant inverse association between mitogen IFN-gamma response and CMV-DNAemia > 1000 copies/mL was observed (P < 0.001). During the observational period, 5 CMV end-organ manifestations were observed. In three of the CMV cases the CMV-QFT yielded indeterminate results. Conclusions While CMV-QFT reactivity indicates CMV-specific immunity, indeterminate results due to negative mitogen IFN-gamma response might reflect HIV-1-induced immunodeficiency. Thus, dependency upon CD4+ T cell count should be considered when interpreting CMV-QFT results. PMID:26322514

Performance of the Abbott RealTime CT/NG for detection of Chlamydia trachomatis and Neisseria gonorrhoeae.

PubMed

Gaydos, C A; Cartwright, C P; Colaninno, P; Welsch, J; Holden, J; Ho, S Y; Webb, E M; Anderson, C; Bertuzis, R; Zhang, L; Miller, T; Leckie, G; Abravaya, K; Robinson, J

2010-09-01

A multicenter clinical study was conducted to evaluate the performance characteristics of the Abbott RealTime CT/NG assay, a multiplex real-time PCR assay, for simultaneous detection of Chlamydia trachomatis and Neisseria gonorrhoeae. The specimens were collected from a total of 3,832 male and female subjects at 16 geographically diverse sites. Specimens included male and female urine samples, male urethral swabs, female endocervical swabs, and self-collected and clinician-collected vaginal swabs. Specimens were tested with the automated Abbott RealTime CT/NG assay, Aptima Combo 2 assay (Gen-Probe), ProbeTec ET CT/GC assay (Becton Dickinson), and culture for N. gonorrhoeae. The Aptima Combo 2 assay, the ProbeTec assay, and the N. gonorrhoeae culture were used as the reference assays. For each subject, a patient infected status (PIS) was determined based on the combined results from the reference assays. The overall prevalence in female subjects was 8.9% for C. trachomatis and 3.8% for N. gonorrhoeae. The overall male prevalence was 18.2% for C. trachomatis and 16.7% for N. gonorrhoeae. The overall sensitivity and specificity of the Abbott RealTime CT/NG assay were 92.4% and 99.2% for C. trachomatis and 96.9% and 99.7% for N. gonorrhoeae, respectively. In comparison, the sensitivity and specificity, respectively, for the Aptima Combo 2 assay were 94.5% and 99.0% for C. trachomatis and 96.1% and 99.5% for N. gonorrhoeae, and those for the ProbeTec ET assay were 90.3% and 99.5% for C. trachomatis and 92.0% and 97.3% for N. gonorrhoeae in this study. The Abbott RealTime CT/NG assay offers C. trachomatis and N. gonorrhoeae dual detection with high sensitivity and specificity. The automated assay provides a useful alternative nucleic acid amplification assay for clinical laboratories and clinicians.

Performance of the Abbott RealTime CT/NG for Detection of Chlamydia trachomatis and Neisseria gonorrhoeae▿

PubMed Central

Gaydos, C. A.; Cartwright, C. P.; Colaninno, P.; Welsch, J.; Holden, J.; Ho, S. Y.; Webb, E. M.; Anderson, C.; Bertuzis, R.; Zhang, L.; Miller, T.; Leckie, G.; Abravaya, K.; Robinson, J.

2010-01-01

A multicenter clinical study was conducted to evaluate the performance characteristics of the Abbott RealTime CT/NG assay, a multiplex real-time PCR assay, for simultaneous detection of Chlamydia trachomatis and Neisseria gonorrhoeae. The specimens were collected from a total of 3,832 male and female subjects at 16 geographically diverse sites. Specimens included male and female urine samples, male urethral swabs, female endocervical swabs, and self-collected and clinician-collected vaginal swabs. Specimens were tested with the automated Abbott RealTime CT/NG assay, Aptima Combo 2 assay (Gen-Probe), ProbeTec ET CT/GC assay (Becton Dickinson), and culture for N. gonorrhoeae. The Aptima Combo 2 assay, the ProbeTec assay, and the N. gonorrhoeae culture were used as the reference assays. For each subject, a patient infected status (PIS) was determined based on the combined results from the reference assays. The overall prevalence in female subjects was 8.9% for C. trachomatis and 3.8% for N. gonorrhoeae. The overall male prevalence was 18.2% for C. trachomatis and 16.7% for N. gonorrhoeae. The overall sensitivity and specificity of the Abbott RealTime CT/NG assay were 92.4% and 99.2% for C. trachomatis and 96.9% and 99.7% for N. gonorrhoeae, respectively. In comparison, the sensitivity and specificity, respectively, for the Aptima Combo 2 assay were 94.5% and 99.0% for C. trachomatis and 96.1% and 99.5% for N. gonorrhoeae, and those for the ProbeTec ET assay were 90.3% and 99.5% for C. trachomatis and 92.0% and 97.3% for N. gonorrhoeae in this study. The Abbott RealTime CT/NG assay offers C. trachomatis and N. gonorrhoeae dual detection with high sensitivity and specificity. The automated assay provides a useful alternative nucleic acid amplification assay for clinical laboratories and clinicians. PMID:20668135

HCV-RNA quantification in liver bioptic samples and extrahepatic compartments, using the abbott RealTime HCV assay.

PubMed

Antonucci, FrancescoPaolo; Cento, Valeria; Sorbo, Maria Chiara; Manuelli, Matteo Ciancio; Lenci, Ilaria; Sforza, Daniele; Di Carlo, Domenico; Milana, Martina; Manzia, Tommaso Maria; Angelico, Mario; Tisone, Giuseppe; Perno, Carlo Federico; Ceccherini-Silberstein, Francesca

2017-08-01

We evaluated the performance of a rapid method to quantify HCV-RNA in the hepatic and extrahepatic compartments, by using for the first time the Abbott RealTime HCV-assay. Non-tumoral (NT), tumoral (TT) liver samples, lymph nodes and ascitic fluid from patients undergoing orthotopic-liver-transplantation (N=18) or liver resection (N=4) were used for the HCV-RNA quantification; 5/22 patients were tested after or during direct acting antivirals (DAA) treatment. Total RNA and DNA quantification from tissue-biopsies allowed normalization of HCV-RNA concentrations in IU/μg of total RNA and IU/10 6 liver-cells, respectively. HCV-RNA was successfully quantified with high reliability in liver biopsies, lymph nodes and ascitic fluid samples. Among the 17 untreated patients, a positive and significant HCV-RNA correlation between serum and NT liver-samples was observed (Pearson: rho=0.544, p=0.024). Three DAA-treated patients were HCV-RNA "undetectable" in serum, but still "detectable" in all tested liver-tissues. Differently, only one DAA-treated patient, tested after sustained-virological-response, showed HCV-RNA "undetectability" in liver-tissue. HCV-RNA was successfully quantified with high reliability in liver bioptic samples and extrahepatic compartments, even when HCV-RNA was "undetectable" in serum. Abbott RealTime HCV-assay is a good diagnostic tool for HCV quantification in intra- and extra-hepatic compartments, whenever a bioptic sample is available. Copyright © 2017 Elsevier B.V. All rights reserved.

Transitioning cytomegalovirus viral load testing from a laboratory developed test to the cobas® CMV quantitative nucleic acid assay.

PubMed

Payne, Michael; Merrick, Linda; Lawson, Tanya; Ritchie, Gordon; Lowe, Christopher

2018-04-16

Commutability between human cytomegalovirus (CMV) viral load assays (VLA) is poor, despite the development of a WHO CMV International Standard (CMV IS). We evaluated a new CMV VLA, cobas ® CMV, as compared to our current laboratory developed CMV VLA (LDT), for clinical use. Both the LDT and cobas ® CMV were run in parallel for 109 patient samples. In addition, 104 replicates, over 8 dilutions, of the CMV IS were tested. Conversion factors and correlation between the two assays were calculated. The correlation coefficient between the LDT and cobas ® CMV was 0.91 for patient samples. The Bland-Altman graph displayed a systematic bias of +0.31 log 10 for the cobas ® CMV as compared to the LDT. The bias was greater for lower CMV viral loads. This increase in CMV viral loads was not seen with testing of the CMV IS dilutions by both the LDT and cobas ® CMV. CMV VLA inter-assay commutability continues to be an issue when switching CMV testing platforms and requires communication between the laboratory and clinicians during the transition period to prevent misinterpretation of results. © 2018 Wiley Periodicals, Inc.

Monitoring of Cytomegalovirus (CMV)-Specific Cell-Mediated Immunity in Heart Transplant Recipients: Clinical Utility of the QuantiFERON-CMV Assay for Management of Posttransplant CMV Infection.

PubMed

Chiereghin, Angela; Potena, Luciano; Borgese, Laura; Gibertoni, Dino; Squarzoni, Diego; Turello, Gabriele; Petrisli, Evangelia; Piccirilli, Giulia; Gabrielli, Liliana; Grigioni, Francesco; Lazzarotto, Tiziana

2018-04-01

The clinical utility of the QuantiFERON-CMV (QFN-CMV) assay in heart transplant recipients was assessed. Forty-four cytomegalovirus (CMV)-seropositive patients were enrolled: 17 received antiviral prophylaxis, and 27 were managed preemptively. CMV-DNAemia monitoring was performed by the use of a quantitative real-time PCR assay. The QFN-CMV assay was retrospectively performed on blood samples collected at five posttransplant time points. A higher proportion of patients with an indeterminate QFN-CMV result after the suspension of prophylaxis than of patients who showed a global T-cell responsiveness developed CMV infection ( P = 0.036). Patients who reconstituted a CMV-specific response following the first CMV-DNAemia-positive result (42.9%) showed a median CMV-DNAemia peak 1 log of magnitude lower than that seen with patients with indeterminate results, and all controlled viral replication spontaneously. The 25% of patients with an indeterminate result developed CMV disease. In the preemptive strategy group, no differences in the development of subsequent infection, magnitude of viral load, and viral control were observed on the basis of QFN-CMV measurements performed before and after the first CMV-DNAemia-positive result. Considering both CMV prevention strategies, viral relapse was associated with the failure to reconstitute CMV-specific cell-mediated immunity (CMI) after the resolution of the first episode of CMV infection ( P = 0.032). QFN-CMV measurements can be a useful tool for identifying patients (i) at higher risk of developing infection after discontinuing antiviral prophylaxis, (ii) with late CMV infection who would benefit from appropriate antiviral interventions, and (iii) at higher risk of viral relapses. QFN-CMV measurements taken within 1 month posttransplantation (early period) are not revealing. Copyright © 2018 American Society for Microbiology.

Latent cytomegalovirus infection and innate immune function following a 75 km cycling time trial.

PubMed

LaVoy, Emily C P; Nieman, David C; Henson, Dru A; Shanely, R Andrew; Knab, Amy M; Cialdella-Kam, Lynn; Simpson, Richard J

2013-10-01

This study compared the acute immune response, inflammation, and lipid peroxidation to a 75 km cycling time trial in male athletes testing positive or negative for latent cytomegalovirus (CMV) infection. Trained cyclists (N = 20) were tested for CMV serostatus, and cycled 75 km on a mountainous course using indoor trainers with continuous workload monitoring. Pre-, post-, and 1 h post-exercise blood samples were analyzed for total blood leukocyte counts, blood granulocyte (GR) and monocyte (MO) phagocytosis (PHAG) and oxidative burst activity (OBA), four plasma cytokines, and plasma F2-isoprostanes. Forty percent of the subjects tested positive for CMV. No differences in subject characteristics were found between CMVpos and CMVneg groups. Mean power (57.3 ± 1.6, 59.4 ± 1.8 % maximal Watts, p = 0.803), heart rate (87.0 ± 1.0, 86.5 ± 1.3 % maximal heart rate, p = 0.376), and total time (2.56 ± 0.08, 2.60 ± 0.08 h, p = 0.744) to complete the 75 km cycling time trial did not differ between CMVpos and CMVneg groups. Whereas exercise induced significant changes in total blood leukocyte counts, GR and MO-PHAG, four plasma cytokines, and plasma F2-isoprostanes (p < 0.05, ω(2) > 0.03), these exercise-induced changes did not differ between CMVpos and CMVneg groups (p > 0.05, ω(2) < 0.01). CMV serostatus does not appear to influence these innate immune responses or markers of inflammation and lipid peroxidation in response to a single bout of heavy exertion.

Breast Milk-Acquired Cytomegalovirus Infection and Disease in Very Low Birth Weight and Premature Infants

PubMed Central

Lanzieri, Tatiana M.; Dollard, Sheila C.; Josephson, Cassandra D.; Schmid, D. Scott; Bialek, Stephanie R.

2016-01-01

Introduction Very low birth weight (VLBW) and premature infants are at risk of developing postnatal cytomegalovirus (CMV) disease, including CMV-related sepsis-like syndrome (CMV-SLS). Estimates of breast milk-acquired CMV infection and disease among these infants in the United States are lacking. Methods We performed a systematic review and meta-analysis to estimate the pooled proportions (and 95% confidence intervals) of VLBW and premature infants born to CMV-seropositive women with breast milk-acquired CMV infection and CMV-SLS. We combined these proportions with population-based rates of CMV seropositivity, breast milk feeding, VLBW and prematurity to estimate annual rates of breast milk-acquired CMV infection and CMV-SLS in the United States. Results In our meta-analysis, among 299 infants fed untreated breast milk, we estimated 19% (11%–32%) acquired CMV infection and 4% (2%–7%) developed CMV-SLS. Assuming these proportions, we estimated a rate of breast milk-acquired CMV infection among VLBW and premature infants in the United States of 6.5% (3.7%–10.9%) and 1.4% (0.7%–2.4%) of CMV-SLS, corresponding to 600 infants with CMV-SLS in 2008. Among 212 infants fed frozen breast milk, our meta-analysis proportions were 13% (7%–24%) for infection and 5% (2%–12%) for CMV-SLS, yielding slightly lower rates of breast milk-acquired CMV infection (4.4%; 2.4%–6.8%) but similar rates of CMV-SLS (1.7%; 0.7%–4.1%). Conclusions Breast milk-acquired CMV infection presenting with CMV-SLS is relatively rare. Prospective studies to better define the burden of disease are needed to refine guidelines for feeding breast milk from CMV-seropositive mothers to VLBW and premature infants. PMID:23713111

Priorities for CMV vaccine development

PubMed Central

Krause, Philip R.; Bialek, Stephanie R.; Boppana, Suresh B.; Griffiths, Paul D.; Laughlin, Catherine A.; Ljungman, Per; Mocarski, Edward S.; Pass, Robert F.; Read, Jennifer S.; Schleiss, Mark R.; Plotkin, Stanley A.

2015-01-01

A multidisciplinary meeting addressed priorities related to development of vaccines against cytomegalovirus (CMV), the cause of congenital CMV (cCMV) disease and of serious disease in the immunocompromised. Participants discussed optimal uses of a CMV vaccine, aspects of clinical study design, and the value of additional research. A universal childhood CMV vaccine could potentially rapidly reduce cCMV disease, as infected children are sources of viral transmission to seronegative and seropositive mothers. A vaccine administered to adolescents or adult women could also reduce cCMV disease by making them immune prior to pregnancy. Clinical trials of CMV vaccines in women should evaluate protection against cCMV infection, an essential precursor of cCMV disease, which is a more practical and acceptable endpoint for assessing vaccine effects on maternal-fetal transmission. Clinical trials of vaccines to evaluate prevention of CMV disease in stem cell transplant recipients could use CMV viremia at a level triggering preemptive antiviral therapy as an endpoint, because widespread use of preemptive and prophylactic antivirals has rendered CMV-induced disease too rare to be a practical endpoint for clinical trials. In solid organ transplant patients, CMV-associated disease is sufficiently common for use as a primary endpoint. Additional research to advance CMV vaccine development should include identifying factors that predict fetal loss due to CMV, determining age-specific incidence and transmission rates, defining the mechanism and relative contributions of maternal reactivation and re-infection to cCMV disease, developing assays that can distinguish between reactivation and re-infection in seropositive vaccinees, further defining predictors of sequelae from cCMV infection, and identifying clinically relevant immune response parameters to CMV (including developing validated assays that could assess CMV antibody avidity) that could lead to the establishment of immune correlates of protection. PMID:24129123

Fully automated assay of glycohemoglobin with the Abbott IMx analyzer: novel approaches for separation and detection.

PubMed

Wilson, D H; Bogacz, J P; Forsythe, C M; Turk, P J; Lane, T L; Gates, R C; Brandt, D R

1993-10-01

We describe a novel assay for measuring glycohemoglobin directly from anticoagulated whole blood with the Abbott IMx analyzer. The glycohemoglobin is labeled with a soluble polyanionic affinity reagent and the anionic complex is then captured with a cationic solid-phase matrix. Glycohemoglobin is quantified by measuring the quenching by heme of the static fluorescence from an added fluorophore. The assay is standardized to report both percent total glycohemoglobin (%GHb) and percent hemoglobin A1c (%HbA1c). Glucose, bilirubin, triglycerides, labile fraction, and hemoglobin variants do not interfere in the assay. Within- and between-run CVs are approximately 4-5%, with total CVs of approximately 6.5%. Highly significant linear correlations (r > 0.97) were obtained in comparison studies with two major assay methodologies. The time to obtain one result is approximately 10 min (including assay of a control), 56 min for 22 results. We describe the development, standardization, and validation of this new method.

Immune Monitoring for CMV in Transplantation.

PubMed

Yong, Michelle K; Lewin, Sharon R; Manuel, Oriol

2018-03-14

Immune monitoring to determine when and how the recovery of cytomegalovirus (CMV)-specific T-cells occurs post-transplantation may help clinicians to risk stratify individuals at risk of complications from CMV. We aimed to review all recent clinical studies using CMV immune monitoring in the pre- and post-transplant setting including the use of recently developed standardized assays (Quantiferon-CMV and the CMV ELISPOT) to better understand in whom, when, and how immune monitoring is best used. Pre-transplant assessment of CMV immunity in solid-organ transplant recipients where CMV seropositive recipients had undetectable cell-mediated responses despite past immunity has shown that they are at a much higher risk of developing CMV reactivation. Post-transplant CMV immune monitoring can guide (shorten or prolong) the duration of antiviral prophylaxis, identify recipients at risk of post-prophylaxis CMV disease, and predict recurrent CMV reactivation. Thus, CMV immune monitoring, in addition to current clinical and DNA-based monitoring for CMV, has the potential to be incorporated into routine clinical care to better improve CMV management in both the stem and solid-organ transplant population.

COMPARISON OF VISUAL PROGNOSIS AND CLINICAL FEATURES OF CYTOMEGALOVIRUS RETINITIS IN HIV AND NON-HIV PATIENTS.

PubMed

Kim, Dong Yoon; Jo, Jaehyuck; Joe, Soo Geun; Kim, June-Gone; Yoon, Young Hee; Lee, Joo Yong

2017-02-01

To compare the visual prognosis and clinical features of cytomegalovirus (CMV) retinitis between HIV and non-HIV patients. Retrospective cross-sectional study on patients diagnosed with CMV retinitis. Depending on the presence of HIV infection, best-corrected visual acuity (VA) and clinical feature of CMV retinitis were analyzed. The clinical characteristics associated with poor visual prognosis after antiviral treatment were also identified. A total of 78 eyes (58 patients) with CMV retinitis were included in this study: 21 eyes and 57 eyes in HIV and non-HIV patients, respectively. Best-corrected VA was not significantly different between HIV and non-HIV patients. The rate of foveal involvement, retinal detachment, involved zone, and mortality did not significantly differ between the two groups. Visual acuity after antiviral treatment was significantly worse (pretreatment logarithm of the minimal angle of resolution best-corrected VA, 0.54 ± 0.67 [Snellen VA, 20/63]; posttreatment logarithm of the minimal angle of resolution best-corrected VA, 0.77 ± 0.94 [Snellen VA, 20/125]; P = 0.014). Poor visual prognosis was significantly associated with Zone 1 involvement, retinal detachment, and a poor general condition. The overall visual prognosis and the clinical features of CMV retinitis do not differ between HIV and non-HIV patients. The visual prognosis of CMV retinitis still remains quite poor despite advancements in antiviral treatment. This poor prognosis after antiviral treatment is associated with retinal detachment during follow-up, Zone 1 involvement, and the poor general condition of the patient.

Clinical and laboratory differences between Epstein-Barr and cytomegalovirus infectious mononucleosis in children.

PubMed

Medović, Rasa; Igrutinović, Zoran; Radojević-Marjanović, Ruzica; Marković, Slavica; Rasković, Zorica; Simović, Aleksandra; Tanasković-Nestorović, Jelena; Radovanović, Marija; VuIetić, Blijana

2016-01-01

Infective mononucleosis is most commonly caused by Epstein-Barr virus (EBV), and in smaller percentage by cytomegalovirus (CMV). The aim of this paper was to determine the clinical and laboratory differences between EBV and CMV infectious mononucleosis in children. Cohort retrospective analytical research was conducted. We used data from medical history in six years period and monitored anamnestic data, frequency of inspection and palpation obtained data during physical examination, several laboratory tests, abdomen ultrasonography examination finding and emergence of disease complications. Statistical processing of data has been performed using SPSS 20. Total number of examined children was 137, out of which 85.4% were with EBV and 14.6% with CMV infection. Affected children were most commonly younger than eight years. Boys were affected more often. There was no difference in frequency of high temperature, sore throat, bad breath, and respiratory symptomatology between examined children. Differences were discovered in frequency of stomachaches, eyelid swelling, skin rash and fatigue. Differences were not proven in the frequency of angina, lymphadenopathy and splenohepatomegaly between the groups. Values of transaminases and lactic dehydrogenases significantly decreased after seven days of hospitalization in both groups. In children with EBV, values of transaminases declined faster than in children with CMV. Anemia and bacterial superinfection of pharynx were most common disease complications. Thrombocytopenia was more common in children with CMV infection. Average duration of hospitalization was 6.7 days. In children with CMV abdominal pain, eyelid swelling, skin rash, fatigue and thrombocytopenia were more common. In children with EBV values of transaminases declined significantly faster.

Evaluation of serial urine viral cultures for the diagnosis of cytomegalovirus infection in neonates and infants.

PubMed

Chisholm, Karen M; Aziz, Natali; McDowell, Michal; Guo, Frances P; Srinivas, Nivedita; Benitz, William E; Norton, Mary E; Gutierrez, Kathleen; Folkins, Ann K; Pinsky, Benjamin A

2014-01-01

Cytomegalovirus (CMV) is the most common cause of congenital infection worldwide. Urine viral culture is the standard for CMV diagnosis in neonates and infants. The objectives of this study were to compare the performance of serial paired rapid shell vial cultures (SVC) and routine viral cultures (RVC), and to determine the optimal number of cultures needed to detect positive cases. From 2001 to 2011, all paired CMV SVC and RVC performed on neonates and infants less than 100 days of age were recorded. Testing episodes were defined as sets of cultures performed within 7 days of one another. A total of 1264 neonates and infants underwent 1478 testing episodes; 68 (5.4%) had at least one episode with a positive CMV culture. In episodes where CMV was detected before day 21 of life, the first specimen was positive in 100% (16/16) of cases. When testing occurred after 21 days of life, the first specimen was positive in 82.7% (43/52) of cases, requiring three cultures to reach 100% detection. The SVC was more prone to assay failure than RVC. Overall, when RVC was compared to SVC, there was 86.0% positive agreement and 99.9% negative agreement. In conclusion, three serial urine samples are necessary for detection of CMV in specimens collected between day of life 22 and 99, while one sample may be sufficient on or before day of life 21. Though SVC was more sensitive than RVC, the risk of SVC failure supports the use of multimodality testing to optimize detection.

Cytomegalovirus retinitis associated with acquired immunodeficiency syndrome.

PubMed

Geng, Shuang; Ye, Jun-jie; Zhao, Jia-liang; Li, Tai-sheng; Han, Yang

2011-04-01

Cytomegalovirus (CMV) retinitis is the most severe intraocular complication that results in total retinal destruction and loss of visual acuity in patients with acquired immunodeficiency syndrome (AIDS). This study aimed to investigate the fundus characteristics, systemic manifestations and therapeutic outcomes of CMV retinitis associated with AIDS. It was a retrospective case series. CMV retinitis was present in 39 eyes (25 patients). Best corrected visual acuities, anterior segment, fundus features, fundus fluorescence angiography (FFA) and CD4(+) T-lymphocyte counts of the patients with CMV retinitis associated with AIDS were analyzed. Intravitreal injections of ganciclovir (400 µg) were performed in 4 eyes (2 patients). Retinal vasculitis, dense, full-thickness, yellow-white lesions along vascular distribution with irregular granules at the border, and hemorrhage on the retinal surface were present in 28 eyes. The vitreous was clear or mildly opaque. Late stage of the retinopathy was demonstrated in 8 eyes characterized as atrophic retina, sclerotic and attenuated vessels, retinal pigment epithelium (RPE) atrophy, and optic nerve atrophy. Retinal detachment was found in 3 eyes. The average CD4(+) T-lymphocyte count in peripheral blood of the patients with CMV retinitis was (30.6 ± 25.3) × 10(6)/L (range, (0 - 85) × 10(6)/L). After intravitreal injections of ganciclovir, visual acuity was improved and fundus lesions regressed. CMV retinitis is the most severe and the most common intraocular complication in patients with AIDS. For the patients with yellow-white retinal lesions, hemorrhage and retinal vasculitis without clear cause, human immunodeficiency virus (HIV) serology should be performed. Routine eye examination is also indicated in HIV positive patients.

Product development: the making of the Abbott ARCHITECT.

PubMed

Kisner, H J

1997-01-01

Many laboratorians have a limited perspective on what is involved in developing an instrument and bringing it to market. This article traces the product development process used by Abbott Diagnostics Division that resulted in Abbott being named the 1996 Concurrent Engineering Company of the Year for the design of the ARCHITECT.

78 FR 23220 - Foreign-Trade Zone 22-Chicago, Illinois, Authorization of Production Activity, Abbott...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-18

... DEPARTMENT OF COMMERCE Foreign-Trade Zones Board [B-91-2012] Foreign-Trade Zone 22--Chicago, Illinois, Authorization of Production Activity, Abbott Laboratories, Inc., AbbVie, Inc. (Pharmaceutical Production), North Chicago, Illinois, Area On December 14, 2012, Abbott Laboratories, Inc., and AbbVie, Inc...

The outcome of HIV-positive late presenters according to detectable CMV DNA and anti-CMV treatment.

PubMed

Bigliano, Paolo; Calcagno, Andrea; Lucchini, Anna; Audagnotto, Sabrina; Montrucchio, Chiara; Marinaro, Letizia; Alcantarini, Chiara; Ghisetti, Valeria; Di Perri, Giovanni; Bonora, Stefano

2018-01-26

HIV late presenters are at high risk of cytomegalovirus (CMV) reactivation and end-organ disease. CMV viraemia has been associated with poor survival but the effect of anti-CMV treatment has not been studied in this setting. HIV-positive patients were included in a retrospective study if presenting with <350 CD4 + T-cells/μl and starting an antiretroviral treatment within 3 months of the diagnosis. Primary end point was 5-year survival according to the presence of CMV viraemia, CMV end-organ disease and anti-CMV treatment. 302 patients were included. 157 patients (52%) presented CMV viraemia (CMV-V) and 44 (14.6%) CMV end-organ disease (CMV-EOD). 5-year mortality was higher in CMV-EOD and CMV-V patients than in CMV-negative patients (11.4 versus 9.6 versus 0%; P=0.002). In patients with CMV-V, 5-year mortality was numerically higher in untreated patients (12.9% versus 6.9%; P=0.257) without reaching statistical significance. At univariate analysis the diagnosis of serious opportunistic infections (cryptococcosis, progressive multifocal leukoencephalopathy, lymphoma; P=0.001) and the absence of a negative CMV DNA in the follow-up (P<0.001) were associated with poor outcome. At multivariate analysis HCV coinfection (P=0.016; aOR 6.98, 95% CI 1.50, 32.59), the absence of a negative CMV DNA in the follow-up (P<0.001; aOR 19.40, 95% CI 3.70, 101.64) and marginally the absence of anti-CMV treatment (P=0.052; aOR 4.944, 95% CI 0.99, 24.73) were independent predictors of poor outcome. CMV reactivation in HIV-positive patients with poor immunity is associated with worse prognosis: the pre-emptive use of anti-CMV therapy was associated with a better outcome in patients with CMV-V.

Genomic Sequencing and Characterization of Cynomolgus Macaque Cytomegalovirus▿

PubMed Central

Marsh, Angie K.; Willer, David O.; Ambagala, Aruna P. N.; Dzamba, Misko; Chan, Jacqueline K.; Pilon, Richard; Fournier, Jocelyn; Sandstrom, Paul; Brudno, Michael; MacDonald, Kelly S.

2011-01-01

Cytomegalovirus (CMV) infection is the most common opportunistic infection in immunosuppressed individuals, such as transplant recipients or people living with HIV/AIDS, and congenital CMV is the leading viral cause of developmental disabilities in infants. Due to the highly species-specific nature of CMV, animal models that closely recapitulate human CMV (HCMV) are of growing importance for vaccine development. Here we present the genomic sequence of a novel nonhuman primate CMV from cynomolgus macaques (Macaca fascicularis; CyCMV). CyCMV (Ottawa strain) was isolated from the urine of a healthy, captive-bred, 4-year-old cynomolgus macaque of Philippine origin, and the viral genome was sequenced using next-generation Illumina sequencing to an average of 516-fold coverage. The CyCMV genome is 218,041 bp in length, with 49.5% G+C content and 84% protein-coding density. We have identified 262 putative open reading frames (ORFs) with an average coding length of 789 bp. The genomic organization of CyCMV is largely colinear with that of rhesus macaque CMV (RhCMV). Of the 262 CyCMV ORFs, 137 are homologous to HCMV genes, 243 are homologous to RhCMV 68.1, and 200 are homologous to RhCMV 180.92. CyCMV encodes four ORFs that are not present in RhCMV strain 68.1 or 180.92 but have homologies with HCMV (UL30, UL74A, UL126, and UL146). Similar to HCMV, CyCMV does not produce the RhCMV-specific viral homologue of cyclooxygenase-2. This newly characterized CMV may provide a novel model in which to study CMV biology and HCMV vaccine development. PMID:21994460

Breast milk-acquired cytomegalovirus infection and disease in VLBW and premature infants.

PubMed

Lanzieri, Tatiana M; Dollard, Sheila C; Josephson, Cassandra D; Schmid, D Scott; Bialek, Stephanie R

2013-06-01

Very low birth weight (VLBW) and premature infants are at risk for developing postnatal cytomegalovirus (CMV) disease, including CMV-related sepsis-like syndrome (CMV-SLS) for which estimates [corrected] in the United States are lacking. We performed a systematic review and meta-analysis to estimate the pooled proportions (and 95% confidence intervals) of VLBW and premature infants born to CMV-seropositive women with breast milk-acquired CMV infection and CMV-SLS. We combined these proportions with population-based rates of CMV seropositivity, breast milk feeding, VLBW, and prematurity to estimate annual rates of breast milk-acquired CMV infection and CMV-SLS in the United States. In our meta-analysis, among 299 infants fed untreated breast milk, we estimated 19% (11%-32%) acquired CMV infection and 4% (2%-7%) developed CMV-SLS. Assuming these proportions, we estimated a rate of breast milk-acquired CMV infection among VLBW and premature infants in the United States of 6.5% (3.7%-10.9%) and 1.4% (0.7%-2.4%) of CMV-SLS, corresponding to 600 infants with CMV-SLS in 2008. Among 212 infants fed frozen breast milk, our meta-analysis proportions were 13% (7%-24%) for infection and 5% (2%-12%) for CMV-SLS, yielding slightly lower rates of breast milk-acquired CMV infection (4.4%; 2.4%-8.2%) but similar rates of CMV-SLS (1.7%; 0.7%-4.1%). Breast milk-acquired CMV infection presenting with CMV-SLS is relatively rare. Prospective studies to better define the burden of disease are needed to refine guidelines for feeding breast milk from CMV-seropositive mothers to VLBW and premature infants.

Compartmentalized Cytomegalovirus Replication and Transmission in the Setting of Maternal HIV-1 Infection

PubMed Central

Slyker, Jennifer; Farquhar, Carey; Atkinson, Claire; Ásbjörnsdóttir, Kristjana; Roxby, Alison; Drake, Alison; Kiarie, James; Wald, Anna; Boeckh, Michael; Richardson, Barbra; Odem-Davis, Katherine; John-Stewart, Grace; Emery, Vincent

2014-01-01

Background. Cytomegalovirus (CMV) infection is associated with adverse outcomes in human immunodeficiency virus (HIV)–exposed infants. Determinants of vertical CMV transmission in the setting of maternal HIV-1 infection are not well-defined. Methods. CMV and HIV-1 levels were measured in plasma, cervical secretions, and breast milk of 147 HIV-1–infected women to define correlates of maternal CMV replication and infant CMV acquisition. Results. Although few women had detectable CMV in plasma (4.8%), the majority had detectable CMV DNA in cervical secretions (66%) and breast milk (99%). There was a strong association between cervical CMV detection during pregnancy and later breast milk levels (β = 0.47; P = .005). Plasma HIV-1 level and CD4 counts were associated with CMV in the cervix and breast milk. However HIV-1 levels within the cervix and breast milk were not associated with CMV within these compartments. Maternal breast milk CMV levels (hazard ratio [HR], 1.4; P = .003) and maternal CD4 < 450 cells/mm3 (HR, 1.8; P = .008) were independently associated with infant CMV acquisition; each log10 increase in breast milk CMV was associated with a 40% increase in infant infection. The breast milk CMV level required to attain a 50% probability of CMV transmission increased with higher maternal CD4 counts, increasing from 3.55 log10 CMV DNA copies/mL at a CD4 count of 350 cells/mm3 to 5.50 log10 CMV DNA copies/mL at a CD4 count of 1000 cells/mm3. Conclusions. Breast milk CMV levels and maternal CD4 count are major determinants of CMV transmission in the setting of maternal HIV-1. Maternal immune reconstitution or lowering breast milk CMV levels may reduce vertical CMV transmission. PMID:24192386

Insertion and deletion mutagenesis of the human cytomegalovirus genome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spaete, R.R.; Mocarski, E.S.

1987-10-01

Studies on human cytomegalovirus (CMV) have been limited by a paucity of molecular genetic techniques available for manipulating the viral genome. The authors have developed methods for site-specific insertion and deletion mutagenesis of CMV utilizing a modified Escherichia coli lacZ gene as a genetic marker. The lacZ gene was placed under the control of the major ..beta.. gene regulatory signals and inserted into the viral genome by homologous recombination, disrupting one of two copies of this ..beta.. gene within the L-component repeats of CMV DNA. They observed high-level expression of ..beta..-galactosidase by the recombinant in a temporally authentic manner, withmore » levels of this enzyme approaching 1% of total protein in infected cells. Thus, CMV is an efficient vector for high-level expression of foreign gene products in human cells. Using back selection of lacZ-deficient virus in the presence of the chromogenic substrate 5-bromo-4-chloro-3-indolyl ..beta..-D-galactoside, they generated random endpoint deletion mutants. Analysis of these mutant revealed that CMV DNA sequences flanking the insert had been removed, thereby establishing this approach as a means of determining whether sequences flanking a lacZ insertion are dispensable for viral growth. In an initial test of the methods, they have shown that 7800 base pairs of one copy of L-component repeat sequences can be deleted without affecting viral growth in human fibroblasts.« less

Treatment of cytomegalovirus infection and disease pre- and post-quantitative nucleic acid test standardization: does use of a more sensitive assay lead to longer treatment duration?

PubMed

Dioverti, M Veronica; Lahr, Brian; Razonable, Raymund R

2016-02-01

Quantitative cytomegalovirus (CMV) nucleic acid testing (NAT) has been standardized using the World Health Organization (WHO) international calibration standard. A new FDA-approved WHO-calibrated assay (CA) was found to be more sensitive than a laboratory-developed test (LDT). We hypothesized that monitoring therapeutic response using a more sensitive assay may lead to longer antiviral therapy in solid organ and hematopoietic stem cell transplant patients with CMV infection. We reviewed transplant patients with CMV disease retrospectively, and divided them into two groups: those diagnosed and managed based on LDT and those managed using WHO-CA. Compared to patients monitored by LDT, the time to reach an undetectable viral load was significantly longer in the group monitored by the WHO-CA. However, a trend toward shorter duration of antiviral treatment was observed (median, 34 vs. 41 d; p = 0.058), with earlier discontinuation of induction antiviral therapy upon reaching undetectable viral load using WHO-CA (11 vs. 18 d; p = 002). We concluded that despite using a more sensitive CMV NAT, the total duration of antiviral treatment was not significantly prolonged in transplant patients with CMV infection and disease. Relapse rates did not differ between the two groups. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Comparison of treatment regimens for cytomegalovirus retinitis in patients with AIDS in the era of highly active antiretroviral therapy.

PubMed

Jabs, Douglas A; Ahuja, Alka; Van Natta, Mark; Dunn, J P; Yeh, Steven

2013-06-01

To describe the outcomes of different treatment approaches for cytomegalovirus (CMV) retinitis in the era of highly active antiretroviral therapy (HAART). Prospective cohort study, the Longitudinal Study of the Ocular Complications of AIDS. A total of 250 patients with CMV retinitis and a CD4+ T-cell count <100 cells/μl (n = 221) at enrollment or incident retinitis (n = 29) during cohort follow-up. The effects of systemic therapy (vs. intraocular therapy only) on systemic outcomes and the effect of intraocular therapies (ganciclovir implants, intravitreal injections) on ocular outcomes were evaluated. Mortality, CMV dissemination, retinitis progression, and treatment side effects. Regimens containing systemic anti-CMV therapy were associated with a 50% reduction in mortality (adjusted hazard ratio [HR], 0.5; 95% confidence interval [CI], 0.3-0.7; P = 0.006), a 90% reduction in new visceral CMV disease (adjusted HR, 0.1; 95% CI, 0.04-0.4; P = 0.004), and among those with unilateral CMV retinitis at presentation, an 80% reduction in second eye disease (adjusted HR, 0.2; 95% CI, 0.1-0.5; P = 0.0005) when compared with those using only intraocular therapy (implants or injections). Compared with systemic treatment only, regimens containing intravitreal injections had greater rates of retinitis progression (adjusted HR, 3.4; P = 0.004) and greater visual field loss (for loss of one half of the normal field, adjusted HR, 5.5; P < 0.01). Intravitreal implants were not significantly better than systemic therapy (adjusted HR for progression, 0.5; P = 0.26; adjusted HR for loss of one half of the visual field, 0.5; P = 0.45), but the sample size was small. Hematologic and renal side effect rates were similar between those groups with and without systemic anti-CMV therapy. The rate of endophthalmitis was 0.017 per eye-year (EY) (95% CI, 0.006-0.05) among those treated with intravitreal injections and 0.01 per EY (95% CI, 0.002-0.04) among those treated with an implant. In the HAART era, systemic anti-CMV therapy, while there is immune compromise, seems to provide benefits in terms of longer survival and decreased CMV dissemination. Proprietary or commercial disclosure may be found after the references. Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

CMV blood test

MedlinePlus

CMV antibody tests ... never been infected with CMV have no detectable antibodies to CMV. Normal value ranges may vary slightly ... The presence of antibodies to CMV indicates a current or past ... CMV. If the number of antibodies (called the antibody titer) ...

75 FR 340 - Approval for Expansion of Subzone 22F, Abbott Molecular, Inc. (Pharmaceutical and Molecular...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-05

... DEPARTMENT OF COMMERCE Foreign-Trade Zones Board [Order No. 1654] Approval for Expansion of Subzone 22F, Abbott Molecular, Inc. (Pharmaceutical and Molecular Diagnostic Products), Chicago, IL, Area... manufacturing authority on behalf of Abbott Molecular, Inc., within FTZ 22F in Des Plaines and Elk Grove Village...

Abbott Students Attending Charter Schools: Funding Disparities and Legal Implications

ERIC Educational Resources Information Center

Bulkley, Katrina

2007-01-01

Most of New Jersey's charter schools are located in the state's poorer, urban school districts, or "Abbott" districts, and exclusively serve students from those communities. A number of other schools are located outside of the Abbott districts but enroll students from these districts. Specifically, of the 50 charter schools operating in…

Harmonization of the Bayer ADVIA Centaur and Abbott AxSYM automated B-type natriuretic peptide assay in patients on hemodialysis.

PubMed

Barak, Mira; Weinberger, Ronit; Marcusohn, Jerom; Froom, Paul

2005-01-01

There are two fully automated high-throughput clinical instruments for brain natriuretic peptide (BNP) assays, the Bayer ADVIA Centaur assay, and the Abbott AxSYM assay. Although both recommend a cut-off value of 100 pg/mL, we are unaware of previous studies that have compared the unadjusted results of the two methods, required for proper evaluation of patients undergoing this test on different platforms. From 43 hemodialysis patients, 80 paired samples were collected by venipuncture into plastic evacuated tubes containing EDTA. The Bayer assay yielded lower values than the Abbott assay, with linear regression of 0.53 x Abbott assay (95% confidence interval, 0.50-0.56) being forced through 0, demonstrating an r(2)-value of 0.954. Regression for the Abbott assay was 1.79 x Bayer assay (95% CI, 1.69-1.89). The cut-off values for abnormal BNP results analyzed on the Abbott system are not identical to those on the Bayer system, and this needs to be taken into account when comparing studies on the clinical utility of these systems.

ABT-773 (Abbott Laboratories).

PubMed

Lawrence, L E

2001-06-01

ABT-773 is a macrolide antibacterial agent under development by Abbott Laboratories and Taisho Pharmaceutical Co Ltd for the potential treatment of bacterial infection [266579]. As of February 2001, ABT-773 had entered phase III trials in the US [398274]. Japanese phase II trials were expected to commence in June 2000 and a phase II trial is being designed for respiratory infections, with Abbott expecting filing in March 2002 [360455]. The bioavailability of ABT-773 in humans is unaffected by food [383228] and in a phase I, randomized, double-blind trial in healthy males only mild adverse effects, usually affecting the gastrointestinal system, were observed [383208]. Under an agreement, Abbott and Taisho are conducting joint research to discover new compounds; Abbott will have worldwide marketing, manufacturing and supply rights (except in Japan), and Taisho will receive royalties on Abbott's sales in consideration of granted rights. In Japan, the companies will co-market any resulting compounds [266579]. ABT-773 demonstrated good activity in vitro and in vivo against Streptococcus pneumoniae and Staphylococcus aureus [383229], [383231], and was highly potent even against macrolide-resistant [382149], [382150] and invasive [383782] S pneumoniae.

Impact of inter-genotypic recombination and probe cross-reactivity on the performance of the Abbott RealTime HCV Genotype II assay for hepatitis C genotyping.

PubMed

Sridhar, Siddharth; Yip, Cyril C Y; Chan, Jasper F W; To, Kelvin K W; Cheng, Vincent C C; Yuen, Kwok-Yung

2018-05-01

The Abbott RealTime HCV Genotype II assay (Abbott-RT-HCV assay) is a real-time PCR based genotyping method for hepatitis C virus (HCV). This study measured the impact of inter-genotypic recombination and probe cross-reactivity on the performance of the Abbott-RT-HCV assay. 517 samples were genotyped using the Abbott-RT-HCV assay over a one-year period, 34 (6.6%) were identified as HCV genotype 1 without further subtype designation raising the possibility of inaccurate genotyping. These samples were subjected to confirmatory sequencing. 27 of these 34 (79%) samples were genotype 1b while five (15%) were genotype 6. One HCV isolate was an inter-genotypic 1a/4o recombinant. This is a novel natural HCV recombinant that has never been reported. Inter-genotypic recombination and probe cross-reactivity can affect the accuracy of the Abbott-RT-HCV assay, both of which have significant implications on antiviral regimen choice. Confirmatory sequencing of ambiguous results is crucial for accurate genotyping. Copyright © 2018 Elsevier Inc. All rights reserved.

Assignment of cytomegalovirus infection status in infants awaiting solid organ transplant: Viral detection methods as adjuncts to serology.

PubMed

Burton, Catherine E; Dragan, Tatiana; Mabilangan, Curtis A; O'Brien, Sheila F; Fearon, Margaret; Scalia, Vito; Preiksaitis, Jutta K

2018-05-24

Assignment of CMV infection status in infants awaiting SOT is challenging as passive maternal antibody can lead to false-positive serology. Since 2000, our protocol has recommended sending throat and urine samples for CMV viral detection, culture, or NAAT, for CMV-seropositive infants <18 months awaiting SOT. We reviewed pretransplant CMV serology for 152 infants and, for CMV seropositives, examined relationships between CMV IgG OD values, age, and CMV viral detection to explore time to clearance of maternal CMV IgG and evaluate viral detection in assignment of pretransplant CMV infection status. The proportion of CMV-seropositive infants decreased from 52% in infants 0-6 months of age to 28% in those 12-18 months. Among CMV-seropositive infants, median OD was significantly higher in the 6- to 12- and 12- to 18-month groups compared to the 0- to 6-month group. Distribution of OD by age group suggested that maternal antibody cleared before 12 months. Of 59 eligible CMV-seropositive infants, 49 (83%) had CMV viral detection studies and 18 of 49 (36.7%) had detectable CMV: 9 of 30 (30.0%) infants 0-6 months, 7 of 15 (46.7%) infants 6-12 months, and 2 of 4 (50.0%) infants 12-18 months. CMV viral detection studies are useful to confirm positive CMV infection status in CMV-seropositive infants awaiting SOT. Maternal CMV IgG likely clears before 12 months. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Early viral-specific T-cell testing predicts late Cytomegalovirus reactivation following Liver Transplantation.

PubMed

Sood, S; Haifer, C; Yu, L; Pavlovic, J; Gow, P J; Jones, R M; Visvanathan, K; Angus, P W; Testro, A G

2018-05-29

Although antiviral prophylaxis is effective in preventing early cytomegalovirus (CMV) reactivation following liver transplantation (OLT), it predisposes patients to late CMV after prophylaxis has ceased. QuantiFERON-CMV (QFN-CMV, Qiagen, The Netherlands) measures an individual's viral-specific immune response. Fifty-nine OLT recipients were prospectively monitored post-OLT in an observational cohort study. QFN-CMV was performed at regular time-points. An absolute QFN-CMV <0.1IU/mL was considered non-reactive. 50/59 (84.7%) had a reactive QFN-CMV by M6. 38/59 (64.4%) had antiviral prophylaxis or treatment before M6, with 31/38 (81.6%) developing a reactive QFN-CMV by 6 months. Over 90% already had a reactive result as early as 3 months post-transplant. 3 patients (5.08%) developed late CMV between 6-12 months (median 251 days) - all had a non-reactive M6 QFN-CMV. 2/3 experienced CMV disease. Non-reactive M6 QFN-CMV was significantly associated with late CMV (OR=54.4, PPV=0.33, NPV=1.00, p=0.003). Although only 5% of recipients developed late CMV, 2/3 suffered CMV disease. M6 QFN-CMV has an excellent NPV for late CMV, suggesting patients who exhibit a robust ex-vivo immune response at M6 can safely cease CMV monitoring. Furthermore, >90% already express viral-specific immunity as early as 3 months. Conceivably, antiviral prophylaxis could be discontinued early in these patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Risk factors for cytomegalovirus retinitis in patients with cytomegalovirus viremia after hematopoietic stem cell transplantation.

PubMed

Jeon, Sohee; Lee, Won Ki; Lee, Yongeun; Lee, Dong Gun; Lee, Jong Wook

2012-09-01

To evaluate the risk factors for cytomegalovirus (CMV) retinitis in patients with CMV viremia after hematopoietic stem cell transplantation (HSCT). Retrospective cohort study. We included all patients with CMV viremia detected by polymerase chain reaction after HSCT between April 2009 and August 2011. Risk factors for CMV retinitis were evaluated in the cohort of 270 patients with CMV viremia, who survived ≥ 12 weeks after HSCT and were screened for CMV retinitis. Retrospective review of clinical records and laboratory results. Survival analysis of patients in the cohort and frequency of CMV retinitis in relation to various factors. Variables analyzed were demographics, human leukocyte antigen (HLA) matched versus mismatched, related versus unrelated donor, preconditioning regimens, delayed engraftment of lymphocyte, presence of acute or chronic graft-versus-host disease, highest CMV DNA level in blood (copies/ml), cumulative period of CMV viremia (weeks), and CMV infection verified by culture or immunohistology in bronchoalveolar lavage or visceral biopsy specimens. Of the 708 patients who underwent HSCT during the study period, 363 (51%) developed CMV viremia after HSCT. Of the 363 patients with CMV viremia, 270 underwent retinal examination for CMV retinitis. We detected CMV retinitis in 15 of 270 patients with CMV viremia. In the univariate analysis, HLA-mismatched HSCT, HSCT from an unrelated donor, engraftment day, peak CMV DNA level, and duration of viremia were associated with the development of CMV retinitis. In the adjusted multivariate analysis, only peak CMV DNA blood levels predicted the development of CMV retinitis (hazard ratio, 25.0; 95% confidence interval, 3.0-210.8). An additional validity analysis by receiver operating characteristic area under curve suggested that a cutoff of 7.64 × 10(4) copies/mL best predicted the development of CMV retinitis by CMV DNA levels in blood. The development of CMV retinitis should be carefully monitored in patients with a significant viral load, which is represented by a peak CMV DNA level >7.64 × 10(4) copies/ml and a long duration of CMV viremia, especially when patients received HSCT from an unrelated or HLA-mismatched donor and showed delayed lymphocyte engraftment. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Factors associated with the development of cytomegalovirus infection following solid organ transplantation.

PubMed

da Cunha-Bang, Caspar; Sørensen, Søren S; Iversen, Martin; Sengeløv, Henrik; Hillingsø, Jens G; Rasmussen, Allan; Mortensen, Svend A; Fox, Zoe V; Kirkby, Nikolai S; Christiansen, Claus B; Lundgren, Jens D

2011-05-01

Infection with cytomegalovirus (CMV) remains a potentially serious complication in transplant patients. In this study we explored the risk factors for CMV infection in the 12 months following a solid organ transplantation (n = 242) in patients monitored for CMV infection from 2004 to 2007. CMV infection was defined as 2 consecutive quantifiable CMV-polymerase chain reaction (PCR) values or 1 measurement of >3000 copies/ml. Data describing pre- and post-transplantation variables were extracted from electronic health records. Time to CMV infection was investigated using Cox proportional hazards analysis. Overall, 31% (75/242) of solid organ transplant patients developed CMV infection: 4/8 (50.0%) heart, 15/43 (34.9%) liver, 30/89 (33.7%) lung and 26/102 (25.5%) kidney transplant patients. The risk of CMV infection according to donor (D)/recipient (R) CMV serostatus (positive + or negative-) was highest for D+/R-(adjusted hazard ratio 2.6, 95% confidence interval 1.6-4.2) vs D+/R+, and was reduced for D-/R+(adjusted hazard ratio 0.2, 95% confidence interval 0.2-0.8) vs D+/R+. Positive donor CMV-serostatus is a major risk factor for CMV-infection in CMV-na ve recipients, but also in recipients with positive CMV-serostatus. Conversely, if donor is CMV serostatus is negative, the risk of CMV infection is low, irrespective of recipients CMV-serostatus. These findings suggest poorer immune function towards donor-induced strains of CMV versus recipient own latent strains.

Transfusion-transmitted CMV infection - current knowledge and future perspectives.

PubMed

Ziemann, M; Thiele, T

2017-08-01

Transmission of human cytomegalovirus (CMV) via transfusion (TT-CMV) may still occur and remains a challenge in the treatment of immunocompromised CMV-seronegative patients, e.g. after stem cell transplantation, and for low birthweight infants. Measures to reduce the risk of TT-CMV have been evaluated in clinical studies, including leucocyte depletion of cellular blood products and/or the selection of CMV-IgG-negative donations. Studies in large blood donor cohorts indicate that donations from newly CMV-IgG-positive donors should bear the highest risk for transmitting CMV infections because they contain the highest levels of CMV-DNA, and early CMV antibodies cannot neutralise CMV. Based on this knowledge, rational strategies to reduce the residual risk of TT-CMV using leucoreduced blood products could be designed. However, there is a lack of evidence that CMV is still transmitted by transfusion of leucoreduced units. In low birthweight infants, most (if not all) CMV infections are caused by breast milk feeding or congenital transmission rather than by transfusion of leucoreduced blood products. For other patients at risk, no definitive data exist about the relative importance of alternative transmission routes of CMV compared to blood transfusion. As a result, only the conduction of well-designed studies addressing strategies to prevent TT-CMV and the thorough examination of presumed cases of TT-CMV will achieve guidance for the best transfusion regimen in patients at risk. © 2017 British Blood Transfusion Society.

Detection of human cytomegalovirus (CMV) DNA in feces has limited value in predicting CMV enteritis in patients with intestinal graft-versus-host disease after allogeneic stem cell transplantation.

PubMed

Sun, Y-Q; Xu, L-P; Han, T-T; Zhang, X-H; Wang, Y; Han, W; Wang, F-R; Wang, J-Z; Chen, H; Chen, Y-H; Yan, C-H; Chen, Y; Liu, K-Y; Huang, X-J

2015-10-01

Cytomegalovirus (CMV) enteritis after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is difficult to diagnose. We aimed to evaluate the sensitivity and specificity of the detection of CMV DNA in feces for predicting CMV enteritis. HSCT patients with intestinal graft-versus-host disease (GVHD) were enrolled if they met the following criteria: (i) underwent a colonoscopy and (ii) peripheral blood and feces specimens were available for CMV DNA detection within 24 h of colonoscopy. The colonoscopy histology was used as the gold standard for diagnosing CMV enteritis. Fifty-six patients underwent 58 colonoscopy examinations, and 7 were diagnosed as having CMV enteritis. Within 24 h of colonoscopy, 9 patients had detectable CMV in the feces and 19 patients had detectable CMV in the plasma, respectively. In the 7 patients with CMV enteritis, only 2 had detectable CMV in the stool, resulting in a sensitivity of 28.6%. In the 51 patients without CMV enteritis, 44 had no detectable CMV in the stool, with a specificity of 86.3%. We concluded that CMV detection in the feces was not a good predictor of CMV enteritis in patients with intestinal GVHD after allo-HSCT. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cytomegalovirus neutralization by hyperimmune and standard intravenous immunoglobulin preparations.

PubMed

Planitzer, Christina B; Saemann, Marcus D; Gajek, Hartwig; Farcet, Maria R; Kreil, Thomas R

2011-08-15

Cytomegalovirus (CMV) remains one of the most important pathogens after transplantation, potentially leading to CMV disease, allograft dysfunction, acute, and chronic rejection and opportunistic infections. Immunoglobulin G (IgG) preparations with high antibody titers against CMV are a valuable adjunctive prevention and treatment option for clinicians and apart from standard intravenous immunoglobulin (IVIG), CMV hyperimmune preparations are available. The CMV antibody titer of these preparations is typically determined by Enzyme-linked immunosorbent assay (ELISA), also used for the selection of high titer plasma donors for the production of the CMV Hyperimmune product. However, CMV ELISA titers do not necessarily correlate with CMV antibody function which is determined by virus neutralization tests. CMV antibody titers were determined by both ELISA and virus neutralization assay and the IgG subclass distribution was compared between a CMV hyperimmune licensed in Europe and standard IVIG preparations. Although the expected high CMV IgG ELISA antibody titers were confirmed for three lots of a CMV hyperimmune preparation, the functionally more relevant CMV neutralizing antibody titers were significantly higher for 31 lots of standard IVIG preparations. Moreover, considerably lower IgG3 levels were found for the CMV hyperimmune preparation compared with standard IVIG preparations. The higher functional CMV neutralization titers of standard IVIG preparations and the better availability of these preparations, suggest that these products could be a valuable alternative to the CMV hyperimmune preparation.

Comparison of the clinical performances of the AdvanSure HPV Screening Real-Time PCR, the Abbott Real-Time High-Risk HPV Test, and the Hybrid Capture High-Risk HPV DNA Test for Cervical Cancer Screening.

PubMed

Chung, Hae-Sun; Hahm, Chorong; Lee, Miae

2014-09-01

The clinical performance of three human papillomavirus (HPV) DNA commercial assays for cervical cancer screening was evaluated; the AdvanSure HPV Screening Real-Time PCR (AdvanSure PCR; LG Life Sciences) that was developed recently for the detection of both high-risk and low-risk genotypes, the Abbott RealTime High-Risk HPV Test (Abbott PCR; Abbott Molecular) and the Hybrid Capture High-Risk HPV DNA test (HC2; Qiagen). The three different HPV DNA tests were compared using cytology samples obtained from 619 women who underwent routine cervical cancer screening. The gold-standard assay was histopathological confirmation of cervical intraepithelial neoplasia of grade 2 or worse. The clinical sensitivities of the AdvanSure PCR, the Abbott PCR and the HC2 for the detection of cervical intraepithelial neoplasia of grade 2 or worse were 95.5%, 95.5% and 100%, respectively, while the clinical specificities were 61.6%, 86.4% and 83.3%, respectively. There were no significant differences in the clinical sensitivities of the Abbott PCR and the AdvanSure PCR compared to the HC2. The clinical specificities of the Abbott PCR and the AdvanSure PCR for the detection of HPV types 16/18 were 97.8% and 98.5%, respectively. For cervical cancer screening, all three tests showed relatively good clinical sensitivities, but the AdvanSure PCR had lower clinical specificity than the Abbott PCR and the HC2. The AdvanSure PCR and the Abbott PCR assays have the advantage of being automated and the ability to distinguish between HPV types 16/18 and other HPV types. The two real-time PCR assays could be useful tools in HPV testing for cervical cancer screening. Copyright © 2014 Elsevier B.V. All rights reserved.

Immunological Prediction of Cytomegalovirus (CMV) Replication Risk in Solid Organ Transplantation Recipients: Approaches for Regulating the Targeted Anti-CMV Prevention Strategies

PubMed Central

2017-01-01

The current cytomegalovirus (CMV) prevention strategies in solid organ transplantation (SOT) recipients have contributed towards overcoming the detrimental effects caused by CMV lytic infection, and improving the long-term success rate of graft survival. Although the quantification of CMV in peripheral blood is the standard method, and an excellent end-point for diagnosing CMV replication and modulating the anti-CMV prevention strategies in SOT recipients, a novel biomarker mimicking the CMV control mechanism is required. CMV-specific immune monitoring can be employed as a basic tool predicting CMV infection or disease after SOT, since uncontrolled CMV replication mostly originates from the impairment of immune responses against CMV under immunosuppressive conditions in SOT recipients. Several studies conducted during the past few decades have indicated the possibility of measuring the CMV-specific cell-mediated immune response in clinical situations. Among several analytical assays, the most advancing standardized tool is the QuantiFERON®-CMV assay. The T-Track® CMV kit that uses the standardized enzyme-linked immunospot assay is also widely employed. In addition to these assays, immunophenotyping and intracellular cytokine analysis using flow cytometry (with fluorescence-labeled monoclonal antibodies or peptide-major histocompatibility complex multimers) needs to be adequately standardized and validated for potential clinical applications. PMID:29027383

Prevention strategies differentially modulate the impact of cytomegalovirus replication on CD8(+) T-cell differentiation in high-risk solid organ transplant patients.

PubMed

Cantisán, Sara; Páez-Vega, Aurora; Pérez-Romero, Pilar; Montejo, Miguel; Cordero, Elisa; Gracia-Ahufinger, Irene; Martín-Gandul, Cecilia; Maruri, Naroa; Aguado, Rocío; Solana, Rafael; Torre-Cisneros, Julián

2016-08-01

The present study aimed to determine whether antiviral prevention strategies against cytomegalovirus (CMV) infection used in high-risk D+R- solid organ transplanted patients can modulate the impact of CMV replication on CD8(+) T-cell differentiation. The different CD8(+) T-cell subpopulations were measured at a single point when at least one year had elapsed since transplantation. A total of 68 D+R- patients were included, of which 33 underwent pre-emptive therapy and 35 received prophylaxis. Multivariate analysis showed that CMV replication was associated with the expansion of CD28־ EMRA CD8(+) T cells in patients managed pre-emptively but not in patients under prophylaxis (21.4% vs. 3.6%). This finding is likely related to the higher frequency of CMV recurrence observed in patients under pre-emptive therapy compared to those under prophylaxis (75% vs. 14.3%; p < 0.001). In fact, multivariate analysis showed that having more than one replication episode was associated with a 17.2% increase (p = 0.001) in the percentage of CD28־ EMRA CD8(+) T cells compared to "no episode" and with a 10.9% increase with respect to "single episodes" (p = 0.025). Additionally, patients with IFNγ response to CMV (QuantiFERON-CMV Reactive) had a higher percentage of late-differentiated CD8(+) T cells than patients lacking this response. In summary, recurrent CMV replication in D+R- patients under pre-emptive therapy was associated with the expansion of CD28־ EMRA CD8(+) T cells, which might have a short-term beneficial effect related to the high functionality of this T-cell subpopulation. Nevertheless, we cannot rule out that this accumulation might have a long-term detrimental effect related to immunosenescence and inflammation. Copyright © 2016 Elsevier B.V. All rights reserved.

CMV immune evasion and manipulation of the immune system with aging.

PubMed

Jackson, Sarah E; Redeker, Anke; Arens, Ramon; van Baarle, Debbie; van den Berg, Sara P H; Benedict, Chris A; Čičin-Šain, Luka; Hill, Ann B; Wills, Mark R

2017-06-01

Human cytomegalovirus (HCMV) encodes numerous proteins and microRNAs that function to evade the immune response and allow the virus to replicate and disseminate in the face of a competent innate and acquired immune system. The establishment of a latent infection by CMV, which if completely quiescent at the level of viral gene expression would represent an ultimate in immune evasion strategies, is not sufficient for lifelong persistence and dissemination of the virus. CMV needs to reactivate and replicate in a lytic cycle of infection in order to disseminate further, which occurs in the face of a fully primed secondary immune response. Without reactivation, latency itself would be redundant for the virus. It is also becoming clear that latency is not a totally quiescent state, but is characterized by limited viral gene expression. Therefore, the virus also needs immune evasion strategies during latency. An effective immune response to CMV is required or viral replication will cause morbidity and ultimately mortality in the host. There is clearly a complex balance between virus immune evasion and host immune recognition over a lifetime. This poses the important question of whether long-term evasion or manipulation of the immune response driven by CMV is detrimental to health. In this meeting report, three groups used the murine model of CMV (MCMV) to examine if the contribution of the virus to immune senescence is set by the (i) initial viral inoculum, (ii) inflation of T cell responses, (iii) or the balance between functionally distinct effector CD4+ T cells. The work of other groups studying the CMV response in humans is discussed. Their work asks whether the ability to make immune responses to new antigens is compromised by (i) age and HCMV carriage, (ii) long-term exposure to HCMV giving rise to an overall immunosuppressive environment and increased levels of latent virus, or (iii) adapted virus mutants (used as potential vaccines) that have the capacity to elicit conventional and unconventional T cell responses.

Cytomegalovirus disease in lung transplantation: impact of recipient seropositivity and duration of antiviral prophylaxis.

PubMed

Hammond, S P; Martin, S T; Roberts, K; Gabardi, S; Fuhlbrigge, A L; Camp, P C; Goldberg, H J; Marty, F M; Baden, L R

2013-04-01

A recent randomized trial demonstrated that 1 year of antiviral prophylaxis for cytomegalovirus (CMV) after lung transplantation is superior to 3 months of treatment for prevention of CMV disease. However, it is uncertain if a shorter duration of prophylaxis might result in a similar rate of CMV disease among select lung transplant (LT) recipients who are at lower risk for CMV disease, based on baseline donor (D) and recipient (R) CMV serologies. We retrospectively assessed incidence, cumulative probability, and predictors of CMV disease and viremia in LT recipients transplanted between July 2004 and December 2009 at our center, where antiviral CMV prophylaxis for 6-12 months is standard. Of 129 LT recipients, 94 were at risk for CMV infection based on donor CMV seropositivity (D+) or recipient seropositivity (R+); 14 developed CMV disease (14.9%): 11 with CMV syndrome, 2 with pneumonitis, and 1 with gastrointestinal disease by the end of follow-up (October 2010); 17 developed asymptomatic CMV viremia (18.1%). The cumulative probability of CMV disease was 17.4% 18 months after transplantation. CMV D+/R- recipients who routinely received 1 year of prophylaxis were more likely to develop CMV disease compared with D+/R+ or D-/R+ recipients, who routinely received 6 months of prophylaxis (12/45 vs. 2/25 vs. 0/24, P = 0.005). Recipients who stopped CMV prophylaxis before 12 months (in D+/R- recipients) and 6 months (in R+ recipients) tended to develop CMV disease more than those who did not (9/39 vs. 3/41, P = 0.06). On a 6-month CMV prophylaxis protocol, few R+ recipients developed CMV disease in this cohort. In contrast, despite a 12-month prophylaxis protocol, D+/R- LT recipients remained at highest risk for CMV disease. © 2012 John Wiley & Sons A/S.

Total Triiodothyronine by Fluorescence Polarization Immunoassay (FPIA),

DTIC Science & Technology

Graves ’ disease . Traditionally, radioimmunoassays (RIA) have been employed for the determination of total T3. Enzyme immunoassays (EIA) and fluorescence immunoassays (FIA) have been developed for many of the analytes that formerly were measured using RIA. One variation of this new generation of immunoassays is fluorescence polarization. A fluorescence polarization immunoassay (FPIA) method for total T3 has been automated by adaptation to the TDx (Abbott, Chicago, IL) clinical analyzer. The TDx total T3 assay has been evaluated as a replacement for an RIA total T3

Assessment of the T-SPOT.CMV interferon-γ release assay in renal transplant recipients: A single center cohort study.

PubMed

Chanouzas, Dimitrios; Small, Alexander; Borrows, Richard; Ball, Simon

2018-01-01

The measurement of CMV specific cellular immunity in organ transplant recipients could contribute additional acuity to serology based, CMV infection risk stratification, facilitating optimisation of immunosuppression and anti-viral prophylaxis. A pilot study of renal transplant recipient (RTR's) responses in the T-SPOT.CMV ELISPOT based assay. 108 RTR's were recruited 3 months post-transplantation, immediately prior to the cessation of stratified anti-viral prophylaxis, used in recipients from seropositive donors. RTR's were monitored for CMV viremia and disease. Cellular responses to peptides derived from CMV IE1 and pp65 were measured, using the T-SPOT.CMV assay. At recruitment, no CMV specific cellular immunity was detected by T-SPOT.CMV in CMV seronegative recipients (IE1 ≤ 1spot / 2.5x105 PBMC's; pp65 ≤ 3 spots / 2.5x105 PBMC's). At recruitment, CMV sero-positive recipients who made a robust response to both IE1 (>25 spots / 2.5x105 PBMC's) and pp65 (>50 spots / 2.5x105 PBMC's), were less likely to develop high level viremia than those who responded to one or neither antigen (0/28 vs 5/25; p<0.02). In CMV seronegative RTR's, CMV specific cellular immunity measured by T-SPOT.CMV was not detected prior to cessation of anti-viral prophylaxis. This differs from recent reports of CMV specific cellular immunity in a proportion of CMV seronegative RTR's, associated with protection from CMV infection. In seropositive RTR's, a dual response to IE1 and pp65 at recruitment, was associated with protection from subsequent viremia. This suggests that assessing the diversity of response to CMV antigens, may enhance risk stratification in this group.

Preformed Frequencies of Cytomegalovirus (CMV)–Specific Memory T and B Cells Identify Protected CMV-Sensitized Individuals Among Seronegative Kidney Transplant Recipients

PubMed Central

Lúcia, Marc; Crespo, Elena; Melilli, Edoardo; Cruzado, Josep M.; Luque, Sergi; Llaudó, Inés; Niubó, Jordi; Torras, Joan; Fernandez, Núria; Grinyó, Josep M.; Bestard, Oriol

2014-01-01

Background. Cytomegalovirus (CMV) infection remains a major complication after kidney transplantation. Baseline CMV risk is typically determined by the serological presence of preformed CMV-specific immunoglobulin (Ig) G antibodies, even though T-cell responses to major viral antigens are crucial when controlling viral replication. Some IgG-seronegative patients who receive an IgG-seropositive allograft do not develop CMV infection despite not receiving prophylaxis. We hypothesized that a more precise evaluation of pretransplant CMV-specific immune-sensitization using the B and T-cell enzyme-linked immunospot assays may identify CMV-sensitized individuals more accurately, regardless of serological evidence of CMV-specific IgG titers. Methods. We compared the presence of preformed CMV-specific memory B and T cells in kidney transplant recipients between 43 CMV IgG–seronegative (sR−) and 86 CMV IgG–seropositive (sR+) patients. Clinical outcome was evaluated in both groups. Results. All sR+ patients showed a wide range of CMV-specific memory T- and B-cell responses. High memory T- and B-cell frequencies were also clearly detected in 30% of sR− patients, and those with high CMV-specific T-cell frequencies had a significantly lower incidence of late CMV infection after prophylactic therapy. Receiver operating characteristic curve analysis for predicting CMV viremia and disease showed a high area under the receiver operating characteristic curve (>0.8), which translated into a high sensitivity and negative predictive value of the test. Conclusions. Assessment of CMV-specific memory T- and B-cell responses before kidney transplantation among sR− recipients may help identify immunized individuals more precisely, being ultimately at lower risk for CMV infection. PMID:25048845

Cytomegalovirus Infection in Pediatric Hematopoietic Stem Cell Transplantation: Risk Factors for Primary Infection and Cases of Recurrent and Late Infection at a Single Center

PubMed Central

Rowe, R. Grant; Guo, Dongjing; Lee, Michelle; Margossian, Steven; London, Wendy B.; Lehmann, Leslie

2017-01-01

Cytomegalovirus (CMV) infection is a significant source of morbidity and mortality in allogeneic stem cell transplantation (SCT). We identified a cohort of 91 pediatric SCT patients at risk (defined as either donor and/or recipient seropositivity) for CMV infection at our institution. We retrospectively categorized at-risk SCT recipients as those who (1) were at risk of CMV infection in the post-SCT period, (2) had documented CMV infection before SCT, (3) experienced recurrence of post-SCT CMV viremia, or (4) experienced late post-SCT CMV viremia; categories were not mutually exclusive. We analyzed the impact of SCT-related factors on incidence of CMV infection and outcome, and we described the outcome of each of these cohorts. In univariate analysis, recipient CMV seropositivity, use of umbilical cord blood graft, and acute graft-versus-host disease (GVHD) predicted post-SCT CMV viremia, and the effects of acute GVHD (odds ratio, 4.018; 95% confidence interval, 1.032 to 15.643) and CMV seropositivity (odds ratio, 16.525; 95% confidence interval, 2.041 to 133.803) were confirmed in multivariate analysis. Patients with recurrence of post-SCT CMV viremia had a 50% all-cause mortality rate, compared with 12% in all 91 patients. Patients with pre-SCT CMV infection had a high incidence of post-SCT CMV infection but could successfully undergo SCT with antiviral prophylaxis and pre-emptive CMV treatment. All patients with late CMV infection had prior GVHD. Theses findings identify risk factors for post-SCT CMV infection and provide novel descriptions of childhood SCT recipients with pre-SCT, recurrent, and late CMV infection, which may contribute to risk stratification strategies for CMV at-risk patients in pediatric allogeneic SCT. PMID:27090959

Functional impairment of CMV-reactive cellular immunity during pregnancy.

PubMed

Reuschel, Edith; Barabas, Sascha; Zeman, Florian; Bendfeldt, Hanna; Rascle, Anne; Deml, Ludwig; Seelbach-Goebel, Birgit

2017-02-01

Cytomegalovirus (CMV) is the most common congenital viral infection. Mother-to-child transmission can cause severe child disability. Intact CMV-specific cell-mediated immunity (CMI) was shown to prevent uncontrolled replication in healthy individuals. This study aimed to determine whether CMV-specific CMI is impaired in pregnant women, thus potentially increasing the overall risk for active CMV replication and transmission. CMV-specific CMI in peripheral blood of 60 pregnant women was determined using T-Track® CMV for detection of IE-1 and pp65-reactive effector cells by IFN-γ ELISpot, and compared to the CMV-IgG and -IgM serostatus. CMV-specific CMI was detected in 65% of CMV-seropositive pregnant women. Five percent of CMV-IgG seronegative women showed IE-1- but not pp65-reactive cells. The overall number of CMV-reactive cells in pregnant women was significantly lower compared to a matched non-pregnant control group (P < 0.001). No significant difference in CMV-specific CMI was detected in the course of the three trimesters of pregnancy of CMV-IgG seropositive women. Postpartum (median days postnatal = 123), IE-1- and pp65-specific CMI remained significantly lower than in the non-pregnant control group (P < 0.001 and 0.0032, respectively). Functional analysis of CMV-reactive immune cells using T-Track® CMV therefore suggests a systemic down-regulation of CMV-specific CMI in pregnant women. Further studies are needed to investigate whether this may be indicative of a higher susceptibility to CMV reactivation or transmission. J. Med. Virol. 89:324-331, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Cytomegalovirus infections in unrelated cord blood transplantation in pediatric patients: incidence, risk factors, and outcomes.

PubMed

Al-Hajjar, Sami; Al Seraihi, Amal; Al Muhsen, Saleh; Ayas, Mouhab; Al Jumaah, Suliman; Al Jefri, Abdullah; Shoukri, Mohamed; El Solh, Hassan

2011-01-01

Stem cells from umbilical cord blood (CB) have increasingly become a viable alternate source of progenitor cells for hematopoietic cell transplantation (HSCT). Cytomegalovirus (CMV) is thought to contribute significantly to HSCT morbidity and mortality. Retrospective case-control study in patients at tertiary care center. We determined the incidence, risk factors and outcomes for CMV infection and disease after unrelated cord blood transplantation (UCBT) in children. Between 2003 and 2007, 73 pediatric patients underwent UCBT and 68% of recipients were CMV seropositive. The overall incidence of CMV infection, early and late CMV infection was 58.9% (43/73), 62.8% (27/43), and 37.4% (16/43), respectively. in patients with early CMV infection, 6 of 27 (22%) patients progressed to develop CMV end-organ disease including pneumonitis and retinitis. High levels CMV antigenemia ≥70 infected cells by pp65 antigenemia assay + PMNs, P=.237) were associated with a higher risk of progression to CMV disease. The development of CMV infections was higher in CMV-seropositive recipients (P<.001) and in those who developed graft-versus-host-diseases (GVhD) (P<.001). other risk factors for CMV infection include the use of high-dose corticosteroids (P<.001) and older age of the recipient at the time of transplant (P<.002). Late CMV infection was strongly associated with a previous history of early CMV infection (P<.001). CMV infection is a significant complication in UCBT recipients in pediatric patients and is associated with an increase in transplant-related morbidity and mortality. Risk factors for CMV infections after UCBT include GvHD, use of corticosteroids, underlying diseases (hematologic malignancies) and older age. Late CMV infection was strongly associated with a previous history of CMV infection.

The potential association of CMV-specific CD8+ T lymphocyte reconstitution with the risk of CMV reactivation and persistency in post allogeneic stem cell transplant patients.

PubMed

Shams El-Din, Ahmed Ali; El-Desoukey, Nermeen Ahmed; Amin Tawadrous, Dalia Gamil; Fouad, Neveen Mohammed Baha El-Din; Abdel-Mooti, Mohammed; Hotar, Said Fathy

2018-01-09

development of cytomegalovirus (CMV)-specific CD8+ T cell response is crucial in preventing symptomatic CMV infection specially, in stem cell transplant (SCT) patients. The aim of this study was to evaluate CMV-specific CD8+ T cell reconstitution in allogeneic SCT recipients and to study the possible association between CMV-specific CD8+ T cell recovery with protection from CMV reactivation and persistency. Human leuKocyte antigen (HLA)-tetramers were used for CMV-specific CD8+ cell quantitation by Flow cytometry in twenty post-allogeneic SCT patients. Nine patients (45%) developed rapid recovery of CMV-specific CD8+ cells, among them; 7 patients (78%) had no CMV reactivation in the first 95 days post-transplant. Five patients had developed persistent CMV viremia; all of them had not developed CMV-specific CD8+ recovery till day 95 post-transplant. Patients with persistent CMV viremia had a statistically significant lower means of CMV-specific CD8+ percent and absolute count compared to those without persistent viremia (p = .001, .015), respectively. The incidence of CMV reactivation and persistency was higher among patients with delayed CMV-specific CD8+ reconstitution in the first 95 days post-transplant. CMV-specific CD8+ cells can help in categorizing patients into risk groups: (early recovery/low risk) and (delayed recovery/increased risk), this tool may guide clinicians in the selection of patients who may profit from prophylactic antiviral therapy and frequent viral monitoring.

Role of Cytomegalovirus (CMV) IgG Avidity Testing in Diagnosing Primary CMV Infection during Pregnancy

PubMed Central

Lapé-Nixon, Mary

2014-01-01

The risk of intrauterine transmission of cytomegalovirus (CMV) during pregnancy is much greater for women who contract primary CMV infection after conception than for women with evidence of infection (circulating CMV antibodies) before conception. Thus, laboratory tests that aid in the identification of recent primary CMV infection are important tools for managing the care of pregnant women suspected of having been exposed to CMV. CMV IgM detection is a sensitive marker of primary CMV infection, but its specificity is poor because CMV IgM is also produced during viral reactivation and persists following primary infection in some individuals. Studies conducted over the last 20 years convincingly demonstrate that measurement of CMV IgG avidity is both a sensitive and a specific method for identifying pregnant women with recent primary CMV infection and thus at increased risk for vertical CMV transmission. IgG avidity is defined as the strength with which IgG binds to antigenic epitopes expressed by a given protein; it matures gradually during the 6 months following primary infection. Low CMV IgG avidity is an accurate indicator of primary infection within the preceding 3 to 4 months, whereas high avidity excludes primary infection within the preceding 3 months. In this minireview, we summarize published data demonstrating the clinical utility of CMV IgG avidity results for estimating time since primary infection in pregnant women, describe commercially available CMV IgG avidity assays, and discuss some of the issues and controversies surrounding CMV IgG avidity testing during pregnancy. PMID:25165026

Is gammaglobulin anti-CMV warranted in lung transplantation?

PubMed

García-Gallo, C López; Gil, P Ussetti; Laporta, R; Carreño, M C; de Pablo, A; Ferreiro, M J

2005-11-01

The usefulness of anti-CMV hyperimmune gammaglobulin (IgG-CMV, Cytotec) in lung transplant patients (LTx) is controversial. The objective of this study was to analyze the effectiveness of IgG-CMV in our LTx receptors. A retrospective study of LTx recipients treated with IgG-CMV as prophylaxis or as treatment for invasive disease. We used IgG-CMV associated with IV ganciclovir (GCV) as treatment for invasive disease. High-risk patients (CMV-negative recipients from CMV-positive donors; CMV-/+) were also with IgG-CMV prophylaxis during the first year. Other prophylactic uses of IgG-CMV were as an alternative to GCV in patients with related GCV toxicity, and as preemptive therapy in cases of persistent positive viral load (antigenemia > or = 1 cell and/or a PCR > or = 400) although oral GCV administration. Between January 2000 and August 2003, 14 of the 74 lung transplant recipients (19%) received IgG-CMV as treatment for invasive disease (4 cases: 2 gastritis, 1 esophagitis, 1 hepatitis) and/or as prophylaxis (14 cases). All patients treated for invasive disease evolved favorably. No therapeutic failure were observed in CMV-/+ patients during treatment. Three of the six patients treated with IgG-CMV developed positive antigenemia despite treatment. The four patients treated for persistent antigenemia while receiving oral GCV achieved neutralization during the first month of treatment. IgG-CMV associated with Gancyclovir is effective as treatment for invasive disease and as pre-emptive therapy in patients with persistent positive viral load. In CMV-/+ recipients, IgG-CMV prevents pneumonitis and delays the development of invasive disease after the first year.

Abbott Preschool Program Longitudinal Effects Study: Fifth Grade Follow-Up

ERIC Educational Resources Information Center

Barnett, W. Steven; Jung, Kwanghee; Youn, Min-Jong; Frede, Ellen C.

2013-01-01

New Jersey's Abbott Preschool program is of broad national and international interest because the Abbott program provides a model for building a high-quality system of universal pre-K through public-private partnerships that transform the existing system. The program offers high-quality pre-K to all children in 31 New Jersey communities with high…

The Abbott Preschool Program: Fifth Year Report on Enrollment and Budget

ERIC Educational Resources Information Center

Applewhite, Erain; Hirsch, Lesley

2003-01-01

The New Jersey Supreme Court's 1998 ruling in Abbott v. Burke represents the first judicial directive in the nation that public education must include a high-quality, well-planned preschool program starting at age three. This decision applies to 30 urban school districts, known as the Abbott districts, that serve approximately 25 percent of the…

Screening for seemingly healthy newborns with congenital cytomegalovirus infection by quantitative real-time polymerase chain reaction using newborn urine: an observational study

PubMed Central

Yamaguchi, Akira; Oh-ishi, Tsutomu; Arai, Takashi; Sakata, Hideaki; Adachi, Nodoka; Asanuma, Satoshi; Oguma, Eiji; Kimoto, Hirofumi; Matsumoto, Jiro; Fujita, Hidetoshi; Uesato, Tadashi; Fujita, Jutaro; Shirato, Ken; Ohno, Hideki; Kizaki, Takako

2017-01-01

Objective Approximately 8–10% of newborns with asymptomatic congenital cytomegalovirus (cCMV) infection develop sensorineural hearing loss (SNHL). However, the relationship between CMV load, SNHL and central nervous system (CNS) damage in cCMV infection remains unclear. This study aimed to examine the relationship between urinary CMV load, SNHL and CNS damage in newborns with cCMV infection. Study design The study included 23 368 newborns from two maternity hospitals in Saitama Prefecture, Japan. Urine screening for cCMV infection (quantitative real-time PCR) and newborn hearing screening (automated auditory brainstem response (AABR) testing) were conducted within 5 days of birth to examine the incidence of cCMV infection and SNHL, respectively. CNS damage was assessed by MRI of cCMV-infected newborns. Results The incidence of cCMV infection was 60/23 368 (0.257%; 95% CI 0.192% to 0.322%). The geometric mean urinary CMV DNA copy number in newborns with cCMV was 1.79×106 copies/mL (95% CI 7.97×105 to 4.02×106). AABR testing revealed abnormalities in 171 of the 22 229 (0.769%) newborns whose parents approved hearing screening. Of these 171 newborns, 22 had SNHL (12.9%), and 5 of these 22 were infected with cCMV (22.7%). Newborns with both cCMV and SNHL had a higher urinary CMV DNA copy number than newborns with cCMV without SNHL (p=0.036). MRI revealed CNS damage, including white matter abnormalities, in 83.0% of newborns with cCMV. Moreover, newborns with CNS damage had a significantly greater urinary CMV load than newborns without CNS damage (p=0.013). Conclusions We determined the incidence of cCMV infection and urinary CMV DNA copy number in seemingly healthy newborns from two hospitals in Saitama Prefecture. SNHL and CNS damage were associated with urinary CMV DNA copy number. Quantification of urinary CMV load may effectively predict the incidence of late-onset SNHL and neurodevelopmental disorders. PMID:28110288

Performance of NucliSens HIV-1 EasyQ Version 2.0 compared with six commercially available quantitative nucleic acid assays for detection of HIV-1 in China.

PubMed

Xu, Sihong; Song, Aijing; Nie, Jianhui; Li, Xiuhua; Wang, Youchun

2010-10-01

Six HIV-1 viral load assays have been widely used in China. These include the Cobas Amplicor HIV-1 Monitor Version 1.5 ('Amplicor'), Cobas AmpliPrep/Cobas TaqMan HIV-1 test Version 1.0 ('CAP/CTM'), Versant HIV-1 RNA Version 3.0 (branched DNA [bDNA]-based assay; 'Versant bDNA'), Abbott RealTime HIV-1 assay ('Abbott RealTime'), NucliSens HIV-1 QT (nucleic acid sequence-based amplification assay; 'NucliSens NASBA'), and NucliSens EasyQ HIV-1 Version 1.1 ('EasyQ V1.1'). Recently, an updated version of EasyQ V1.1, NucliSens EasyQ HIV-1 Version 2.0 ('EasyQ V2.0') was introduced into China. It is important to evaluate the impact of HIV-1 genotypes on the updated assay compared with the other commercial available assays in China. A total of 175 plasma samples with different HIV-1 clades prevalent in China were collected from treatment-naïve patients. The viral loads of those samples were determined with the seven HIV-1 viral load assays, and the quantitative differences between them were evaluated. Overall, EasyQ V2.0 exhibited a significant correlation (R = 0.769-0.850, p ≤ 0.001) and high agreement (94.77-97.13%, using the Bland-Altman model) with the other six assays. Although no significant differences between EasyQ V2.0 and the other six assays were observed when quantifying clade B' samples, there were statistically significant differences between EasyQ V2.0 and the Amplicor, Versant bDNA, and Abbott RealTime assays when quantifying clade BC samples, and between EasyQ V2.0 and the Versant bDNA and Abbott RealTime assays when quantifying clade AE samples. For clade BC samples, the quantitative differences between EasyQ V2.0 and the Amplicor, Versant bDNA, and Abbott RealTime assays exceeded 0.5 log(10) IU/mL in approximately 50% of samples and exceeded 1 log(10) IU/mL in approximately 15% of samples. For clade AE samples, the quantitative differences between EasyQ V2.0 and the CAP/CTM, Versant bDNA, and Abbott RealTime assays exceeded 0.5 log(10) IU/mL in approximately 50% of samples, and the differences between EasyQ V2.0 and CAP/CTM exceeded 1 log(10) IU/mL in approximately 15% of samples. Genotypes may affect the quantification of HIV-1 RNA, especially in clade BC samples with respect to EasyQ V2.0 and the Amplicor, Versant bDNA, or Abbott RealTime assays, and in clade AE samples with respect to EasyQ V2.0 and the Versant bDNA or Abbott RealTime assays. It is therefore strongly suggested that, where possible, the HIV-1 viral load in infected patients be quantified at follow-up by the same version of the same assay that was used initially.

Quantiferon-Cytomegalovirus assay: A potentially useful tool in the evaluation of CMV-specific CD8+ T-cell reconstitution in pediatric hematopoietic stem cell transplant patients.

PubMed

Paouri, Bilio; Soldatou, Alexandra; Petrakou, Eftihia; Theodosaki, Maria; Tsentidis, Charalampos; Kaisari, Katerina; Oikonomopoulou, Christina; Matsas, Minos; Goussetis, Eugenios

2018-05-18

Pediatric HSCT recipients are at high risk for CMV reactivation due to their immature immune system and therapy following transplantation. Reconstitution of CMV-specific T-cell immunity is associated with control and protection against CMV. The clinical utility of monitoring CMV-specific CMI to predict CMV viremia in pediatric HSCT patients using the Quantiferon-CMV (QIAGEN ® ) test was investigated prospectively. Thirty-seven pediatric allogeneic HSCT recipients were enrolled from 3/2010-6/2012. CMV viremia was detected via weekly real-time PCR. The Quantiferon-CMV test was conducted pretransplant, early after transplantation, 30, 90, 180, 270, and 360 days post-transplantation. The incidence of CMV viremia was 51% (19/37) with half of the episodes within ≤30 days post-transplant. Fifteen patients showed CMV-specific immunity (average of 82 days). The cumulative incidence of CMV reactivation in patients who developed CMV-specific immunity was lower than those who did not (15% vs 53%; P = .023). The ROC statistical analysis showed that the AUC was 0.725 in predicting viremia, for Quantiferon-CMV test. In this cohort, the Quantiferon-CMV assay was a valuable method for identifying pediatric HSCT patients at high risk for CMV viremia, suggesting potential clinical utility to individualize patient's management post-transplant. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Translational informatics approach for identifying the functional molecular communicators linking coronary artery disease, infection and inflammation

PubMed Central

SHARMA, ANKIT; GHATGE, MADANKUMAR; MUNDKUR, LAKSHMI; VANGALA, RAJANI KANTH

2016-01-01

Translational informatics approaches are required for the integration of diverse and accumulating data to enable the administration of effective translational medicine specifically in complex diseases such as coronary artery disease (CAD). In the current study, a novel approach for elucidating the association between infection, inflammation and CAD was used. Genes for CAD were collected from the CAD-gene database and those for infection and inflammation were collected from the UniProt database. The cytomegalovirus (CMV)-induced genes were identified from the literature and the CAD-associated clinical phenotypes were obtained from the Unified Medical Language System. A total of 55 gene ontologies (GO) termed functional communicator ontologies were identifed in the gene sets linking clinical phenotypes in the diseasome network. The network topology analysis suggested that important functions including viral entry, cell adhesion, apoptosis, inflammatory and immune responses networked with clinical phenotypes. Microarray data was extracted from the Gene Expression Omnibus (dataset: GSE48060) for highly networked disease myocardial infarction. Further analysis of differentially expressed genes and their GO terms suggested that CMV infection may trigger a xenobiotic response, oxidative stress, inflammation and immune modulation. Notably, the current study identified γ-glutamyl transferase (GGT)-5 as a potential biomarker with an odds ratio of 1.947, which increased to 2.561 following the addition of CMV and CMV-neutralizing antibody (CMV-NA) titers. The C-statistics increased from 0.530 for conventional risk factors (CRFs) to 0.711 for GGT in combination with the above mentioned infections and CRFs. Therefore, the translational informatics approach used in the current study identified a potential molecular mechanism for CMV infection in CAD, and a potential biomarker for risk prediction. PMID:27035874

Cytomegalovirus Viral Load in Bronchoalveolar Lavage to Diagnose Lung Transplant Associated CMV Pneumonia.

PubMed

Lodding, Isabelle Paula; Schultz, Hans Henrik; Jensen, Jens-Ulrik; Kirkby, Nikolai; Perch, Michael; Andersen, Claus; Lundgren, Jens D; Iversen, Martin

2018-02-01

The diagnostic yield for cytomegalovirus (CMV) polymerase chain reaction (PCR) viral load in bronchoalveolar lavage (BAL) or in plasma to diagnose CMV pneumonia in lung transplant recipients remains uncertain and was investigated in a large cohort of consecutive lung transplant recipients. Bronchoscopies within the first year of lung transplantation with CMV detectable in BAL by PCR (ie, viral load, ≥273 IU/mL) were included (66 recipients; 145 bronchoscopies); at each bronchoscopy episode, 2 independent experts reviewed clinical and laboratory information to determine whether the patient at that time fulfilled the criteria for CMV pneumonia per current international recommendations. Corresponding plasma CMV PCR viral load determined at time of the bronchoscopy (n = 126) was also studied. Optimal CMV PCR viral load cutoff for CMV pneumonia diagnosis was determined using receiver operating characteristics. CMV was detected in BAL with CMV PCR in 145 episodes, and 34 (23%) of these episodes fulfilled the criteria for CMV pneumonia. The area under the curve-receiver operating characteristics for CMV in BAL was 90% at the optimum cutoff (4545 IU/mL) with a corresponding sensitivity of 91% and specificity of 77% (in plasma the corresponding values were 274 IU/mL, 63% and 76%, respectively). CMV PCR viral load in BAL had a high performance to diagnose CMV pneumonia in lung transplant recipients; plasma CMV viral load did not reliably aid as a diagnostic tool.

Immunological Prediction of Cytomegalovirus (CMV) Replication Risk in Solid Organ Transplantation Recipients: Approaches for Regulating the Targeted Anti-CMV Prevention Strategies.

PubMed

Han, Sang Hoon

2017-09-01

The current cytomegalovirus (CMV) prevention strategies in solid organ transplantation (SOT) recipients have contributed towards overcoming the detrimental effects caused by CMV lytic infection, and improving the long-term success rate of graft survival. Although the quantification of CMV in peripheral blood is the standard method, and an excellent end-point for diagnosing CMV replication and modulating the anti-CMV prevention strategies in SOT recipients, a novel biomarker mimicking the CMV control mechanism is required. CMV-specific immune monitoring can be employed as a basic tool predicting CMV infection or disease after SOT, since uncontrolled CMV replication mostly originates from the impairment of immune responses against CMV under immunosuppressive conditions in SOT recipients. Several studies conducted during the past few decades have indicated the possibility of measuring the CMV-specific cell-mediated immune response in clinical situations. Among several analytical assays, the most advancing standardized tool is the QuantiFERON®-CMV assay. The T-Track® CMV kit that uses the standardized enzyme-linked immunospot assay is also widely employed. In addition to these assays, immunophenotyping and intracellular cytokine analysis using flow cytometry (with fluorescence-labeled monoclonal antibodies or peptide-major histocompatibility complex multimers) needs to be adequately standardized and validated for potential clinical applications. Copyright © 2017 by The Korean Society of Infectious Diseases and Korean Society for Chemotherapy.

Cytomegalovirus pp65 antigenemia-guided pre-emptive treatment with ganciclovir after allogeneic stem transplantation: a single-center experience.

PubMed

Manteiga, R; Martino, R; Sureda, A; Labeaga, R; Brunet, S; Sierra, J; Rabella, N

1998-11-01

The optimal prophylactic strategy for cytomegalovirus (CMV) disease after allogeneic hematopoietic stem cell transplantation has not yet been established. The aim of this study was to analyze our single-center experience with a uniform protocol of CMV antigenemia-guided pre-emptive treatment with ganciclovir (GCV) after allografting. Fifty-two consecutive adult patients, 48 of them transplanted from HLA-identical matched related donors were included. T cell-depleted marrow or peripheral blood were used in 21 cases. After engraftment, weekly blood samples were tested for CMV pp65 antigenemia and viremia (conventional cultures) until day +100. GCV was started if CMV antigenemia and/or CMV viremia were detected. CMV infection (CMV-I) was found in 19 patients (37%). Seven patients suffered from CMV disease (CMV-D), three colitis and four pneumonias. There was one death directly related to CMV-D and three further cases died from refractory GVHD with CMV-D. Only one patient developed CMV pneumonia without any previous positive antigenemia and/or viremia. Multivariate analysis identified grades II-IV acute GVHD (P = 0.02) and peripheral blood stem cell transplantation (P = 0.03) to be risk factors for developing CMV-I. In conclusion, this monitoring protocol allowed early treatment of CMV-I without progression to CMV-D. Pre-emptive therapy had the additional advantage of avoiding GCV administration in most of our allograft recipients.

Valganciclovir (VGCV) followed by cytomegalovirus (CMV) hyperimmune globulin compared to VGCV for 200 days in abdominal organ transplant recipients at high risk for CMV infection: A prospective, randomized pilot study.

PubMed

Fleming, James N; Taber, David J; Weimert, Nicole A; Nadig, Satish; McGillicuddy, John W; Bratton, Charles F; Baliga, Prabhakar K; Chavin, Kenneth D

2017-12-01

With the advent of effective antivirals against cytomegalovirus (CMV), use of CMV hyperimmune globulin (HIG) has decreased. Although antiviral prophylaxis in patients at high risk for CMV is effective, many patients still have late infection, never developing antibodies sufficient to achieve immunity. Utilizing a combination of antiviral and CMV HIG may allow patients to achieve immunity and decrease late CMV infections. This was a prospective randomized, open-label, pilot study comparing valganciclovir (VGCV) prophylaxis for 200 days vs VGCV for 100 days followed by CMV HIG in abdominal transplant recipients at high risk for CMV. The primary outcome was a comparison of late CMV disease. Forty patients were randomized to VGCV for 200 days (n = 20) or VGCV for 100 days followed by 3 doses of monthly CMV HIG (n = 20). Numerically, more overall CMV infections occurred in the CMV HIG group (45 vs 20%, P = .09). No differences in overall CMV infections or late CMV disease were seen between groups (20% vs 15%, P = 1.00 and 0 vs 0, P = 1.00). All CMV disease occurred within 200 days, with 63% occurring while patients were on VGCV. No differences were found in toxicities, graft function, or rejection between groups. Patients with CMV infection at any time had a higher body weight than those who did not have an infection (82 vs 95 kg, P = .049). Use of CMV HIG sequentially with prophylaxis may be an effective and affordable prophylactic regimen in abdominal transplant recipients at high risk for CMV, and warrants larger prospective study. Increased monitoring for patients with obesity may be warranted. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cytomegalovirus infection and disease reduce 10-year cardiac allograft vasculopathy-free survival in heart transplant recipients.

PubMed

Johansson, Inger; Andersson, Rune; Friman, Vanda; Selimovic, Nedim; Hanzen, Lars; Nasic, Salmir; Nyström, Ulla; Sigurdardottir, Vilborg

2015-12-24

Cytomegalovirus (CMV) is associated with an increased risk of cardiac allograft vasculopathy (CAV), the major limiting factor for long-term survival after heart transplantation (HTx). The purpose of this study was to evaluate the impact of CMV infection during long-term follow-up after HTx. A retrospective, single-centre study analyzed 226 HTx recipients (mean age 45 ± 13 years, 78 % men) who underwent transplantation between January 1988 and December 2000. The incidence and risk factors for CMV infection during the first year after transplantation were studied. Risk factors for CAV were included in an analyses of CAV-free survival within 10 years post-transplant. The effect of CMV infection on the grade of CAV was analyzed. Survival to 10 years post-transplant was higher in patients with no CMV infection (69 %) compared with patients with CMV disease (55 %; p = 0.018) or asymptomatic CMV infection (54 %; p = 0.053). CAV-free survival time was higher in patients with no CMV infection (6.7 years; 95 % CI, 6.0-7.4) compared with CMV disease (4.2 years; CI, 3.2-5.2; p < 0.001) or asymptomatic CMV infection (5.4 years; CI, 4.3-6.4; p = 0.013). In univariate analysis, recipient age, donor age, coronary artery disease (CAD), asymptomatic CMV infection and CMV disease were significantly associated with CAV-free survival. In multivariate regression analysis, CMV disease, asymptomatic CMV infection, CAD and donor age remained independent predictors of CAV-free survival at 10 years post-transplant. CAV-free survival was significantly reduced in patients with CMV disease and asymptomatic CMV infection compared to patients without CMV infection. These findings highlight the importance of close monitoring of CMV viral load and appropriate therapeutic strategies for preventing asymptomatic CMV infection.

Cytomegalovirus disease in kidney transplant recipients: incidence, clinical profile, and risk factors.

PubMed

Cordero, E; Casasola, C; Ecarma, R; Danguilan, R

2012-04-01

Cytomegalovirus (CMV) is one of the most frequently encountered opportunistic viral pathogens in renal transplantation. Approximately 60% of transplant recipients will have CMV infection and >20% will develop symptomatic disease. With the advancement of immunosuppression, variation in the occurrence and pattern of infections is possible. We described the incidence, clinical profile, outcome, and risk factors for development of CMV disease among renal transplant recipients. We studied patients who underwent transplantation from January 2005-December 2009 admitted for CMV disease. CMV infection was present if the patient had at least 1 of the following: positive early antigen detection in blood or tissues, positive CMV antigenemia, or a 4-fold increase in pretransplantation CMV antibody titer. CMV disease was diagnosed if CMV infection was accompanied by clinical signs and symptoms. Descriptive statistics included measures of central tendency for continuous numerical variables and percentage-frequency distribution for categorical variables z test, Wilcoxon-Mann-Whitney test, and Fisher exact test were used to determine risk factors for CMV disease. About 1502 renal transplantations were done during the study period with mean follow-up of 33.8 months. CMV disease was confirmed in 85 (5.8%) recipients who developed 88 CMV disease episodes. Of the 85 patients who had CMV disease, 55% developed ≤ 3 months posttransplantation. Fever was the most common presenting symptom, 53% had coinfection, and case fatality rate was 11%. Risk factors that were statistically significant in the development of CMV disease were as follows: recipient/donor relationship (P = .0115), CMV donor+/recipient- (P = .004), and recent rejection treatment (P = .0084). Incidence of CMV disease was 5.8% with fever as the most common presenting symptom and 55% developed CMV disease ≤ 3 months posttransplantation. Coinfection occurred in 53% and case fatality rate in 11%. Risk factors for developing CMV disease included CMV donor+/recipient- and recent acute rejection treatment. Copyright © 2012 Elsevier Inc. All rights reserved.

About CMV (Cytomegalovirus)

MedlinePlus

... About CDC.gov . Redirect - Testing and Diagnosis of CMV Infection Recommend on Facebook Tweet Share Compartir We ... to update your bookmark: https://www.cdc.gov/cmv/overview.html CMV Home About CMV Babies Born ...

Adaptive NK cell and KIR-expressing T cell responses are induced by CMV and are associated with protection against CMV reactivation after allogeneic donor hematopoietic cell transplantation1

PubMed Central

Davis, Zachary B.; Cooley, Sarah A.; Cichocki, Frank; Felices, Martin; Wangen, Rose; Luo, Xianghua; DeFor, Todd E.; Bryceson, Yenan T.; Diamond, Don J.; Brunstein, Claudio; Blazar, Bruce R.; Wagner, John E.; Weisdorf, Daniel J.; Horowitz, Amir; Guethlein, Lisbeth A.; Parham, Peter; Verneris, Michael R.; Miller, Jeffrey S.

2015-01-01

Cytomegalovirus (CMV) reactivates in >30% of CMV seropositive patients after allogeneic hematopoietic cell transplantation (HCT). Previously, we reported an increase of NK cells expressing NKG2C, CD57 and inhibitory killer-cell immunoglobulin-like receptors (KIRs) in response to CMV reactivation post-HCT. These NK cells persist after the resolution of infection and display ‘adaptive’ or memory properties. Despite these findings, the differential impact of persistent/inactive vs. reactivated CMV on NK vs. T cell maturation following HCT from different graft sources has not been defined. We compared the phenotype of NK and T cells from 292 recipients of allogeneic sibling (n = 118) or umbilical cord blood (UCB; n = 174) grafts based on recipient pre-transplant CMV serostatus and post-HCT CMV reactivation. This cohort was utilized to evaluate CMV-dependent increases in KIR-expressing NK cells exhibiting an ‘adaptive’ phenotype (NKG2C+CD57+). Compared to CMV seronegative recipients, those who reactivated CMV (React+) had the highest adaptive cell frequencies, while intermediate frequencies were observed in CMV seropositive recipients harboring persistent/non-replicating CMV. The same effect was observed in T cells and CD56+ T cells. These adaptive lymphocyte subsets were increased in CMV seropositive recipients of sibling, but not UCB grafts, and correlated with lower rates of CMV reactivation (sibling 33% vs. UCB 51%; p<0.01). These data suggest that persistent/non-replicating recipient CMV induces rapid production of adaptive NK and T cells from mature cells from sibling, but not UCB grafts. These adaptive lymphocytes are associated with protection from CMV reactivation. PMID:26055301

Replication of CMV in the gut of HIV-infected individuals and epithelial barrier dysfunction

PubMed Central

Somsouk, Ma; Hunt, Peter W.

2017-01-01

Although invasive cytomegalovirus (CMV) disease is uncommon in the era of antiretroviral therapy (ART), asymptomatic CMV coinfection is nearly ubiquitous in HIV infected individuals. While microbial translocation and gut epithelial barrier dysfunction may promote persistent immune activation in treated HIV infection, potentially contributing to morbidity and mortality, it has been unclear whether CMV replication in individuals with no symptoms of CMV disease might play a role in this process. We hypothesized that persistent CMV replication in the intestinal epithelium of HIV/CMV-coinfected individuals impairs gut epithelial barrier function. Using a combination of state-of-the-art in situ hybridization technology (RNAscope) and immunohistochemistry, we detected CMV DNA and proteins and evidence of intestinal damage in rectosigmoid samples from CMV-positive individuals with both untreated and ART-suppressed HIV infection. Two different model systems, primary human intestinal cells differentiated in vitro to form polarized monolayers and a humanized mouse model of human gut, together demonstrated that intestinal epithelial cells are fully permissive to CMV replication. Independent of HIV, CMV disrupted tight junctions of polarized intestinal cells, significantly reducing transepithelial electrical resistance, a measure of monolayer integrity, and enhancing transepithelial permeability. The effect of CMV infection on the intestinal epithelium is mediated, at least in part, by the CMV-induced proinflammatory cytokine IL-6. Furthermore, letermovir, a novel anti-CMV drug, dampened the effects of CMV on the epithelium. Together, our data strongly suggest that CMV can disrupt epithelial junctions, leading to bacterial translocation and chronic inflammation in the gut and that CMV could serve as a target for therapeutic intervention to prevent or treat gut epithelial barrier dysfunction during HIV infection. PMID:28241080

Cytomegalovirus (CMV) DNA load in plasma for the diagnosis of CMV disease before engraftment in hematopoietic stem-cell transplant recipients.

PubMed

Limaye, A P; Huang, M L; Leisenring, W; Stensland, L; Corey, L; Boeckh, M

2001-02-01

Among hematopoietic stem-cell transplant (HSCT) recipients, cytomegalovirus (CMV) disease before engraftment is rare but often fatal, and cell-based diagnostic tests have low sensitivity in this clinical setting. We used the quantitative real-time polymerase chain reaction (PCR) assay to test for CMV DNA in plasma samples from 15 HSCT recipients who developed CMV disease before engraftment and from 33 matched control patients. CMV DNA was detected in plasma in 14 (93.3%) of the 15 patients who had CMV disease before engraftment, compared with 5 (15.2%) of 33 control patients (P<.001). CMV DNA was detected a median of 13 days before the onset of CMV disease (range, 0-35 days). The maximum CMV virus load in plasma was >1 log(10) higher among case patients than among control patients (median, 1700 [range, 50 to 5.5x107] vs. <50 [range, <50-350] CMV DNA copies/mL plasma, respectively; P<.001). Quantitative PCR for CMV DNA in plasma appears to be useful for the identification of HSCT recipients at risk for CMV disease before engraftment.

Assessing the risk of CMV reactivation and reconstitution of antiviral immune response post bone marrow transplantation by the QuantiFERON-CMV-assay and real time PCR.

PubMed

Krawczyk, Adalbert; Ackermann, Jessica; Goitowski, Birgit; Trenschel, Rudolf; Ditschkowski, Markus; Timm, Jörg; Ottinger, Hellmut; Beelen, Dietrich W; Grüner, Nico; Fiedler, Melanie

CMV reactivation is a major cause of severe complications in allogeneic hematopoietic stem cell transplant (HSCT) recipients. The risk of CMV reactivation depends on the serostatus (+/-) of the donor (D) and recipient (R). The reconstitution of CMV-specific T-cell responses after transplantation is crucial for the control of CMV reactivation. The study aimed to determine the cellular immune status correlating with protection from high-level CMV viremia (>5000 copies/ml) and disease. We monitored CMV-specific cellular immune responses in 9 high-risk (D-/R+), 14 intermediate risk (D+/R+) and 3 low risk individuals (D+/R-), and 8 CMV negative controls (D-/R-). Interferon- γ (IFN-γ) levels as a marker for the CD8+ T-cell response were determined by the QuantiFERON-CMV-assay and compared to viral loads determined by PCR. Early CMV reactivation was detected in all high-risk and 13/14 intermediate risk individuals. High-level viremia was detected in 5/7 high and 7/14 intermediate risk patients. Reconstitution of the CMV-specific cellular immune response started from 3 months after transplantation and resulted in protection against CMV reactivation. Re-establishing of CMV-specific T-cell immune responses with IFN- γ levels >8.9 IU/ml is crucial for protection from high-level CMV viremia. Monitoring of HSCT-recipients with the QuantiFERON-CMV-assay might be of great benefit to optimize antiviral treatment. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

A Targeted Approach for Congenital Cytomegalovirus Screening Within Newborn Hearing Screening

PubMed Central

McCollister, Faye P.; Sabo, Diane L.; Shoup, Angela G.; Owen, Kris E.; Woodruff, Julie L.; Cox, Edith; Mohamed, Lisa S.; Choo, Daniel I.; Boppana, Suresh B.

2017-01-01

BACKGROUND AND OBJECTIVE: Congenital cytomegalovirus (cCMV) infection remains a leading cause of childhood hearing loss. Currently universal CMV screening at birth does not exist in the United States. An alternative approach could be testing infants who do not pass their newborn hearing screening (NHS) for cCMV. This study was undertaken to evaluate whether a targeted approach will identify infants with CMV-related sensorineural hearing loss (SNHL). METHODS: Infants born at 7 US medical centers received NHS and were also screened for cCMV while in the newborn nursery. Infants who tested positive for CMV received further diagnostic audiologic evaluations to identify or confirm hearing loss. RESULTS: Between 2007 and 2012, 99 945 newborns were screened for both hearing impairment and cCMV. Overall, 7.0% of CMV-positive infants did not pass NHS compared with 0.9% of CMV-negative infants (P < .0001). Among the cCMV infants who failed NHS, diagnostic testing confirmed that 65% had SNHL. In addition, 3.6% of CMV-infected infants who passed their NHS had SNHL confirmed by further evaluation during early infancy. NHS in this cohort identified 57% of all CMV-related SNHL that occurred in the neonatal period. CONCLUSIONS: A targeted CMV approach that tests newborns who fail their NHS identified the majority of infants with CMV-related SNHL at birth. However, 43% of the infants with CMV-related SNHL in the neonatal period and cCMV infants who are at risk for late onset SNHL were not identified by NHS. PMID:28049114

Cethromycin: A-195773, A-195773-0, A-1957730, Abbott-195773, ABT 773.

PubMed

2007-01-01

Cethromycin [ABT 773, A-195773, Abbott-195773, A-1957730, A-195773-0] is a once-daily ketolide antibiotic that originated from Abbott Laboratories' research into next-generation compounds to the macrolide antibacterial, clarithromycin. The aim of the research programme was to maintain the positive attributes of clarithromycin and to add the property of efficacy against macrolide-resistant organisms. Cethromycin acts by binding to the 23S molecule of the 50S ribosomal subunit. Advanced Life Sciences is conducting multinational, pivotal phase III trials of cethromycin for the treatment of mild-to-moderate community-acquired pneumonia, phase II/III trials for treatment of acute bacterial sinusitis, as well as preclinical trials for the treatment of anthrax. Advanced Life Sciences plans to advance discussions with prospective commercialisation partners for cethromycin during 2006. Abbott Laboratories and Taisho Pharmaceutical entered a collaboration to develop and commercialise new macrolide antibacterials in October 1997. Each company brought its existing macrolides into the collaboration and both companies were to jointly develop novel new macrolides. Abbott was to have exclusive marketing, manfacturing and supply rights worldwide (except in Japan) to any compounds resulting from this collaboration. Taisho was to receive royalties on Abbott's sales in consideration of granted rights. In Japan, the two companies were to co-market any resulting macrolide antibacterials. This agreement extended to the development of cethromycin; however, the agreement was suspended in April 2004 and appears to have been terminated. Abbott exclusively licensed cethromycin to Advanced Life Sciences worldwide excluding Japan in December 2004. Advanced Life Sciences initiated commercial manufacturing agreements for cethromycin with DSM and Cardinal Health in May 2006. In March 2006, Advanced Life Sciences completed private placement of $US36 million from which the net proceeds will be used to advance development of cethromycin. The company plans to submit an NDA for cethromycin in 2007. In Japan, phase II trials were being conducted with Abbott's partner, Taisho Pharmaceutical. Although development in the US had been put on hold, Abbott was to continue to support product development in Japan by Taisho. However, in April 2004, Taisho and Abbott Japan decided to suspend co-development activities for cethromycin. A patent has been granted for cethromycin (US patent number 5 866 549) that expires in September 2016.

Comparison of quantitative cytomegalovirus (CMV) PCR in plasma and CMV antigenemia assay: clinical utility of the prototype AMPLICOR CMV MONITOR test in transplant recipients.

PubMed

Caliendo, A M; St George, K; Kao, S Y; Allega, J; Tan, B H; LaFontaine, R; Bui, L; Rinaldo, C R

2000-06-01

The correlation between the prototype AMPLICOR CMV MONITOR test (Roche Molecular Systems), a quantitative PCR assay, and the cytomegalovirus (CMV) pp65 antigenemia assay was evaluated in transplant recipients. Sequential blood specimens were collected on 29 patients (491 specimens), the leukocyte fraction was tested by CMV antigenemia, and quantitative PCR was performed on plasma specimens. None of the 15 patients (242 specimens) who were antigenemia negative were positive for CMV DNA by PCR, and none of these patients developed active CMV disease. There were 14 antigenemia-positive patients, 8 of whom developed active CMV disease. In all patients, there was a good association between the antigenemia and PCR assays. Ganciclovir-resistant virus was isolated from three patients with active CMV disease. These three patients had persistently elevated levels of antigenemia and CMV DNA by PCR when resistance to ganciclovir developed. This standardized, quantitative CMV PCR assay on plasma has clinical utility for the diagnosis of active disease and in monitoring the response to antiviral therapy in transplant recipients.

Comparison of Quantitative Cytomegalovirus (CMV) PCR in Plasma and CMV Antigenemia Assay: Clinical Utility of the Prototype AMPLICOR CMV MONITOR Test in Transplant Recipients

PubMed Central

Caliendo, Angela M.; St. George, Kirsten; Kao, Shaw-Yi; Allega, Jessica; Tan, Ban-Hock; LaFontaine, Robert; Bui, Larry; Rinaldo, Charles R.

2000-01-01

The correlation between the prototype AMPLICOR CMV MONITOR test (Roche Molecular Systems), a quantitative PCR assay, and the cytomegalovirus (CMV) pp65 antigenemia assay was evaluated in transplant recipients. Sequential blood specimens were collected on 29 patients (491 specimens), the leukocyte fraction was tested by CMV antigenemia, and quantitative PCR was performed on plasma specimens. None of the 15 patients (242 specimens) who were antigenemia negative were positive for CMV DNA by PCR, and none of these patients developed active CMV disease. There were 14 antigenemia-positive patients, 8 of whom developed active CMV disease. In all patients, there was a good association between the antigenemia and PCR assays. Ganciclovir-resistant virus was isolated from three patients with active CMV disease. These three patients had persistently elevated levels of antigenemia and CMV DNA by PCR when resistance to ganciclovir developed. This standardized, quantitative CMV PCR assay on plasma has clinical utility for the diagnosis of active disease and in monitoring the response to antiviral therapy in transplant recipients. PMID:10834964

CLSI-based transference and verification of CALIPER pediatric reference intervals for 29 Ortho VITROS 5600 chemistry assays.

PubMed

Higgins, Victoria; Truong, Dorothy; Woroch, Amy; Chan, Man Khun; Tahmasebi, Houman; Adeli, Khosrow

2018-03-01

Evidence-based reference intervals (RIs) are essential to accurately interpret pediatric laboratory test results. To fill gaps in pediatric RIs, the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) project developed an age- and sex-specific pediatric RI database based on healthy pediatric subjects. Originally established for Abbott ARCHITECT assays, CALIPER RIs were transferred to assays on Beckman, Roche, Siemens, and Ortho analytical platforms. This study provides transferred reference intervals for 29 biochemical assays for the Ortho VITROS 5600 Chemistry System (Ortho). Based on Clinical Laboratory Standards Institute (CLSI) guidelines, a method comparison analysis was performed by measuring approximately 200 patient serum samples using Abbott and Ortho assays. The equation of the line of best fit was calculated and the appropriateness of the linear model was assessed. This equation was used to transfer RIs from Abbott to Ortho assays. Transferred RIs were verified using 84 healthy pediatric serum samples from the CALIPER cohort. RIs for most chemistry analytes successfully transferred from Abbott to Ortho assays. Calcium and CO 2 did not meet statistical criteria for transference (r 2 <0.70). Of the 32 transferred reference intervals, 29 successfully verified with approximately 90% of results from reference samples falling within transferred confidence limits. Transferred RIs for total bilirubin, magnesium, and LDH did not meet verification criteria and are not reported. This study broadens the utility of the CALIPER pediatric RI database to laboratories using Ortho VITROS 5600 biochemical assays. Clinical laboratories should verify CALIPER reference intervals for their specific analytical platform and local population as recommended by CLSI. Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Utility of the Abbott RealTime HCV Genotype Plus RUO assay used in combination with the Abbott RealTime HCV Genotype II assay.

PubMed

He, Chao; Germer, Jeffrey J; Ptacek, Elizabeth R; Bommersbach, Carl E; Mitchell, P Shawn; Yao, Joseph D C

Hepatitis virus C (HCV) genotype (GT) determination and subtype (ST) differentiation (1a versus 1b) remain important for the selection of appropriate direct-acting antiviral (DAA) therapy. This study is a retrospective comparison of HCV GT and ST result distribution when using the Abbott RealTime HCV Genotype II assay (HCVGT II) alone and in combination with the Abbott RealTime HCV Genotype Plus RUO assay (HCVGT Plus) for routine testing of clinical serum specimens at a reference laboratory. HCVGT II results of specimens tested from June 2014 through January 2016 (period 1) were compared with combined results from HCVGT II and HCVGT Plus (HCVGT II/Plus) performed from January 2016 through January 2017 (period 2). A total of 44,127 and 25,361 specimens were tested during periods 1 and 2, respectively. Use of HCVGT II/Plus significantly reduced the frequency of GT 1 results without ST (0.4%) when compared to preliminary HCVGT II results during period 2 (5.3%; p < 0.01) and final HCVGT II results in period 1 (5.5%; p < 0.01). HCVGT II/Plus also resulted in GT 6 reactivity in 38 specimens with results of "HCV detected" (n = 17) or GT 1 (n = 21) following initial HCVGT II testing during period 2. When compared to the use of HCVGT II alone, HCVGT II/Plus significantly reduced the frequency of GT 1 without ST results observed in a large reference laboratory, while also enabling the identification of HCV GT 6. Copyright © 2018 Elsevier B.V. All rights reserved.

Assigning Cytomegalovirus (CMV) Status in Children Awaiting Organ Transplant: Viral Shedding, CMV-Specific T-cells and CD27-CD28-CD4+ T-cells.

PubMed

Burton, Catherine E; Sester, Martina; Robinson, Joan L; Eurich, Dean T; Preiksaitis, Jutta K; Urschel, Simon

2018-05-24

Passive antibodies, maternal or transfusion-acquired, make serologic determination of pre-transplant cytomegalovirus (CMV) status unreliable. We evaluated 3 assays un-affected by passive antibodies, in assignment of CMV infection status in children awaiting solid organ transplant and in controls: i) CMV Nucleic Acid Amplification Testing (NAAT), quantification of ii) CMV-specific CD4+T-cells, and iii) CD27-CD28-CD4+T-cells. Our results highlight that CMV NAAT, from urine and oropharynx, is useful in confirming positive CMV status. Detection of CMV-specific CD4+T-cells was sensitive and specific in children >18 months but was less sensitive in children <12 months. CD27-CD28- CD4+T-cells are not likely useful in CMV risk-stratification in children.

Identifying Cytomegalovirus Complications Using the Quantiferon-CMV Assay After Allogeneic Hematopoietic Stem Cell Transplantation.

PubMed

Yong, Michelle K; Cameron, Paul U; Slavin, Monica; Morrissey, C Orla; Bergin, Krystal; Spencer, Andrew; Ritchie, David; Cheng, Allen C; Samri, Assia; Carcelain, Guislaine; Autran, Brigitte; Lewin, Sharon R

2017-06-01

A simple test to identify recovery of CMV-specific T-cell immunity following hematopoietic stem cell transplantation (HSCT) could assist clinicians in managing CMV-related complications. In an observational, multicenter, prospective study of 94 HSCT recipients we evaluated CMV-specific T-cell immunity at baseline, 3, 6, 9, and 12 months after transplant using the Quantiferon-CMV, an enzyme-linked immunosorbent spot assay (ELISpot), and intracellular cytokine staining. At 3 months after HSCT, participants who developed CMV disease (n = 8) compared with CMV reactivation (n = 26) or spontaneous viral control (n = 25) had significantly lower CD8+ T-cell production of interferon-γ (IFN-γ) in response to CMV antigens measured by Quantiferon-CMV (P = .0008). An indeterminate Quantiferon-CMV result had a positive predictive value of 83% and a negative predictive value of 98% for identifying participants at risk of further CMV reactivation. Participants experiencing CMV reactivation compared with patients without CMV reactivation had a reduced proportion of polyfunctional (IFN-γ+/tumor necrosis factor α-positive) CD4+ and CD8+ T cells and a higher proportion of interleukin 2-secreting cells (P = .01 and P = .002, respectively). Quantifying CMV-specific T-cell immunity after HSCT can identify participants at increased risk of clinically relevant CMV-related outcomes. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Assessment of the T-SPOT.CMV interferon-γ release assay in renal transplant recipients: A single center cohort study

PubMed Central

Borrows, Richard; Ball, Simon

2018-01-01

Background The measurement of CMV specific cellular immunity in organ transplant recipients could contribute additional acuity to serology based, CMV infection risk stratification, facilitating optimisation of immunosuppression and anti-viral prophylaxis. Methods A pilot study of renal transplant recipient (RTR’s) responses in the T-SPOT.CMV ELISPOT based assay. 108 RTR’s were recruited 3 months post-transplantation, immediately prior to the cessation of stratified anti-viral prophylaxis, used in recipients from seropositive donors. RTR’s were monitored for CMV viremia and disease. Cellular responses to peptides derived from CMV IE1 and pp65 were measured, using the T-SPOT.CMV assay. Results At recruitment, no CMV specific cellular immunity was detected by T-SPOT.CMV in CMV seronegative recipients (IE1 ≤ 1spot / 2.5x105 PBMC’s; pp65 ≤ 3 spots / 2.5x105 PBMC’s). At recruitment, CMV sero-positive recipients who made a robust response to both IE1 (>25 spots / 2.5x105 PBMC’s) and pp65 (>50 spots / 2.5x105 PBMC’s), were less likely to develop high level viremia than those who responded to one or neither antigen (0/28 vs 5/25; p<0.02). Conclusions In CMV seronegative RTR’s, CMV specific cellular immunity measured by T-SPOT.CMV was not detected prior to cessation of anti-viral prophylaxis. This differs from recent reports of CMV specific cellular immunity in a proportion of CMV seronegative RTR’s, associated with protection from CMV infection. In seropositive RTR’s, a dual response to IE1 and pp65 at recruitment, was associated with protection from subsequent viremia. This suggests that assessing the diversity of response to CMV antigens, may enhance risk stratification in this group. PMID:29558479

Screening for seemingly healthy newborns with congenital cytomegalovirus infection by quantitative real-time polymerase chain reaction using newborn urine: an observational study.

PubMed

Yamaguchi, Akira; Oh-Ishi, Tsutomu; Arai, Takashi; Sakata, Hideaki; Adachi, Nodoka; Asanuma, Satoshi; Oguma, Eiji; Kimoto, Hirofumi; Matsumoto, Jiro; Fujita, Hidetoshi; Uesato, Tadashi; Fujita, Jutaro; Shirato, Ken; Ohno, Hideki; Kizaki, Takako

2017-01-20

Approximately 8-10% of newborns with asymptomatic congenital cytomegalovirus (cCMV) infection develop sensorineural hearing loss (SNHL). However, the relationship between CMV load, SNHL and central nervous system (CNS) damage in cCMV infection remains unclear. This study aimed to examine the relationship between urinary CMV load, SNHL and CNS damage in newborns with cCMV infection. The study included 23 368 newborns from two maternity hospitals in Saitama Prefecture, Japan. Urine screening for cCMV infection (quantitative real-time PCR) and newborn hearing screening (automated auditory brainstem response (AABR) testing) were conducted within 5 days of birth to examine the incidence of cCMV infection and SNHL, respectively. CNS damage was assessed by MRI of cCMV-infected newborns. The incidence of cCMV infection was 60/23 368 (0.257%; 95% CI 0.192% to 0.322%). The geometric mean urinary CMV DNA copy number in newborns with cCMV was 1.79×10 6 copies/mL (95% CI 7.97×10 5 to 4.02×10 6 ). AABR testing revealed abnormalities in 171 of the 22 229 (0.769%) newborns whose parents approved hearing screening. Of these 171 newborns, 22 had SNHL (12.9%), and 5 of these 22 were infected with cCMV (22.7%). Newborns with both cCMV and SNHL had a higher urinary CMV DNA copy number than newborns with cCMV without SNHL (p=0.036). MRI revealed CNS damage, including white matter abnormalities, in 83.0% of newborns with cCMV. Moreover, newborns with CNS damage had a significantly greater urinary CMV load than newborns without CNS damage (p=0.013). We determined the incidence of cCMV infection and urinary CMV DNA copy number in seemingly healthy newborns from two hospitals in Saitama Prefecture. SNHL and CNS damage were associated with urinary CMV DNA copy number. Quantification of urinary CMV load may effectively predict the incidence of late-onset SNHL and neurodevelopmental disorders. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Recent advances in CMV tropism, latency, and diagnosis during aging.

PubMed

Leng, Sean X; Kamil, Jeremy; Purdy, John G; Lemmermann, Niels A; Reddehase, Matthias J; Goodrum, Felicia D

2017-06-01

Human cytomegalovirus (CMV) is one of the largest viruses known to cause human diseases. Chronic CMV infection, as defined by anti-CMV IgG serology, increases with age and is highly prevalent in older adults. It has complex biology with significant immunologic and health consequences. This article aims to summarize research findings presented at the 6th International Workshop on CMV and Immunosenescence that relate to advances in the areas of CMV tropism, latency, CMV manipulation of cell metabolism, and T cell memory inflation, as well as novel diagnostic evaluation and translational research of chronic CMV infection in older adults. Information summarized here represents the current state of knowledge in these important fields. Investigators have also identified a number of areas that deserve further and more in-depth investigation, including building more precise parallels between mouse CMV (mCMV) and human CMV (HCMV) research. It is hoped that this article will also stimulate engaging discussion on strategies and direction to advance the science to the next level.

Cytomegalovirus (CMV) research in immune senescence comes of age: overview of the 6th International Workshop on CMV and Immunosenescence.

PubMed

Nikolich-Žugich, Janko; van Lier, René A W

2017-06-01

Cytomegalovirus (CMV) is one of the most complex and most ubiquitous latent persistent viruses, with a considerable ability to evade and manipulate the immune system. Following an early-life infection, most immunocompetent humans spend several decades living with CMV, and, because the virus in these hosts does not cause manifest disease, CMV can be considered part of normal aging for more than half of humanity. However, there is accumulating evidence that CMV carriage is not a null event and that both potentially harmful and potentially beneficial outcomes emanate from the interaction of CMV with its mammalian hosts. This article provides an overview of the 6th International Workshop on CMV and Immunosenescence, highlighting the advances in the field made in the past two years, as related to CMV epidemiology/geroscience, CMV virology with an accent on latency, and CMV immune evasion and immune recognition of the virus and its antigens.

Poor CMV-specific CD8+ T central memory subset recovery at early stage post-HSCT associates with refractory and recurrent CMV reactivation.

PubMed

Liu, Jing; Chang, Ying-Jun; Yan, Chen-Hua; Xu, Lan-Ping; Jiang, Zheng-Fan; Zhang, Xiao-Hui; Liu, Kai-Yan; Huang, Xiao-Jun

2016-09-01

Refractory and recurrent cytomegalovirus (CMV) reactivation were independent risk factors of CMV disease and transplant-related mortality post allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our aims were to identify the recovery of CMV-specific CD8+ T cells with a central memory phenotype (TCM) associated with refractory and recurrent CMV reactivation. We analyzed findings in a prospective study comprising (n = 107) post allo-HSCT. CMV-specific CD8+ T cells were determined using HLA class I pentamers together with extended phenotypic analyses. The patients with lower level of CMV-specific CD8+ TCM at day 30 post-HSCT had an increased risk of refractory and recurrent CMV (68.5%) comparing with the higher one (13.2%) (p < 0.001) and poorer long term CMV-specific CD8+ T cell reconstitution post-HSCT (p = 0.026). Multivariate analysis revealed that CMV-specific CD8+ TCM at day 30 was an independent prognostic factor for refractory and recurrent reactivation (p = 0.002). The CMV-specific CD8+ TCM subset at day 30 post-HSCT is associated with CMV-specific T cell immunity recovery as well as the refractory and recurrent CMV reactivation post-HSCT. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

The effect of induction therapy on established CMV specific T cell immunity in living donor kidney transplantation.

PubMed

Stranavova, L; Hruba, P; Girmanova, E; Tycova, I; Slavcev, A; Fronek, J; Slatinska, J; Reinke, P; Volk, H-D; Viklicky, O

2018-05-04

Cytomegalovirus (CMV) infection influences both short and long term outcomes in immunosuppressed organ transplant recipients. The aim of this study was to evaluate the effect of different induction immunosuppression regimens on CMV specific T cell response in patients with already established CMV immunity. In 24 seropositive living donor kidney recipients, the frequency of CMV specific T cells was determined by ELISPOT (Enzyme-Linked ImmunoSpot) assay prior and 6 months after transplantation. Recipients' peripheral blood mononuclear cells were stimulated with immediate-early (IE1) and phosphoprotein 65 (pp65) CMV-derived peptide pools and the number of cells producing interferon gamma (IFN-gamma) was assessed. Patients received quadruple immunosuppression based either on depletive rabbit antithymocyte globulin (rATG) or non-depletive basiliximab induction and tacrolimus/mycophenolate mofetil/steroids. Patients with rATG induction received valgancyclovir prophylaxis. No effects of different induction agents on CMV specific T cell immunity were found at sixth month after kidney transplantation. There were no associations among dialysis vintage, pretransplant CMV specific T cell immunity, and later CMV DNAemia. Similarly, no effect of CMV prophylaxis on CMV specific T cell immunity was revealed. This study shows no effect of posttransplant immunosuppression on CMV specific T cell immunity in living donor kidney transplant recipients with CMV immunity already established, regardless of lymphocyte depletion and CMV prophylaxis.

IL-23 plasma level is strongly associated with CMV status and reactivation of CMV in renal transplant recipients.

PubMed

Sadeghi, Mahmoud; Lahdou, Imad; Opelz, Gerhard; Mehrabi, Arianeb; Zeier, Martin; Schnitzler, Paul; Daniel, Volker

2016-10-03

Cytomegalovirus seropositivity is an independent risk factor for atherosclerosis in patients with ESRD. Donor CMV seropositivity is associated with higher graft loss. Dendritic cells, macrophages and Th17 lymphocytes are defined as producers of IL-23. IL-23 is thought to be involved in the promotion of Th17 cell polarization. Latent CMV-induced Th17 might be involved in the pathogenesis of CMV infection in patients with ESRD. We aimed to evaluate associations of Th17-dependent cytokines with ESRD, CMV status and post-transplant outcome in kidney transplantation. IL-21 plasma levels were similar in patients and healthy controls (p = 0.47), whereas IL-9 (p = 0.02) and IL-23 (p < 0.0001) levels were significantly higher in ESRD patients. CMV-seronegative (p = 0.002) and -seropositive (p < 0.001) patients had significantly higher IL-23 plasma levels than controls. CMV-seropositive patients showed excessively higher IL-23 (p < 0.001) plasma levels than CMV-seronegative patients. Patients with post-transplant CMV reactivation had higher IL-23 plasma levels than patients without CMV reactivation (p = 0.025). Our results indicate that latent CMV induces IL-23. IL-23 might be an inflammatory mediator of latent CMV infection in patients with ESRD and predisposes patients for post-transplant CMV reactivation.

Control of Cytomegalovirus Viremia after Allogeneic Stem Cell Transplantation: A Review on CMV-Specific T Cell Reconstitution.

PubMed

van der Heiden, Pim; Marijt, Erik; Falkenburg, Fred; Jedema, Inge

2018-04-04

Recipients of allogeneic stem cell transplantation (alloSCT) are at risk for reactivation of endogenous herpesviruses due to profound and prolonged T cell deficiency following conditions such as graft-versus-host disease, immunosuppression, and/or T cell depletion. Reactivation of endogenous cytomegalovirus (CMV) is the most frequently occurring herpesvirus reactivation following alloSCT. Antiviral medication is often used in pre-emptive treatment strategies initiated when increases in CMV viral loads are detected as a result of active reactivation of the virus. Despite pre-emptive antiviral treatment, the incidence of CMV disease in CMV-seropositive alloSCT patients is still 10% at 1 year following alloSCT. This illustrates the necessity for adequate CMV-specific T cell immunity for long-term control of CMV and prevention of CMV disease. In this review, we analyzed the available studies on the influence of donor CMV status on CMV-specific T cell reconstitution and CMV disease. Furthermore, we reviewed the available studies on the safety and efficacy of adoptive transfer of donor CMV-specific T cells for the prevention and treatment of CMV disease following alloSCT, including studies on adoptive transfer of third-party CMV-specific T cells as a possible alternative when donor T cells are not available. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

The Roche Immunoturbidimetric Albumin Method on Cobas c 501 Gives Higher Values Than the Abbott and Roche BCP Methods When Analyzing Patient Plasma Samples.

PubMed

Helmersson-Karlqvist, Johanna; Flodin, Mats; Havelka, Aleksandra Mandic; Xu, Xiao Yan; Larsson, Anders

2016-09-01

Serum/plasma albumin is an important and widely used laboratory marker and it is important that we measure albumin correctly without bias. We had indications that the immunoturbidimetric method on Cobas c 501 and the bromocresol purple (BCP) method on Architect 16000 differed, so we decided to study these methods more closely. A total of 1,951 patient requests with albumin measured with both the Architect BCP and Cobas immunoturbidimetric methods were extracted from the laboratory system. A comparison with fresh plasma samples was also performed that included immunoturbidimetric and BCP methods on Cobas c 501 and analysis of the international protein calibrator ERM-DA470k/IFCC. The median difference between the Abbott BCP and Roche immunoturbidimetric methods was 3.3 g/l and the Roche method overestimated ERM-DA470k/IFCC by 2.2 g/l. The Roche immunoturbidimetric method gave higher values than the Roche BCP method: y = 1.111x - 0.739, R² = 0.971. The Roche immunoturbidimetric albumin method gives clearly higher values than the Abbott and Roche BCP methods when analyzing fresh patient samples. The differences between the two methods were similar at normal and low albumin levels. © 2016 Wiley Periodicals, Inc.

Cosmological perturbations in the (1 + 3 + 6)-dimensional space-times

NASA Astrophysics Data System (ADS)

Tomita, K.

2014-12-01

Cosmological perturbations in the (1+3+6)-dimensional space-times including photon gas without viscous processes are studied on the basis of Abbott et al.'s formalism [R. B. Abbott, B. Bednarz, and S. D. Ellis, Phys. Rev. D 33, 2147 (1986)]. Space-times consist of outer space (the 3-dimensional expanding section) and inner space (the 6-dimensional section). The inner space expands initially and later contracts. Abbott et al. derived only power-type solutions, which appear at the final stage of the space-times, in the small wave-number limit. In this paper, we derive not only small wave-number solutions, but also large wave-number solutions. It is found that the latter solutions depend on the two wave-numbers k_r and k_R (which are defined in the outer and inner spaces, respectively), and that the k_r-dependent and k_R-dependent parts dominate the total perturbations when (k_r/r(t))/(k_R/R(t)) ≫ 1 or ≪ 1, respectively, where r(t) and R(t) are the scale-factors in the outer and inner spaces. By comparing the behaviors of these perturbations, moreover, changes in the spectrum of perturbations in the outer space with time are discussed.

Prevalence of herpes simplex types 1 and 2, varicella zoster virus, cytomegalovirus, immunoglobulin G antibodies among female university students in Syria.

PubMed

Barah, Faraj

2012-09-01

To examine the current seroepidemiology of immunoglobulin (Ig)G for herpes simplex virus types 1 and 2 (HSV 1-2), varicella zoster virus (VZV), and cytomegalovirus (CMV) among university females of childbearing age in Syria. A cross-sectional study was conducted to examine the female students of the Pharmacy College, Kalamoon University, Deratiah, Syria, where 316 sera were collected from October 2009 to November 2010, and subjected to HSV 1-2, VZV, and CMV IgG screening and titration using enzyme-linked immunosorbent assay-based techniques in the Microbiology Laboratory. A total of 164 participants were positive for HSV 1-2 IgG giving a prevalence of 52%, leaving a relatively high proportion of susceptibility among the tested group. For VZV, 91% of the participants (n=287) were positive for its specific IgG, while, regarding CMV, 74.5% (n=235) were positive, and 25.5% were negative for CMV specific IgG. Although most participants were seropositive for herpes viruses IgG, suggesting a natural virus circulation within the community, screening for protective immunity is suggested against HSV, since a relatively high proportion of tested females are still susceptible. In addition, and because of its nasty outcomes during pregnancy, IgG against CMV should also be tested. High percentage of positivity towards VZV could be explained due to introduction of the new vaccine program, and therefore, further analysis during pregnancy is not recommended.

Using theory-based messages to motivate U.S. pregnant women to prevent cytomegalovirus infection: results from formative research.

PubMed

Levis, Denise M; Hillard, Christina L; Price, Simani M; Reed-Gross, Erika; Bonilla, Erika; Amin, Minal; Stowell, Jennifer D; Clark, Rebekah; Johnson, Delaney; Mask, Karen; Carpentieri, Cynthia; Cannon, Michael J

2017-12-14

An estimated 1 in 150 infants is born each year with congenital cytomegalovirus (CMV); nearly 1 in 750 suffers permanent disabilities. Congenital CMV is the result of a pregnant woman becoming infected with CMV. Educating pregnant women about CMV is currently the best approach to prevention. Limited research is available on how to effectively communicate with women about CMV. We conducted formative research on fear appeals theory-based messages about CMV and prevention with U.S. women. Fear appeal theories suggest that message recipients will take action if they feel fear. First, we conducted in-depth interviews (N = 32) with women who had young children who tested positive for CMV. Second, we conducted eight focus groups (N = 70) in two phases and two cities (Phase 2: Atlanta, GA; Phase 3: San Diego, CA) with pregnant women and non-pregnant women who had young children. Few participants knew about CMV before the focus groups. Participants reviewed and gave feedback on messages created around fear appeals theory-based communication concepts. The following concepts were tested in one or more of the three phases of research: CMV is severe, CMV is common, CMV is preventable, CMV preventive strategies are similar to other behavior changes women make during pregnancy, CMV preventive strategies can be incorporated in moderation to reduce exposure, and CMV is severe but preventable. Participants recommended communicating that CMV is common by using prevalence ratios (e.g., 1 in 150) or comparing CMV to other well-known disabilities. To convey the severity of CMV, participants preferred stories about CMV along with prevention strategies. Participants also welcomed prevention strategies when it included a message about risk reduction. In general, participants said messages were motivating, even if they felt that it could be difficult to make certain behavior changes. Findings from this research can contribute to future efforts to educate pregnant women about CMV, especially regarding use of fear appeals-based messages. Pregnant women may face certain challenges to practicing prevention strategies but, overall, are motivated make changes to increase their chances of having a healthy baby.

Cytomegalovirus (CMV) DNA Quantitation in Bronchoalveolar Lavage Fluid From Hematopoietic Stem Cell Transplant Recipients With CMV Pneumonia

PubMed Central

Stevens-Ayers, Terry; Travi, Giovanna; Huang, Meei-Li; Cheng, Guang-Shing; Xie, Hu; Leisenring, Wendy; Erard, Veronique; Seo, Sachiko; Kimball, Louise; Corey, Lawrence; Pergam, Steven A; Jerome, Keith R.

2017-01-01

Abstract Background. Quantitative cytomegalovirus (CMV) DNA–specific polymerase chain reaction (PCR) analysis is widely used as a surveillance method for hematopoietic stem cell transplant (HCT) recipients. However, no CMV DNA threshold exists in bronchoalveolar lavage (BAL) to differentiate pneumonia from pulmonary shedding. Methods. We tested archived BAL fluid samples from 132 HCT recipients with CMV pneumonia and 139 controls (100 patients with non-CMV pneumonia, 18 with idiopathic pneumonia syndrome [IPS], and 21 who were asymptomatic) by quantitative CMV and β-globin DNA–specific PCR. Results. Patients with CMV pneumonia had higher median viral loads (3.9 log10 IU/mL; interquartile range [IQR], 2.6–6.0 log10 IU/mL) than controls (0 log10 IU/mL [IQR, 0–1.6 log10 IU/mL] for patients with non-CMV pneumonia, 0 log10 IU/mL [IQR, 0–1.6 log10 IU/mL] for patients with IPS, and 1.63 log10 IU/mL [IQR, 0–2.5 log10 IU/mL] for patients who were asymptomatic; P < .001 for all comparisons to patients with CMV pneumonia). Receiver operating characteristic curve analyses and predictive models identified a cutoff CMV DNA level of 500 IU/mL to differentiate between CMV pneumonia and pulmonary shedding, using current CMV pneumonia prevalence figures. However, different levels may be appropriate in settings of very high or low CMV pneumonia prevalence. The presence of pulmonary copathogens, radiographic presentation, or pulmonary hemorrhage did not alter predictive values. Conclusion. CMV DNA load in BAL can be used to differentiate CMV pneumonia from pulmonary shedding. PMID:28181657

Cytomegalovirus (CMV) DNA Quantitation in Bronchoalveolar Lavage Fluid From Hematopoietic Stem Cell Transplant Recipients With CMV Pneumonia.

PubMed

Boeckh, Michael; Stevens-Ayers, Terry; Travi, Giovanna; Huang, Meei-Li; Cheng, Guang-Shing; Xie, Hu; Leisenring, Wendy; Erard, Veronique; Seo, Sachiko; Kimball, Louise; Corey, Lawrence; Pergam, Steven A; Jerome, Keith R

2017-05-15

Quantitative cytomegalovirus (CMV) DNA-specific polymerase chain reaction (PCR) analysis is widely used as a surveillance method for hematopoietic stem cell transplant (HCT) recipients. However, no CMV DNA threshold exists in bronchoalveolar lavage (BAL) to differentiate pneumonia from pulmonary shedding. We tested archived BAL fluid samples from 132 HCT recipients with CMV pneumonia and 139 controls (100 patients with non-CMV pneumonia, 18 with idiopathic pneumonia syndrome [IPS], and 21 who were asymptomatic) by quantitative CMV and β-globin DNA-specific PCR. Patients with CMV pneumonia had higher median viral loads (3.9 log10 IU/mL; interquartile range [IQR], 2.6-6.0 log10 IU/mL) than controls (0 log10 IU/mL [IQR, 0-1.6 log10 IU/mL] for patients with non-CMV pneumonia, 0 log10 IU/mL [IQR, 0-1.6 log10 IU/mL] for patients with IPS, and 1.63 log10 IU/mL [IQR, 0-2.5 log10 IU/mL] for patients who were asymptomatic; P < .001 for all comparisons to patients with CMV pneumonia). Receiver operating characteristic curve analyses and predictive models identified a cutoff CMV DNA level of 500 IU/mL to differentiate between CMV pneumonia and pulmonary shedding, using current CMV pneumonia prevalence figures. However, different levels may be appropriate in settings of very high or low CMV pneumonia prevalence. The presence of pulmonary copathogens, radiographic presentation, or pulmonary hemorrhage did not alter predictive values. CMV DNA load in BAL can be used to differentiate CMV pneumonia from pulmonary shedding. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Current concepts on cytomegalovirus infection after liver transplantation.

PubMed

Lee, Sang-Oh; Razonable, Raymund R

2010-09-27

Cytomegalovirus (CMV) is the most common viral pathogen that negatively impacts on the outcome of liver transplantation. CMV cause febrile illness often accompanied by bone marrow suppression, and in some cases, invades tissues including the transplanted allograft. In addition, CMV has been significantly associated with an increased predisposition to allograft rejection, accelerated hepatitis C recurrence, and other opportunistic infections, as well as reduced overall patient and allograft survival. To negate the adverse effects of CMV on outcome, its prevention, whether through antiviral prophylaxis or preemptive therapy, is regarded as an essential component to the medical management of liver transplant patients. Two recent guidelines have suggested that antiviral prophylaxis or preemptive therapy are similarly effective in preventing CMV disease in modest-risk CMV-seropositive liver transplant recipients, while antiviral prophylaxis is the preferred strategy over preemptive therapy for the prevention of CMV disease in high-risk recipients [CMV-seronegative recipients of liver allografts from CMV-seropositive donors (D+/R-)]. However, antiviral prophylaxis has only delayed the onset of CMV disease in many CMV D+/R- liver transplant recipients, and at least in one study, such occurrence of late-onset primary CMV disease was significantly associated with increased mortality after liver transplantation. Therefore, optimized strategies for prevention are needed, and aggressive treatment of CMV infection and disease should be pursued. The standard treatment of CMV disease consists of intravenous ganciclovir or oral valganciclovir, and if feasible, one should also reduce the degree of immunosuppression. In one recent controlled clinical trial, valganciclovir was found to be as effective and safe as intravenous ganciclovir for the treatment of mild to moderate CMV disease in solid organ (including liver) transplant recipients. In this article, the authors review the current state and the future perspectives of prevention and treatment of CMV disease after liver transplantation.

Immune predispositions for cytomegalovirus retinitis in AIDS. The HNRC Group.

PubMed Central

Schrier, R D; Freeman, W R; Wiley, C A; McCutchan, J A

1995-01-01

CMV retinitis develops in approximately 28-35% of all AIDS patients at later stages of disease, often leading to blindness. To determine whether the subset of AIDS patients who developed CMV retinitis (CMV-R) were immunologically predisposed, T cell proliferation responses to CMV were examined prospectively in an HIV infected, HLA typed, longitudinal study population. Individuals who developed CMV-R had significantly lower T cell proliferation responses to CMV, both early and late in disease, compared to CD4 matched controls who have not developed CMV-R. Since HLA proteins influence T-cell recognition, phenotypes of 21 CMV-R patients were examined to determine whether certain HLA alleles were associated with low immune response and predisposed AIDS patients to CMV-R. HLA DR7 and B44 were at increased (nearly twice the expected) frequency in those with CMV-R. The combined association of either B44, 51 or DR7 with CMV-R was highly significant (P = .008, relative risk of CMV-R = 15) with correction for multiple comparisons. Low immune responses were twice as frequent in those with (61%) compared to those without (30%) predisposing alleles. Thus, AIDS patients with immunogenetically related hyporesponsiveness to CMV antigens may be at increased risk of retinitis. PMID:7706482

[Prevalence of anti-CMV antibodies in blood donors in the Sfax region (value in blood transfusion)].

PubMed

Gargouri, J; Elleuch, H; Karray, H; Rekik, H; Hammami, A

2000-01-01

Detection of anti-CMV antibodies was carried out in sera of healthy blood donors, divided into groups of 20 according to age and sex. Sera were tested for anti-CMV by an ELISA test (Enzygnost anti-CMV/IgG-Behring). Among 280 sera, 272 were positive for IgG to CMV (97.14%). The prevalence of those antibodies was high in all age stratum (95-100%) but was higher in women than in men (98.57% versus 95.71%). The titre of IgG to CMV was superior to 12 Ul/ml in 56.43% of CMV positive donors. So, the leucocyte removal is the only alternative for the prevention of post-transfusional CMV infection. The high percentage of donors with anti-CMV antibodies level more than to 12 Ul/ml allow to consider the use of plasmapheresis for preparing specific immunoglobulins to CMV.

Partnering for Preschool: A Study of Center Directors in New Jersey's Mixed-Delivery Abbott Program. Research Report

ERIC Educational Resources Information Center

Whitebook, Marcy; Ryan, Sharon; Kipnis, Fran; Sakai, Laura

2008-01-01

In a series of New Jersey Supreme Court decisions known as Abbott v. Burke, the 28 (now 31) urban school districts serving the state's poorest students were ordered to create systems of high-quality preschool for all three- and four-year-old children, beginning in the 1999-2000 school year. The Abbott Preschool Program now serves approximately…

Fulfilling the Promise of Abbott: The Lighthouse Assessment Process--Improving Programs through Measured Outcomes. Policy Progress, Spring 2004

ERIC Educational Resources Information Center

Association for Children of New Jersey, 2004

2004-01-01

In an attempt to better prepare young children for the challenges of kindergarten and first grade, the Supreme Court of New Jersey, in its 1998 landmark decision of "Abbott v. Burke" (Abbott V), required the State's poorest school districts to implement high quality, intensive preschool for all 3-and 4-year old children. To take…

Protective Cytomegalovirus (CMV)-Specific T-Cell Immunity Is Frequent in Kidney Transplant Patients without Serum Anti-CMV Antibodies

PubMed Central

Litjens, Nicolle H. R.; Huang, Ling; Dedeoglu, Burç; Meijers, Ruud W. J.; Kwekkeboom, Jaap; Betjes, Michiel G. H.

2017-01-01

The absence of anti-cytomegalovirus (CMV) immunoglobulin G (IgG) is used to classify pretransplant patients as naïve for CMV infection (CMVneg patients). This study assessed whether pretransplant CMV-specific T-cell immunity exists in CMVneg patients and whether it protects against CMV infection after kidney transplantation. The results show that CMV-specific CD137+IFNγ+CD4+ and CD137+IFNγ+CD8+ memory T cells were present in 46 and 39% of CMVneg patients (n = 28) although at much lower frequencies compared to CMVpos patients (median 0.01 versus 0.58% for CD4+ and 0.05 versus 0.64% for CD8+ T cells) with a less differentiated CD28-expressing phenotype. In line with these data, CMV-specific proliferative CD4+ and CD8+ T cells were observed in CMVneg patients, which significantly correlated with the frequency of CMV-specific T cells. CMV-specific IgG antibody-secreting cells (ASC) could be detected at low frequency in 36% of CMVneg patients (1 versus 45 ASC/105 cells in CMVpos patients). CMVneg patients with pretransplant CMV-specific CD137+IFNγ+CD4+ T cells had a lower risk to develop CMV viremia after transplantation with a CMVpos donor kidney (relative risk: 0.43, P = 0.03). In conclusion, a solitary CMV-specific T-cell response without detectable anti-CMV antibodies is frequent and clinically relevant as it is associated with protection to CMV infection following transplantation with a kidney from a CMVpos donor. PMID:28955345

CMV mismatch does not affect patient and graft survival in UK renal transplant recipients.

PubMed

Johnson, Rachel J; Clatworthy, Menna R; Birch, Rhiannon; Hammad, Abdul; Bradley, J Andrew

2009-07-15

Cytomegalovirus (CMV) is one of the major infections encountered posttransplantation. UK Guidelines (2003) recommend CMV prophylaxis or screening with preemptive treatment for all high risk recipients. Studies predating the widespread use of CMV prophylaxis have shown that CMV seronegative recipients (R-) receiving a renal allograft from a CMV seropositive donor (D+) have worse outcomes than those avoiding primary CMV infection. Therefore, it has been suggested that CMV matching should be a part of the UK national deceased donor kidney allocation scheme. We examined patient and allograft survival according to donor and recipient CMV serostatus in 10,190 UK adult and pediatric deceased donor renal transplant recipients transplanted between 2000 and 2007. We also ascertained CMV prophylaxis strategies in all UK renal transplant units. Twenty-one of the 22 UK renal transplant centers used prophylactic oral valganciclovir for 3 months posttransplant in the D+R- transplants, having done so for a median of 4 years. Unadjusted data showed that D+R+ rather than D+R- transplants had the lowest patient and allograft survivals at 3 years posttransplant. However, after adjustment for donor age, there was no significant effect of donor and recipient CMV serostatus on allograft or patient survival. These findings suggest that in an era where CMV prophylaxis is used routinely in D+R- transplants, the previously noted adverse effects of primary CMV infection on allograft and patient survival can be avoided (perhaps through a reduction in the incidence and/or severity of primary CMV infection), without using a CMV-matching allocation scheme.

Increased risk of complicated CMV infection with the use of mycophenolate mofetil in allogeneic stem cell transplantation.

PubMed

Hambach, L; Stadler, M; Dammann, E; Ganser, A; Hertenstein, B

2002-06-01

Mycophenolate mofetil (MMF) is increasingly used for prophylaxis and therapy of GVHD in allogeneic stem cell transplantation. In some recent reports of use of MMF in solid organ transplantation a high incidence of CMV disease has been described. We evaluated the frequency and course of active CMV infection in patients who received MMF compared to those who did not receive MMF after allogeneic stem cell transplantation. We retrospectively analyzed 48 adult patients who consecutively underwent unmanipulated allogeneic bone marrow (n = 15) or peripheral stem cell transplantation (n = 33) from HLA-compatible family donors (n = 30) or unrelated donors (n = 18) from February 1997 to September 2000 at our institution. Only patients who were evaluable for the first 100 days were included in this analysis. Sixteen patients received MMF post transplant (MMF+). CMV-antigenemia was monitored by CMV-pp65 antigen. CMV-antigenemia occurred in 14 patients and was virtually only observed in CMV-IgG+ recipients (13/23, 56%). CMV-IgG+/MMF+ patients developed a higher incidence of CMV-antigenemia (8/9, 89%) compared to the CMV-IgG+/MMF- patients (5/14, 35%; P < 0.05). Moreover, five of six patients with persistent or recurrent CMV-antigenemia received MMF. No patient in either group developed CMV disease or died of CMV-related complications. In multivariate analysis including MMF treatment, unrelated vs related donor, GVHD, CMV-serostatus of the donor and stem cell graft type, only MMF treatment was found to be a significant risk factor for both overall and complicated CMV infection.

Lower incidence of CMV infection and acute rejections with valganciclovir prophylaxis in lung transplant recipients

PubMed Central

2013-01-01

Background Cytomegalovirus (CMV) is the most common opportunistic infection following lung transplantation. CMV replication in the lung allograft is described as accelerating the development of bronchiolitis obliterans syndrome (BOS). Finding a strategy to prevent CMV infection is an important issue. Methods We performed a retrospective, single-centre study of 114 lung transplant recipients (LTRs) who underwent lung transplantation from January 2001 to December 2006. In a smaller cohort of 88 CMV seropositive (R+) LTRs, three months of valganciclovir prophylaxis (2004-2006) was compared to three months of oral ganciclovir (2001-2003) with respect to the incidence of CMV infection/disease, the severity of CMV disease, acute rejection, BOS-free 4 year survival and 4 year survival. In the whole group of 114 LTRs the impact of CMV infection on long-term survival (BOS free 4 year survival and 6 year survival) was assessed. Results For the cohort of 88 CMV seropositive LTRs, the incidence of CMV infection/disease at one year was lower in the valganciclovir group compared to the ganciclovir group (24% vs. 54%, p = 0.003). There was a tendency towards reduced CMV disease, from 33% to 20% and a significant lower incidence of asymptomatic CMV infection (22% vs. 4%, p = 0.005). A lower incidence of acute rejection was observed in the valganciclovir group. However, there was no significant difference between the two groups in BOS free 4 year survival and 4 year survival. For the entire group of 114 LTRs, BOS-free 4 year survival for recipients with CMV disease was (32%, p = 0.005) and among those with asymptomatic CMV infection (36%, p = 0.061) as compared with patients without CMV infection (69%). Six year survival was lower among patients with CMV disease, (64%, p = 0.042) and asymptomatic CMV infection (55%, p = 0.018) than patients without CMV infection (84%). Conclusions A lower incidence of CMV infection/disease and acute rejections was observed with valganciclovir (3 months) when compared to oral ganciclovir (3 months). The long-term impact of CMV infection/disease was significant for BOS-free survival and survival. PMID:24325216

Diagnostic usefulness of dynamic changes of CMV-specific T-cell responses in predicting CMV infections in HCT recipients.

PubMed

Jung, Jiwon; Lee, Hyun-Jung; Kim, Sun-Mi; Kang, Young-Ah; Lee, Young-Shin; Chong, Yong Pil; Sung, Heungsup; Lee, Sang-Oh; Choi, Sang-Ho; Kim, Yang Soo; Woo, Jun Hee; Lee, Jung-Hee; Lee, Je-Hwan; Lee, Kyoo-Hyung; Kim, Sung-Han

2017-02-01

CMV-specific cell mediated immune responses before and after hematopoietic stem cell transplantation (HCT) can categorize patients as at high or low risk of CMV development. We evaluated the usefulness of the CMV-specific T-cell ELISPOT assay for predicting the development of CMV infections after HCT in recipients with donor-positive and recipient-positive CMV serology (D+/R+ ). CMV pp65 and IE1-specific ELISPOT assays were performed before HCT (D0), and at 30 (D30) and 90 (D90) days after HCT. Of the 84 HCT recipients with D+/R+, 42 (50%) developed≥1 episode of CMV infection. Thirty-nine (64%) of 61 patients with Δ(D30-D0) pp65<42 developed CMV infections compared with 3 (14%) of 21 patients with Δ(D30-D0) pp65≥42 (P<0.001). Twenty-three (74%) of 31 patients with Δ(D30-D0) IE1<-4 developed CMV infections compared with 19 (37%) of 51 patients with Δ(D30-D0) IE1≥-4 (P=0.001). pp65 Δ(D30-D0) ≥42 had 93% sensitivity for ruling out subsequent CMV infection, and pp65 Δ(D30-D0)<42 followed by Δ(D30-D0) IE1<-4 had 100% specificity for ruling in the subsequent CMV infection. In addition, 10 (53%) of 19 patients with Δ(D90-D30) pp65<23 had relapsing CMV infections, compared with 3 (15%) of 20 patients with Δ(D90-D30) pp65≥23 (P=0.02). The sensitivity and specificity of Δ(D90-D30) pp65 were 77% (95% CI 50-92) and 65% (95% CI, 46-81). Dynamic change in the CMV-specific ELISPOT assay before versus after HCT appears to predict the subsequent development of CMV infection and relapsing CMV infection. Copyright © 2016 Elsevier B.V. All rights reserved.

Cytomegalovirus (CMV) DNA quantification in bronchoalveolar lavage fluid of immunocompromised patients with CMV pneumonia.

PubMed

Beam, Elena; Germer, Jeffrey J; Lahr, Brian; Yao, Joseph D C; Limper, Andrew Harold; Binnicker, Matthew J; Razonable, Raymund R

2018-01-01

Cytomegalovirus (CMV) pneumonia causes major morbidity and mortality. Its diagnosis requires demonstration of viral cytopathic changes in tissue, entailing risks of lung biopsy. This study aimed to determine CMV viral load (VL) thresholds in bronchoalveolar lavage fluid (BALF) for diagnosis of CMV pneumonia in immunocompromised patients. CMV VL in BALF was studied in 17 patients (83% transplant recipients) and 21 control subjects with and without CMV pneumonia, respectively, using an FDA-approved PCR assay (Cobas ® AmpliPrep/Cobas TaqMan ® CMV Test, Roche Molecular Systems, Inc.) calibrated to the WHO International Standard for CMV DNA (NIBSC: 09/162). Receiver operating characteristic curve analysis produced a BALF CMV VL threshold of 34 800, IU/mL with 91.7% sensitivity and 100.0% specificity for diagnosis of possible, probable, and proven CMV pneumonia in transplant patients, while a threshold of 656 000 IU/mL yielded 100% sensitivity and specificity among biopsy-proven cases. For all immunocompromised patients, a VL threshold of 274 IU/mL was selected. VL thresholds also were normalized to BALF cell count yielding a threshold of 0.32 IU/10 6 cells with 91.7% sensitivity and 90.5% specificity for possible, probable, and proven CMV pneumonia in transplant recipients. Monitoring CMV VL in BALF may be a less invasive method for diagnosing CMV pneumonia in immunocompromised patients. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Evaluation of New Quantitative Assays for Diagnosis and Monitoring of Cytomegalovirus Disease in Human Immunodeficiency Virus-Positive Patients

PubMed Central

Pellegrin, Isabelle; Garrigue, Isabelle; Binquet, Christine; Chene, Genevieve; Neau, Didier; Bonot, Pascal; Bonnet, Fabrice; Fleury, Herve; Pellegrin, Jean-Luc

1999-01-01

Cobas Amplicor CMV Monitor (CMM) and Quantiplex CMV bDNA 2.0 (CMV bDNA 2.0), two new standardized and quantitative assays for the detection of cytomegalovirus (CMV) DNA in plasma and peripheral blood leukocytes (PBLs), respectively, were compared to the CMV viremia assay, pp65 antigenemia assay, and the Amplicor CMV test (P-AMP). The CMV loads were measured in 384 samples from 58 human immunodeficiency virus (HIV) type 1-infected, CMV-seropositive subjects, including 13 with symptomatic CMV disease. The assays were highly concordant (agreement, 0.88 to 0.97) except when the CMV load was low. Quantitative results for plasma and PBLs were significantly correlated (Spearman ρ = 0.92). For PBLs, positive results were obtained 125 days before symptomatic CMV disease by CMV bDNA 2.0 and 124 days by pp65 antigenemia assay, whereas they were obtained 46 days before symptomatic CMV disease by CMM and P-AMP. At the time of CMV disease diagnosis, the sensitivity, specificity, and positive and negative predictive values of CMV bDNA 2.0 were 92.3, 97.8, 92.3, and 97.8%, respectively, whereas they were 92.3, 93.3, 80, and 97.8%, respectively, for the pp65 antigenemia assay; 84.6, 100, 100, and 95.7%, respectively, for CMM; and 76.9, 100, 100, and 93.8%, respectively, for P-AMP. Considering the entire follow-up, the sensitivity, specificity, and positive and negative predictive values of CMV bDNA 2.0 were 92.3, 73.3, 52.1, and 97.1%, respectively, whereas they were 100, 55.5, 39.4, and 100%, respectively, for the pp65 antigenemia assay; 92.3, 86.7, 66.7, and 97.5%, respectively, for CMM; and 84.6, 91.1, 73.3, and 95.3%, respectively, for P-AMP. Detection of CMV in plasma is technically easy and, despite its later positivity (i.e., later than in PBLs), can provide enough information sufficiently early so that HIV-infected patients can be effectively treated. In addition, these standardized quantitative assays accurately monitor the efficacy of anti-CMV treatment. PMID:10488165

Impact of minimum contrast media volumes during elective percutaneous coronary intervention for prevention of contrast-induced nephropathy in patients with stable coronary artery disease.

PubMed

Ebisawa, Soichiro; Kurita, Tairo; Tanaka, Nobuyoshi; Nasu, Kenya; Kimura, Masashi; Ito, Tatsuya; Kinoshita, Yoshihisa; Tsuchikane, Etsuo; Terashima, Mitsuyasu; Suzuki, Takahiko

2016-01-01

Contrast-induced nephropathy (CIN) is an important complication following percutaneous coronary intervention (PCI). The clinical importance of a minimum contrast media volume (CMV) for PCI to prevent CIN has not been well evaluated. The purpose of this study was to evaluate the impact of minimum CMV to prevent CIN after PCI. In this study, 2052 consecutive patients who underwent elective PCI in our institute were analyzed. We divided patients into two groups according to CMV: a minimum CMV PCI group [CMV ≤50 ml (n = 94)] and a non-minimum CMV PCI group [CMV >50 ml (n = 1958)]. CIN occurred in 160 (7.8 %) patients. The incidence of CIN was significantly lower in the minimum CMV PCI group than in the non-minimum CMV PCI group (2.1 vs. 8.1 %; P = 0.03). According to multivariate analysis, elderly patients and diabetes mellitus patients were at high risk of developing CIN in this study population. When analyzing only high-risk patients, the incidence of CIN was also significantly lower in the minimum CMV group than in the non-minimum CMV group (2.6 vs. 10.3 %; P = 0.03). Minimum CMV PCI could reduce the incidence of CIN, particularly in high-risk patients; as such, defining the minimum CMV clinical cut-off values may be useful for the prevention of CIN.

Impact of Pharmacist Involvement in Early Identification and Enrollment in Patient Assistance Programs on CMV Outcomes in Transplantation.

PubMed

Byrns, Jennifer S; Pilch, Nicole W; Taber, David J

2016-04-01

No data exist evaluating the utilization of patient assistance programs (PAPs) on cytomegalovirus (CMV)-related outcomes. To determine whether early identification and enrollment in PAPs can prevent CMV-related events. Retrospective analysis of patients at risk of CMV reactivation who received kidney and/or pancreas transplants. Two groups were evaluated with patients receiving oral valganciclovir for CMV prophylaxis through enrollment in PAPs or oral acyclovir with preemptive CMV monitoring. Primary outcomes include the incidence of CMV infection. Secondary outcomes include a cost benefit analysis, incidence of rejection, patient/graft survival, and time to CMV infection. There were 97 patients identified; valganciclovir through PAPs (n = 39) and preemptive CMV quantitative nucleic acid testing monitoring (n = 58). The incidence of CMV viremia was lower in the PAP group (12.8% vs 36.2%, respectively; P = .021). There were no significant differences in CMV syndrome/disease, acute rejection, graft loss, or death between the groups. The time to CMV infection was shorter in the preemptive group. Cost benefit analysis found that hiring a full time pharmacy employee for enrolling patients in PAPs was cost beneficial for the institution/health care system. Early identification and enrollment of patients in PAPs reduces the incidence of CMV viremia. Pharmacists play a crucial role in this process. © The Author(s) 2014.

Primary response against cytomegalovirus during antiviral prophylaxis with valganciclovir, in solid organ transplant recipients

PubMed Central

La Rosa, Corinna; Limaye, Ajit P.; Krishnan, Aparna; Blumstein, Gideon; Longmate, Jeff; Diamond, Don J.

2012-01-01

Antiviral prophylaxis has proved successful for prevention of cytomegalovirus (CMV) disease in solid organ transplant (SOT) patients; though emerging data suggest that antiviral agents interfere with immunity, and may inhibit immune-priming. In this context, we investigated levels and phenotype of primary CMV-specific immune responses that developed during antiviral prophylaxis in a cohort of CMV seronegative recipients (R−) of a SOT from a seropositive donor (D+). We longitudinally monitored CMV viral load, antibodies and levels of the negative immuno-modulator IL-10. PBMC were stimulated with CMV-specific peptide libraries to measure CD137 activation marker on CMV-specific T-cells and levels of PD-1 receptor, which is overexpressed on exhausted T-cells. Unexpectedly, the majority (13/18) of D+R− patients who developed a primary CMV response showed early post-transplant CMV-specific responses, though levels of PD-1 on CMV-specific T-cells remained elevated throughout prophylaxis. A strong inverse association was found between levels of plasma IL-10 and CMV-specific cellular immune responses. Our study suggests that during prophylaxis, subclinical CMV infection might have occurred in the D+R− patients, and primary CMV-specific responses were detected early post-transplant when levels of plasma IL-10 were low. Extended prophylaxis or antiviral treatment did not appear to suppress CMV-specific antibodies or T-cells, which however showed exhaustion phenotypes. PMID:21672050

Prevalence, Characteristics, and One-Year Follow-Up of Congenital Cytomegalovirus Infection in Isfahan City, Iran.

PubMed

Karimian, Pegah; Yaghini, Omid; Nasr Azadani, Hossein; Mohammadizadeh, Majid; Arabzadeh, Seyed Ali Mohammad; Adibi, Atosa; Rahimi, Hamid

2016-01-01

Introduction. Need of neonatal screening for Cytomegalovirus (CMV) infection is under debate, in part because of limited data on importance of the disease regarding the prevalence of congenital CMV (cCMV) infection and associated morbidity and mortality. We aimed to evaluate the prevalence and prognosis of cCMV infection in Iran, where there is high maternal seroprevalence of CMV. Methodology . This prospective study was conducted in Isfahan city, Iran, from 2014 to 2016. CMV was investigated in urine specimens by using the real-time polymerase chain reaction (RT-PCR) method. CMV-infected infants were examined for clinical and laboratory findings attributed to CMV infection and followed up for one year. Results. Among 1617 studied neonates, eight (0.49%) were positive for CMV infection. CMV-infected neonates were more likely to be preterm than noninfected ones (25% versus 4.5%, p = 0.0508), and they had lower birth weight. Three out of the eight CMV-infected neonates had transient symptoms at birth. At follow-up, one case had mild hearing loss. Most patients had impaired growth during the one-year follow-up. Conclusions. The primary object of this study was determination of prevalence of cCMV infection in Iran as a developing country, which was at the lower range compared with other such countries. cCMV infection may result in short-term impairment in growth.

CMV information: print, online, phone, video.

PubMed

1996-10-04

There are a number of treatment options available for cytomegalovirus (CMV) and approved preventive treatments for persons at high risk. Partnership in Vision has published a CMV Retinitis Report. A one-hour continuing medication education course entitled CMV Prophylaxis and Intraocular Therapy is available on the World Wide Web. The National Association of People with AIDS (NAPWA) has extended its CMV information hotline. Cidofovir is a new drug approved for marketing for CMV treatment. It is infused only once every two weeks. CMV videotapes are available from Hoffman-La Roche.

Evaluation of the new restandardized Abbott Architect 25-OH Vitamin D assay in vitamin D-insufficient and vitamin D-supplemented individuals.

PubMed

Annema, Wijtske; Nowak, Albina; von Eckardstein, Arnold; Saleh, Lanja

2017-09-19

Recently, Abbott Diagnostics has restandardized the Architect 25(OH)D assay against the NIST SRM 2972. We have evaluated the analytical and clinical performance of the restandardized Architect 25(OH)D assay and compared its performance with a NIST-traceable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method and the Roche total 25(OH)D assay in vitamin D-insufficient individuals before and after vitamin D 3 supplementation. Frozen serum samples were obtained from 88 healthy subjects with self-perceived fatigue and vitamin D-insufficiency <50 nmol L -1 who were randomized to receive a single 100 000 IU dose of vitamin D 3 (n = 48) or placebo (n = 40). Total 25(OH)D concentrations were measured before and 4 weeks after supplementation by the restandardized Architect 25(OH)D assay, LC-MS/MS, and Roche assay. The Architect 25(OH)D assay showed an intra- and inter-assay imprecision of <5%. Comparison of the Architect assay with the LC-MS/MS method showed a good correlation in both vitamin D-insufficient and vitamin D-supplemented subjects, however, with a negative mean bias of 17.4% and 8.9%, respectively. As compared to the Roche assay, the Abbott assay underestimated 25(OH)D results in insufficient subjects (<50 nmol L -1 ) with a mean negative bias of 17.1%, this negative bias turned into a positive bias in supplemented subjects. Overall there was a moderate agreement in classification of vitamin D-insufficient and -supplemented individuals into different vitamin D states between the Architect 25(OH)D method and LC-MS/MS. The routine use of the restandardized Architect 25(OH)D results in a slight underestimation of circulating total 25(OH)D levels at lower concentrations and thus potential misclassification of vitamin D status. © 2017 Wiley Periodicals, Inc.

Comparison of Standardized Cytomegalovirus (CMV) Viral Load Thresholds in Whole Blood and Plasma of Solid Organ and Hematopoietic Stem Cell Transplant Recipients with CMV Infection and Disease.

PubMed

Dioverti, M Veronica; Lahr, Brian D; Germer, Jeffrey J; Yao, Joseph D; Gartner, Michelle L; Razonable, Raymund R

2017-01-01

Quantification of cytomegalovirus (CMV) deoxyribonucleic acid (DNA) has important diagnostic, prognostic, and therapeutic implications in the management of transplant recipients. We aimed to assess a viral load in plasma and whole blood that distinguishes CMV disease from asymptomatic infection in a cohort of solid organ and hematopoietic stem cell transplantation. We prospectively measured and compared CMV viral load in paired plasma and whole blood samples collected from transplant recipients with CMV infection and disease. Cytomegalovirus viral loads were determined by a commercially available US Food and Drug Administration-approved quantitative assay (COBAS AmpliPrep/COBAS TaqMan CMV Test [CAP/CTM CMV]) calibrated to the first World Health Organization International Standard for CMV DNA quantification. Moderate agreement of CMV viral load was observed between plasma and whole blood, with 31% of samples having discordant findings, particularly among samples with low DNA levels. Among the subset of samples where both paired samples had quantifiable levels, we observed a systematic bias that reflected higher viral load in whole blood compared with plasma. Based on receiver operating curve analysis, an initial plasma CMV viral load threshold of 1700 IU/mL in solid organ transplant recipients (sensitivity 80%, specificity 74%) and 1350 IU/mL in allogeneic hematopoietic stem cell transplant recipients (sensitivity 87%, specificity 87%) distinguished CMV disease and asymptomatic infection. This study identifies standardized viral load thresholds that distinguish CMV disease from asymptomatic infection using CAP/CTM CMV assay. We propose these thresholds as potential triggers to be evaluated in prospective studies of preemptive therapy. Plasma was better than whole blood for measuring viral load using the CAP/CTM CMV assay.

CMV antigenemia following bone marrow transplantation: risk factors and outcomes.

PubMed

Osarogiagbon, R U; Defor, T E; Weisdorf, M A; Erice, A; Weisdorf, D J

2000-01-01

Cytomegalovirus (CMV) infection remains a major problem in blood and bone marrow transplant (BMT) recipients. Recent efforts have been directed at prevention, early diagnosis, and treatment of CMV disease following BMT. Assay for CMV early antigen pp65 on circulating leukocytes has been shown to be sensitive, and specific in detecting early CMV infection. We examined the frequency, risk factors, and outcomes of a positive CMV antigen assay in 118 consecutive BMT patients. Forty-three (36%) of the 118 patients developed CMV antigenemia a median of 26 days post-BMT (range, -6 to 209 days). The incidence of antigenemia in autologous, related donor, and unrelated donor BMT recipients was 15%, 50%, and 48%, respectively (P < .01) and was lower in CMV-seronegative patients (19% versus 51% in seropositive patients; P < .01). Patients with grade II to IV acute graft-versus-host disease (GVHD) had 2.2 times the risk of antigenemia of patients with no or only limited GVHD (P = .03). Age at transplantation, underlying disease, CMV prophylaxis regimen, and GVHD prophylaxis regimen did not affect the risk of CMV antigenemia. Ten of the 43 antigenemic patients, all CMV-seropositive allogeneic BMT (alloBMT) recipients, developed CMV organ disease a median of 101 days (range, 28-283 daya) post-BMT. These data suggest that CMV-seropositive alloBMT patients are at highest risk for CMV antigenemia and for organ disease as well. CMV disease may occur before antigenemia is detectable in leukopenic patients and may also develop late post-BMT, even in patients still receiving antiviral prophylaxis. In high-risk groups, intensive surveillance continuing for more than 6 months after BMT may be indicated.

Recent advances in the therapy and prevention of CMV infections.

PubMed

Nichols, W G; Boeckh, M

2000-02-01

The introduction of highly active antiretroviral therapy (HAART) for HIV has had a major impact on the treatment of CMV disease in HIV-infected individuals. There is mounting evidence that in patients with CMV retinitis who have a sustained response to HAART, CMV maintenance treatment can be discontinued without relapse of retinitis. In HAART-naïve individuals with newly diagnosed CMV retinitis, the optimal timing for the initiation of HAART relative to the start of anti-CMV treatment is currently unknown. New local therapies for CMV retinitis (e.g. ganciclovir implant, the new antisense compound fomivirsen) provide treatment options in situations where high local drug delivery is warranted. A treatment algorithm for CMV disease in the HAART era is proposed. In the transplant setting, ganciclovir and foscarnet remain the major compounds used for treatment of CMV disease. In marrow and stem cell transplant recipients, CMV pneumonia still carries a high mortality. Ganciclovir in combination with CMV-specific immunoglobulin or regular intravenous IG remains the treatment of choice for CMV pneumonia; extended antiviral maintenance for several months is recommended in patients with continued immunosuppression. Preemptive treatment based on virologic markers (e.g. pp65 antigenemia, CMV DNA) has been very successful in reducing the incidence of early CMV disease in the transplant setting. The duration of preemptive treatment should be guided by the underlying immunosuppression and virologic markers. Late CMV disease is a challenge in marrow and stem cell transplant recipients, and occurs increasingly in highly immunosuppressed solid organ transplant recipients as well. Recent advances in prophylaxis strategies include oral ganciclovir for liver transplant recipients and valacyclovir for kidney transplant recipients.

Maude Abbott and the Origin and Mysterious Disappearance of the Canadian Medical War Museum.

PubMed

Wright, James R; Alberti, Samuel J M M; Lyons, Christopher; Fraser, Richard S

2018-05-07

- In the early 1900s, it was common practice to retain, prepare, and display instructive pathologic specimens to teach pathology to medical trainees and practitioners; these collections were called medical museums. Maude Abbott established her reputation by developing expertise in all aspects of medical museum work. She was a founder of the International Association of Medical Museums (later renamed the International Academy of Pathology) and became an internationally renowned expert on congenital heart disease. Her involvement in the Canadian Medical War Museum (CMWM) is less well known. - To explore Abbott's role in the development of the CMWM during and after World War I and to trace its history. - Available primary and secondary historical sources were reviewed. - Instructive pathologic specimens derived from Canadian soldiers dying during World War I were shipped to the Royal College of Surgeons in London, which served as a clearinghouse for museum specimens from Dominion forces. The Canadian specimens were repatriated to Canada, prepared by Abbott, and displayed at several medical meetings. Abbott, because she was a woman, could not enlist and so she reported to a series of enlisted physicians with no expertise in museology. Plans for a permanent CMWM building in Ottawa eventually failed and Abbott maintained the collection at McGill (Montreal, Quebec, Canada) until her death in 1940. We trace the CMWM after her death. - Sadly, after Abbott had meticulously prepared these precious teaching specimens so that their previous owners' ultimate sacrifice would continue to help their military brethren, the relics were bureaucratically lost.

Transient Oral Human Cytomegalovirus Infections Indicate Inefficient Viral Spread from Very Few Initially Infected Cells.

PubMed

Mayer, Bryan T; Krantz, Elizabeth M; Swan, David; Ferrenberg, James; Simmons, Karen; Selke, Stacy; Huang, Meei-Li; Casper, Corey; Corey, Lawrence; Wald, Anna; Schiffer, Joshua T; Gantt, Soren

2017-06-15

Cytomegalovirus (CMV) is acquired by the oral route in children, and primary infection is associated with abundant mucosal replication, as well as the establishment of latency in myeloid cells that results in lifelong infection. The efficiency of primary CMV infection in humans following oral exposure, however, is unknown. We consistently detected self-limited, low-level oral CMV shedding events, which we termed transient CMV infections, in a prospective birth cohort of 30 highly exposed CMV-uninfected infants. We estimated the likelihood of transient oral CMV infections by comparing their observed frequency to that of established primary infections, characterized by persistent high-level shedding, viremia, and seroconversion. We developed mathematical models of viral dynamics upon initial oral CMV infection and validated them using clinical shedding data. Transient infections comprised 76 to 88% of oral CMV shedding events. For this high percentage of transient infections to occur, we identified two mathematical prerequisites: a very small number of initially infected oral cells (1 to 4) and low viral infectivity (<1.5 new cells infected/cell). These observations indicate that oral CMV infection in infants typically begins with a single virus that spreads inefficiently to neighboring cells. Thus, although the incidence of CMV infection is high during infancy, our data provide a mechanistic framework to explain why multiple CMV exposures are typically required before infection is successfully established. These findings imply that a sufficiently primed immune response could prevent CMV from establishing latent infection in humans and support the achievability of a prophylactic CMV vaccine. IMPORTANCE CMV infects the majority of the world's population and is a major cause of birth defects. Developing a vaccine to prevent CMV infection would be extremely valuable but would be facilitated by a better understanding of how natural human CMV infection is acquired. We studied CMV acquisition in infants and found that infections are usually brief and self-limited and are successfully established relatively rarely. Thus, although most people eventually acquire CMV infection, it usually requires numerous exposures. Our analyses indicate that this is because the virus is surprisingly inefficient, barely replicating well enough to spread to neighboring cells in the mouth. Greater knowledge of why CMV infection usually fails may provide insight into how to prevent it from succeeding. Copyright © 2017 American Society for Microbiology.

Transient Oral Human Cytomegalovirus Infections Indicate Inefficient Viral Spread from Very Few Initially Infected Cells

PubMed Central

Mayer, Bryan T.; Krantz, Elizabeth M.; Swan, David; Ferrenberg, James; Simmons, Karen; Selke, Stacy; Huang, Meei-Li; Casper, Corey; Corey, Lawrence; Wald, Anna; Schiffer, Joshua T.

2017-01-01

ABSTRACT Cytomegalovirus (CMV) is acquired by the oral route in children, and primary infection is associated with abundant mucosal replication, as well as the establishment of latency in myeloid cells that results in lifelong infection. The efficiency of primary CMV infection in humans following oral exposure, however, is unknown. We consistently detected self-limited, low-level oral CMV shedding events, which we termed transient CMV infections, in a prospective birth cohort of 30 highly exposed CMV-uninfected infants. We estimated the likelihood of transient oral CMV infections by comparing their observed frequency to that of established primary infections, characterized by persistent high-level shedding, viremia, and seroconversion. We developed mathematical models of viral dynamics upon initial oral CMV infection and validated them using clinical shedding data. Transient infections comprised 76 to 88% of oral CMV shedding events. For this high percentage of transient infections to occur, we identified two mathematical prerequisites: a very small number of initially infected oral cells (1 to 4) and low viral infectivity (<1.5 new cells infected/cell). These observations indicate that oral CMV infection in infants typically begins with a single virus that spreads inefficiently to neighboring cells. Thus, although the incidence of CMV infection is high during infancy, our data provide a mechanistic framework to explain why multiple CMV exposures are typically required before infection is successfully established. These findings imply that a sufficiently primed immune response could prevent CMV from establishing latent infection in humans and support the achievability of a prophylactic CMV vaccine. IMPORTANCE CMV infects the majority of the world's population and is a major cause of birth defects. Developing a vaccine to prevent CMV infection would be extremely valuable but would be facilitated by a better understanding of how natural human CMV infection is acquired. We studied CMV acquisition in infants and found that infections are usually brief and self-limited and are successfully established relatively rarely. Thus, although most people eventually acquire CMV infection, it usually requires numerous exposures. Our analyses indicate that this is because the virus is surprisingly inefficient, barely replicating well enough to spread to neighboring cells in the mouth. Greater knowledge of why CMV infection usually fails may provide insight into how to prevent it from succeeding. PMID:28381570

Cytomegalovirus (CMV) DNA load predicts relapsing CMV infection after solid organ transplantation.

PubMed

Sia, I G; Wilson, J A; Groettum, C M; Espy, M J; Smith, T F; Paya, C V

2000-02-01

Cytomegalovirus (CMV) DNA load was analyzed as a marker for relapse of CMV infection in 24 solid organ transplant patients with CMV infection or disease who received a fixed 14-day course of intravenous ganciclovir. Viral load was measured in blood samples obtained before and at the completion of treatment. Eight (33%) of 24 patients developed relapsing CMV infection. Median pretreatment viral loads were higher in the relapsing group (80,150 copies/106 leukocytes) than in the nonrelapsing group (5500 copies/106 leukocytes; P=.007). The relapsing group also had persistent detectable viral DNA (median, 5810 copies/106 leukocytes) after treatment, whereas it was undetectable in the nonrelapsing group (P<. 0001). Primary CMV infection (seronegative recipients of seropositive organs, D+R-) was an independent marker for CMV relapse (P=.03), and these patients had higher pre- and posttreatment viral loads than did non-D+/R- patients (P<.0001 and P=.0014, respectively). CMV DNA load is a useful marker for individualizing antiviral treatment of CMV infection in solid organ transplant recipients.

Laboratory testing for cytomegalovirus among pregnant women in the United States: a retrospective study using administrative claims data

PubMed Central

2012-01-01

Background Routine cytomegalovirus (CMV) screening during pregnancy is not recommended in the United States and the extent to which it is performed is unknown. Using a medical claims database, we computed rates of CMV-specific testing among pregnant women. Methods We used medical claims from the 2009 Truven Health MarketScan® Commercial databases. We computed CMV-specific testing rates using CPT codes. Results We identified 77,773 pregnant women, of whom 1,668 (2%) had a claim for CMV-specific testing. CMV-specific testing was significantly associated with older age, Northeast or urban residence, and a diagnostic code for mononucleosis. We identified 44 women with a diagnostic code for mononucleosis, of whom 14% had CMV-specific testing. Conclusions Few pregnant women had CMV-specific testing, suggesting that screening for CMV infection during pregnancy is not commonly performed. In the absence of national surveillance for CMV infections during pregnancy, healthcare claims are a potential source for monitoring practices of CMV-specific testing. PMID:23198949

Brief Report: Soluble CD163 in CMV-Infected and CMV-Uninfected Subjects on Virologically Suppressive Antiretroviral Therapy in the ICONA Cohort.

PubMed

Vita, Serena; Lichtner, Miriam; Marchetti, Giulia; Mascia, Claudia; Merlini, Esther; Cicconi, Paola; Vullo, Vincenzo; Viale, Pierluigi; Costantini, Andrea; DʼArminio Monforte, Antonella

2017-03-01

To contribute to the understanding of the role played by cytomegalovirus (CMV) in sustaining monocyte/macrophage-mediated immune activation in antiretroviral therapy treated HIV-infected subjects. We selected 23 CMV-uninfected and 46 CMV-infected HIV+ subjects, matched for age, CD4 nadir, HIV infection duration, and viral hepatitis serostatus. All subjects were on successful antiretroviral therapy since at least 1 year. A group of 16 healthy donors with similar age and sex was also included. Plasma levels of tumor necrosis factor-alpha, interleukin-6, sCD163, sCD14, and CMV immunoglobulin G levels were measured in duplicate with human enzyme-linked immunosorbent assay kits. We found significantly higher sCD163 plasma levels in HIV+CMV+ compared with HIV+CMV- subjects and healthy donors. This augmentation was confirmed also when subjects positive for hepatitis C virus-Ab were excluded from analysis. Interestingly, a correlation between anti-CMV immunoglobulin G levels and sCD163, tumor necrosis factor-alpha, interleukin-6, and sCD14 in HIV+CMV+ subjects was found. CMV coinfection could be a major driver of monocyte/macrophage activation in virally suppressed HIV+ individuals and might explain the increased risk of non-AIDS morbidity/mortality in HIV/CMV-coinfected subjects.

Provision of cellular blood components to CMV-seronegative patients undergoing allogeneic stem cell transplantation in the UK: survey of UK transplant centres.

PubMed

Morton, S; Peniket, A; Malladi, R; Murphy, M F

2017-12-01

To identify current UK practice with regards to provision of blood components for cytomegalovirus (CMV)-seronegative, potential, allogeneic stem cell recipients of seronegative grafts. Infection with CMV remains a major cause of morbidity and mortality after allogeneic stem cell transplantation (aSCT). CMV transmission has been a risk associated with the transfusion of blood components from previously exposed donors, but leucocyte reduction has been demonstrated to minimise this risk. In 2012, the UK Advisory Committee for the Safety of Tissues and Organs (SaBTO) recommended that CMV-unselected components could be safely transfused without increased risk of CMV transmission. We surveyed UK aSCT centres to establish current practice. Fifteen adult and seven paediatric centres (75%) responded; 22·7% continue to provide components from CMV-seronegative donors. Reasons cited include the continued perceived risk of CMV transmission by blood transfusion, its associated morbidity and concerns regarding potential for ambiguous CMV serostatus in seronegative potential transplant recipients due to passive antibody transfer from CMV-seropositive blood donors, leading to erroneous donor/recipient CMV matching at transplant. The survey demonstrated a surprisingly high rate (22.7%) of centres continuing to provide blood components from CMV-seronegative donors despite SaBTO guidance. © 2017 British Blood Transfusion Society.

[Prognosis value of the pp65 antigenemia and semi-quantitative PCR in the detection of the CMV reactivation in bone marrow grafted patients].

PubMed

Ksouri, H; Lakhal, A; Ben Amor, R; Torjman, L; Achour, W; Ben Othmen, T; Ladeb, S; Abdelkefi, A; Slim, A; Abdeladhim, A; Ben Hassen, A

2006-07-01

In this article a Cytomegalovirus (CMV) antigenemia and semiquantitative PCR retrospective evaluation of 26 bone marrow allo-grafted patients for different haematological disease is reported. Eighteen patients had a CMV reactivation despite a prophylactic treatment, seven of those patients had both positive antigenemia pp65 and positive semi-quantitative CMV PCR. During CMV reactivation, 3 patients developed a CMV disease despite a pre-emptive therapy. The follow up of the antigenemia was performed since D21 until D100 post transplantation, the antigenemia positivity occurred at D53 and was preceded about 7 days by CMV PCR positivity The CMV disease wasn't associated with a high viral load. All patients that had CMV reactivation had a positive CMV serology before the graft, whereas only 37.5% of the patients who did not reactivate had a positive CMV serology. Respectively half patients who reactivated and only 12.5% of those who didn't had a Graft versus host disease (GVHD), witch preceded the reactivation about 21 days in six of the formers. Clinical and biological signs presented by our patients in this cases report, seems to be associated more with the GVHD than with CMV reactivation.

CMV pneumonia in allogeneic BMT recipients undergoing early treatment of pre-emptive ganciclovir therapy.

PubMed

Machado, C M; Dulley, F L; Boas, L S; Castelli, J B; Macedo, M C; Silva, R L; Pallota, R; Saboya, R S; Pannuti, C S

2000-08-01

The incidence, treatment and outcome of CMV interstitial pneumonia (CMV-IP) were reviewed in 139 consecutive allogeneic BMT patients undergoing extended CMV antigenemia surveillance and two different ganciclovir (GCV) strategies to control CMV infection. Nineteen cases of CMV-IP were reviewed, 16 of 63 patients (25.4%) who received early GCV treatment (ET) and three of 76 patients (3.9%) who received preemptive (PE) GCV therapy. In the ET group, the median time for occurrence of CMV-IP was 55 (range 36 to 311) days. Two patients had three episodes of CMV-IP recurrences after day +100. CMV-IP-related death occurred in two patients (15.4%). In the PE group, 41 patients received pre-emptive GCV therapy prompted by the appearance of positive antigenemia > or =2 cells. The median time for the occurrence of CMV-IP was 92 (range 48 to 197) days. Response to therapy was observed when GCV was introduced within 6 days of antigenemia positivity. The use of IVIg in association with GCV did not play a major role in response to therapy. The median time for occurrence of CMV-IP was delayed during PE strategy and the cost-effectiveness of CMV surveillance after day +100 should be investigated in this population.

Cytomegalovirus urinary excretion and long term outcome in children with congenital cytomegalovirus infection. Congenital CMV Longitudinal Study Group.

PubMed

Noyola, D E; Demmler, G J; Williamson, W D; Griesser, C; Sellers, S; Llorente, A; Littman, T; Williams, S; Jarrett, L; Yow, M D

2000-06-01

Cytomegalovirus (CMV) is the most frequent cause of congenital infection, and both symptomatic and asymptomatic infants may have long term sequelae. Children with congenital CMV infection are chronically infected and excrete CMV in the urine for prolonged periods. However, the effect of prolonged viral replication on the long term outcome of these children is unknown. To determine whether duration of CMV excretion is associated with outcome at 6 years of life in symptomatic and asymptomatic congenitally infected children. Longitudinal cohort study. Children congenitally infected with CMV were identified at birth and followed prospectively in a study of long term effects of congenital CMV infection. The relationship between duration of CMV urinary excretion and growth, neurodevelopment and presence and progression of sensorineural hearing loss (SNHL) at 6 years of age was determined. There was no significant difference in the duration of viral urinary excretion between children born with asymptomatic (median, 4.55 years) and symptomatic (median, 2.97 years) congenital CMV infection (P = 0.11). Furthermore there was no association between long term growth or cognitive outcome and duration of viral excretion. However, a significantly greater proportion of children who excreted CMV for <4 years had SNHL and progressive SNHL compared with children with CMV excretion >4 years (P = 0.019, P = 0.009, respectively). Children congenitally infected with CMV are chronically infected for years, but the duration of CMV urinary excretion is not associated with abnormalities of growth, or neurodevelopmental deficits. However, SNHL and progressive SNHL were associated with a shorter duration of CMV excretion.

Window period donations during primary cytomegalovirus infection and risk of transfusion-transmitted infections.

PubMed

Ziemann, Malte; Heuft, Hans-Gert; Frank, Kerstin; Kraas, Sabine; Görg, Siegfried; Hennig, Holger

2013-05-01

Donors with short interdonation intervals (e.g., apheresis donors) have an increased risk of window period donations. The frequency of cytomegalovirus (CMV) window period donations is important information to decide whether selection of seronegative donors might be advantageous for patients at risk for transfusion-transmitted CMV infections (TT-CMV). CMV seroconversion in 93 donors with positive results in routine CMV antibody testing within at most 35 days after the last seronegative sample was evaluated by Western blot and/or a second antibody test. In donors with unconfirmed seroconversion, an additional later sample was tested. Concentration of CMV DNA was determined in pre- and postseroconversion samples. CMV seroconversion was confirmed in 12 donors (13%). Among these, the last seronegative sample was CMV DNA positive in three donors (25%, below 30 IU/mL). The first seropositive sample was CMV DNA positive in 10 donors (83%, maximum 1600 IU/mL). Both prevalence and median concentration of CMV DNA were higher in the first seropositive sample (p = 0.004 and p = 0.02), with maximum concentrations being reached about 2 weeks after seroconversion. No CMV DNA was detected in samples from donors with unconfirmed seroconversion. At least in donors with short interdonation intervals, most suspected CMV seroconversions are due to false-positive results of the screening test. As window period donations are rare and contain less CMV DNA than the first seropositive donation, avoidance of blood products from primarily seropositive donors is especially helpful to avoid TT-CMV if donors with short interdonation intervals are concerned. © 2013 American Association of Blood Banks.

Management of cytomegalovirus infection and disease in liver transplant recipients

PubMed Central

Bruminhent, Jackrapong; Razonable, Raymund R

2014-01-01

Cytomegalovirus (CMV) is one of the most common viral pathogens causing clinical disease in liver transplant recipients, and contributing to substantial morbidity and occasional mortality. CMV causes febrile illness often accompanied by bone marrow suppression, and in some cases, invades tissues including the transplanted liver allograft. In addition, CMV has been significantly associated with an increased predisposition to acute and chronic allograft rejection, accelerated hepatitis C recurrence, and other opportunistic infections, as well as reduced overall patient and allograft survival. To negate the adverse effects of CMV infection on transplant outcome, its prevention, whether through antiviral prophylaxis or preemptive therapy, is an essential component to the management of liver transplant recipients. Two recently updated guidelines have suggested that antiviral prophylaxis or preemptive therapy are similarly effective in preventing CMV disease in modest-risk CMV-seropositive liver transplant recipients, while antiviral prophylaxis is the preferred strategy over preemptive therapy for the prevention of CMV disease in high-risk recipients [CMV-seronegative recipients of liver allografts from CMV-seropositive donors (D+/R-)]. However, antiviral prophylaxis has only delayed the onset of CMV disease in many CMV D+/R- liver transplant recipients, and such occurrence of late-onset CMV disease was significantly associated with increased all-cause and infection-related mortality after liver transplantation. Therefore, a search for better strategies for prevention, such as prolonged duration of antiviral prophylaxis, a hybrid approach (antiviral prophylaxis followed by preemptive therapy), or the use of immunologic measures to guide antiviral prophylaxis has been suggested to prevent late-onset CMV disease. The standard treatment of CMV disease consists of intravenous ganciclovir or oral valganciclovir, and if feasible, reduction in pharmacologic immunosuppression. In one clinical trial, oral valganciclovir was as effective as intravenous ganciclovir for the treatment of mild to moderate CMV disease in solid organ (including liver) transplant recipients. The aim of this article is to provide a state-of-the art review of the epidemiology, diagnosis, prevention, and treatment of CMV infection and disease after liver transplantation. PMID:25018848

Evaluating Laboratory Performance on Point-of-Care Glucose Testing with Six Sigma Metric for 151 Institutions in China.

PubMed

Fei, Yang; Wang, Wei; He, Falin; Zhong, Kun; Wang, Zhiguo

2015-10-01

The aim of this study was to use Six Sigma(SM) (Motorola Trademark Holdings, Libertyville, IL) techniques to analyze the quality of point-of-care (POC) glucose testing measurements quantitatively and to provide suggestions for improvement. In total, 151 laboratories in China were included in this investigation in 2014. Bias and coefficient of variation were collected from an external quality assessment and an internal quality control program, respectively, for POC glucose testing organized by the National Center for Clinical Laboratories. The σ values and the Quality Goal Index were used to evaluate the performance of POC glucose meters. There were 27, 30, 57, and 37 participants in the groups using Optium Xceed™ (Abbott Diabetes Care, Alameda, CA), Accu-Chek(®) Performa (Roche, Basel, Switzerland), One Touch Ultra(®) (Abbott), and "other" meters, respectively. The median of the absolute value of percentage difference varied among different lots and different groups. Among all the groups, the Abbott One Touch Ultra group had the smallest median of absolute value of percentage difference except for lot 201411, whereas the "other" group had the largest median in all five lots. More than 85% of participate laboratories satisfied the total allowable error (TEa) requirement in International Organization for Standardization standard 15197:2013, and 85.43% (129/151) of laboratories obtained intralaboratory coefficient of variations less than 1/3TEa. However, Six Sigma techniques suggested that 41.72% (63/151) to 65.56% (99/151) of the laboratories needed to improve their POC glucose testing performance, in either precision, trueness, or both. Laboratories should pay more attention on the practice of POC glucose testing and take actions to improve their performance. Only in this way can POC glucose testing really function well in clinical practice.

Type I Interferon Elevates Co-Regulatory Receptor Expression on CMV- and EBV-Specific CD8 T Cells in Chronic Hepatitis C

PubMed Central

Owusu Sekyere, Solomon; Suneetha, Pothakamuri Venkata; Hardtke, Svenja; Falk, Christine Susanne; Hengst, Julia; Manns, Michael Peter; Cornberg, Markus; Wedemeyer, Heiner; Schlaphoff, Verena

2015-01-01

Hepatitis C virus (HCV) readily sets up persistence in a large fraction of infected hosts. Mounting epidemiological and immunological evidence suggest that HCV’s persistence could influence immune responses toward unrelated pathogens and vaccines. Nonetheless, the fundamental contribution of the inflammatory milieu during persistent HCV infection in impacting immune cells specific for common pathogens such as CMV and EBV has not been fully studied. As the co-regulatory receptors PD-1, Tim-3, and 2B4 have all been shown to be vital in regulating CD8+ T cell function, we assessed their expression on CMV/EBV-specific CD8+ T cells from patients with chronic hepatitis C (CHC) and healthy controls ex vivo and upon stimulation with virus-specific peptides in vitro. Total and CMV/EBV-specific CD8+ T cells expressing PD-1, Tim-3, and 2B4 were highly enriched in patients with CHC compared to healthy individuals ex vivo. In vitro peptide stimulation further potentiated the differential co-regulatory receptor expression of PD-1, Tim-3, and 2B4, which then culminated in an enhanced functionality of CMV/EBV-specific CD8+ T cells in CHC patients. Comprehensively analyzing plasma cytokines between the two cohorts, we observed that not only was IFNα-2a dominant among 21 other inflammatory mediators elevated in CHC patients but it also correlated with PD-1 and Tim-3 expressions ex vivo. Importantly, IFNα-2a further caused upregulation of these markers upon in vitro peptide stimulation. Finally, we could prospectively study patients receiving novel IFN-free antiviral therapy. Here, we observed that treatment-induced clearance of HCV resulted in a partial reversion of the phenotype of CMV/EBV-specific CD8+ T cells in patients with CHC. These data reveal an alteration of the plasma concentrations of IFNα-2a together with other inflammatory mediators during CHC, which appeared to pervasively influence co-regulatory receptor expression on CMV/EBV-specific CD8+ T cells. PMID:26113847

CMV and Immunosenescence: from basics to clinics

PubMed Central

2012-01-01

Alone among herpesviruses, persistent Cytomegalovirus (CMV) markedly alters the numbers and proportions of peripheral immune cells in infected-vs-uninfected people. Because the rate of CMV infection increases with age in most countries, it has been suggested that it drives or at least exacerbates “immunosenescence”. This contention remains controversial and was the primary subject of the Third International Workshop on CMV & Immunosenescence which was held in Cordoba, Spain, 15-16th March, 2012. Discussions focused on several main themes including the effects of CMV on adaptive immunity and immunosenescence, characterization of CMV-specific T cells, impact of CMV infection and ageing on innate immunity, and finally, most important, the clinical implications of immunosenescence and CMV infection. Here we summarize the major findings of this workshop. PMID:23114110

CMV and Immunosenescence: from basics to clinics.

PubMed

Solana, Rafael; Tarazona, Raquel; Aiello, Allison E; Akbar, Arne N; Appay, Victor; Beswick, Mark; Bosch, Jos A; Campos, Carmen; Cantisán, Sara; Cicin-Sain, Luka; Derhovanessian, Evelyna; Ferrando-Martínez, Sara; Frasca, Daniela; Fulöp, Tamas; Govind, Sheila; Grubeck-Loebenstein, Beatrix; Hill, Ann; Hurme, Mikko; Kern, Florian; Larbi, Anis; López-Botet, Miguel; Maier, Andrea B; McElhaney, Janet E; Moss, Paul; Naumova, Elissaveta; Nikolich-Zugich, Janko; Pera, Alejandra; Rector, Jerrald L; Riddell, Natalie; Sanchez-Correa, Beatriz; Sansoni, Paolo; Sauce, Delphine; van Lier, Rene; Wang, George C; Wills, Mark R; Zieliński, Maciej; Pawelec, Graham

2012-10-31

Alone among herpesviruses, persistent Cytomegalovirus (CMV) markedly alters the numbers and proportions of peripheral immune cells in infected-vs-uninfected people. Because the rate of CMV infection increases with age in most countries, it has been suggested that it drives or at least exacerbates "immunosenescence". This contention remains controversial and was the primary subject of the Third International Workshop on CMV & Immunosenescence which was held in Cordoba, Spain, 15-16th March, 2012. Discussions focused on several main themes including the effects of CMV on adaptive immunity and immunosenescence, characterization of CMV-specific T cells, impact of CMV infection and ageing on innate immunity, and finally, most important, the clinical implications of immunosenescence and CMV infection. Here we summarize the major findings of this workshop.

The immune response to human CMV

PubMed Central

La Rosa, Corinna; Diamond, Don J

2012-01-01

This review will summarize and interpret recent literature regarding the human CMV immune response, which is among the strongest measured and is the focus of attention for numerous research groups. CMV is a highly prevalent, globally occurring infection that rarely elicits disease in healthy immunocompetent hosts. The human immune system is unable to clear CMV infection and latency, but mounts a spirited immune-defense targeting multiple immune-evasion genes encoded by this dsDNA β-herpes virus. Additionally, the magnitude of cellular immune response devoted to CMV may cause premature immune senescence, and the high frequencies of cytolytic T cells may aggravate vascular pathologies. However, uncontrolled CMV viremia and life-threatening symptoms, which occur readily after immunosuppression and in the immature host, clearly indicate the essential role of immunity in maintaining asymptomatic co-existence with CMV. Approaches for harnessing the host immune response to CMV are needed to reduce the burden of CMV complications in immunocompromised individuals. PMID:23308079

CMV in Hematopoietic Stem Cell Transplantation

PubMed Central

de la Cámara, Rafael

2016-01-01

Due to its negative impact on the outcome of stem cell transplant (SCT) and solid organ transplant patients (SOT) CMV has been called “the troll of transplantation”. One of the greatest advances in the management of SCT has been the introduction of the preemptive strategy. Since its introduction, the incidence of the viremia, as expected, remains unchanged but there has been a marked decline in the incidence of early CMV disease. However, in spite of the advances in prevention of CMV disease, CMV is still today an important cause of morbidity and mortality. Late CMV disease is still occurring in a significant proportion of patients and the so-called indirect effects of CMV are causing significant morbidity and mortality. Fortunately there have been several advances in the development of new antivirals, adoptive immunotherapy and DNA-CMV vaccines that might transform the management of CMV in the near future. PMID:27413524

CMV allograft pancreatitis: diagnosis, treatment, and histological features.

PubMed

Klassen, D K; Drachenberg, C B; Papadimitriou, J C; Cangro, C B; Fink, J C; Bartlett, S T; Weir, M R

2000-05-15

Cytomegalovirus (CMV) infection is a common problem in solid organ transplant recipients. CMV infection of pancreas allografts is not, however, well described. We report the clinical presentation, histologic findings, treatment, and outcome in four patients with CMV allograft pancreatitis. These patients presented 18 weeks to 44 months after transplantation with elevated serum amylase and lipase and were suspected to have acute rejection. Percutaneous pancreas allograft biopsy specimens showed evidence of tissue invasive CMV infection. One patient had simultaneous CMV infection and acute rejection. Prolonged treatment with ganciclovir resulted in clinical and histologic resolution of the CMV disease. Rejection was successfully treated. Primary CMV infection in seronegative recipients seemed to be a risk factor. Three patients maintain normal allograft function; one patient lost function due to chronic rejection. The histology of tissue-invasive CMV pancreas allograft infection and its differentiation from acute rejection is described. Prompt diagnosis and prolonged therapy with antiviral agents can result in maintenance of allograft function.

Approach to cytomegalovirus infections in patients with ulcerative colitis

PubMed Central

Park, Sung Chul; Jeen, Yoon Mi; Jeen, Yoon Tae

2017-01-01

Cytomegalovirus (CMV) reactivation is common in patients with severe ulcerative colitis (UC), and may ref lect exacerbation of mucosal inf lammation and/or administration of immunosuppressants. The question of whether CMV is an active pathogen or ‘an innocent bystander’ in the exacerbation of UC remains controversial. Patients with UC exacerbated by reactivated CMV experience worse prognoses than those without CMV reactivation and antiviral therapy significantly reduces the need for colectomy in patients with severe UC and high-grade CMV infection, indicating that CMV plays a role in UC prognosis. Therefore, the CMV status of patients on immunosuppressants, particularly those with steroid-refractory or -dependent UC, should be tested. When CMV is detected, be performed based on should adequate treatment the extent of the viral load and the presence of certain clinical features including a large ulcer. Anti-tumor necrosis factor agents may be useful for treating CMV colitis complicating UC. PMID:28490715

Characterization, genetic diversity, and evolutionary link of Cucumber mosaic virus strain New Delhi from India.

PubMed

Koundal, Vikas; Haq, Qazi Mohd Rizwanul; Praveen, Shelly

2011-02-01

The genome of Cucumber mosaic virus New Delhi strain (CMV-ND) from India, obtained from tomato, was completely sequenced and compared with full genome sequences of 14 known CMV strains from subgroups I and II, for their genetic diversity. Sequence analysis suggests CMV-ND shares maximum sequence identity at the nucleotide level with a CMV strain from Taiwan. Among all 15 strains of CMV, the encoded protein 2b is least conserved, whereas the coat protein (CP) is most conserved. Sequence identity values and phylogram results indicate that CMV-ND belongs to subgroup I. Based on the recombination detection program result, it appears that CMV is prone to recombination, and different RNA components of CMV-ND have evolved differently. Recombinational analysis of all 15 CMV strains detected maximum recombination breakpoints in RNA2; CP showed the least recombination sites.

Quantitative analysis of CMV DNA in children the first year after liver transplantation.

PubMed

Kullberg-Lindh, Carola; Ascher, Henry; Krantz, Marie; Lindh, Magnus

2003-08-01

CMV infection is a major problem after solid organ transplantation especially in children where primary infection is more common than in adults. Early diagnosis is critical and might be facilitated by quantitative analysis of CMV DNA in blood. In this retrospective study of 18 children who had a liver transplantation 1995-2000, serum samples were analysed by Cobas Amplicor Monitor (Roche). Four patients developed symptomatic CMV infection at a mean time of 4 wk after transplantation. They showed maximum CMV DNA levels in serum of 26 400, 1900, 1300 and 970 copies/mL, respectively. In comparison, CA Monitor was positive, at a low level (415 copies/mL), in one of 11 patients with asymptomatic (4) or latent (7) infection. CMV IgM was detected at significant levels (> or =1/80) in all four patients with symptomatic, and in one with asymptomatic CMV infection. Eight patients were given one or several courses of ganciclovir. Five of these lacked symptoms of CMV disease, and had low (415 copies/mL) or undetectable CMV DNA in serum. The data suggest that quantitative analysis of CMV DNA may be of value in early identification of CMV disease and for avoiding unnecessary antiviral treatment.

The Immunology of Posttransplant CMV Infection: Potential Effect of CMV Immunoglobulins on Distinct Components of the Immune Response to CMV

PubMed Central

Carbone, Javier

2016-01-01

Abstract The immune response to cytomegalovirus (CMV) infection is highly complex, including humoral, cellular, innate, and adaptive immune responses. Detection of CMV by the innate immune system triggers production of type I IFNs and inflammatory cytokines which initiate cellular and humoral responses that are critical during the early viremic phase of CMV infection. Sustained control of CMV infection is largely accounted for by cellular immunity, involving various T-cell and B-cell subsets. In solid organ transplant patients, global suppression of innate and adaptive immunities by immunosuppressive agents limits immunological defense, including inhibition of natural killer cell activity with ongoing lowering of Ig levels and CMV-specific antibody titers. This is coupled with a short-term suppression of CMV-specific T cells, the extent and duration of which can predict risk of progression to CMV viremia. CMV immunoglobulin (CMVIG) preparations have the potential to exert immunomodulatory effects as well as providing passive immunization. Specific CMVIG antibodies and virus neutralization might be enhanced by modulation of dendritic cell activity and by a decrease in T-cell activation, effects which are of importance during the initial phase of infection. In summary, the role of CMVIG in reconstituting specific anti-CMV antibodies may be enhanced by some degree of modulation of the innate and adaptive immune responses, which could help to control some of the direct and indirect effects of CMV infection. PMID:26900990

The Immunology of Posttransplant CMV Infection: Potential Effect of CMV Immunoglobulins on Distinct Components of the Immune Response to CMV.

PubMed

Carbone, Javier

2016-03-01

The immune response to cytomegalovirus (CMV) infection is highly complex, including humoral, cellular, innate, and adaptive immune responses. Detection of CMV by the innate immune system triggers production of type I IFNs and inflammatory cytokines which initiate cellular and humoral responses that are critical during the early viremic phase of CMV infection. Sustained control of CMV infection is largely accounted for by cellular immunity, involving various T-cell and B-cell subsets. In solid organ transplant patients, global suppression of innate and adaptive immunities by immunosuppressive agents limits immunological defense, including inhibition of natural killer cell activity with ongoing lowering of Ig levels and CMV-specific antibody titers. This is coupled with a short-term suppression of CMV-specific T cells, the extent and duration of which can predict risk of progression to CMV viremia. CMV immunoglobulin (CMVIG) preparations have the potential to exert immunomodulatory effects as well as providing passive immunization. Specific CMVIG antibodies and virus neutralization might be enhanced by modulation of dendritic cell activity and by a decrease in T-cell activation, effects which are of importance during the initial phase of infection. In summary, the role of CMVIG in reconstituting specific anti-CMV antibodies may be enhanced by some degree of modulation of the innate and adaptive immune responses, which could help to control some of the direct and indirect effects of CMV infection.

Clinical evaluation of the new Roche platform of serological and molecular cytomegalovirus-specific assays in the diagnosis and prognosis of congenital cytomegalovirus infection.

PubMed

Chiereghin, Angela; Pavia, Claudia; Gabrielli, Liliana; Piccirilli, Giulia; Squarzoni, Diego; Turello, Gabriele; Gibertoni, Dino; Simonazzi, Giuliana; Capretti, Maria Grazia; Lanari, Marcello; Lazzarotto, Tiziana

2017-10-01

Clinical evaluation of the Elecsys ® CMV IgM, IgG, IgG Avidity and COBAS AmpliPrep/COBAS TaqMan CMV (COBAS CMV) assays (Roche Diagnostics AG) in the diagnosis and prognosis of congenital CMV infection was performed. In this study, 150 preselected clinical samples (50 primary infection sera, 50 amniotic fluid [AF] and 50 newborn urine) were processed using Roche serological/molecular CMV-specific tests. Results were compared with those obtained by routine assays (comparator assays). The Elecsys ® CMV IgM and IgG assays showed a perfect agreement (100%) with the comparator assays. Using the combination of the Elecsys ® CMV IgM and IgG Avidity assays results, a primary infection was identified in 100% of cases. Inappropriate avidity CMV IgG values in two samples with very low IgG values (<6 AU/mL) were observed. COBAS CMV assay showed an agreement equal to 98% and 100% with comparator assays by processing AF and urine samples, respectively. Among AF with quantitative results, Lin's concordance correlation was 0.933 and comparator-COBAS CMV assays gave CMV-DNA loads differing by <0.5 log 10 DNA. Finally, higher CMV-DNA levels in AF samples were associated with a symptomatic outcome (p=0.003). The Roche CMV-specific assays compared well with the comparator assays, thus providing to be suitable for clinical use. Copyright © 2017 Elsevier B.V. All rights reserved.

Low cytomegalovirus-specific T-cell counts at reactivation are associated with progression to high-level viremia or disease in seropositive recipients of hematopoietic cell grafts from seropositive but not seronegative donors.

PubMed

Hoegh-Petersen, Mette; Roa, Lina; Liu, Yiping; Zhou, Feng; Ugarte-Torres, Alejandra; Louie, Polly; Fonseca, Kevin; Khan, Faisal; Russell, James A; Storek, Jan

2012-02-01

Identifying patients who spontaneously resolve cytomegalovirus (CMV) reactivation could spare these patients from the toxicity of antiviral drugs such as ganciclovir. The role of CMV-specific T cells in clearing CMV viremia in patients who do not receive ganciclovir has not been evaluated. We assessed this in patients with CMV viremia between 50 and 50 000 genome copies/mL, because our threshold for initiating ganciclovir is 50 000 copies/mL. We enumerated CMV-specific T cells in 39 CMV seropositive hematopoietic cell transplantation (HCT) recipients within 4 days of the first positive CMV polymerase chain reaction (PCR). CMV-specific T cells were defined as cells that upon stimulation with CMV lysate or pp65 overlapping peptides produced interferon (IFN)-γ, tumor necrosis factor (TNF)-α or interleukin (IL)-2, alone or in combination. Among Donor (D+), Recipient (R+) patients, unifunctional CMV-specific CD4 T-cells were higher in patients who spontaneously resolved CMV viremia (did not receive ganciclovir) versus those who progressed (received ganciclovir) (median 0.20 versus 0.02/μL lysate-stimulated cells, P < 0.05, and 0.26 versus 0.05/μL pp65 peptide-stimulated cells, P<0.05). Among D- R+ patients, there was no difference between patients with spontaneous resolution or progression; all subsets of CMV-specific T cells measured were barely detectable, in both patients with spontaneous resolution and those with progression. Among D+ R+ patients (but not D- R+ patients), high CMV-specific CD4 T-cell counts identify patients who can spontaneously resolve CMV reactivation. In D- R+ patients, immune mechanisms other than T cells may control the progression from reactivation to high-level viremia/disease.

Proposed clinical case definition for cytomegalovirus-immune recovery retinitis.

PubMed

Ruiz-Cruz, Matilde; Alvarado-de la Barrera, Claudia; Ablanedo-Terrazas, Yuria; Reyes-Terán, Gustavo

2014-07-15

Cytomegalovirus (CMV) retinitis has been extensively described in patients with advanced or late human immunodeficiency virus (HIV) disease under ineffective treatment of opportunistic infection and antiretroviral therapy (ART) failure. However, there is limited information about patients who develop active cytomegalovirus retinitis as an immune reconstitution inflammatory syndrome (IRIS) after successful initiation of ART. Therefore, a case definition of cytomegalovirus-immune recovery retinitis (CMV-IRR) is proposed here. We reviewed medical records of 116 HIV-infected patients with CMV retinitis attending our institution during January 2003-June 2012. We retrospectively studied HIV-infected patients who had CMV retinitis on ART initiation or during the subsequent 6 months. Clinical and immunological characteristics of patients with active CMV retinitis were described. Of the 75 patients under successful ART included in the study, 20 had improvement of CMV retinitis. The remaining 55 patients experienced CMV-IRR; 35 of those developed CMV-IRR after ART initiation (unmasking CMV-IRR) and 20 experienced paradoxical clinical worsening of retinitis (paradoxical CMV-IRR). Nineteen patients with CMV-IRR had a CD4 count of ≥50 cells/µL. Six patients with CMV-IRR subsequently developed immune recovery uveitis. There is no case definition for CMV-IRR, although this condition is likely to occur after successful initiation of ART, even in patients with high CD4 T-cell counts. By consequence, we propose the case definitions for paradoxical and unmasking CMV-IRR. We recommend close follow-up of HIV-infected patients following ART initiation. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

CMV-infected kidney grafts drive the expansion of blood-borne CMV-specific T cells restricted by shared class I HLA molecules via presentation on donor cells.

PubMed

Gatault, Philippe; Al-Hajj, Sally; Noble, Johan; Chevallier, Eloi; Piollet, Marie; Forconi, Catherine; Gaudy-Graffin, Catherine; Thibault, Gilles; Miquelestorena-Standley, Elodie; Halimi, Jean-Michel; Büchler, Matthias; Lemoine, Roxane; Baron, Christophe

2018-01-27

We aimed to determine the role of cytomegalovirus (CMV)-infected donor cells in the development of a CMV-specific immune response in kidney transplant recipients. We assessed the CMV pp65-specific immune response by using interferon-ɣ ELISPOT and dextramers in peripheral blood mononuclear cells from 115 recipients (D+R- 31, D+R + 44, D-R + 40) late after transplantation (mean 59 ± 42 months). Receiving a kidney from a D+ donor resulted in a higher number of IFN-ɣ-producing anti-CMV T cells (P = .004). This effect disappeared with the absence of shared HLA class I specificities between donors and recipients (P = .430). To confirm the role of donor cells in stimulating the expansion of newly developed CMV-specific CD8 + T cells after transplantation, we compared the number of HLA-A2-restricted CMV-specific CD8 + T cells in primo-infected recipients who received an HLA-A2 or non-HLA-A2 graft. The median of anti-CMV pp65 T cells restricted by HLA-A2 was very low for patients who received a non-HLA-A2 graft vs an HLA-A2 graft (300 [0-14638] vs. 17972 [222-85594] anti-CMV pp65 CD8 + T cells/million CD8 + T cells, P = .001). This adds new evidence that CMV-infected kidney donor cells present CMV peptides and drive an inflation of memory CMV-specific CD8 + T cells, likely because of frequent CMV replications within the graft. © 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.

CMV infection in a cohort of HIV-exposed infants born to mothers receiving antiretroviral therapy during pregnancy and breastfeeding.

PubMed

Pirillo, Maria Franca; Liotta, Giuseppe; Andreotti, Mauro; Jere, Haswel; Sagno, Jean-Baptiste; Scarcella, Paola; Mancinelli, Sandro; Buonomo, Ersilia; Amici, Roberta; Marazzi, Maria Cristina; Vella, Stefano; Palombi, Leonardo; Giuliano, Marina

2017-02-01

Antiretroviral therapy has been shown to reduce rates of congenital CMV infection. Little information is available on the possible impact of antiretroviral therapy on postnatal breastfeeding-associated CMV infection acquisition. A cohort of 89 HIV-infected mothers and their children was studied. Women received antiretroviral therapy from week 25 of gestation until 6 months postpartum or indefinitely if meeting the criteria for treatment. All women were evaluated for CMV IgG presence and CMV DNA in breast milk. Children were tested for CMV infection by either the presence of IgM or the presence of CMV DNA in plasma at 1, 6 and 12 months and by the presence of IgG at 24 months. All mothers had high titers of CMV DNA in breast milk (5.7 log at Month 1 and 5.1 log at Month 6). Cumulative CMV infection rates were 60.3 % at Month 6, 69 % at Month 12 and 96.4 % at Month 24. There was a significant negative correlation between the duration of antiretroviral treatment during pregnancy and levels of CMV DNA in breast milk at Month 1 (P = 0.033). There was a trend for a correlation between high titers of CMV DNA in breast milk at 6 months and CMV infection at 6 months (P = 0.069). In this cohort, more than 95 % of the children had acquired CMV infection by 2 years of age. Besides breastfeeding, which played a major role, also horizontal transmission between 1 and 2 years was certainly relevant in determining CMV infection acquisition.

Cytomegalovirus prophylaxis in seropositive renal transplant recipients receiving thymoglobulin induction therapy: outcome and risk factors for late CMV disease.

PubMed

Reusing, Jose O; Feitosa, Emanoela B; Agena, Fabiana; Pierroti, Lígia C; Azevedo, Luiz S F; Kotton, Camille N; David-Neto, Elias

2018-05-29

Anti-thymocyte globulin (ATG) therapy is a risk factor for CMV disease in renal transplant (RTx) recipients and therefore antiviral prophylaxis is commonly used. We evaluated the outcome of our current policy of 90 days of CMV prophylaxis in seropositive recipients given ATG and the risk factors for the occurrence of CMV disease after prophylaxis. We studied a retrospective cohort of 423 RTx (2010-2014) CMV-seropositive adults given ATG induction therapy. 54 (13%) patients developed cytomegalovirus (CMV) disease at a median of 163 days after transplant, of which 29 (54%) had viral syndrome and 25 (46%) had invasive disease. Median prophylaxis time (94 days) and immunosuppressive drugs were similar between groups (CMV vs no-CMV). Those with CMV disease had more deceased donors and higher donor age, lower lymphocyte count, and lower median eGFR at day 90. Multivariable logistic regression analysis at day 90 and 180 found that eGFR ≤ 40 ml/min/1.73 m 2 (but not acute rejection) was associated with late CMV disease. In a separate validation cohort of 124 patients with 8% late CMV disease, eGFR ≤ 45 and lymphocyte count ≤ 800 cells/mm 3 at the end of prophylaxis remained predictive of late CMV disease occurrence. These data indicate that antiviral prophylaxis adequately prevented CMV in seropositive recipients given ATG, but late disease still occurred. Low eGFR and low lymphocyte count at the end of prophylaxis may help identify patients at higher risk of CMV disease. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Cytomegalovirus IgG Level and Avidity in Breastfeeding Infants of HIV-Infected Mothers in Malawi

PubMed Central

Wiener, Jeffrey; Chang, Tiffany S.; Dollard, Sheila C.; Amin, Minal M.; Ellington, Sascha; Kayira, Dumbani; van der Horst, Charles; Jamieson, Denise J.

2015-01-01

Cytomegalovirus (CMV) infection is common among infants of HIV-infected mothers in resource-limited settings. We examined the prevalence and timing of infant CMV infection during the first year of life using IgG antibody and avidity among HIV-exposed infants in Malawi and correlated the results with the presence of detectable CMV DNA in the blood. The Breastfeeding, Antiretrovirals and Nutrition (BAN) study randomized 2,369 mothers and their infants to maternal antiretrovirals, infant nevirapine, or neither for 28 weeks of breastfeeding, followed by weaning. Stored plasma specimens were tested for CMV IgG and antibody avidity from a random subset of infants who had been previously tested with blood CMV PCR and had available specimens at birth and at 24 and 48 weeks of age. Ninety-four of 127 infants (74.0%) tested at 24 weeks of age had CMV IgG of low or intermediate avidity, signifying primary CMV infections. An additional 22 infants (17.3%) had IgG of high avidity; 19 of them had CMV DNA detected in their blood, indicating infant infections. Taken together, these results show that the estimated prevalence of CMV infection at 24 weeks was 88.9%. By 48 weeks of age, 81.3% of infants had anti-CMV IgG; most of them (70.9%) had IgG of high avidity. The CMV serology and avidity testing, combined with the PCR results, confirmed a high rate of primary CMV infection by 6 months of life among breastfeeding infants of HIV-infected mothers. The CMV PCR in blood detected most, but not all, infant CMV infections. PMID:26424831

Regulatory function of cytomegalovirus-specific CD4{sup +}CD27{sup -}CD28{sup -} T cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tovar-Salazar, Adriana; Patterson-Bartlett, Julie; Jesser, Renee

2010-03-15

CMV infection is characterized by high of frequencies of CD27{sup -}CD28{sup -} T cells. Here we demonstrate that CMV-specific CD4{sup +}CD27{sup -}CD28{sup -} cells are regulatory T cells (T{sub R}). CD4{sup +}CD27{sup -}CD28{sup -} cells sorted from CMV-stimulated PBMC of CMV-seropositive donors inhibited de novo CMV-specific proliferation of autologous PBMC in a dose-dependent fashion. Compared with the entire CMV-stimulated CD4{sup +} T-cell population, higher proportions of CD4{sup +}CD27{sup -}CD28{sup -} T{sub R} expressed FoxP3, TGFbeta, granzyme B, perforin, GITR and PD-1, lower proportions expressed CD127 and PD1-L and similar proportions expressed CD25, CTLA4, Fas-L and GITR-L. CMV-CD4{sup +}CD27{sup -}CD28{sup -}more » T{sub R} expanded in response to IL-2, but not to CMV antigenic restimulation. The anti-proliferative effect of CMV-CD4{sup +}CD27{sup -}CD28{sup -} T{sub R} significantly decreased after granzyme B or TGFbeta inhibition. The CMV-CD4{sup +}CD27{sup -}CD28{sup -} T{sub R} of HIV-infected and uninfected donors had similar phenotypes and anti-proliferative potency, but HIV-infected individuals had higher proportions of CMV-CD4{sup +}CD27{sup -}CD28{sup -} T{sub R}. The CMV-CD4{sup +}CD27{sup -}CD28{sup -} T{sub R} may contribute to the downregulation of CMV-specific and nonspecific immune responses of CMV-infected individuals.« less

Rapid generation of combined CMV-specific CD4+ and CD8+ T-cell lines for adoptive transfer into recipients of allogeneic stem cell transplants.

PubMed

Rauser, Georg; Einsele, Hermann; Sinzger, Christian; Wernet, Dorothee; Kuntz, Gabriele; Assenmacher, Mario; Campbell, John D M; Topp, Max S

2004-05-01

Adoptive transfer of cytomegalovirus (CMV)-specific T cells can restore long-lasting, virus-specific immunity and clear CMV viremia in recipients of allogeneic stem cell transplants if CD4(+) and CD8(+) CMV-specific T cells are detected in the recipient after transfer. Current protocols for generating virus-specific T cells use live virus, require leukapheresis of the donor, and are time consuming. To circumvent these limitations, a clinical-scale protocol was developed to generate CMV-specific T cells by using autologous cellular and serum components derived from a single 500-mL blood draw. CMV-specific T cells were stimulated simultaneously with CMV-specific major histocompatibility complex class I (MHC I)- restricted peptides and CMV antigen. Activated T cells were isolated with the interferon-gamma (IFN-gamma) secretion assay and expanded for 10 days. In 8 randomly selected, CMV-seropositive donors, 1.34 x 10(8) combined CD4(+) and CD8(+) CMV-specific T cells, on average, were generated, as determined by antigen-triggered IFN-gamma production. CMV-infected fibroblasts were efficiently lysed by the generated T cells, and CMV-specific CD4(+) and CD8(+) T cells expanded if they were stimulated with natural processed antigen. On the other hand, CD4(+) and CD8(+) T cell-mediated alloreactivity of generated CMV-specific T-cell lines was reduced compared with that of the starting population. In conclusion, the culture system developed allowed the rapid generation of allodepleted, highly enriched, combined CD4(+) and CD8(+) CMV-specific T cells under conditions mimicking good manufacturing practice.

Asymptomatic CMV infections in long-term renal transplant recipients are associated with the loss of FcRγ from LIR-1+ NK cells.

PubMed

Makwana, Nandini B; Foley, Bree; Lee, Silvia; Fernandez, Sonia; Irish, Ashley B; Price, Patricia

2016-11-01

While it is established that cytomegalovirus (CMV) disease affects NK-cell profiles, the functional consequences of asymptomatic CMV replication are unclear. Here, we characterize NK cells in clinically stable renal transplant recipients (RTRs; n = 48) >2 years after transplantation. RTRs and age-matched controls (n = 32) were stratified by their CMV serostatus and the presence of measurable CMV DNA. CMV antibody or CMV DNA influenced expression of NKG2C, LIR-1, NKp30, NKp46, and FcRγ, a signaling adaptor molecule, on CD56 dim NK cells. Phenotypic changes ascribed to CMV were clearer in RTRs than in control subjects and affected NK-cell function as assessed by TNF-α and CD107a expression. The most active NK cells were FcRγ - LIR-1 + NKG2C - and displayed high antibody-dependent cell cytotoxicity responses in the presence of immobilized CMV glycoprotein B reactive antibody. However, perforin levels in supernatants from RTRs with active CMV replication were low. Overall we demonstrate that CMV can be reactivated in symptom-free renal transplant recipients, affecting the phenotypic, and functional profiles of NK cells. Continuous exposure to CMV may maintain and expand NK cells that lack FcRγ but express LIR-1. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Detection of cytomegalovirus (CMV) antigens in kidney biopsies and transplant nephrectomies as a marker for renal graft dysfunction.

PubMed

Gerstenkorn, C; Robertson, H; Mohamed, M A; O'Donnell, M; Ali, S; Talbot, D

2000-11-01

Chronic rejection accounts for the greatest loss of renal allografts. HLA mismatching has been minimised by organ allocation and new immunosuppressive drugs have been employed, but the average cadaveric graft survival still does not exceed 12 years. Though the aetiology is multifactorial, one contributory factor for this condition is cytomegalovirus (CMV). Detection of CMV in kidney biopsies and sera can diagnose and monitor this inflammatory event and define its role in chronic nephropathy. Twenty five biopsies taken at the time of transplantation, 10 biopsies for graft dysfunction and tissue blocks from 20 explanted kidney grafts were collected and investigated for CMV antigens by immunohistochemistry. Tissue samples were snap frozen and cryostat sections were incubated with monoclonal antibodies for CMV antigens followed by immunoperoxidase staining. In 12 out of 20 transplant nephrectomies CMV antigens were found. Only two of these patients had clinical CMV disease. Time 0 biopsies from CMV seronegative donors (n = 11) and CMV seropositive donors (n = 14) were negative for CMV antigens. The prevalence of CMV antigens in grafts lost due to chronic rejection was 60%. These antigens were not found within the time 0 biopsies, but were detected in 30% of biopsies taken at the time of clinical graft dysfunction. CMV appears to contribute to chronic rejection even without clinical disease.

CMV retinitis

MedlinePlus

Cytomegalovirus (CMV) retinitis is a viral infection of the retina of the eye resulting in inflammation. ... CMV retinitis is caused by a member of a group of herpes-type viruses. Infection with CMV ...

Impact of Infliximab and Cyclosporine on the Risk of Colectomy in Hospitalized Patients with Ulcerative Colitis Complicated by Cytomegalovirus-A Multicenter Retrospective Study.

PubMed

Kopylov, Uri; Papamichael, Konstantinos; Katsanos, Konstantinos; Waterman, Matti; Bar-Gil Shitrit, Ariella; Boysen, Trine; Portela, Francisco; Peixoto, Armando; Szilagyi, Andrew; Silva, Marco; Maconi, Giovanni; Har-Noy, Ofir; Bossuyt, Peter; Mantzaris, Gerassimos; Barreiro de Acosta, Manuel; Chaparro, Maria; Christodoulou, Dimitrios K; Eliakim, Rami; Rahier, Jean-Francois; Magro, Fernando; Drobne, David; Ferrante, Marc; Sonnenberg, Elena; Siegmund, Britte; Muls, Vinciane; Thurm, Tamara; Yanai, Henit; Dotan, Iris; Raine, Tim; Levin, Avi; Israeli, Eran; Ghalim, Fahd; Carbonnel, Franck; Vermeire, Severine; Ben-Horin, Shomron; Roblin, Xavier

2017-09-01

Cytomegalovirus (CMV) is frequently detected in patients with ulcerative colitis (UC). The impact of CMV infection on the outcome of UC exacerbation remains unclear. The benefit of combining antiviral with anti-inflammatory treatment has not been evaluated yet. The aim of this study was to compare the outcome of CMV-positive hospitalized patients with UC treated with antiviral therapy either alone or combined with salvage anti-inflammatory therapy (infliximab [IFX] or cyclosporine A [CsA]). This was a multicenter retrospective study of hospitalized CMV-positive patients with UC. The patients were classified into 2 groups: antiviral-if treated with antivirals alone; combined-if treated with both antiviral and anti-inflammatory therapy. The outcomes included the rate of colectomy in both arms during the course of hospitalization and after 3/12 months. A total of 110 patients were included; 47 (42.7%) patients did not receive IFX nor CsA; 36 (32.7%) received IFX during hospitalization or within 1 month before hospitalization; 20 (18.1%) patients received CsA during hospitalization; 7 (6.4%) were exposed to both IFX and CsA. The rate of colectomy was 14.5% at 30 days, 20.0% at 3 months, and 34.8% at 12 months. Colectomy rates were similar across treatment groups. No clinical and demographic variables were independently associated with the risk of colectomy. IFX or cyclosporine therapy is not associated with additional risk for colectomy over antiviral therapy alone in hospitalized CMV-positive patients with UC.

Characterising variation in five genetic loci of cytomegalovirus during treatment for congenital infection.

PubMed

Kadambari, Seilesh; Atkinson, Claire; Luck, Suzanne; Macartney, Malcolm; Conibear, Tim; Harrison, Ian; Booth, Clare; Sharland, Mike; Griffiths, Paul D

2017-03-01

Cytomegalovirus (CMV) is the most common congenital infection in humans and a leading cause of sensorineural hearing loss. Ganciclovir (6 mg/kg twice daily for 42 days) has been shown to reduce hearing deterioration and is used in clinical practice. Vaccines and passive administration of antibody are being evaluated in randomized controlled trials in allograft candidates, women of childbearing age, and pregnant women with primary CMV infection. To help define genetic variation in each of the targets of these therapeutic interventions, we amplified and sequenced genes UL97 (site utilised for ganciclovir phosphorylation), UL55 (glycoprotein B (gB) vaccine target) and UL128, UL130, and UL131a (specific monoclonal antibody targets). Serial blood, saliva, and urine samples (total 120) obtained from nine infants with symptomatic congenital CMV treated with 42 days' ganciclovir were analyzed. All samples tested were UL97 wild type at baseline and none developed mutations during treatment, showing no selection of resistance. The prevalences of UL55 genotypes were 28% gB1, 22% gB2, 1% gB3, and mixed in 20% samples. No mutations were noted in UL128-131a. Phylogenetic tree analysis showed that sequences with variations were found in multiple body sites of individual patients, so there was no evidence of body site compartmentalization of particular strains of CMV. The significance of these results for changes in diagnostic practices and therapeutic interventions against CMV are discussed. J. Med. Virol. 89:502-507, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

CMV sinusitis as the initial manifestation of AIDS.

PubMed

Jütte, A; Fätkenheuer, G; Hell, K; Salzberger, B

2000-03-01

Cytomegalovirus (CMV) disease is a typical late-stage complication of AIDS. Only six cases of CMV sinusitis have been reported in the literature. This is the first case of CMV sinusitis leading to the diagnosis of HIV and CMV retinitis. Diseases of the sinonasal tract may represent an initial manifestation of HIV or AIDS.

Detection of cytomegalovirus DNA in fecal samples as a method for CMV enterocolitis diagnosis after allogeneic stem cell transplantation.

PubMed

Zavrelova, Alzbeta; Radocha, Jakub; Pliskova, Lenka; Paterova, Pavla; Vejrazkova, Eva; Cyrany, Jiri; Gabalec, Filip; Podhola, Miroslav; Zak, Pavel

2018-05-16

Cytomegalovirus enterocolitis is a rare but potentially life threatening complication after allogeneic stem cell transplantation. Its early diagnosis and treatment are essential for a successful outcome. To determine the potential benefit of fecal CMV DNA detection in the diagnosis of CMV colitis among stem cell transplant recipients. Biopsies from the lower gastrointestinal tract, taken during 69 episodes of diarrhea, were compared with fecal samples previously examined for CMV DNA in 45 patients after allogeneic stem cell transplantation. Six confirmed cases of CMV colitis were observed, with 16 out of 69 (23%) fecal samples proving positive for CMV DNA. Only one positive sample correlated with histologically confirmed CMV colitis, and 15 samples were evaluated as false positive. These results provide a 16.7% sensitivity and 76.2% specificity in the diagnosis of CMV enterocolitis. The examination of fecal samples for the presence of CMV DNA has very low potential in the diagnosis of CMV enterocolitis after allogeneic stem cell transplantation; therefore, a biopsy of the gastrointestinal mucosa is still warranted for correct diagnosis.

Maternal cell-mediated cytolysis of CMV-infected fetal cells and the outcome of pregnancy in the guinea pig.

PubMed

Harrison, C J; Myers, M G

1989-01-01

Cytolytic recognition of CMV-infected syngeneic fetal guinea pig cells by maternal peripheral blood mononuclear cells (PBMC) was suppressed late in pregnancies of uninfected guinea pig breeders with less than 25% conceptus loss. A small subset of less successful uninfected pregnancies with greater than or equal to 50% fetal wastage exhibited only partial suppression of cytolytic activity against CMV-infected fetal cells. Primary CMV infection of dams extending into early pregnancy induced augmented cytolysis of CMV-infected fetal cells, but not MA104 NK cell targets, throughout gestation and resulted in 70% loss of conceptus. Decreased suppression of cytolytic activity against CMV-infected fetal cells in uninfected pregnancy was also associated with runting of newborn pups, which was not as severe as that observed in congenitally CMV-exposed or CMV-infected pups. Congenitally infected pups were affected more than their exposed but uninfected litter mates. Lack of suppression of cytolysis of CMV-infected syngeneic fetal cells, whether spontaneous or CMV-infection-induced, appears to be associated with poor pregnancy outcome.

Cytomegalovirus infection in the bone marrow transplant patient.

PubMed

Bhat, Vivek; Joshi, Amit; Sarode, Rahul; Chavan, Preeti

2015-12-24

Cytomegalovirus (CMV) infection is an important contributor to the morbidity and mortality associated with bone marrow transplantation (BMT). Infection may lead to CMV disease involving multiple organs such as pneumonia, gastroenteritis, retinitis, central nervus system involvement and others. CMV seropositivity is an important risk factor and approximately half of BMT recipients will develop clinically significant infection most commonly in the first 100 d post-transplant. The commonly used tests to diagnose CMV infection in these patients include the pp65 antigenemia test and the CMV DNA polymerase chain reaction (PCR) assay. Because of its greater sensitivity and lesser turnaround time, the CMV PCR is nowadays the preferred test and serves as a main guide for pre-emptive therapy. Methods of CMV prevention include use of blood products from seronegative donors or leukodepleted products. Prophylaxis or pre-emptive therapy strategies for CMV prevention may be used post-transplant with the latter becoming more common. The commonly used antivirals for pre-emptive therapy and CMV disease management include intravenous gancyclovir and foscarnet. The role of intravenous immunoglobulin, although used commonly in CMV pneumonia is not clear.

Cytomegalovirus and immunotherapy: opportunistic pathogen, novel target for cancer and a promising vaccine vector.

PubMed

Quinn, Michael; Erkes, Dan A; Snyder, Christopher M

2016-02-01

Cytomegalovirus (CMV) is a β-herpesvirus that infects most people in the world and is almost always asymptomatic in the healthy host. However, CMV persists for life, requiring continuous immune surveillance to prevent disease and thus, CMV is a frequent complication in immune compromised patients. Many groups have been exploring the potential for adoptive T-cell therapies to control CMV reactivation as well as the progression of solid tumors harboring CMV. In addition, CMV itself is being explored as a vaccine vector for eliciting potent T-cell responses. This review will discuss key features of the basic biology of CMV-specific T cells as well as highlighting unanswered questions and ongoing work in the development of T-cell-based immunotherapies to target CMV.

Levels of anti-CMV antibodies are modulated by the frequency and intensity of virus reactivations in kidney transplant patients.

PubMed

Iglesias-Escudero, María; Moro-García, Marco Antonio; Marcos-Fernández, Raquel; García-Torre, Alejandra; Álvarez-Argüelles, Marta Elena; Suárez-Fernández, María Luisa; Martínez-Camblor, Pablo; Rodríguez, Minerva; Alonso-Arias, Rebeca

2018-01-01

Anti-CMV (cytomegalovirus) antibody titers are related to immune alterations and increased risk of mortality. To test whether they represent a marker of infection history, we analyzed the effect of viral reactivations on the production of specific antibodies in kidney transplant patients. We quantified CMV-DNAemia and antibody titers in 58 kidney transplant patients before transplantation and during a follow-up of 315 days (standard deviation, SD: 134.5 days). In order to calculate the intensity of the infection, we plotted the follow-up time of the infection on the x-axis and the number of DNA-CMV copies on the y-axis and calculated the area under the curve (CMV-AUC). The degree of T-lymphocyte differentiation was analyzed with flow cytometry, the cells were labelled with different monoclonal antibodies in order to distinguish their differentiation state, from naive T-cells to senescent T-cells. Peak viremia was significantly higher in patients experiencing a primary infection (VI) compared to patients experiencing viral reactivation (VR). Our data indicate that the overall CMV viral load over the course of a primary infection is significantly higher than in a reactivation of a previously established infection. Whereas patients who experienced an episode of CMV reactivation during the course of our observation showed increased levels of CMV-specific antibodies, patients who did not experience CMV reactivation (WVR) showed a drop in CMV antibody levels that corresponds to an overall drop in antibody levels, probably due to the continuing immunosuppression after the renal transplant. We found a positive correlation between the CMV viremia over the course of the infection or reactivation and the CMV-specific antibody titers in the examined patients. We also observed a positive correlation between anti-CMV titers and T-cell differentiation. In conclusion, our data show that anti-CMV antibody titers are related to the course of CMV infection in kidney transplant patients.

Prevalence of CMV infection among staff in a metropolitan children's hospital - occupational health screening findings.

PubMed

Stranzinger, Johanna; Kindel, Jutta; Henning, Melanie; Wendeler, Dana; Nienhaus, Albert

2016-01-01

Background: Staff in children's hospitals may run an increased risk of cytomegalovirus (CMV) contact infection leading to a congenital CMV fetopathy during pregnancy. The main risk factor is close contact with inapparent carriers of CMV among infants (<3 years). We therefore examined CMV seroprevalence (SP) and possible risk factors for CMV infection among staff at a children's hospital. Method: In 2014, staff at a metropolitan children's hospital were offered a CMV antibody test in the context of occupational health screening. Besides of anti-CMV immunoglobulin G (anti-CMV IgG) gender, age, profession, number of children and migration background were assessed and used as independent variables in multiple logistic regression. Women without a migration background (MIG) were considered as a separate group. Results: The study included 219 employees. Women showed a significant higher risk than men of being CMV-positive (adjusted odds ratio [aOR] 3.0; 95% CI 1.1-7.8). The risk among age groups of 30 and over was double that of the under-30s (aOR 2.0; 95% CI 1.0-3.9); among those aged 40-plus it was aOR 2.3 (95% CI 1.1-4.7). Staff with an MIG tested more often positive than those without an MIG (95.5% versus 45.7%). CMV SP was 47.7% among women without an MIG. In this subgroup the probability of CMV infection increased with age (p=0.08) as well. Conclusion: In the staff group as a whole there was a significant correlation between CMV SP, country of origin and age. We found no significant differences between occupational groups; perhaps our random sample was too small. Given the low CMV SP particularly in those without MIG, women who want to have children in particular must be protected from CMV infection. Follow-up studies should be undertaken to test whether good workplace hygiene offers sufficient protection for pregnant women and could be an alternative to prohibiting certain activities.

Levels of anti-CMV antibodies are modulated by the frequency and intensity of virus reactivations in kidney transplant patients

PubMed Central

Marcos-Fernández, Raquel; García-Torre, Alejandra; Álvarez-Argüelles, Marta Elena; Suárez-Fernández, María Luisa; Martínez-Camblor, Pablo; Rodríguez, Minerva; Alonso-Arias, Rebeca

2018-01-01

Anti-CMV (cytomegalovirus) antibody titers are related to immune alterations and increased risk of mortality. To test whether they represent a marker of infection history, we analyzed the effect of viral reactivations on the production of specific antibodies in kidney transplant patients. We quantified CMV-DNAemia and antibody titers in 58 kidney transplant patients before transplantation and during a follow-up of 315 days (standard deviation, SD: 134.5 days). In order to calculate the intensity of the infection, we plotted the follow-up time of the infection on the x-axis and the number of DNA-CMV copies on the y-axis and calculated the area under the curve (CMV-AUC). The degree of T-lymphocyte differentiation was analyzed with flow cytometry, the cells were labelled with different monoclonal antibodies in order to distinguish their differentiation state, from naive T-cells to senescent T-cells. Peak viremia was significantly higher in patients experiencing a primary infection (VI) compared to patients experiencing viral reactivation (VR). Our data indicate that the overall CMV viral load over the course of a primary infection is significantly higher than in a reactivation of a previously established infection. Whereas patients who experienced an episode of CMV reactivation during the course of our observation showed increased levels of CMV-specific antibodies, patients who did not experience CMV reactivation (WVR) showed a drop in CMV antibody levels that corresponds to an overall drop in antibody levels, probably due to the continuing immunosuppression after the renal transplant. We found a positive correlation between the CMV viremia over the course of the infection or reactivation and the CMV-specific antibody titers in the examined patients. We also observed a positive correlation between anti-CMV titers and T-cell differentiation. In conclusion, our data show that anti-CMV antibody titers are related to the course of CMV infection in kidney transplant patients. PMID:29641536

Comparison of the AdvanSure human papillomavirus screening real-time PCR, the Abbott RealTime High Risk human papillomavirus test, and the Hybrid Capture human papillomavirus DNA test for the detection of human papillomavirus.

PubMed

Hwang, Yusun; Lee, Miae

2012-05-01

We evaluated the performance of various commercial assays for the molecular detection of human papillomavirus (HPV); the recently developed AdvanSure HPV Screening real-time PCR assay (AdvanSure PCR) and the Abbott RealTime High Risk HPV PCR assay (Abbott PCR) were compared with the Hybrid Capture 2 HPV DNA Test (HC2). All 3 tests were performed on 177 samples, and any sample that showed a discrepancy in any of the 3 tests was genotyped using INNO-LiPA HPV genotyping and/or sequencing. On the basis of these results, we obtained a consensus HPV result, and the performance of each test was evaluated. We also evaluated high-risk HPV 16/18 detection by using the 2 real-time PCR assays. Among the 177 samples, 65 were negative and 75 were positive in all 3 assays; however, the results of the 3 assays with 37 samples were discrepant. Compared with the consensus HPV result, the sensitivities and specificities of HC2, AdvanSure PCR, and Abbott PCR were 97.6%, 91.7%, and 86.9% and 83.9%, 98.8%, and 100.0%, respectively. For HPV type 16/18 detection, the concordance rate between the AdvanSure PCR and Abbott PCR assays was 98.3%; however, 3 samples were discrepant (positive in AdvanSure PCR and negative in Abbott PCR) and were confirmed as HPV type 16 by INNO-LiPA genotyping and/or sequencing. For HPV detection, the AdvanSure HPV Screening real-time PCR assay and the Abbott PCR assay are less sensitive but more specific than the HC2 assay, but can simultaneously differentiate type 16/18 HPV from other types.

Clinical evaluation of the Abbott RealTime MTB Assay for direct detection of Mycobacterium tuberculosis-complex from respiratory and non-respiratory samples.

PubMed

Hinić, Vladimira; Feuz, Kinga; Turan, Selda; Berini, Andrea; Frei, Reno; Pfeifer, Karin; Goldenberger, Daniel

2017-05-01

Rapid and reliable diagnosis is crucial for correct management of tuberculosis. The Abbott RealTime MTB Assay represents a novel qualitative real-time PCR assay for direct detection of M. tuberculosis-complex (MTB) DNA from respiratory samples. The test targets two highly conserved sequences, the multi-copy insertion element IS6110 and the protein antigen B (PAB) gene of MTB, allowing even the detection of IS6610-deficient strains. We evaluated this commercial diagnostic test by analyzing 200 respiratory and, for the first time, 87 non-respiratory clinical specimens from our tertiary care institution and compared its results to our IS6110-based in-house real-time PCR for MTB as well as MTB culture. Overall sensitivity for Abbott RealTime MTB was 100% (19/19) in smear positive and 87.5% (7/8) in smear negative specimens, while the specificity of the assay was 100% (260/260). For both non-respiratory smear positive and smear negative specimens Abbott RealTime MTB tests showed 100% (8/8) sensitivity and 100% (8/8) specificity. Cycle threshold (Ct) value analysis of 16 MTB positive samples showed a slightly higher Ct value of the Abbott RealTime MTB test compared to our in-house MTB assay (mean delta Ct = 2.55). In conclusion, the performance of the new Abbott RealTime MTB Assay was highly similar to culture and in-house MTB PCR. We document successful analysis of 87 non-respiratory samples with the highly automated Abbott RealTime MTB test with no inhibition observed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cytomegalovirus Retinitis and the Acquired Immune Deficiency Syndrome: Bench to Bedside: LXVII Edward Jackson Memorial Lecture

PubMed Central

Jabs, Douglas A.

2010-01-01

Purpose To update information on cytomegalovirus (CMV) retinitis in patients with the acquired immune deficiency syndrome (AIDS) and to integrate information on its pathogenesis and clinical outcomes. Design Literature review. Methods Selected articles from the medical literature, particularly large epidemiologic studies, including the Johns Hopkins Cytomegalovirus Retinitis Cohort Study, the Longitudinal Study of the Ocular Complications of AIDS, and the Cytomegalovirus Retinitis and Viral Resistance Study, were reviewed. Clinical information is discussed in light of knowledge on CMV, its pathogenesis, and its interactions with human immunodeficiency virus (HIV). Results Cytomegalovirus uses several mechanisms to evade the immune system and establish latent infection in immunologically normal hosts. With immune deficiency, such as late-stage AIDS, CMV reactivates, is disseminated to the eye, and establishes a productive infection, resulting in retinal necrosis. HIV and CMV potentiate each other: CMV accelerates HIV disease, and CMV retinitis is associated with increased mortality. Randomized clinical trials have demonstrated the efficacy of treatments for CMV retinitis. Systemically-administered treatment for CMV retinitis decreases AIDS mortality. Highly active antiretroviral therapy (HAART), effectively suppresses HIV replication, resulting in immune recovery, which, if sufficient, controls retinitis without anti-CMV therapy. Resistant CMV, detected in the blood, correlates with resistant virus in the eye and is associated with worse clinical outcomes, including mortality. Host factors, including host genetics and access to care, play a role in the development of CMV retinitis. Conclusions Clinical outcomes of CMV retinitis in patients with AIDS are dependent on characteristics of the virus and host and on HIV–CMV interactions. PMID:21168815

Transfer of minimally manipulated CMV-specific T cells from stem cell or third-party donors to treat CMV infection after allo-HSCT.

PubMed

Neuenhahn, M; Albrecht, J; Odendahl, M; Schlott, F; Dössinger, G; Schiemann, M; Lakshmipathi, S; Martin, K; Bunjes, D; Harsdorf, S; Weissinger, E M; Menzel, H; Verbeek, M; Uharek, L; Kröger, N; Wagner, E; Kobbe, G; Schroeder, T; Schmitt, M; Held, G; Herr, W; Germeroth, L; Bonig, H; Tonn, T; Einsele, H; Busch, D H; Grigoleit, G U

2017-10-01

Cytomegalovirus (CMV) infection is a common, potentially life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). We assessed prospectively the safety and efficacy of stem cell-donor- or third-party-donor-derived CMV-specific T cells for the treatment of persistent CMV infections after allo-HSCT in a phase I/IIa trial. Allo-HSCT patients with drug-refractory CMV infection and lacking virus-specific T cells were treated with a single dose of ex vivo major histocompatibility complex-Streptamer-isolated CMV epitope-specific donor T cells. Forty-four allo-HSCT patients receiving a T-cell-replete (D + repl; n=28) or T-cell-depleted (D + depl; n=16) graft from a CMV-seropositive donor were screened for CMV-specific T-cell immunity. Eight D + depl recipients received adoptive T-cell therapy from their stem cell donor. CMV epitope-specific T cells were well supported and became detectable in all treated patients. Complete and partial virological response rates were 62.5% and 25%, respectively. Owing to longsome third-party donor (TPD) identification, only 8 of the 57 CMV patients transplanted from CMV-seronegative donors (D - ) received antigen-specific T cells from partially human leukocyte antigen (HLA)-matched TPDs. In all but one, TPD-derived CMV-specific T cells remained undetectable. In summary, adoptive transfer correlated with functional virus-specific T-cell reconstitution in D + depl patients. Suboptimal HLA match may counteract expansion of TPD-derived virus-specific T cells in D - patients.

Awareness of cytomegalovirus and risk factors for susceptibility among pregnant women, in Montreal, Canada.

PubMed

Wizman, Sarah; Lamarre, Valérie; Coic, Lena; Kakkar, Fatima; Le Meur, Jean-Baptiste; Rousseau, Céline; Boucher, Marc; Tapiero, Bruce

2016-03-15

Advances in diagnostic and therapeutic modalities for congenital cytomegalovirus (CMV) infection have generated a mounting interest in identifying mothers susceptible to CMV. The objectives of this study were to evaluate the prevalence and socio-demographic determinants of CMV susceptibility and CMV awareness, among pregnant women, in Montreal, Quebec. Between April and December 2012, women delivering at Centre Hospitalier Universitaire Sainte Justine were recruited for the study. Stored serum from the first trimester of pregnancy was tested for CMV IgG. Knowledge about CMV and socio-demographic characteristics were collected via standardized questionnaire. Four hundred and ninety one women were enrolled in the study. Overall, 225 mothers (46%) were seronegative for CMV, and 85% (n = 415) were unaware of CMV or the associated risks in pregnancy. Significant risk factors for CMV seronegative status included Canadian vs. foreign born (aOR 6.88, 95% CI 4.33-10.94), and high vs. low family income (aOR 4.68, 95% CI 2.09-10.48). Maternal employment status was the only significant predictor of CMV unawareness, with unemployed mothers at the highest risk (aOR 85.6, 95% CI 17.3-421.3). Nearly half of pregnant women studied were at risk of primary infection, and yet, the majority was unaware of potential risks associated with CMV. Canadian born mothers and those with a high socioeconomic status were more likely to be CMV seronegative. Increased education about CMV infection, through public health interventions and obstetrician/pediatric counseling, is needed for all pregnant women.

HIV-1-RNA in seminal plasma correlates with detection of HIV-1-DNA in semen cells, but not with CMV shedding, among MSM on successful antiretroviral regimens.

PubMed

Gantner, Pierre; Assoumou, Lambert; Leruez-Ville, Marianne; David, Ludivine; Suzan-Monti, Marie; Costagliola, Dominique; Rouzioux, Christine; Ghosn, Jade

2016-11-01

Intermittent seminal HIV-RNA detection can occur in MSM despite concomitant plasma virological control on combined ART (cART). We undertook the present study to determine if seminal HIV detection was associated with seminal cytomegalovirus (CMV) detection or detection of HIV-infected cells in semen. Longitudinal semen samples from HIV-1-infected MSM on successful cART enrolled in the EVARIST ANRS EP 49 study were analysed. We first conducted a case-control analysis (ratio 1 : 3) to assess HIV-DNA detection in semen cells in the 20 patients with detectable HIV-RNA in seminal plasma (cases) matched with 60 participants with undetectable HIV-RNA (controls) based on total HIV-DNA load in blood cells. Second, we measured CMV-DNA in all seminal plasma samples. HIV-1-DNA in semen cells was detected on at least one sample visit in 12/20 cases and 11/60 controls. Detection of HIV-RNA in seminal plasma was associated significantly with the detection of HIV-DNA in semen cells [OR, 7.6 (95% CI, 2.1-28.4); P = 0.002] when adjusted on total HIV-DNA in blood cells. CMV-DNA was detected in 107/273 seminal plasma samples with a median value of 3.62 log 10 copies/mL (IQR, 2.83-4.38), yielding a prevalence of 39.2%. Seminal CMV-DNA shedding [OR, 1.5 (95% CI, 0.6-3.6); P = 0.343] was not associated with the risk of detection of HIV-RNA in seminal plasma. The presence of HIV-DNA in semen cells was predictive of HIV-RNA detection, suggesting that viral particles arise through local HIV replication by infected semen cells. Despite virological control, compartmentalization of HIV in the genital tract might act in residual replication and transmission. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

[Prospective study on the impact of infantile cytomegalovirus infection on growth and development of infants].

PubMed

2010-05-01

To understand the situation of postnatal cytomegalovirus (CMV) infection in Beijing and its impact on infant. From November 2004 to March 2008, a multicenter cohort study on maternal, neonatal and infantile CMV infection was carried out in four hospitals in Beijing. Two hundred and ten infants without congenital infections were enrolled into this study. Their serum IgG antibody to CMV was determined at the age of 1 year. According to the results of CMV DNA at 12 weeks of age and the CMV IgG results at 1 year of age, they were divided into three groups, perinatal infection group, postnatal infection group and postnatal non-infection group. The information of their mothers, the data of their growth and development at 1 year of age, development quotient, their eyes and their auditory function were analyzed. The risk factors of the postnatal cytomegalovirus infection were analyzed by multi-factorial logistic regression. Of the 210 infants, 42 had perinatal infection, 98 had postnatal infection and 70 had no infection. The postnatal cytomegalovirus infection rate was 46.40%, taken into account the congenital infection rate and perinatal infection rate, the total cytomegalovirus infection rate was 66.85% at 1 year of age. The clinical manifestation, developmental status and the quotient of development from three groups at birth and at 1 year of age were analyzed. No significant difference was found. In postnatal cytomegalovirus infection group the rates of breast feeding, mixed feeding and formula feeding were 87.76%, 9.18% and 3.06%, respectively; while in no infection group the rates were 61.43%, 21.43% and 17.14%, respectively(chi(2) = 17.040, P < 0.01). CMV infection is present widely in China. Non-breast feeding is an important protective factor. Postnatal cytomegalovirus infection in infants had no significant impact on the health and development of infants.

Tissue reservoirs of antiviral T cell immunity in persistent human CMV infection

PubMed Central

Gordon, Claire L.; Thome, Joseph J.C.; Igarashi, Suzu

2017-01-01

T cell responses to viruses are initiated and maintained in tissue sites; however, knowledge of human antiviral T cells is largely derived from blood. Cytomegalovirus (CMV) persists in most humans, requires T cell immunity to control, yet tissue immune responses remain undefined. Here, we investigated human CMV-specific T cells, virus persistence and CMV-associated T cell homeostasis in blood, lymphoid, mucosal and secretory tissues of 44 CMV seropositive and 28 seronegative donors. CMV-specific T cells were maintained in distinct distribution patterns, highest in blood, bone marrow (BM), or lymph nodes (LN), with the frequency and function in blood distinct from tissues. CMV genomes were detected predominantly in lung and also in spleen, BM, blood and LN. High frequencies of activated CMV-specific T cells were found in blood and BM samples with low virus detection, whereas in lung, CMV-specific T cells were present along with detectable virus. In LNs, CMV-specific T cells exhibited quiescent phenotypes independent of virus. Overall, T cell differentiation was enhanced in sites of viral persistence with age. Together, our results suggest tissue T cell reservoirs for CMV control shaped by both viral and tissue-intrinsic factors, with global effects on homeostasis of tissue T cells over the lifespan. PMID:28130404

Tissue reservoirs of antiviral T cell immunity in persistent human CMV infection.

PubMed

Gordon, Claire L; Miron, Michelle; Thome, Joseph J C; Matsuoka, Nobuhide; Weiner, Joshua; Rak, Michael A; Igarashi, Suzu; Granot, Tomer; Lerner, Harvey; Goodrum, Felicia; Farber, Donna L

2017-03-06

T cell responses to viruses are initiated and maintained in tissue sites; however, knowledge of human antiviral T cells is largely derived from blood. Cytomegalovirus (CMV) persists in most humans, requires T cell immunity to control, yet tissue immune responses remain undefined. Here, we investigated human CMV-specific T cells, virus persistence and CMV-associated T cell homeostasis in blood, lymphoid, mucosal and secretory tissues of 44 CMV seropositive and 28 seronegative donors. CMV-specific T cells were maintained in distinct distribution patterns, highest in blood, bone marrow (BM), or lymph nodes (LN), with the frequency and function in blood distinct from tissues. CMV genomes were detected predominantly in lung and also in spleen, BM, blood and LN. High frequencies of activated CMV-specific T cells were found in blood and BM samples with low virus detection, whereas in lung, CMV-specific T cells were present along with detectable virus. In LNs, CMV-specific T cells exhibited quiescent phenotypes independent of virus. Overall, T cell differentiation was enhanced in sites of viral persistence with age. Together, our results suggest tissue T cell reservoirs for CMV control shaped by both viral and tissue-intrinsic factors, with global effects on homeostasis of tissue T cells over the lifespan. @Gordon et al.

Pancreatic Anastomosis Leak 15 Years after Simultaneous Pancreas-Kidney Transplantation from Late-Onset Allograft Cytomegalovirus Duodenal Ulcers Presenting with Gross Hematuria

PubMed Central

Tantisattamo, Ekamol; Chung, Heath; Okado, Manami

2013-01-01

Cytomegalovirus (CMV) infection is one of the most important causes of morbidity and mortality in solid organ transplantation. It can present with hematuria, the most common urological complication in the early post-simultaneous pancreas-kidney (SPK) transplant period. In SPK transplantation, CMV infection usually occurs 1 month after transplantation. We report an instance of bladder-drained SPK transplant presenting with recurrent gross hematuria from CMV infected duodenal graft ulcers 15 years after preserved well-functioning grafts. Serum quantitative Polymerase Chain Reaction (qPCR) for CMV was negative. Postmortem duodenal graft staining for CMV was positive, and revealed the cause of the inciting ulcer. To our knowledge, our patient is the first reported case of very late onset invasive CMV disease causing duodenal graft ulcers 15 years after transplantation, as previously reported cases of posttransplant CMV disease occurred only as late as 18 months. In addition, the absence of correlation between CMV viremia and CMV-infected duodenal allograft in SPK transplant has not been reported. Our case demonstrates that CMV viral load is -unreliable to diagnose invasive CMV disease, and tissue biopsy should be obtained to avoid missed diagnosis causing high morbidity and mortality. PMID:24349888

Cytomegalovirus-Specific CD4+ T-cell Responses and CMV-IgG Levels are associated with Neurocognitive Impairment in People Living with HIV.

PubMed

Ballegaard, Vibe; Pedersen, Karin Kaereby; Pedersen, Maria; Brændstrup, Peter; Kirkby, Nikolai; Buus, Anette Stryhn; Ryder, Lars P; Gerstoft, Jan; Nielsen, Susanne Dam

2018-05-30

Mechanisms leading to neurocognitive impairment (NCI) in people living with HIV (PLWHIV) on stable antiretroviral therapy (cART) remain unknown. We investigated the association between CMV immunity, HIV-specific variables and NCI in PLWHIV on stable cART and with low comorbidity. 52 PLWHIV on stable cART and 31 HIV-uninfected controls matched on age, gender, education and comorbidity were tested with a neurocognitive test-battery and CMV-immunoglobulin G (CMV-IgG) levels were measured. In PLWHIV, CMV-specific (CMV-pp65 and CMV-gB) CD4+ and CD8+ T-cell responses were measured using intracellular-cytokine-staining and flowcytometry. NCI was defined as a global-deficit-scale score (GDS-score) ≥ 0.5. GDS-scores and domain-specific-scores defined severity of NCI. Logistic and linear multivariate regression analyses were used. NCI was detected in 30.8% of PLWHIV, and HIV was associated with an adjusted odds ratio (aOR) of 5.18 (95%CI: 1.15; 23.41, p=0.033) for NCI. In PLWHIV, higher CMV-specific CD4+ T-cell responses increased the probability of NCI with an aOR of 1.68 (95%CI: 1.10; 2.57) for CMV-pp65 or an aOR of 3.73 (95%CI: 1.61; 16.98) for CMV-gB, respectively. Similar associations were not found with CMV-IgG or CMV-specific CD8+ T-cells, but when assessing severity of NCI, higher CMV-IgG (per 100 U/ml) was associated with worse GDS-scores (β=0.08 (0.01-0.16), p=0.044), specifically in the domain of speed of information processing (β=0.20 (0.04-0.36, p=0.019). PLWHIV had increased risk of NCI. Excess risk may be associated with CMV-specific CD4+ T-cell responses and CMV-IgG. Larger longitudinal studies investigating the impact of CMV immunity on risk of NCI are warranted.

49 CFR 383.37 - Employer responsibilities.

Code of Federal Regulations, 2010 CFR

2010-10-01

... operate a CMV in the United States: (a) During any period in which the driver has a CMV driver's license suspended, revoked, or canceled by a State, has lost the right to operate a CMV in a State, or has been disqualified from operating a CMV; (b) During any period in which the driver has more than one CMV driver's...

Cytomegalovirus retinitis in a patient with secondary acute lymphosarcoma leukemia undergoing allogeneic hematopoietic stem-cell transplantation

PubMed Central

Zhao, Ning; Liu, Lei; Xu, Junjie

2017-01-01

Abstract Rationale: Cytomegalovirus (CMV) retinitis is a common opportunistic infection in immunocompromised patients, which may lead to blindness. CMV retinitis is not an uncommon infectious disease in patients with immune regulatory abnormalities, for example, human immunodeficiency virus (HIV) patients. However, CMV retinitis in a patient with acute lymphosarcoma leukemia (ALL) undergoing allogeneic hematopoietic stem-cell transplantation (HSCT) phase is very rare. Patient concerns: A case of CMV retinitis in a patient receiving immunosuppressive therapy as a part of ALL allogeneic HSCT is described including the pathogenesis, clinical signs, and therapy. Diagnoses: CMV retinitis. Interventions: Ganciclovir intravitreal injection at weekly intervals for 4 weeks. Outcomes: Patient's vision had improved and the load of CMV deoxyribonucleic acid (DNA) in the aqueous humor declined. The CMV retinitis and perivascular of retina infiltration regressed. Lessons: We propose that the concentration of CMV DNA load in the aqueous humor could be useful in making the diagnosis and in selecting the optimal treatment in this kind of CMV retinitis. PMID:28489788

Cytomegalovirus retinitis in a patient with secondary acute lymphosarcoma leukemia undergoing allogeneic hematopoietic stem-cell transplantation: A rare case report: a care-compliant article.

PubMed

Zhao, Ning; Liu, Lei; Xu, Junjie

2017-05-01

Cytomegalovirus (CMV) retinitis is a common opportunistic infection in immunocompromised patients, which may lead to blindness. CMV retinitis is not an uncommon infectious disease in patients with immune regulatory abnormalities, for example, human immunodeficiency virus (HIV) patients. However, CMV retinitis in a patient with acute lymphosarcoma leukemia (ALL) undergoing allogeneic hematopoietic stem-cell transplantation (HSCT) phase is very rare. A case of CMV retinitis in a patient receiving immunosuppressive therapy as a part of ALL allogeneic HSCT is described including the pathogenesis, clinical signs, and therapy. CMV retinitis. Ganciclovir intravitreal injection at weekly intervals for 4 weeks. Patient's vision had improved and the load of CMV deoxyribonucleic acid (DNA) in the aqueous humor declined. The CMV retinitis and perivascular of retina infiltration regressed. We propose that the concentration of CMV DNA load in the aqueous humor could be useful in making the diagnosis and in selecting the optimal treatment in this kind of CMV retinitis.

HHV-6 reactivation is often associated with CMV infection in liver transplant patients.

PubMed

Lautenschlager, I; Linnavuori, K; Lappalainen, M; Suni, J; Höckerstedt, K

2000-01-01

Human herpesvirus 6 (HHV-6) infection has been recently reported in liver transplant patients. HHV-6 is closely related to cytomegalo-virus (CMV), and some interaction between the viruses has been suggested. In this study, the post-transplant HHV-6 antigenemia was investigated in relation to symptomatic CMV infections in adult liver transplant patients. CMV infections were diagnosed by the pp65 antigenemia test and by viral cultures. HHV-6 infections were demonstrated by the HHV-6 antigenemia test and by serology. Significant symptomatic CMV infection was diagnosed in 42 of 75 patients during the first 6 months after transplantation. All CMV infections were successfully treated with ganciclovir. Concurrent HHV-6 antigenemia was detected in 21 (50%) of 42 patients with CMV infection. All HHV-6 infections were reactivations. HHV-6 also responded to the antiviral treatment, but with less clear effect. In conclusion, HHV-6 reactivation is often associated with CMV infection in liver transplant patients. The results support the suggestion that CMV and HHV-6 may have interactions.

Aphid vector population density determines the emergence of necrogenic satellite RNAs in populations of cucumber mosaic virus.

PubMed

Betancourt, Mónica; Fraile, Aurora; Milgroom, Michael G; García-Arenal, Fernando

2016-06-01

The satellite RNAs of cucumber mosaic virus (CMV) that induce systemic necrosis in tomato plants (N-satRNA) multiply to high levels in the infected host while severely depressing CMV accumulation and, hence, its aphid transmission efficiency. As N-satRNAs are transmitted into CMV particles, the conditions for N-satRNA emergence are not obvious. Model analyses with realistic parameter values have predicted that N-satRNAs would invade CMV populations only when transmission rates are high. Here, we tested this hypothesis experimentally by passaging CMV or CMV+N-satRNAs at low or high aphid densities (2 or 8 aphids/plant). As predicted, high aphid densities were required for N-satRNA emergence. The results showed that at low aphid densities, random effects due to population bottlenecks during transmission dominate the epidemiological dynamics of CMV/CMV+N-satRNA. The results suggest that maintaining aphid populations at low density will prevent the emergence of highly virulent CMV+N-satRNA isolates.

Performance evaluation of the Abbott CELL-DYN Ruby and the Sysmex XT-2000i haematology analysers.

PubMed

Leers, M P G; Goertz, H; Feller, A; Hoffmann, J J M L

2011-02-01

Two mid-range haematology analysers (Abbott CELL-DYN Ruby and Sysmex XT-2000i) were evaluated to determine their analytical performance and workflow efficiency in the haematology laboratory. In total 418 samples were processed for determining equivalence of complete blood count (CBC) measurements, and 100 for reticulocyte comparison. Blood smears served for assessing the agreement of the differential counts. Inter-instrument agreement for most parameters was good although small numbers of discrepancies were observed. Systematic biases were found for mean cell volume, reticulocytes, platelets and mean platelet volume. CELL-DYN Ruby WBC differentials were obtained with all samples while the XT-2000i suppressed differentials partially or completely in 13 samples (3.1%). WBC subpopulation counts were otherwise in good agreement with no major outliers. Following first-pass CBC/differential analysis, 88 (21%) of XT-2000i samples required further analyser processing compared to 18 (4.3%) for the CELL-DYN Ruby. Smear referrals for suspected WBC/nucleated red blood cells and platelet abnormalities were indicated for 106 (25.4%) and 95 (22.7%) of the XT-2000i and CELL-DYN Ruby samples respectively. Flagging efficiencies for both analysers were found to be similar. The Sysmex XT-2000i and Abbott CELL-DYN Ruby analysers have broadly comparable analytical performance, but the CELL-DYN Ruby showed superior first-pass efficiency. © 2010 Blackwell Publishing Ltd.

Detection of antibodies to hepatitis B core antigen using the Abbott ARCHITECT anti-HBc assay: analysis of borderline reactive sera.

PubMed

Ollier, Laurence; Laffont, Catherine; Kechkekian, Aurore; Doglio, Alain; Giordanengo, Valérie

2008-12-01

Routine use of the automated chemiluminescent microparticle immunoassay Abbott ARCHITECT anti-HBc for diagnosis of hepatitis B is limited in case of borderline reactive sera with low signal close to the cut-off index. In order to determine the significance of anti-HBc detection when borderline reactivity occurs using the ARCHITECT anti-HBc assay, a comparative study was designed. 3540 serum samples collected over a 2-month period in the hospital of Nice were examined for markers of HBV infection (HBsAg, anti-HBs and anti-HBc). One hundred seven samples with sufficient volume and with borderline reactivity by the ARCHITECT assay were tested by two other anti-HBc assays, a microparticle enzyme immunoassay (MEIA, AxSYM Core, Abbott Laboratories, IL, USA) and an enzyme linked fluorescent assay (ELFA, VIDAS Anti-HBc Total II, bioMérieux, Lyon, France). Only 46 samples were confirmed by the AxSYM and the VIDAS assays. Additional serological information linked to patient history showed that the remaining samples (61) were false positives (11), had low titer of anti-HBc antibodies (13), or were inconclusive (37). This comparative study highlighted the existence of a grey zone around the cut-off index. Confirmative results through a different immunoassay are needed to confirm the diagnosis of HBV on borderline reactive sera using the ARCHITECT anti-HBc assay.

CMV drives the expansion of highly functional memory T cells expressing NK-cell receptors in renal transplant recipients.

PubMed

Makwana, Nandini; Foley, Bree; Fernandez, Sonia; Lee, Silvia; Irish, Ashley; Pircher, Hanspeter; Price, Patricia

2017-08-01

Cytomegalovirus (CMV) is a common opportunistic infection encountered in renal transplant recipients (RTRs) and may be reactivated without symptoms at any time post-transplant. We describe how active and latent CMV affect T-cell subsets in RTRs who are stable on maintenance therapy. T-cell responses to CMV were assessed in RTRs (n = 54) >2 years post-transplant, and healthy controls (n = 38). Seven RTRs had CMV DNA detectable in plasma. CMV antibody and DNA aligned with increased proportions of CD8 + T cells and reduced CD4/CD8 ratios. This paralleled an expansion of effector memory T-cell (T EM ), terminally differentiated T-cell (T EMRA ) and CD57 + T EMRA cell populations. Expression of NK-cell receptors, LIR-1 and KLRG1 on CD4 + and CD8 + CD57 + T EM and T EMRA cells correlated with elevated interferon-γ and cytotoxic responses to anti-CD3 and increased cytotoxic responses to CMV phosphoprotein (pp) 65 in RTRs who carried CMV DNA. CD8 + T cells from all CMV seropositive RTRs responded efficiently to CMV immediate early (IE) -1 peptides. The data show that latent and active CMV infection can alter T-cell subsets in RTRs many years after transplantation, and up-regulate T-cell expression of NK-cell receptors. This may enhance effector responses of CD4 + and CD8 + T cells against CMV. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

CD8 T-Cell Expansion and Inflammation Linked to CMV Coinfection in ART-treated HIV Infection

PubMed Central

Freeman, Michael L.; Mudd, Joseph C.; Shive, Carey L.; Younes, Souheil-Antoine; Panigrahi, Soumya; Sieg, Scott F.; Lee, Sulggi A.; Hunt, Peter W.; Calabrese, Leonard H.; Gianella, Sara; Rodriguez, Benigno; Lederman, Michael M.

2016-01-01

Background. Persistent CD8 T-cell expansion, low CD4/CD8 T-cell ratios, and heightened inflammation persist in antiretroviral therapy (ART)-treated human immunodeficiency virus (HIV) infection and are associated with increased risk of morbid outcomes. We explored the role of cytomegalovirus (CMV) infection in CD8 lymphocytosis and inflammation in ART-treated HIV infection. Methods. Absolute CD4 and CD8 T-cell counts were abstracted from clinical records and compared among 32 HIV-infected CMV-seronegative subjects, 126 age, CD4 and gender-matched HIV-infected CMV-seropositive subjects, and among 21 HIV-uninfected controls (9 CMV-negative, 12 CMV-positive). Plasma inflammatory indices were measured in a subset by ELISA. Results. Median CD8 counts/µL were higher in HIV-positive/CMV-positive patients (795) than in HIV-positive/CMV-negative subjects (522, P = .006) or in healthy controls (451, P = .0007), whereas CD8 T-cell counts were similar to controls' levels in HIV-positive/CMV-negative subjects. Higher plasma levels of IP-10 (P = .0011), TNF-RII (P = .0002), and D-dimer (P = .0444) were also found in coinfected patients than in HIV-positive/CMV-negative subjects. Conclusions. CMV infection is associated with higher CD8 T-cell counts, resultant lower CD4/CD8 ratios, and increased systemic inflammation in ART-treated HIV infection. CMV infection may contribute to risk for morbid outcomes in treated HIV infection. PMID:26400999

Risk factors of CMV infection in patients after umbilical cord blood transplantation: a multicenter study in China

PubMed Central

Tong, Juan; Liu, Huilan; Geng, Liangquan; Zheng, Changcheng; Tang, Baolin; Song, Kaidi; Yao, Wen; Liu, Xin

2013-01-01

Objective This retrospective study examined risk factors for cytomegalovirus (CMV) infection after umbilical cord blood transplantation (UCBT) and the impact of CMV infection on patient survival. Methods In all 176 patients, plasma CMV DNA was negative prior to the transplantation, and examined twice a week for 100 d, and then once weekly for additional 300 d. Preemptive antiviral therapy (ganciclovir or foscarnet) was started in patients with >1,000/mL copies of CMV DNA but no full-blown CMV disease, and was discontinued upon two consecutive negative reports of blood CMV DNA test. The survival and risk factors for CMV infection or disease were examined using logistic regression. Results CMV infection developed in 71% (125/176) of the patients, with a median onset of 32 d. Four patients (2.3%) developed CMV disease. Neither the 5-year overall survival (OS) nor event-free survival (EFS) differed significantly in infected patients vs. those with no infection (59.4% vs. 64.8%, P=0.194; 53.4% vs. 59.1%, P=0.226). A stepwise multivariate analysis indicated an association of CMV infection with age, high-dose glucocorticoids, the number of transplanted CD34+ cells, and the number of platelet transfusion, but not with gender, the conditioning regimen, and the day of neutrophil recovery and chronic graft-versus-host disease (cGVHD). Conclusions CMV infection is very common after UCBT, but does not seem to affect long-term survival with preemptive antiviral treatment. PMID:24385697

A prospective study of a quantitative PCR ELISA assay for the diagnosis of CMV pneumonia in lung and heart-transplant recipients.

PubMed

Barber, L; Egan, J J; Lomax, J; Haider, Y; Yonan, N; Woodcock, A A; Turner, A J; Fox, A J

2000-08-01

Qualitative polymerase chain reaction (PCR) for the identification of cytomegalovirus (CMV) infection has a low predictive value for the identification of CMV pneumonia. This study prospectively evaluated the application of a quantitative PCR Enzyme-Linked Immuno-Sorbent Assay (ELISA) assay in 9 lung- and 18 heart-transplant recipients who did not receive ganciclovir prophylaxis. DNA was collected from peripheral blood polymorphonuclear leucocytes (PMNL) posttransplantation. Oligonucleotide primers for the glycoprotein B gene (149 bp) were used in a PCR ELISA assay using an internal standard for quantitation. CMV disease was defined as histological evidence of end organ damage. The median level CMV genome equivalents in patients with CMV disease was 2665/2 x 10(5) PMNL (range 1,200 to 61,606) compared to 100 x 10(5) PMNL (range 20 to 855) with infection but no CMV disease (p = 0.036). All patients with CMV disease had genome equivalents levels of >1200/2 x 10(5) PMNL. A cut-off level of 1,200 PMNL had a positive predictive value for CMV disease of 100% and a negative predictive value of 100%. The first detection of levels of CMV genome equivalents above a level of 1200/2 x 10(5) PMNL was at a median of 58 days (range 47 to 147) posttransplant. Quantitative PCR assays for the diagnosis of CMV infection may predict patients at risk of CMV disease and thereby direct preemptive treatment to high-risk patients.

Inbred guinea pig model of intrauterine infection with cytomegalovirus.

PubMed

Griffith, B P; McCormick, S R; Booss, J; Hsiung, G D

1986-01-01

Outbred guinea pigs have previously been utilized in an experimental model for the study of congenital infection with cytomegalovirus (CMV). Development of an inbred model of intrauterine CMV infection would allow analysis of the cells involved in CMV immunity, studies of transplacental CMV transfer, and investigation of the cellular immune factors that participate in intrauterine CMV infections. This study was therefore designed to assess the inbred guinea pig as a model for the study of congenital CMV infection. Intrauterine fetal and placental infection with CMV was demonstrated in inbred Strain 2 guinea pigs, and the maternal factors influencing transplacental transmission of CMV were evaluated. Infectious virus was recovered from placentas and offspring of mothers that experienced primary CMV infection during pregnancy, but not from placentas and offspring of mothers that were inoculated with CMV prior to pregnancy. However, histologic lesions consisting of focal necrosis and inflammation were seen in tissues of offspring from both groups of mothers. Inoculation of seronegative pregnant Strain 2 animals with low doses of virus (2.5 to 3.5 log10 TCID50) resulted in both placental and fetal CMV infection without significant maternal death. Infection of placentas and offspring occurred in utero regardless of the stage of pregnancy. In addition, infectious virus was detectable in fetal tissues at the time of maternal viremia but also later during the course of maternal infection, ie, 4 weeks after inoculation. These findings indicate that the inbred guinea pig model can be used to investigate the pathogenesis of intrauterine CMV infections.

Co-infection of two beta-herpesviruses (CMV and HHV-7) as an increased risk factor for 'CMV disease' in patients undergoing renal transplantation.

PubMed

Chapenko, S; Folkmane, I; Tomsone, V; Amerika, D; Rozentals, R; Murovska, M

2000-10-01

The ubiquity of human cytomegalovirus (CMV) and human herpesvirus-7 (HHV-7), as well as activation of these viruses during immunosuppression, allows the suggestion that both viruses could participate in the development of 'CMV disease' in patients after renal transplantation (RT). The aim of our research was to study the prevalence of latent CMV and HHV-7 infections in patients before RT, to determine interaction between these viruses in dual infection and possible association of their reactivation with the progression of 'CMV disease' after RT. Peripheral blood samples were collected from 49 patients before and up to 10-12 wk after RT. The methods used for diagnostics of viral infections were: serology, nested polymerase chain reaction (nPCR) analysis of peripheral blood leukocytes (PBL) and plasma, and virus isolation in cell cultures (morphological changes, nPCR analysis of cellular and cell-free samples, indirect immunofluorescence analysis). Before RT, CMV and HHV-7 DNAs were detected in PBL but not in the plasma samples, which indicates the presence of latent viral infection in patients. Latent dual (CMV + HHV-7) infection was prevalent (51.0%) in 49 patients, while CMV and HHV-7 infections alone were detected in 26.5 and 12.2% of patients, respectively. Risk of viral disease after RT, for recipients with latent dual infection before RT, was 12- and 2.2-fold higher in comparison with CMV and HHV-7 infections alone, respectively. Frequency of dual infection in 18 recipients with 'viral syndrome' or 'CMV disease' after RT was reliably higher (13/18, 81.3%) than CMV (1/18, 6.2%) (p < 0.025) and HHV-7 (2/18, 12.5%) (p < 0.025) infections alone. HHV-7 reactivation preceded CMV reactivation in 77.0% of the cases of dual infection in the recipients with viral disease and reactivation of both viruses preceded the development of viral disease. Severe 'CMV disease' developed in 2 out of 2 recipients with CMV primary infection and 'viral syndrome' in 1 recipient with CMV reinfection. The reactivation of CMV was detected in all recipients prior to onset of the disease. Correlation was shown between reactivation of latent HHV-7 infection and development of febrile syndrome in 2 out of 2 recipients with HHV-7 infection alone. Taking into account that dual infection is an increased risk factor for 'viral syndrome' and 'CMV disease' development, screening diagnostic should include testing for both viral infections in transplant donors as well as in recipients before and after RT.

Antagonism of the Protein Kinase R Pathway in Human Cells by Rhesus Cytomegalovirus.

PubMed

Child, Stephanie J; Hickson, Sarah E; Bayer, Avraham; Malouli, Daniel; Früh, Klaus; Geballe, Adam P

2018-03-15

While cytomegalovirus (CMV) infections are often limited in host range by lengthy coevolution with a single host species, a few CMVs are known to deviate from this rule. For example, rhesus macaque CMV (RhCMV), a model for human CMV (HCMV) pathogenesis and vaccine development, can replicate in human cells, as well as in rhesus cells. Both HCMV and RhCMV encode species-specific antagonists of the broadly acting host cell restriction factor protein kinase R (PKR). Although the RhCMV antagonist of PKR, rTRS1, has very limited activity against human PKR, here, we show it is essential for RhCMV replication in human cells because it prevents human PKR from phosphorylating the translation initiation factor eIF2α, thereby allowing continued translation and viral replication. Although rTRS1 is necessary for RhCMV replication, it is not sufficient to rescue replication of HCMV lacking its own PKR antagonists in human fibroblasts. However, overexpression of rTRS1 in human fibroblasts enabled HCMV expressing rTRS1 to replicate, indicating that elevated levels or early expression of a weak antagonist can counteract a resistant restriction factor like human PKR. Exploring potential mechanisms that might allow RhCMV to replicate in human cells revealed that RhCMV makes no less double-stranded RNA than HCMV. Rather, in human cells, RhCMV expresses rTRS1 at levels 2 to 3 times higher than those of the HCMV-encoded PKR antagonists during HCMV infection. These data suggest that even a modest increase in expression of this weak PKR antagonist is sufficient to enable RhCMV replication in human cells. IMPORTANCE Rhesus macaque cytomegalovirus (RhCMV) offers a valuable model for studying congenital human cytomegalovirus (HCMV) pathogenesis and vaccine development. Therefore, it is critical to understand variations in how each virus infects and affects its host species to be able to apply insights gained from the RhCMV model to HCMV. While HCMV is capable only of infecting cells from humans and very closely related species, RhCMV displays a wider host range, including human as well as rhesus cells. RhCMV expresses an antagonist of a broadly acting antiviral factor present in all mammalian cells, and its ability to counter both the rhesus and human versions of this host factor is a key component of RhCMV's ability to cross species barriers. Here, we examine the molecular mechanisms that allow this RhCMV antagonist to function against a human restriction factor. Copyright © 2018 American Society for Microbiology.

49 CFR 383.77 - Substitute for driving skills tests for drivers with military CMV experience.

Code of Federal Regulations, 2013 CFR

2013-10-01

... with military CMV experience. 383.77 Section 383.77 Transportation Other Regulations Relating to... CMV experience. At the discretion of a State, the driving skills test as specified in § 383.113 may be waived for a CMV driver with military CMV experience who is currently licensed at the time of his/her...

49 CFR 383.77 - Substitute for driving skills tests for drivers with military CMV experience.

Code of Federal Regulations, 2012 CFR

2012-10-01

... with military CMV experience. 383.77 Section 383.77 Transportation Other Regulations Relating to... CMV experience. At the discretion of a State, the driving skills test as specified in § 383.113 may be waived for a CMV driver with military CMV experience who is currently licensed at the time of his/her...

49 CFR 383.77 - Substitute for driving skills tests for drivers with military CMV experience.

Code of Federal Regulations, 2014 CFR

2014-10-01

... with military CMV experience. 383.77 Section 383.77 Transportation Other Regulations Relating to... CMV experience. At the discretion of a State, the driving skills test as specified in § 383.113 may be waived for a CMV driver with military CMV experience who is currently licensed at the time of his/her...

Cytomegalovirus replication kinetics in solid organ transplant recipients managed by preemptive therapy.

PubMed

Atabani, S F; Smith, C; Atkinson, C; Aldridge, R W; Rodriguez-Perálvarez, M; Rolando, N; Harber, M; Jones, G; O'Riordan, A; Burroughs, A K; Thorburn, D; O'Beirne, J; Milne, R S B; Emery, V C; Griffiths, P D

2012-09-01

After allotransplantation, cytomegalovirus (CMV) may be transmitted from the donor organ, giving rise to primary infection in a CMV negative recipient or reinfection in one who is CMV positive. In addition, latent CMV may reactivate in a CMV positive recipient. In this study, serial blood samples from 689 kidney or liver transplant recipients were tested for CMV DNA by quantitative PCR. CMV was managed using preemptive antiviral therapy and no patient received antiviral prophylaxis. Dynamic and quantitative measures of viremia and treatment were assessed. Median peak viral load, duration of viremia and duration of treatment were highest during primary infection, followed by reinfection then reactivation. In patients who experienced a second episode of viremia, the viral replication rate was significantly slower than in the first episode. Our data provide a clear demonstration of the immune control of CMV in immunosuppressed patients and emphasize the effectiveness of the preemptive approach for prevention of CMV syndrome and end organ disease. Overall, our findings provide quantitative biomarkers which can be used in pharmacodynamic assessments of the ability of novel CMV vaccines or antiviral drugs to reduce or even interrupt such transmission. © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.

Relationship between cytomegalovirus (CMV) reactivation, CMV-driven immunity, overall immune recovery and graft-versus-leukaemia effect in children.

PubMed

Jeljeli, Mohamed; Guérin-El Khourouj, Valérie; Porcher, Raphael; Fahd, Mony; Leveillé, Sandrine; Yakouben, Karima; Ouachée-Chardin, Marie; LeGoff, Jerome; Cordeiro, Debora Jorge; Pédron, Beatrice; Baruchel, Andre; Dalle, Jean-Hugues; Sterkers, Ghislaine

2014-07-01

The interplay between immune recovery, cytomegalovirus (CMV)-reactivation, CMV-driven immunity and graft-versus-leukaemia effect (GVL) was analysed in 108 children (median age: 8 years) who underwent haematopoietic-stem cell transplantation (HSCT) for acute leukaemia. Follow-up was 2 years unless death or relapse occurred. CMV-polymerase chain reaction (PCR) was programmed weekly until month +3 post-HSCT. Immunomonitoring consisted of sequential lymphocyte subset enumerations and analyses of T-cell proliferative and γ-interferon responses to CMV and to adenovirus. In the 108 recipients, the 2-year relapse rate (RR) was 25% (median time to onset 4·5 months; range: 24 d-17 months). CMV reactivation occurrence was 31% (median time to onset 26 d). Donor/recipient CMV serostatus did not influence RR. Among the 89 recipients disease-free after day +120, i) early CMV-reactivation before day +30 was more frequent (P = 0·01) in the relapse recipient group opposed to the non-relapse group. ii) CD8(+) /CD28(-) and CD4(+) CD45RA(-) T-cell expansions induced by CMV did not influence RR, iii) Recovery of anti-CMV and also anti-adenovirus immunity and of naïve CD4(+) T-cells was faster in the non-relapse group (P = 0·008; 0·009 and 0·002 respectively). In contrast to adult acute myeloid leukaemia, CMV reactivation was associated with increased RR in this paediatric series. Accelerated overall immune recovery rather than CMV-driven immunity had a favourable impact on RR. © 2014 John Wiley & Sons Ltd.

CMV Disease in IBD: Comparison of Diagnostic Tests and Correlation with Disease Outcome.

PubMed

Johnson, Jessica; Affolter, Kajsa; Boynton, Kathleen; Chen, Xinjian; Valentine, John; Peterson, Kathryn

2018-04-30

Significance of cytomegalovirus (CMV) in inflammatory bowel disease (IBD) is unclear due to pathobiology, numerous CMV tests, and disparate treatment outcomes. Retrospective chart review was done on patients with positive qualitative CMV tissue polymerase chain reaction (PCR) from 2005-2013 at a tertiary referral hospital. Frequency of PCR+, hematoxylin and eosin staining(HE)+, histopathology and immunohistochemistry (IHC)+ was assessed. IHC was assessed on a sample of PCR- tissues. Surgery rates were correlated with CMV testing and treatment. PCR was done on 310 samples from 180 patients. Thirty-seven samples were PCR+ (51.4% PCR+ only, 35.1% IHC/PCR+, 13.5% HE/IHC/PCR+). The H&E frequently failed to detect CMV identified on extensive IHC. Of 13 PCR- samples tested with IHC, 100% were negative. Twenty-five patients were CMV+ (40% PCR+, 40% IHC/PCR+, 20% HE/IHC/PCR+). Surgery rates increased with number of positive tests: 60% in IHC/PCR+ and 80% in HE/IHC/PCR+, compared to 26.8% in PCR- or PCR+ (P = 0.03, P = 0.02, respectively). There were 20/25 PCR+ patients who received CMV treatment. Surgery occurred in 80% of HE+ patients despite treatment and 100% of IHC+ patients without treatment. Rates of CMV+ testing and surgical risk varied by test modality. PCR+ results were most frequent but alone did not detect clinically significant CMV. HE+ testing was least frequent and associated with highest surgical rate, despite treatment. CMV treatment may benefit IHC+ patients most, supporting immunostaining as optimal diagnostic test for clinically significant CMV in IBD. In PCR+ samples, HE frequently did not detect CMV identified on extensive IHC. In PCR- samples, data suggest IHC is likely negative. Consider using qualitative PCR to guide extensive immunostaining.

Who Is the Patient at Risk of CMV Recurrence: A Review of the Current Scientific Evidence with a Focus on Hematopoietic Cell Transplantation.

PubMed

Styczynski, Jan

2018-03-01

Cytomegalovirus (CMV) is an agent of global infection, and its acquisition in a population is characterized by an age-dependent rise in seropositivity. After primary infection, CMV remains in the host cells in latent form, and it can reactivate in the case of immune suppression. The risk of CMV recurrence is dependent on the level of incompetency of the immune system, manifested as an impairment of T-cell immunity, including the presence and function of CMV-specific cytotoxic T lymphocytes. This article presents data on the incidence of CMV recurrence in groups of immunocompromised patients, including allogeneic hematopoietic stem cell transplantation (HSCT) patients and other groups of patients, based on a summary of reported data. The median rate of CMV recurrence in HSCT recipients was estimated as 37% after allogeneic transplant and 12% after autologous transplant, 5% in patients with nontransplant hematological malignancies, 14% in recipients of anti-CD52 therapy, 30% in solid organ transplant recipients, 21% in patients with primary immunodeficiencies, 20% during active replication in HIV-positive patients and 3.3% during antiretroviral therapy, 7% in patients with chronic kidney disease, 0.6% in patients with congenital infection, and 0.6% in neonates with primary infection. The highest risk of CMV recurrence and CMV disease is reported for HSCT CMV-seropositive recipients, regardless of donor serostatus. The odds ratio (OR) for CMV recurrence is higher for recipient-positive versus recipient-negative CMV serostatus transplants (OR 8.0), donor-negative/recipient-positive versus donor-positive/recipient-positive CMV serostatus transplants (OR 1.2), unrelated/mismatched versus matched-family donor transplants (OR 1.6), and acute graft-versus-host-disease versus other diseases (OR 3.2). Other risk factors have minor significance.

Cytomegalovirus infection in immunocompetent wheezy infants: the diagnostic value of CMV PCR in bronchoalveolar lavage fluid.

PubMed

Cinel, G; Pekcan, S; Ozçelik, U; Alp, A; Yalçın, E; Doğru Ersöz, D; Kiper, N

2014-08-01

Cytomegalovirus (CMV) pneumonitis in immunocompetent hosts is uncommon but is being recognized more frequently, particularly when presenting as severe viral pneumonia. The objective of this study was to examine lower respiratory tract CMV infection in immunocompetent wheezy infants, based on polymerase chain reaction (PCR) in bronchoalveolar lavage (BAL) fluid, to compare CMV PCR results in BAL and in blood samples and to evaluate the benefits of antiviral ganciclovir therapy in these patients. Retrospective review of the records of patients referred to our tertiary care hospital between January 2000 and July 2010 who had unexplained persistent wheezing and underwent fibreoptic flexible bronchoscopy (FFB). Fibreoptic flexible bronchoscopy was applied to 102 infants with persistent wheezing and diffuse interstitial infiltration on radiological investigations; so CMV PCR in BAL fluid was performed. CMV PCR in BAL fluid was positive in 51 patients. Retrospectively, we had access to the files of 25 of these patients. The mean CMV PCR in BAL fluid was 334 840 copies/mL. Only eight patients had CMV PCR positivity in their blood samples (mean: 2026·3 copies/mL). There was not a relationship between BAL and blood CMV PCR values based on Spearman's correlation analysis (r = -0·008). Fourteen patients had severe respiratory symptoms and received ganciclovir therapy. Twelve of them fully recovered. Bronchoalveolar lavage fluid CMV PCR was superior to blood CMV PCR in diagnosing lower respiratory tract infections caused by CMV in immunocompetent infants. Ganciclovir therapy may be effective in selected immunocompetent wheezy infants with CMV PCR positivity in BAL fluid. © 2014 John Wiley & Sons Ltd.

CMV infection is usually associated with concurrent HHV-6 and HHV-7 antigenemia in liver transplant patients.

PubMed

Lautenschlager, I; Lappalainen, M; Linnavuori, K; Suni, J; Höckerstedt, K

2002-08-01

Human herpesvirus 6 and 7 (HHV-6, HHV-7) have been recently reported in liver transplant patients. HHV-6 may cause fever, neurological disorders and hepatitis. The clinical significance of HHV-7 is less clear. HHV-6 and -7 are closely related to cytomegalovirus (CMV), and interactions between the viruses have also been suggested. In this study, we investigated the post transplant HHV-6 and -7 antigenemia was in relation to symptomatic CMV disease after liver transplantation. Consecutive 34 adult liver allograft recipients transplanted during 1999-2000 were included in the study. CMV infections were diagnosed by the frequent monitoring of pp65-antigenemia and by viral cultures. HHV-6 and -7 were demonstrated, by using immunoperoxidase staining and monoclonal antibodies against the virus specific antigens, in the mononuclear cells from the same blood specimens which were obtained for CMV pp65 monitoring. Altogether 322 blood specimens were analyzed. CMV disease was diagnosed in 12 (35%) patients during the first 3 months (first pp65 positive specimen mean 25 days, range 8-61 days) after transplantation. Concurrent HHV-6 antigenemia was detected in 10/12 (mean 14 days, range 6-22 days) and HHV-7 antigenemia in 9/12 patients (mean 25 days, range 10-89 days) after transplantation. HHV-6 usually appeared slightly before CMV. All CMV infections were successfully treated with ganciclovir and the CMV-antigenemia subsided. HHV-6 and -7 antigenemia also responded to the antiviral treatment, but more slowly than CMV. In conclusion, CMV infection was usually associated with HHV-6 and -7 antigenemia in liver transplant patients. The results support the suggestion that CMV, HHV-6 and -7 may have interactions. The clinical symptoms of CMV infection, may also be linked with HHV-6 or -7.

[Congenital and perinatal infections in the Marche region (Italy): an epidemiological study and differences between ethnic groups].

PubMed

Ruffini, Ermanno; Compagnoni, Luigina; Tubaldi, Lucia; Infriccioli, Giovanna; Vianelli, Patrizia; Genga, Roberto; Bonifazi, Vitaliana; Dieni, Alessandra; Guerrini, Domenico; Basili, Gabriella; Salvatori, Patrizia; DeColli, Rosa; Leone, Luciano; Gesuita, Rosaria

2014-09-01

The purpose of this study was to evaluate the epidemiological data regarding congenital and perinatal infections in the Marche region to verify the existence of differences in relation to maternal country of origin. This prospective study was conducted from May 2001 to April 2012, and it involved all the maternity units of the Marche region. A total of 10232 pregnant women were included, 25.1% of whom were of foreign nationality while the number of births totalled 10371. Estimated uptake of antenatal screening was 80.5% for CMV infection, 98.6% for HBV infection, 97.5% for HCV infection, 97.4% for HIV infection, 93.1% for syphilis and 98.5% for toxoplasmosis. For group B streptococcus vaginal and perianal swabs were performed in 81.2% of all women (78.4% in immigrant and 90.4% in Italian women; the difference was statistically significant [p 0.001]) and 13.6% were positive. The overall prevalence for CMV infection was 72.3% (91.9% in immigrant women) while for toxoplasmosis it was 27.5% (28.8% in immigrant women). The rate of seroconversion in pregnant women investigated for CMV infection was 0.28%, while that for toxoplasmosis was 0.09%. The overall prevalence for HBV infection was 0.79% (4.3% in immigrant and 0.4% in Italian pregnant women; the difference was statistically significant [p 0.001]), 0.4% for HCV infection (1% in immigrant and 0.48% in Italian pregnant women; the difference was not statistically significant [p 0.413]), 0.22% for syphilis (0.8% in immigrant and 0.08% in Italian pregnant women; the difference was not statistically significant [p 0.062]), 0.09% for HIV infection, and 0.03% for tuberculosis. The prevalence of congenital CMV infection was 0.04% and that of congenital toxoplasmosis 0.01%. The prevalence of early-onset infection from Group B streptococcus was 0.029%. No cases were observed of congenital syphilis, congenital tuberculosis or maternal and neonatal HSV infections. The study proves that in the Marche region there is a high percentage of women who undergo prenatal screening, including screening for infections, not offered by the National Health Service, such as CMV and HCV. The data also demonstrate that some infections, such as tuberculosis, HIV and HBV, almost exclusively affect immigrant women. Regarding neonatal infections, the data presented are in line with those in the literature, with the exception of congenital CMV infection, in which the low prevalence observed could be linked to the recent and massive migration of already immunized women.

Cytomegalovirus Urinary Shedding in HIV-infected Pregnant Women and Congenital Cytomegalovirus Infection.

PubMed

Adachi, Kristina; Xu, Jiahong; Ank, Bonnie; Watts, D Heather; Mofenson, Lynne M; Pilotto, Jose Henrique; Joao, Esau; Santos, Breno; Fonseca, Rosana; Kreitchmann, Regis; Pinto, Jorge; Mussi-Pinhata, Marisa M; Gray, Glenda; Theron, Gerhard; Morgado, Mariza G; Bryson, Yvonne J; Veloso, Valdilea G; Klausner, Jeffrey D; Moye, Jack; Nielsen-Saines, Karin

2017-08-01

Cytomegalovirus (CMV) urinary shedding in pregnant women infected with human immunodeficiency virus (HIV) was evaluated to determine whether it poses an increased risk for congenital CMV infection (cCMV). A subset of mother-infant pairs enrolled in the perinatal NICHD HPTN 040 study (distinguished by no antiretroviral use before labor) was evaluated. Maternal and infant urines were tested by qualitative real-time polymerase chain reaction (RT-PCR) for CMV DNA with quantitative RT-PCR performed on positive specimens. Urine specimens were available for 260 women with 85.4% from the Americas and 14.6% from South Africa. Twenty-four women (9.2%) had detectable CMV viruria by qualitative PCR. Maternal CMV viruria was not associated with mean CD4 cell counts or HIV viral load but was associated with younger maternal age (P = .02). Overall, 10 of 260 infants (3.8%) had cCMV. Women with detectable peripartum CMV viruria were more likely to have infants with cCMV than those without: 20.8% (5/24) versus 2.1% (5/236), (P = .0001). Women with CMV viruria had significantly higher rates of HIV perinatal transmission (29.2% vs. 8.1%, P = .002). They were 5 times (adjusted odds ratio [aOR] = 5.6, 95% confidence interval [CI] 1.9-16.8) and nearly 30 times (aOR, 29.7; 95% CI, 5.4-164.2) more likely to transmit HIV and CMV to their infants, respectively. Maternal gonorrhea (aOR, 19.5; 95% CI, 2.5-151.3) and higher maternal HIV log10 viral load (OR, 2.8; 95% CI, 1.3-6.3) were also significant risk factors for cCMV. In this cohort of HIV-infected pregnant women not on antiretrovirals, urinary CMV shedding was a significant risk factor for CMV and HIV transmission to infants. NCT00099359. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com

CMV induces expansion of highly polyfunctional CD4+ T cell subset coexpressing CD57 and CD154.

PubMed

Pera, Alejandra; Vasudev, Anusha; Tan, Crystal; Kared, Hassen; Solana, Rafael; Larbi, Anis

2017-02-01

CD4 + T cells are essential for human CMV infection control. CMV-specific CD4 + T cells possess antiviral functions and participate in anti-CMV humoral/cellular responses. In the elderly, CMV infection impairs immunity to other viruses and has been traditionally associated with T cell senescence; however, recent results suggest that, in younger people, CMV confers immune protection against other pathogens (heterologous immunity). To shed light on this controversy, we analyzed latent CMV infection effects on the quality of young individuals' immune response, specifically, the presence of polyfunctional T cells through an extensive phenotypic and functional characterization of the CD4 + T cell subset. CD154 expression, degranulation (CD107a), and cytokine production (IFN-γ, TNF-α, and IL-2) as well as T cell phenotype markers (CD57, CD28, and CD27) were analyzed. We demonstrate that CD4 + T cells that coexpress CD57 and CD154, which are exclusively present in CMV-positive individuals, are the most polyfunctional CD4 + subset, whereas CD4 + CD27 + CD28 - T cells associate with lower polyfunctionality. Conversely, the frequency of CD4 + CD28 + T cells correlates with higher polyfunctionality of CD4 + CD57 - T cells from CMV-seronegative individuals and CD4 + CD57 + CD154 + T cells from CMV-seropositive individuals. Thus, polyfunctionality is a property of central memory CD4 + T cells in CMV-seronegative individuals, whereas after CMV infection, polyfunctional T cells become highly differentiated, which allows efficient eradication of infections. We extend previous observations of the impact of CMV on CD8 + T cell functionality to the CD4 + T cell compartment, revealing CD57 as a polyfunctionality marker of T cells which expands after CMV infection. CD57 + T cells have been associated with inflammatory conditions, but their potential role in the response against infectious disease and vaccination should now be investigated. © Society for Leukocyte Biology.

Inhibition of Human Cytomegalovirus Replication by Artemisinins: Effects Mediated through Cell Cycle Modulation

PubMed Central

Roy, Sujayita; He, Ran; Kapoor, Arun; Forman, Michael; Mazzone, Jennifer R.; Posner, Gary H.

2015-01-01

Artemisinin-derived monomers and dimers inhibit human cytomegalovirus (CMV) replication in human foreskin fibroblasts (HFFs). The monomer artesunate (AS) inhibits CMV at micromolar concentrations, while dimers inhibit CMV replication at nanomolar concentrations, without increased toxicity in HFFs. We report on the variable anti-CMV activity of AS compared to the consistent and reproducible CMV inhibition by dimer 606 and ganciclovir (GCV). Investigation of this phenomenon revealed that the anti-CMV activity of AS correlated with HFFs synchronized to the G0/G1 stage of the cell cycle. In contact-inhibited serum-starved HFFs or cells arrested at early/late G1 with specific checkpoint regulators, AS and dimer 606 efficiently inhibited CMV replication. However, in cycling HFFs, in which CMV replication was productive, virus inhibition by AS was significantly reduced, but inhibition by dimer 606 and GCV was maintained. Cell cycle analysis in noninfected HFFs revealed that AS induced early G1 arrest, while dimer 606 partially blocked cell cycle progression. In infected HFFs, AS and dimer 606 prevented the progression of cell cycle toward the G1/S checkpoint. AS reduced the expression of cyclin-dependent kinases (CDK) 2, 4, and 6 in noninfected cycling HFFs, while the effect of dimer 606 on these CDKs was moderate. Neither compound affected CDK expression in noninfected contact-inhibited HFFs. In CMV-infected cells, AS activity correlated with reduced CDK2 levels. CMV inhibition by AS and dimer 606 also correlated with hypophosphorylation (activity) of the retinoblastoma protein (pRb). AS activity was strongly associated with pRb hypophosphorylation, while its reduced anti-CMV activity was marked by pRb phosphorylation. Roscovitine, a CDK2 inhibitor, antagonized the anti-CMV activities of AS and dimer 606. These data suggest that cell cycle modulation through CDKs and pRb might play a role in the anti-CMV activities of artemisinins. Proteins involved in this modulation may be identified and targeted for CMV inhibition. PMID:25870074

Risk factors and outcomes of cytomegalovirus viremia in pediatric hematopoietic stem cell transplantation patients.

PubMed

Wu, Jhong-Lin; Ma, Hsuan-Yin; Lu, Chun-Yi; Chen, Jong-Min; Lee, Ping-Ing; Jou, Shiann-Tarng; Yang, Yung-Lin; Chang, Hsiu-Hao; Lu, Meng-Yao; Chang, Luan-Ying; Huang, Li-Min

2017-06-01

Cytomegalovirus (CMV) is a major pathogen causing significant mortality and morbidity in immunocompromised hosts. It is important to find risk factors associated with CMV viremia and its outcome. We investigated the incidence, time of onset, risk factors for CMV viremia, and characteristics of CMV diseases in 57 pediatric patients receiving hematopoietic stem cell transplantation (HSCT). Between August 2011 and March 2014, cases of pediatric HSCT patients at the National Taiwan University Children's Hospital were reviewed. Viremia was identified by plasma CMV real-time polymerase chain reaction (RT-PCR) assay. Eighteen (32%) of the 57 patients developed CMV viremia at a median of 23 days post-HSCT (range -3 to +721 days). Eighty-nine percent (16/18) of CMV viremia occurred within 100 days posttransplantation. Four patients finally had CMV diseases (1 with CMV colitis and 3 with CMV pneumonitis) and one patient died of CMV pneumonitis complicated with pulmonary hemorrhage and sepsis. Significant risk factors associated with CMV viremia via univariate analysis include older age (p = 0.03), leukemic patients [odds ratio (OR): 5.2, 95% confidence interval (CI): 1.52∼17.7, p = 0.008), allogeneic HSCT (OR: 14.57, 95% CI: 1.76∼120.5, p = 0.002), antithymoglobulin (ATG) use before transplantation (OR: 5.09, 95% CI: 1.52∼16.9, p = 0.007), graft-versus-host disease (GvHD) (OR: 10.1, 95% CI: 2.7∼38.7, p < 0.001), and gastrointestinal GvHD (OR: 10.9, 95% CI: 2.72∼43.9, p = 0.001). In pediatric posttransplantation patients, CMV viremia mostly occurred within 100 days after transplantation. Risk factors associated with CMV viremia include older diagnostic age, leukemic patients, unrelated donor HSCT, pretransplant ATG use, GvHD, and gastrointestinal GvHD. Copyright © 2015. Published by Elsevier B.V.

Knowledge of congenital cytomegalovirus (cCMV) among physical and occupational therapists in the United States

PubMed Central

Armstrong-Heimsoth, Amy; Thomas, Jodi

2017-01-01

Congenital cytomegalovirus (cCMV) infections cause more children to have permanent disabilities than Down Syndrome, Fetal Alcohol Syndrome, Spina Bifida, and pediatric HIV/AIDS combined. The risk of infection during pregnancy can be significantly decreased using universal precautions, such as thorough handwashing and cleansing of surfaces and objects that have come into contact with infected body fluids. Children under 3 years of age are commonly asymptomatic excretors of CMV, with the highest viral loads present in saliva. Pediatric therapists have regular close contact with young children, and are thus likely at elevated occupational risk of acquiring CMV. Our objective was to evaluate therapist knowledge of cCMV and its transmission. We recruited American Occupational Therapy Association (AOTA) and American Physical Therapy Association (APTA) members via electronic newsletters and printed flyers from April to September 2015. Participants completed an online, anonymous 24-question survey using Survey Monkey. We compared responses between groups and previously published CMV awareness data using binomial tests of difference of proportions and multiple logistic regression. Our study identified both a low level of therapist awareness and poor demonstrated understanding of cCMV. Self-reported cCMV awareness amongst therapists was greater than awareness in the general population, and equivalent to awareness amongst health care professionals. Whereas 52% of participants self-reported awareness of cCMV, only 18% demonstrated understanding of the behavioral modes of CMV transmission. Fewer therapists reported awareness of cCMV than other, less prevalent conditions. Higher levels of health risk knowledge were associated with greater contact with children. Most participants reported learning about cCMV from the workplace. The knowledge gaps between self-reported awareness of cCMV and demonstrated understanding of modes of transmission described by our results emphasize the need for additional training of therapists. cCMV is preventable, and accurate knowledge of modes of transmission is crucial for the health of practitioners and clients. PMID:28976995

Knowledge of congenital cytomegalovirus (cCMV) among physical and occupational therapists in the United States.

PubMed

Muldoon, Kathleen M; Armstrong-Heimsoth, Amy; Thomas, Jodi

2017-01-01

Congenital cytomegalovirus (cCMV) infections cause more children to have permanent disabilities than Down Syndrome, Fetal Alcohol Syndrome, Spina Bifida, and pediatric HIV/AIDS combined. The risk of infection during pregnancy can be significantly decreased using universal precautions, such as thorough handwashing and cleansing of surfaces and objects that have come into contact with infected body fluids. Children under 3 years of age are commonly asymptomatic excretors of CMV, with the highest viral loads present in saliva. Pediatric therapists have regular close contact with young children, and are thus likely at elevated occupational risk of acquiring CMV. Our objective was to evaluate therapist knowledge of cCMV and its transmission. We recruited American Occupational Therapy Association (AOTA) and American Physical Therapy Association (APTA) members via electronic newsletters and printed flyers from April to September 2015. Participants completed an online, anonymous 24-question survey using Survey Monkey. We compared responses between groups and previously published CMV awareness data using binomial tests of difference of proportions and multiple logistic regression. Our study identified both a low level of therapist awareness and poor demonstrated understanding of cCMV. Self-reported cCMV awareness amongst therapists was greater than awareness in the general population, and equivalent to awareness amongst health care professionals. Whereas 52% of participants self-reported awareness of cCMV, only 18% demonstrated understanding of the behavioral modes of CMV transmission. Fewer therapists reported awareness of cCMV than other, less prevalent conditions. Higher levels of health risk knowledge were associated with greater contact with children. Most participants reported learning about cCMV from the workplace. The knowledge gaps between self-reported awareness of cCMV and demonstrated understanding of modes of transmission described by our results emphasize the need for additional training of therapists. cCMV is preventable, and accurate knowledge of modes of transmission is crucial for the health of practitioners and clients.

Performance Characteristics and Comparison of Abbott and artus Real-Time Systems for Hepatitis B Virus DNA Quantification ▿

PubMed Central

Ismail, Ashrafali M.; Sivakumar, Jayashree; Anantharam, Raghavendran; Dayalan, Sujitha; Samuel, Prasanna; Fletcher, Gnanadurai J.; Gnanamony, Manu; Abraham, Priya

2011-01-01

Virological monitoring of hepatitis B virus (HBV) DNA is critical to the management of HBV infection. With several HBV DNA quantification assays available, it is important to use the most efficient testing system for virological monitoring. In this study, we evaluated the performance characteristics and comparability of three HBV DNA quantification systems: Abbott HBV real-time PCR (Abbott PCR), artus HBV real-time PCR with QIAamp DNA blood kit purification (artus-DB), and artus HBV real-time PCR with the QIAamp DSP virus kit purification (artus-DSP). The lower limits of detection of these systems were established against the WHO international standards for HBV DNA and were found to be 1.43, 82, and 9 IU/ml, respectively. The intra-assay and interassay coefficients of variation of plasma samples (1 to 6 log10 IU/ml) ranged between 0.05 to 8.34% and 0.16 to 3.48% for the Abbott PCR, 1.53 to 26.85% and 0.50 to 12.89% for artus-DB, and 0.29 to 7.42% and 0.94 to 3.01% for artus-DSP, respectively. Ninety HBV clinical samples were used for comparison of assays, and paired quantitative results showed strong correlation by linear regression analysis (artus-DB with Abbott PCR, r = 0.95; Abbott PCR with artus-DSP, r = 0.97; and artus-DSP with artus-DB, r = 0.94). Bland-Altman analysis showed a good level of agreement for Abbott PCR and artus-DSP, with a mean difference of 0.10 log10 IU/ml and limits of agreement of −0.91 to 1.11 log10 IU/ml. No genotype-specific bias was seen in all three systems for HBV genotypes A, C, and D, which are predominant in this region. This finding illustrates that the Abbott real-time HBV and artus-DSP systems show more comparable performance than the artus-DB system, meeting the current guidelines for assays to be used in the management of hepatitis B. PMID:21795507

Performance characteristics and comparison of Abbott and artus real-time systems for hepatitis B virus DNA quantification.

PubMed

Ismail, Ashrafali M; Sivakumar, Jayashree; Anantharam, Raghavendran; Dayalan, Sujitha; Samuel, Prasanna; Fletcher, Gnanadurai J; Gnanamony, Manu; Abraham, Priya

2011-09-01

Virological monitoring of hepatitis B virus (HBV) DNA is critical to the management of HBV infection. With several HBV DNA quantification assays available, it is important to use the most efficient testing system for virological monitoring. In this study, we evaluated the performance characteristics and comparability of three HBV DNA quantification systems: Abbott HBV real-time PCR (Abbott PCR), artus HBV real-time PCR with QIAamp DNA blood kit purification (artus-DB), and artus HBV real-time PCR with the QIAamp DSP virus kit purification (artus-DSP). The lower limits of detection of these systems were established against the WHO international standards for HBV DNA and were found to be 1.43, 82, and 9 IU/ml, respectively. The intra-assay and interassay coefficients of variation of plasma samples (1 to 6 log(10) IU/ml) ranged between 0.05 to 8.34% and 0.16 to 3.48% for the Abbott PCR, 1.53 to 26.85% and 0.50 to 12.89% for artus-DB, and 0.29 to 7.42% and 0.94 to 3.01% for artus-DSP, respectively. Ninety HBV clinical samples were used for comparison of assays, and paired quantitative results showed strong correlation by linear regression analysis (artus-DB with Abbott PCR, r = 0.95; Abbott PCR with artus-DSP, r = 0.97; and artus-DSP with artus-DB, r = 0.94). Bland-Altman analysis showed a good level of agreement for Abbott PCR and artus-DSP, with a mean difference of 0.10 log(10) IU/ml and limits of agreement of -0.91 to 1.11 log(10) IU/ml. No genotype-specific bias was seen in all three systems for HBV genotypes A, C, and D, which are predominant in this region. This finding illustrates that the Abbott real-time HBV and artus-DSP systems show more comparable performance than the artus-DB system, meeting the current guidelines for assays to be used in the management of hepatitis B.

Knowledge and Awareness of Congenital Cytomegalovirus Among Women

PubMed Central

Jeon, Jiyeon; Victor, Marcia; Adler, Stuart P.; Arwady, Abigail; Demmler, Gail; Fowler, Karen; Goldfarb, Johanna; Keyserling, Harry; Massoudi, Mehran; Richards, Kristin; Staras, Stephanie A. S.; Cannon, Michael J.

2006-01-01

Background. Congenital cytomegalovirus (CMV) infection is a leading cause of disabilities in children, yet the general public appears to have little awareness of CMV. Methods. Women were surveyed about newborn infections at 7 different geographic locations. Results. Of the 643 women surveyed, 142 (22%) had heard of congenital CMV. Awareness increased with increasing levels of education (P < .0001). Women who had worked as a healthcare professional had a higher prevalence of awareness of CMV than had other women (56% versus 16%, P < .0001). Women who were aware of CMV were most likely to have heard about it from a healthcare provider (54%), but most could not correctly identify modes of CMV transmission or prevention. Among common causes of birth defects and childhood illnesses, women's awareness of CMV ranked last. Conclusion. Despite its large public health burden, few women had heard of congenital CMV, and even fewer were aware of prevention strategies. PMID:17485810

Vaccination for the prevention of maternal and fetal infection with guinea pig cytomegalovirus.

PubMed

Bia, F J; Griffith, B P; Tarsio, M; Hsiung, G D

1980-11-01

Live guinea pig cytomegalovirus (CMV) vaccine was prepared after 11 serial passages in tissue culture; noninfectious envelope antigen vaccine was prepared by n-octyl glucoside treatment of CMV-derived dense bodies and virions. Hartley strain guinea pigs immunized with either vaccine were compared with guinea pigs inoculated with virulent, salivary gland-passaged CMV (approximating natural infection), with passively immunized animals, and with nonimmune controls. All vaccinated animals had neutralizing antibodies to CMV. After challenge with virulent CMV, animals previously inoculated with either tissue culture-passaged or virulent CMV were protected against acute viremia and death; pregnant animals previously inoculated with live CMV vaccine had lower incidences of viremia and generalized maternal and fetal infection. Envelope antigen-vaccinated and passively immunized pregnant animals showed acute viremia after similar challenge with virulent virus; however, infection was less generalized than that in control animals, and CMV was not isolated from the fetuses of these vaccinated mothers.

Knowledge and Awareness of Congenital Cytomegalovirus Among Women

DOE PAGES

Jeon, Jiyeon; Victor, Marcia; Adler, Stuart P.; ...

2006-01-01

Bmore » ackground . Congenital cytomegalovirus (CMV) infection is a leading cause of disabilities in children, yet the general public appears to have little awareness of CMV. Methods . Women were surveyed about newborn infections at 7 different geographic locations. Results . Of the 643 women surveyed, 142 ( 22 % ) had heard of congenital CMV. Awareness increased with increasing levels of education ( P < .0001 ). Women who had worked as a healthcare professional had a higher prevalence of awareness of CMV than had other women ( 56 % versus 16 % , P < .0001 ). Women who were aware of CMV were most likely to have heard about it from a healthcare provider ( 54 % ), but most could not correctly identify modes of CMV transmission or prevention. Among common causes of birth defects and childhood illnesses, women's awareness of CMV ranked last. Conclusion . Despite its large public health burden, few women had heard of congenital CMV, and even fewer were aware of prevention strategies.« less

Impact of High-Dose Acyclovir Cytomegalovirus Prophylaxis Failure in Abdominal Solid Organ Transplant Recipients.

PubMed

Siodlak, Magdalena; Jorgenson, Margaret R; Descourouez, Jillian L; Leverson, Glen E; Mandelbrot, Didier A; Smith, Jeannina A; Redfield, Robert R

2018-05-25

To evaluate the clinical course and long-term impact of high-dose acyclovir (HD-A, 800 mg 4 times daily) cytomegalovirus (CMV) prophylaxis failure in a CMV- seropositive abdominal solid organ transplant population. Retrospective cohort study. Tertiary academic medical center. A total of 691 adults who received solid organ transplants between January 1, 2008, and June 30, 2013, without lymphocyte-depleting induction and were prescribed 3 months of HD-A prophylaxis at the time of hospital discharge; of those patients, 54 experienced prophylaxis failure, defined as CMV detected via molecular diagnostics or on biopsy while receiving HD-A (prophylaxis failure group), and 637 did not (comparator group). Mean ± SD time to failure was 64 ± 23 days; 98% (53/54 patients) was attributable to viremia diagnosed via positive polymerase chain reaction (PCR). Of these 53 patients, 34% (18 patients) were below the quantifiable range when detected. Median initial and peak CMV PCR for quantifiable readings were 1531 IU/ml (interquartile range [IQR] <250-2947) and 4442 IU/ml (IQR <250-32,500; 19 (36%) had a single detectable CMV PCR. Treatment was required in 56% (30/54 patients), with a median duration of 63 days; 40% (12 patients) were treated with valganciclovir alone, the remainder received intravenous ganciclovir. CMV disease resulted in hospitalization in 28% (15 patients). Immunosuppression was modified in 52% (28 patients). The rate of CMV recurrence after 100 days was significantly higher in the prophylaxis failure group (59% vs 13%, p<0.0001). Higher rates of rejection; higher rates of 1-, 3-, and 5-year graft failure; and higher rates of 1-, 3-, and 5-year mortality were noted in the prophylaxis failure group on univariate analysis (43% vs 30%, p=0.045; 8%, 17%, and 34% vs 4%, 12%, and 17%, p=0.006; and 6%, 17%, and 26% vs 1%, 6%, and 10%, p=0.003, respectively). Multivariate analysis demonstrated an increased risk of graft failure in the prophylaxis failure group (hazard ratio [HR] 1.76, 95% confidence interval [CI] 1-3.1, p=0.0499) and a trend to increased mortality (HR 1.6, 95% CI 0.83-3.1, p=0.16). Prophylaxis failure with HD-A was mostly limited to mild viremia; however, it was associated with significantly reduced long-term graft survival, likely reflecting the negative impact of CMV viremia. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Resistance to Cucumber mosaic virus in Gladiolus plants transformed with either a defective replicase of coat protein subgroup II gene from Cucumber mosaic virus

USDA-ARS?s Scientific Manuscript database

Transgenic Gladiolus plants that contain either Cucumber mosaic virus (CMV) subgroup I coat protein, CMV subgroup II coat protein, CMV replicase, a combination of the CMV subgroups I and II coat proteins, or a combination of the CMV subgroup II coat protein and replicase genes were developed. These...

Effect of Cytomegalovirus Co-Infection on Normalization of Selected T-Cell Subsets in Children with Perinatally Acquired HIV Infection Treated with Combination Antiretroviral Therapy

PubMed Central

Kapetanovic, Suad; Aaron, Lisa; Montepiedra, Grace; Anthony, Patricia; Thuvamontolrat, Kasalyn; Pahwa, Savita; Burchett, Sandra; Weinberg, Adriana; Kovacs, Andrea

2015-01-01

Background We examined the effect of cytomegalovirus (CMV) co-infection and viremia on reconstitution of selected CD4+ and CD8+ T-cell subsets in perinatally HIV-infected (PHIV+) children ≥ 1-year old who participated in a partially randomized, open-label, 96-week combination antiretroviral therapy (cART)-algorithm study. Methods Participants were categorized as CMV-naïve, CMV-positive (CMV+) viremic, and CMV+ aviremic, based on blood, urine, or throat culture, CMV IgG and DNA polymerase chain reaction measured at baseline. At weeks 0, 12, 20 and 40, T-cell subsets including naïve (CD62L+CD45RA+; CD95-CD28+), activated (CD38+HLA-DR+) and terminally differentiated (CD62L-CD45RA+; CD95+CD28-) CD4+ and CD8+ T-cells were measured by flow cytometry. Results Of the 107 participants included in the analysis, 14% were CMV+ viremic; 49% CMV+ aviremic; 37% CMV-naïve. In longitudinal adjusted models, compared with CMV+ status, baseline CMV-naïve status was significantly associated with faster recovery of CD8+CD62L+CD45RA+% and CD8+CD95-CD28+% and faster decrease of CD8+CD95+CD28-%, independent of HIV VL response to treatment, cART regimen and baseline CD4%. Surprisingly, CMV status did not have a significant impact on longitudinal trends in CD8+CD38+HLA-DR+%. CMV status did not have a significant impact on any CD4+ T-cell subsets. Conclusions In this cohort of PHIV+ children, the normalization of naïve and terminally differentiated CD8+ T-cell subsets in response to cART was detrimentally affected by the presence of CMV co-infection. These findings may have implications for adjunctive treatment strategies targeting CMV co-infection in PHIV+ children, especially those that are now adults or reaching young adulthood and may have accelerated immunologic aging, increased opportunistic infections and aging diseases of the immune system. PMID:25794163

Educating women about congenital cytomegalovirus: assessment of health education materials through a web-based survey.

PubMed

Price, Simani M; Bonilla, Erika; Zador, Paul; Levis, Denise M; Kilgo, Christina L; Cannon, Michael J

2014-11-30

Congenital cytomegalovirus (CMV) is the most common congenital infection in the U.S. and can result in permanent disabilities, such as hearing and vision loss, intellectual disability, and psychomotor and language impairments. Women can adopt prevention behaviors in an attempt to reduce their exposure to CMV. Currently, few women are familiar with CMV. To increase awareness of CMV, the Centers for Disease Control and Prevention (CDC) developed draft health education materials. The purpose of this study was to pilot test two health education materials to gauge their appeal and to determine if they increase knowledge about CMV and motivate audiences to seek additional information on CMV and adopt CMV prevention behaviors. African-American (n = 404) and Caucasian women (n = 405), who had a young child and were either pregnant or planning a pregnancy, were recruited to participate in a 15-minute web survey. Participants were randomly assigned to view one of two CMV health education materials, either a factsheet or video. Pre and post survey measures were used to assess changes in knowledge of CMV and motivation to adopt prevention behaviors. We also examined audience preferences regarding materials and motivation. CMV knowledge score increased significantly after presentation of either the video or factsheet (from 3.7 out of 10 to 9.1 out of 10, p <0.001). The average materials appeal score was high, with a mean of 3.6 on a four-point scale, indicating women responded very positively to both materials. Regression analyses indicated that appeal, message involvement (e.g., information seeking, discussing with others), post materials knowledge score, and viewing the video (vs. factsheet) were significantly positively associated with increased support for CMV prevention behaviors. Overall, we found that the health education materials improved women's knowledge of CMV and encouraged them to adopt prevention behaviors. Given the low awareness levels among women currently, these findings suggest that appropriate education materials have the potential to greatly increase knowledge of CMV. As women become more knowledgeable about CMV and transmission routes, we expect they will be more likely to adopt prevention behaviors, thereby reducing their risk of CMV infection.

Prevalence of CMV infection among staff in a metropolitan children’s hospital – occupational health screening findings

PubMed Central

Stranzinger, Johanna; Kindel, Jutta; Henning, Melanie; Wendeler, Dana; Nienhaus, Albert

2016-01-01

Background: Staff in children’s hospitals may run an increased risk of cytomegalovirus (CMV) contact infection leading to a congenital CMV fetopathy during pregnancy. The main risk factor is close contact with inapparent carriers of CMV among infants (<3 years). We therefore examined CMV seroprevalence (SP) and possible risk factors for CMV infection among staff at a children’s hospital. Method: In 2014, staff at a metropolitan children’s hospital were offered a CMV antibody test in the context of occupational health screening. Besides of anti-CMV immunoglobulin G (anti-CMV IgG) gender, age, profession, number of children and migration background were assessed and used as independent variables in multiple logistic regression. Women without a migration background (MIG) were considered as a separate group. Results: The study included 219 employees. Women showed a significant higher risk than men of being CMV-positive (adjusted odds ratio [aOR] 3.0; 95% CI 1.1–7.8). The risk among age groups of 30 and over was double that of the under-30s (aOR 2.0; 95% CI 1.0–3.9); among those aged 40-plus it was aOR 2.3 (95% CI 1.1–4.7). Staff with an MIG tested more often positive than those without an MIG (95.5% versus 45.7%). CMV SP was 47.7% among women without an MIG. In this subgroup the probability of CMV infection increased with age (p=0.08) as well. Conclusion: In the staff group as a whole there was a significant correlation between CMV SP, country of origin and age. We found no significant differences between occupational groups; perhaps our random sample was too small. Given the low CMV SP particularly in those without MIG, women who want to have children in particular must be protected from CMV infection. Follow-up studies should be undertaken to test whether good workplace hygiene offers sufficient protection for pregnant women and could be an alternative to prohibiting certain activities. PMID:27730028

Association between a polymorphism in the human programmed death-1 (PD-1) gene and cytomegalovirus infection after kidney transplantation.

PubMed

Hoffmann, Thomas W; Halimi, Jean-Michel; Büchler, Mathias; Velge-Roussel, Florence; Goudeau, Alain; Al-Najjar, Azmi; Marliere, Jean-Frédéric; Lebranchu, Yvon; Baron, Christophe

2010-01-01

Cytomegalovirus (CMV) infection is the most frequent infectious disease following organ transplantation. Strategies to prevent this infection remain a matter for debate, and discovering genetic risk factors might assist in adapting preventive strategies. By inhibiting IFNgamma production, programmed death 1 (PD-1) has a crucial role in anti-CMV immune response. A single nucleotide polymorphism (SNP) within intron 4 of the gene (rs11568821), called PD-1.3, has recently been reported to be clinically relevant in several immune disorders. However, its association with CMV infection has never been reported. In this study, the risk of CMV infection according to PD-1.3 genotype was investigated in 469 kidney graft recipients transplanted between 1995 and 2005. It was found that the A allele was associated with the risk of CMV infection in seropositive patients who did not receive CMV prophylaxis (OR=2.60, p=0.006). Multivariate analysis including other risk factors for CMV infection showed that this allele was independently associated with CMV infection (OR=2.54; p=0.010). Interestingly, combined analysis of PD-1.3 with the IL12B 3'UTR SNPs (previously shown to be associated with CMV infection) revealed that patients with the PD-1.3 A allele had a much higher risk of CMV infection compared to those having neither risk allele (OR=3.76; p=0.0003). This study identified a new genetic risk factor for CMV infection after kidney transplantation and suggests that an adjustment of CMV prophylaxis based on genetic markers would merit further investigation.

Immunostimulation by cytomegalovirus (CMV): helper T cell-dependent activation of immunoglobulin production in vitro by lymphocytes from CMV-immune donors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yachie, A.; Tosato, G.; Straus, S.E.

1985-08-01

Cytomegalovirus (CMV) is the cause of a number of different diseases ranging from self-limited benign infections in healthy adults to life threatening illnesses among immunocompromised hosts and newborns. Suppression of cell-mediated immunity is often found in cases of acute CMV infection, and in addition, the virus may also be a potent stimulant of lymphoid cells in vivo. The authors studied cellular proliferation and immunoglobulin (Ig) production induced by CMV to determine its effect on human lymphocytes in vitro. The CMV that was added to cultures of lymphocytes from CMV-seronegative donors failed to induce either significant cellular proliferation or Ig production.more » By contrast, CMV-stimulated cultures from CMV-seropositive donors induced both prominent cellular proliferation and Ig production. B cell differentiation into Ig-secreting cells required the presence of T cells, and this T cell help was sensitive to irradiation with 2000 rad and to treatment with cyclosporin A. When T cells were depleted of OKT4+ cells with monoclonal antibody and complement, the co-cultured B cells failed to produce Ig, whereas the depletion of OKT8+ cells had no effect on the Ig-secreting cell response. Inactivation of CMV before culture did not result in a reduction of either cellular proliferation or Ig production. Thus, infection of target cells is not required for in vitro lymphocyte activation by CMV. These results demonstrate that CMV is a potent activator of B cells inducing Ig production in vitro, and that this process requires the presence of virus-specific memory T cells.« less

CMV-specific T-cell immunity in solid organ transplant recipients at low risk of CMV infection. Chronology and applicability in preemptive therapy.

PubMed

Mena-Romo, Juan Damián; Pérez Romero, Pilar; Martín-Gandul, Cecilia; Gentil, Miguel Ángel; Suárez-Artacho, Gonzalo; Lage, Ernesto; Sánchez, Magdalena; Cordero, Elisa

2017-10-01

To characterize whether the CMV-specific cellular immune response can be used as a predictor of the control of CMV infection and disease and determine thresholds in solid organ transplant (SOT) recipients seropositive for CMV (R+). The CMV-specific T-cell response was characterized using intracellular cytokine staining and the evolution of clinical and virological parameters were recorded during the first year after transplantation. Besides having positive CMV serology, only 28.4% patients had positive immunity (CD8 + CD69 + IFN-γ + ≥0.25%) at 2 weeks after transplantation. These patients had less indication of preemptive treatment (p = 0.025) and developed less high grade (≥2000 IU/ml) CMV replication episodes (p = 0.006) than patients with no immunity. Of the 49 patients with a pretransplant sample, only 22.4% had positive immunity, and had a detectable immune response early after transplantation (median of 3.7 weeks). However, only 50% of patients with negative pretransplant immunity acquired a positive immune response and it was significantly later, at a median of 11 weeks (p < 0.001). Patients that developed CMV disease had no CMV-specific immunity. Having CMV-specific CD8 + IFN-γ + cells ≥0.25% before transplant; 0.15% at two weeks or 0.25% at four weeks after transplantation, identifies patients that may spontaneously control CMV infection and may require less monitoring. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Incidence and impact of CMV infection in very low birth weight infants.

PubMed

Turner, Kristen M; Lee, Henry C; Boppana, Suresh B; Carlo, Waldemar A; Randolph, David A

2014-03-01

Congenital cytomegalovirus (CMV) is the leading cause of nongenetic deafness in children in the United States and can cause neurodevelopmental impairment in term infants. Limited data exist regarding congenital CMV infections in preterm infants. We aimed to determine the incidence and association with outcomes of congenital CMV in very low birth weight (VLBW) preterm infants. VLBW infants born in 1993 to 2008 and admitted to the University of Alabama in Birmingham Regional Neonatal ICU were screened on admission for congenital CMV. CMV status and clinical outcomes were identified by using internal patient databases and hospital-based medical records. The primary outcome was death. Secondary outcomes included evidence of neurologic injury in the form of abnormal cranial ultrasound findings, sensorineural hearing loss, or abnormal motor development. Multivariate analysis was performed. Eighteen of 4594 VLBW infants had congenital CMV (0.39%; 95% confidence interval, 0.25%-0.62%). An additional 16 infants (0.35%; 95% confidence interval, 0.21%-0.57%) were identified who acquired CMV postnatally. Congenital CMV was not associated with death. Compared with controls, congenitally infected VLBW infants were more likely to have hearing loss at initial screening (67% vs. 9%, P < .0001) and confirmed at follow-up (83% vs. 2.1%, P < .0001). Congenital CMV was also associated with abnormal neuroimaging (72% vs. 25%, P < .0001) and adverse developmental motor outcomes (43% vs. 9%, P = .02). Acquired CMV was not associated with any adverse outcomes. Congenital CMV in VLBW infants is associated with high rates of neurologic injury and hearing loss but not death.

CMV Infection in Pediatric IBD.

PubMed

Yerushalmy-Feler, Anat; Kern-Isaacs, Sharona; Cohen, Shlomi

2018-03-28

Patients with inflammatory bowel disease (IBD) are predisposed to infections. Cytomegalovirus (CMV) colitis in adult IBD patients, particularly ulcerative colitis (UC), is related to severe or steroid-refractory disease. The aim of this review is to summarize the data on the prevalence and role of CMV colitis in children with IBD. Data on CMV colitis in children continue to be very limited due to its rarity. As in adults, children with coexisting UC and CMV tend to have more severe colitis, are resistant to corticosteroids, and are at high risk for colectomies on short- and long-term follow-up. In children, as in adults, the significance of CMV colitis, in terms of whether CMV is a pathogen that aggravates acute severe colitis or simply reflects disease severity, is still unknown.

Easy fix for clinical laboratories for the false-positive defect with the Abbott AxSym total beta-hCG test.

PubMed

Cole, Laurence A; Khanlian, Sarah A

2004-05-01

False-positive hCG results can lead to erroneous diagnoses and needless chemotherapy and surgery. In the last 2 years, eight publications described cases involving false-positive hCG tests; all eight involved the AxSym test. We investigated the source of this abundance of cases and a simple fix that may be used by clinical laboratories. False-positive hCG was primarily identified by absence of hCG in urine and varying or negative hCG results in alternative tests. Seventeen false-positive serum samples in the AxSym test were evaluated undiluted and at twofold dilution with diluent containing excess goat serum or immunoglobulin. We identified 58 patients with false-positive hCG, 47 of 58 due to the Abbott AxSym total hCGbeta test (81%). Sixteen of 17 of these "false-positive" results (mean 100 mIU/ml) became undetectable when tested again after twofold dilution. A simple twofold dilution with this diluent containing excess goat serum or immunoglobulin completely protected 16 of 17 samples from patients having false-positive results. It is recommended that laboratories using this test use twofold dilution as a minimum to prevent false-positive results.

Survey of fishes and environmental conditions in Abbotts Lagoon, Point Reyes National Seashore, California

USGS Publications Warehouse

Saiki, M.K.; Martin, B.A.

2001-01-01

This study was conducted to gain a better understanding of fishery resources in Abbotts Lagoon, Point Reyes National Seashore. During February/March, May, August, and November 1999, fish were sampled with floating variable-mesh gill nets and small minnow traps from as many as 14 sites in the lagoon. Water temperature, dissolved oxygen, pH, total ammonia(NH3 + NH4+), salinity, turbidity, water depth, and bottom substrate composition were also measured at each site. A total of 2,656 fish represented by eight species was captured during the study. Gill nets captured Sacramento perch, Archoplites interruptus; largemouth bass, Micropterus salmoides; Pacific herring, Clupea pallasi; prickly sculpin, Cottus asper, silver surfperch, Hyperprosopon ellipticum; longfin smelt, Spirinchus thaleichthys; and striped bass, Morone saxatilis; whereas minnow traps captured Sacramento perch; prickly sculpin; and threespine stickleback, Gasterosteus aculeatus. Cluster analysis (Ward's minimum variance method of fish catch statistics identified two major species assemblages-the first dominated by Sacramento perch and, to a lesser extent, by largemouth bass, and the second dominated by Pacific herring and threespine stickleback. Simple discriminant analysis of environmental variables indicated that salinity contributed the most towards separating the two assemblages.

Progressive reduction of CMV-specific CD4+ T cells in HIV-1 infected individuals during antiretroviral therapy.

PubMed

Grosse, V; Schulte, A; Weber, K; Mendila, M; Jacobs, R; Schmidt, R E; Heiken, H

2000-08-01

Visualization of antigen-specific T cells has become an important tool in studying immune responses. The aim of this study was to analyze CMV-specific CD4+ T cells in healthy and HIV-infected individuals. Peripheral blood mononuclear cells (PBMC) were examined for antigen-induced intracellular cytokine responses. We found significant numbers of CMV-specific CD4+ T cells detectable in most CMV-IgG+ HIV-1 infected individuals, whereas CMV-specific CD4+ T cells could not be demonstrated in CMV-IgG- patients. Median frequency of CMV-specific CD4+ T cells were lower in HIV-infected subjects who had been treated with highly active antiretroviral therapy (HAART) for more than 1 year than in untreated HIV-infected individuals. In patients under therapy for less than 1 year median CMV-specific CD4+ T cell responder frequency was higher than in subjects treated for more than 1 year but lower than in untreated subjects. HIV suppression with HAART might lead to a progressive reduction of CMV-specific CD4+ T cells indicating an efficient elimination of an opportunistic pathogen.

Resolution of Mild Ganciclovir-Resistant Cytomegalovirus Disease with Reduced-Dose Cidofovir and CMV-Hyperimmune Globulin.

PubMed

Patel, Samir J; Kuten, Samantha A; Knight, Richard J; Hong, Dana M; Gaber, A Osama

2014-01-01

Ganciclovir-resistant cytomegalovirus (CMV) is associated with significant morbidity in solid organ transplant recipients. Management of ganciclovir-resistant CMV may be complicated by nephrotoxicity which is commonly observed with recommended therapies and/or rejection induced by "indirect" viral effects or reduction of immunosuppression. Herein, we report a series of four high serologic risk (donor CMV positive/recipient CMV negative) kidney transplant patients diagnosed with ganciclovir-resistant CMV disease. All patients initially developed "breakthrough" viremia while still receiving valganciclovir prophylaxis after transplant and were later confirmed to exhibit UL97 mutations after failing to eradicate virus on adequate dosages of valganciclovir. The patients were subsequently and successfully treated with reduced-dose (1-2 mg/kg) cidofovir and CMV-hyperimmune globulin, given in 2-week intervals. In addition, all patients exhibited stable renal function after completion of therapy, and none experienced acute rejection. The combination of reduced-dose cidofovir and CMV-hyperimmune globulin appeared to be a safe and effective regimen in patients with mild disease due to ganciclovir-resistant CMV.

Evaluation of a novel semi-automated HPLC procedure for whole blood cyclosporin A confirms equivalence to adjusted monoclonal values from Abbott TDx.

PubMed

Roberts, Norman B; Dutton, John; Higgins, Gerald; Allars, Lesley

2005-01-01

The problem in the measurement of cyclosporin (CyA) is that the widely used immuno-based assays suffer from interference by metabolites present in unpredictable excess. To resolve this, the consensus view has been to develop more specific and robust procedures for the measurement of CyA alone in order to give values similar to those obtained by HPLC. We developed an alternative strategy based on Abbott poly- and monoclonal assays to derive an adjusted monoclonal value as an equivalent measurement to HPLC. We have now evaluated a recently developed semi-automated HPLC procedure and used it to test the validity of the adjusted monoclonal value. The automated HPLC procedure with online clean-up was optimised for the separation of CyA and internal standard CyD. The assay was simple to use, precise and gave good recovery of cyclosporin from whole blood. Comparisons with the more specific immunoassays Abbott AxSym and EMIT showed close agreement, whereas Abbott monoclonal values indicated up to 20% positive bias. In contrast, the adjusted monoclonal values gave good agreement with HPLC. Data obtained from HPLC linked to tandem mass spectrometry (MS) indicated closer agreement with Abbott monoclonal values than expected, suggesting some positive bias with MS. The benefit of using an adjusted monoclonal value is that a result equivalent to HPLC is obtained, as well as an indication of the concentration of metabolites from the Abbott polyclonal measurement.

Analytical and clinical performance characteristics of the Abbott RealTime MTB RIF/INH Resistance, an assay for the detection of rifampicin and isoniazid resistant Mycobacterium tuberculosis in pulmonary specimens.

PubMed

Kostera, Joshua; Leckie, Gregor; Tang, Ning; Lampinen, John; Szostak, Magdalena; Abravaya, Klara; Wang, Hong

2016-12-01

Clinical management of drug-resistant tuberculosis patients continues to present significant challenges to global health. To tackle these challenges, the Abbott RealTime MTB RIF/INH Resistance assay was developed to accelerate the diagnosis of rifampicin and/or isoniazid resistant tuberculosis to within a day. This article summarizes the performance of the Abbott RealTime MTB RIF/INH Resistance assay; including reliability, analytical sensitivity, and clinical sensitivity/specificity as compared to Cepheid GeneXpert MTB/RIF version 1.0 and Hain MTBDRplus version 2.0. The limit of detection (LOD) of the Abbott RealTime MTB RIF/INH Resistance assay was determined to be 32 colony forming units/milliliter (cfu/mL) using the Mycobacterium tuberculosis (MTB) strain H37Rv cell line. For rifampicin resistance detection, the Abbott RealTime MTB RIF/INH Resistance assay demonstrated statistically equivalent clinical sensitivity and specificity as compared to Cepheid GeneXpert MTB/RIF. For isoniazid resistance detection, the assay demonstrated statistically equivalent clinical sensitivity and specificity as compared to Hain MTBDRplus. The performance data presented herein demonstrate that the Abbott RealTime MTB RIF/INH Resistance assay is a sensitive, robust, and reliable test for realtime simultaneous detection of first line anti-tuberculosis antibiotics rifampicin and isoniazid in patient specimens. Copyright © 2016 The Author. Published by Elsevier Ltd.. All rights reserved.

Cytomegalovirus-Responsive CD8+ T Cells Expand After Solid Organ Transplantation in the Absence of CMV Disease.

PubMed

Higdon, L E; Trofe-Clark, J; Liu, S; Margulies, K B; Sahoo, M K; Blumberg, E; Pinsky, B A; Maltzman, J S

2017-08-01

Cytomegalovirus (CMV) is a major cause of morbidity and mortality in solid organ transplant recipients. Approximately 60% of adults are CMV seropositive, indicating previous exposure. Following resolution of the primary infection, CMV remains in a latent state. Reactivation is controlled by memory T cells in healthy individuals; transplant recipients have reduced memory T cell function due to chronic immunosuppressive therapies. In this study, CD8 + T cell responses to CMV polypeptides immediate-early-1 and pp65 were analyzed in 16 CMV-seropositive kidney and heart transplant recipients longitudinally pretransplantation and posttransplantation. All patients received standard of care maintenance immunosuppression, antiviral prophylaxis, and CMV viral load monitoring, with approximately half receiving T cell-depleting induction therapy. The frequency of CMV-responsive CD8 + T cells, defined by the production of effector molecules in response to CMV peptides, increased during the course of 1 year posttransplantation. The increase commenced after the completion of antiviral prophylaxis, and these T cells tended to be terminally differentiated effector cells. Based on this small cohort, these data suggest that even in the absence of disease, antigenic exposure may continually shape the CMV-responsive T cell population posttransplantation. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

Cytomegalovirus colitis in immunocompetent critically ill patients.

PubMed

Siciliano, Rinaldo F; Castelli, Jussara B; Randi, Bruno A; Vieira, Ricardo D; Strabelli, Tânia M V

2014-03-01

Cytomegalovirus (CMV) is a ubiquitous virus and its reactivation may lead to CMV end-organ disease (CMV EOD) in immunocompromised patients and also in immunocompetent patients when they are critically ill. We aimed to investigate the frequency and the clinical features of proven CMV EOD in previously non-immunosuppressed patients admitted to our institution. From January 2000 to March 2013, the records of all patients with a histopathological diagnosis of CMV EOD at our teaching hospital were reviewed retrospectively. CMV EOD was diagnosed histologically by the identification of true cytomegalic viral inclusion involving endothelial, stromal, and/or epithelial cells on hematoxylin and eosin staining, and was subsequently confirmed by immunohistochemistry using specific antibody against CMV antigens. Immunocompromised patients were excluded. CMV EOD manifesting as colitis was diagnosed in 14 previously immunocompetent intensive care unit (ICU) patients. The mean age of the patients was 64 years. All had co-morbidities and developed shock before CMV EOD. The major manifestation was gastrointestinal bleeding. The in-hospital mortality rate was 71.4% despite specific treatment with ganciclovir. Despite being a rare condition, lower gastrointestinal bleeding in this profile of ICU patients could be the clinical manifestation of CMV colitis, and intensivists should be alert to this condition. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Prospective, comprehensive, and effective viral monitoring in Cuban children undergoing solid organ transplantation.

PubMed

Kourí, Vivian; Correa, Consuelo; Martínez, Pedro A; Sanchez, Lizet; Alvarez, Alina; González, Grehete; Silverio, César E; Hondal, Norma; Florin, Jose; Pérez, Lourdes; Duran, Diana P; Perez, Yardelis; Cazorla, Nancy; Gonzalez, Dalmaris; Jaime, Juan C; Arencibia, Alberto; Sarduy, Sandra; Pérez, Lissette; Soto, Yudira; González, Mabel; Alvarez, Iliana; Dorticós, Elvira; Marchena, Juan J; Solar, Luis; Acosta, Belsy; Savón, Clara; Hengge, Ulrich

2014-01-01

In Cuba, viral monitoring in the post-transplant period was not routinely performed. The aim of this research is to identify the most frequent viruses that affect transplanted Cuban children, by implementing a viral follow-up during the post-transplant period. The study population included all Cuban pediatric patients who underwent solid organ transplantation (SOT) between November 2009 and December 2012. A total of 34 transplanted pediatric patients of kidney (n = 11) and liver (n = 23) were prospectively monitored during a 34-week period for viral DNAemia and DNAuria by simultaneous detection of cytomegalovirus (CMV), Epstein-Barr virus, herpes simplex virus type 1 and 2, varicella zoster virus, human herpesvirus 6, human adenovirus, and polyomaviruses (BKV and JCV) using quantitative real-time polymerase chain reaction (qRT-PCR). Viral genome of at least one virus was detected in 21 of 34 recipients, 18 patients excreted virus in urine while 12 presented DNAemia. CMV (41.2%) and BKV (35.3%) were the most frequent viruses detected during the follow-up. CMV was the virus mainly associated with clinical symptoms and DNAemia. Its excretion in urine (with cut off value of 219 copies/mL) was associated with detection in plasma (p < 0.001); furthermore, CMV viruria was predictive of CMV viremia (OR:8.4, CI:2.4-29.1, p = 0.001). There was no association between high viral load and clinical complications, due to the prompt initiation of preemptive ganciclovir. This comprehensive viral monitoring program effectively prevents the development of critical viral disease, thus urge the implementation of qRT-PCR as routine for viral monitoring of transplanted Cuban organ recipients.

Cytomegalovirus prevention strategies in seropositive kidney transplant recipients: an insight into current clinical practice.

PubMed

Fernández-Ruiz, Mario; Arias, Manuel; Campistol, Josep M; Navarro, David; Gómez-Huertas, Ernesto; Gómez-Márquez, Gonzalo; Díaz, Juan Manuel; Hernández, Domingo; Bernal-Blanco, Gabriel; Cofan, Frederic; Jimeno, Luisa; Franco-Esteve, Antonio; González, Esther; Moreso, Francesc J; Gómez-Alamillo, Carlos; Mendiluce, Alicia; Luna-Huerta, Enrique; Aguado, José María

2015-09-01

There is notable heterogeneity in the implementation of cytomegalovirus (CMV) prevention practices among CMV-seropositive (R+) kidney transplant (KT) recipients. In this prospective observational study, we included 387 CMV R+ KT recipients from 25 Spanish centers. Prevention strategies (antiviral prophylaxis or preemptive therapy) were applied according to institutional protocols at each site. The impact on the 12-month incidence of CMV disease was assessed by Cox regression. Asymptomatic CMV infection, acute rejection, graft function, non-CMV infection, graft loss, and all-cause mortality were also analyzed (secondary outcomes). Models were adjusted for a propensity score (PS) analysis for receiving antiviral prophylaxis. Overall, 190 patients (49.1%) received preemptive therapy, 185 (47.8%) antiviral prophylaxis, and 12 (3.1%) no specific intervention. Twelve-month cumulative incidences of CMV disease and asymptomatic infection were 3.6% and 39.3%, respectively. Patients on prophylaxis had lower incidence of CMV disease [PS-adjusted HR (aHR): 0.10; 95% confidence interval (CI): 0.01-0.79] and asymptomatic infection (aHR: 0.46; 95% CI: 0.29-0.72) than those managed preemptively, with no significant differences according to the duration of prophylaxis. All cases of CMV disease in the prophylaxis group occurred after prophylaxis discontinuation. There were no differences in any of the secondary outcomes. In conclusion, antiviral prophylaxis was associated with a lower occurrence of CMV disease in CMV R+ KT recipients, although such benefit should be balanced with the risk of late-onset disease. © 2015 Steunstichting ESOT.

Comparison of Cytomegalovirus Loads in Plasma and Leukocytes of Patients with Cytomegalovirus Retinitis

PubMed Central

Jabs, Douglas A.; Forman, Michael; Enger, Cheryl; Jackson, J. Brooks

1999-01-01

Cytomegalovirus (CMV) DNA loads in paired leukocyte and plasma samples from 199 patient visits by 66 patients with CMV retinitis were determined. Leukocyte CMV load determinations had a greater range of values (mean, 24,587 copies/106 leukocytes; maximum, 539,000) than did plasma CMV load determinations (mean, 10,302 copies/ml; maximum, 386,000), and leukocyte viral loads were detectable in a greater proportion of patients at the time of diagnosis of CMV retinitis prior to initiation of anti-CMV therapy (82%) than were plasma viral loads (64%) (P = 0.0078). Agreement with CMV blood cultures was slightly better for plasma (κ = 0.68) than for leukocytes (κ = 0.53), due to a greater proportion of patients with detectable viral loads in leukocytes having negative blood cultures. PMID:10203500

Antibody responses to synthetic peptides from cytomegalovirus phosphoprotein 150.

PubMed Central

Sundqvist, V A; Xu, W; Wahren, B

1992-01-01

We have identified antigenic regions within phosphoprotein 150 of human cytomegalovirus (CMV pp150) to which seroreactivity appears in patients with active CMV infection or persists in seropositive persons. A range of 8.3 to 61.6% of healthy CMV-seropositive blood donors were immunoglobulin G positive for single peptides, while 91.6% reacted to a mixture of four peptides. All convalescent-phase serum samples from 26 patients with active CMV infection reacted with either of two peptides encompassing amino acids (aa) 594 to 623 and aa 614 to 643. Patients with a primary CMV infection had patterns of reactivity to single peptides different from those of patients with reactivated CMV infection. The immunoglobulin M antibodies reacted preferentially with the peptides encompassing aa 594 to 663 of CMV pp150. PMID:1328283

Long-term control of CMV retinitis in a patient with idiopathic CD4+ T lymphocytopenia.

PubMed

Yashiro, Shigeko; Fujino, Yujiro; Tachikawa, Natsuo; Inamochi, Kazuya; Oka, Shinichi

2013-04-01

Cytomegalovirus (CMV) retinitis with idiopathic CD4(+) T lymphocytopenia (ICL) is rare and difficult to control. We report a first case for long-term control of CMV retinitis with ICL using interleukin-2 (IL-2) therapy and succeeded in discontinuation of anti-CMV therapy. A 49-year-old Japanese woman was diagnosed with ICL based on low CD4(+) count (72/μl), negative for HIV-1 and -2 antibodies, and absence of any defined immunodeficiency diseases or immunosuppressive therapy. PCR test of the aqueous humor in the right eye was suggestive of CMV retinitis. She was treated with systemic ganciclovir, but after several relapses of CMV retinitis, rhegmatogenous retinal detachment appeared in the right eye and she became blind in that eye. Three years later, she developed CMV retinitis in the left eye. Although she received systemic and focal anti-CMV treatments, the retinitis showed no improvement. Finally, retinal detachment occurred, and she underwent vitrectomy. IL-2 was injected to increase CD4(+) counts. Because of hyperpyrexia, blepharedema, central scotoma, and color anomaly, we changed to low-dose IL-2 therapy with no side effects. Finally, we succeeded in increasing the CD4(+) count to more than 200/μl after discontinuation of low-dose IL-2 therapy. CMV retinitis never recurred after discontinuation of anti-CMV therapy, with good visual acuity of 20/20 in the left eye. She developed blindness of the first affected right eye, whereas the visual acuity of the left eye remains excellent more than 12 years after the onset of CMV retinitis through the combined use of anti-CMV therapy, IL-2 therapy, and vitrectomy.

Higher Anti-CMV IgG Concentrations are Associated with Worse Neurocognitive Performance During Suppressive Antiretroviral Therapy.

PubMed

Letendre, Scott; Bharti, Ajay; Perez-Valero, Ignacio; Hanson, Barbara; Franklin, Donald; Woods, Steven Paul; Gianella, Sara; de Oliveira, Michelli Faria; Heaton, Robert K; Grant, Igor; Landay, Alan L; Lurain, Nell

2018-03-01

To determine the association of CMV infection with neurocognitive performance in HIV+ adults. Cross-sectional, observational, exploratory study. Anti-CMV IgG concentrations in blood and CMV DNA copies in blood and cerebrospinal fluid (CSF) were measured in stored specimens of 80 HIV+ adults who were previously assessed with a standardized, comprehensive neurocognitive test battery. Thirty-eight were taking suppressive antiretroviral therapy (ART, HIV RNA ≤ 50 copies/mL) and 42 were not taking ART. A panel of 7 soluble biomarkers were also measured by immunoassay in CSF. Anti-CMV IgG concentrations ranged from 5.2 to 46.1 U/mL. CMV DNA was detected in 7 (8.8%) blood plasma but in none of the CSF specimens. Higher anti-CMV IgG levels were associated with older age (p=0.0017), lower nadir CD4+ T-cell count (p<0.001), AIDS (p<0.001), and higher soluble CD163 (p=0.009). Higher anti-CMV IgG levels trended toward an association with worse neurocognitive performance overall (p=0.059). This correlation was present in those taking suppressive ART (p=0.0049) but not in those who were not taking ART (p=0.92). Worse neurocognitive performance remained associated with higher anti-CMV IgG levels after accounting for other covariates in multivariate models (Model p=0.0038). Detectable plasma CMV DNA was associated with AIDS (p=0.05) but not with neurocognitive performance. CMV may influence neurocognitive performance in HIV+ adults taking suppressive ART. Future clinical trials of anti-CMV therapy should help determine whether the observed relationships are causal.

Outcomes and prognostic factors of non-HIV patients with pneumocystis jirovecii pneumonia and pulmonary CMV co-infection: A Retrospective Cohort Study.

PubMed

Yu, Qing; Jia, Peng; Su, Li; Zhao, Hong; Que, Chengli

2017-06-05

Pneumocystis jirovecii pneumonia (PJP) and pulmonary cytomegalovirus (CMV) infection are common opportunistic infections among immunocompromised patients. However, few studies have evaluated their co-infection, especially among non-HIV patients. Therefore, we aimed to evaluate the outcomes and prognostic factors among non-HIV patients with PJP according to their CMV infection status. This retrospective study evaluated non-HIV patients who were diagnosed with PJP between January 2009 and January2016.The patients were classified and compared according to their pulmonary CMV infection status (positive infection: bronchoalveolar lavage fluid [BALF] CMV DNA loads of >500copies/mL). Among 70 non-HIV patients with PJP, we identified 38 patients (54.3%) with pulmonary CMV infection. There was no significant difference in the mortality rates for the two groups (p = 0.15). Pulmonary CMV infection was significantly more common among patients who were receiving glucocorticoids and immunosuppressants, compared to corticosteroids only (p = 0.02). Pulmonary CMV infection was also significantly associated with severe dyspnea, a lower PaO 2 /FiO 2 , and the presence of centrilobular nodules (p = 0.008). Higher CMV DNA loads in the BALF were positively associated with mortality (p = 0.012). Combined therapy using corticosteroids and other immunosuppressants may be a risk factor for pulmonary CMV co-infection among patients with PJP. In addition, CMV pneumonia should be considered when centrilobular nodules and/or severe hypoxemia are observed in non-HIV patients with PJP. Furthermore, antiviral treatment should be promptly initiated for patients with a high CMV DNA load in BALF, based on their poor prognosis.

Cytomegalovirus Virions Shed in Urine Have a Reversible Block to Epithelial Cell Entry and Are Highly Resistant to Antibody Neutralization

PubMed Central

Cui, Xiaohong; Adler, Stuart P.; Schleiss, Mark R.; Demmler Harrison, Gail J.

2017-01-01

ABSTRACT Cytomegalovirus (CMV) causes sensorineural hearing loss and developmental disabilities in newborns when infections are acquired in utero. Pregnant women may acquire CMV from oral exposure to CMV in urine or saliva from young children. Neutralizing antibodies in maternal saliva have the potential to prevent maternal infection and, in turn, fetal infection. As CMV uses different viral glycoprotein complexes to enter different cell types, the first cells to be infected in the oral cavity could determine the type of antibodies needed to disrupt oral transmission. Antibodies targeting the pentameric complex (PC) should block CMV entry into epithelial cells but not into fibroblasts or Langerhans cells (which do not require the PC for entry), while antibodies targeting glycoprotein complexes gB or gH/gL would be needed to block entry into fibroblasts, Langerhans cells, or other cell types. To assess the potential for antibodies to disrupt oral acquisition, CMV from culture-positive urine samples (uCMV) was used to study cell tropisms and sensitivity to antibody neutralization. uCMV entered epithelial cells poorly compared with the entry into fibroblasts. CMV-hyperimmune globulin or monoclonal antibodies targeting gB, gH/gL, or the PC were incapable of blocking the entry of uCMV into either fibroblasts or epithelial cells. Both phenotypes were lost after one passage in cultured fibroblasts, suggestive of a nongenetic mechanism. These results suggest that uCMV virions have a reversible block to epithelial cell entry. Antibodies may be ineffective in preventing maternal oral CMV acquisition but may limit viral spread in blood or tissues, thereby reducing or preventing fetal infection and disease. PMID:28404573

Genetic structure and molecular variability of Cucumber mosaic virus isolates in the United States.

PubMed

Nouri, Shahideh; Arevalo, Rafael; Falk, Bryce W; Groves, Russell L

2014-01-01

Cucumber mosaic virus (CMV) has a worldwide distribution and the widest host range of any known plant virus. From 2000 to 2012, epidemics of CMV severely affected the production of snap bean (Phaseulos vulgaris L.) in the Midwest and Northeastern United States. Virus diversity leading to emergence of new strains is often considered a significant factor in virus epidemics. In addition to epidemics, new disease phenotypes arising from genetic exchanges or mutation can compromise effectiveness of plant disease management strategies. Here, we captured a snapshot of genetic variation of 32 CMV isolates collected from different regions of the U.S including new field as well as historic isolates. Nucleotide diversity (π) was low for U.S. CMV isolates. Sequence and phylogenetic analyses revealed that CMV subgroup I is predominant in the US and further showed that the CMV population is a mixture of subgroups IA and IB. Furthermore, phylogenetic analysis suggests likely reassortment between subgroups IA and IB within five CMV isolates. Based on phylogenetic and computational analysis, recombination between subgroups I and II as well as IA and IB in RNA 3 was detected. This is the first report of recombination between CMV subgroups I and II. Neutrality tests illustrated that negative selection was the major force operating upon the CMV genome, although some positively selected sites were detected for all encoded proteins. Together, these data suggest that different regions of the CMV genome are under different evolutionary constraints. These results also delineate composition of the CMV population in the US, and further suggest that recombination and reassortment among strain subgroups does occur but at a low frequency, and point towards CMV genomic regions that differ in types of selection pressure.

Genetic Structure and Molecular Variability of Cucumber mosaic virus Isolates in the United States

PubMed Central

Nouri, Shahideh; Arevalo, Rafael; Falk, Bryce W.; Groves, Russell L.

2014-01-01

Cucumber mosaic virus (CMV) has a worldwide distribution and the widest host range of any known plant virus. From 2000 to 2012, epidemics of CMV severely affected the production of snap bean (Phaseulos vulgaris L.) in the Midwest and Northeastern United States. Virus diversity leading to emergence of new strains is often considered a significant factor in virus epidemics. In addition to epidemics, new disease phenotypes arising from genetic exchanges or mutation can compromise effectiveness of plant disease management strategies. Here, we captured a snapshot of genetic variation of 32 CMV isolates collected from different regions of the U.S including new field as well as historic isolates. Nucleotide diversity (π) was low for U.S. CMV isolates. Sequence and phylogenetic analyses revealed that CMV subgroup I is predominant in the US and further showed that the CMV population is a mixture of subgroups IA and IB. Furthermore, phylogenetic analysis suggests likely reassortment between subgroups IA and IB within five CMV isolates. Based on phylogenetic and computational analysis, recombination between subgroups I and II as well as IA and IB in RNA 3 was detected. This is the first report of recombination between CMV subgroups I and II. Neutrality tests illustrated that negative selection was the major force operating upon the CMV genome, although some positively selected sites were detected for all encoded proteins. Together, these data suggest that different regions of the CMV genome are under different evolutionary constraints. These results also delineate composition of the CMV population in the US, and further suggest that recombination and reassortment among strain subgroups does occur but at a low frequency, and point towards CMV genomic regions that differ in types of selection pressure. PMID:24801880

Increased transplant-related morbidity and mortality in CMV-seropositive patients despite highly effective prevention of CMV disease after allogeneic T-cell-depleted stem cell transplantation.

PubMed

Broers, A E; van Der Holt, R; van Esser, J W; Gratama, J W; Henzen-Logmans, S; Kuenen-Boumeester, V; Löwenberg, B; Cornelissen, J J

2000-04-01

We evaluated the efficacy, toxicity, and outcome of preemptive ganciclovir (GCV) therapy in 80 cytomegalovirus (CMV)-seropositive patients allografted between 1991 and 1996 and compared their outcome to 35 seronegative patients allografted during the same period. Both cohorts were comparable with respect to diagnosis and distribution of high- versus standard-risk patients. All patients received a stem cell graft from an HLA-identical sibling donor, and grafts were partially depleted of T cells in 109 patients. Patients were monitored for CMV antigenemia by leukocyte expression of the CMV-pp65 antigen. Fifty-two periods of CMV reactivation occurring in 30 patients were treated preemptively with GCV. A favorable response was observed in 48 of 50 periods, and only 2 patients developed CMV disease: 1 with esophagitis and 1 with pneumonia. Ten of 30 treated patients developed GCV-related neutropenia (less than 0.5 x 10(9)/L), which was associated with a high bilirubin at the start of GCV therapy. Overall survival at 5 years was 64% in the CMV-seronegative cohort and 40% in the CMV-seropositive cohort (P =.01). Increased treatment-related mortality accounted for inferior survival. CMV seropositivity proved an independent risk factor for developing acute graft-versus-host disease, and acute graft-versus-host disease predicted for higher treatment-related mortality and worse overall survival in a time-dependent analysis. We conclude that, although CMV disease can effectively be prevented by preemptive GCV therapy, CMV seropositivity remains a strong adverse risk factor for survival following partial T-cell-depleted allogeneic stem cell transplantation.

Epidemiology and risk factors for cytomegalovirus infection in glomerular diseases treated with immunosuppressive therapy.

PubMed

Lim, Cynthia C; Tung, Yu Tzu; Tan, Ban Hock; Lee, Puay Hoon; Mok, Irene Yj; Oon, Lynette; Chan, Kwai Peng; Choo, Jason Cj

2017-05-08

Cytomegalovirus (CMV) infections are associated with morbidity and mortality. We aimed to describe the epidemiology, risk factors and outcomes of CMV infection among patients with glomerulonephritis (GN) who received potent immunosuppressants (IS). Single-centre retrospective study of adults with biopsy-proven GN prescribed methylprednisolone (MP), cyclophosphamide (CYC) or rituximab (RTX). Primary endpoint was CMV infection defined by significant CMV antigenemia (>10 positive cells in 10 6 cells) or viremia (>2000 copies/ml). Death was related to CMV if CMV infection occurred within the same hospitalisation as death. Ninety-four patients were studied. CYC was prescribed in 65% and MP in 71% of the cohort. Only 2 patients received RTX and 15 patients received plasma exchanges (PEX). Median follow up was 31.9 (IQR: 13.7, 53.6) months. CMV infection occurred in 13 patients (13.8%) at 1.3 (0.6, 3.0) months from biopsy. Patients with CMV infection had higher serum creatinine [404 (272, 619) vs. 159 (93, 317) µmol/L, p < 0.001] and greater proteinuria [UPCR 7.5, (4.8, 11.8) vs. 4.2 (2.3, 8.4) g/g, p = 0.02] than those who did not have CMV infection. Also, more patients received CYC (92% vs. 60%, p = 0.03), RTX (15% vs. 0, p = 0.02) and PEX (38% vs. 12%, p = 0.01) than those who did not have CMV infection. Two patients had CMV-related deaths. CMV infection is common in GN patients receiving potent IS. Surveillance and possibly anti-viral prophylaxis should be considered for high-risk patients. This article is protected by copyright. All rights reserved.

Quantification of cytomegalovirus (CMV) viral load by the hybrid capture assay allows for early detection of CMV disease in lung transplant recipients.

PubMed

Bhorade, S M; Sandesara, C; Garrity, E R; Vigneswaran, W T; Norwick, L; Alkan, S; Husain, A N; McCabe, M A; Yeldandi, V

2001-09-01

We prospectively compared the hybrid capture system (HCS) assay with conventional cell culture and shell vial assay for the detection of cytomegalovirus (CMV) infection and disease in the lung transplant population. Between January 1999 and February 2000, 34 lung transplant patients at Loyola University Medical Center, who were considered to be at risk for CMV disease, underwent surveillance testing for CMV cell culture, shell vial assay and HCS assay according to a pre-determined schedule. In addition, bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy were performed at regular intervals and for clinical indications. All BAL samples were sent for CMV cultures and biopsy specimens were analyzed for histopathologic evidence of CMV by immunoperoxidase staining using antibody to early immediate nuclear antigen. Ten patients developed CMV disease/syndrome during the course of the study. The sensitivity, specificity, positive predictive value and negative predictive value were >90% for the HCS assay. The sensitivity of the HCS assay (90%) was statistically significantly higher than the sensitivity of either the SV assay (40%) or the cell culture (50%). In addition, the HCS assay was able to detect CMV 50 +/- 67 days prior to clinical evidence of CMV disease and an average of 36 days prior to the other detection techniques. The HCS assay is a sensitive diagnostic technique able to reliably detect CMV disease earlier than other diagnostic methods in the lung transplant population. Future studies may be able to evaluate whether pre-emptive anti-viral therapy targeted to specific viral loads using the HCS assay will be beneficial in preventing morbidity associated with CMV disease.

Cytomegalovirus seropositivity is associated with herpes zoster

PubMed Central

Ogunjimi, Benson; Hens, Niel; Pebody, Richard; Jansens, Hilde; Seale, Holly; Quinlivan, Mark; Theeten, Heidi; Goossens, Herman; Breuer, Judy; Beutels, Philippe

2015-01-01

Herpes zoster (HZ) is caused by VZV reactivation that is facilitated by a declined immunity against varicella-zoster virus (VZV), but also occurs in immunocompetent individuals. Cytomegalovirus (CMV) infection is associated with immunosenescence meaning that VZV-specific T-cells could be less responsive. This study aimed to determine whether CMV infection could be a risk factor for the development of HZ. CMV IgG serostatus was determined in stored serum samples from previously prospectively recruited ambulatory adult HZ patients in the UK (N = 223) in order to compare the results with those from UK population samples (N = 1545) by means of a logistic regression (controlling for age and gender). Furthermore, we compared the UK population CMV seroprevalence with those from population samples from other countries (from Belgium (N1 = 1741, N2 = 576), USA (N = 5572) and Australia (N = 2080)). Furthermore, CMV IgG titers could be compared between UK HZ patients and Belgium N2 population samples because the same experimental set-up for analysis was used. We found UK ambulatory HZ patients to have a higher CMV seroprevalence than UK population samples (OR 1.56 [1.11 2.19]). CMV IgG seropositivity was a significant risk factor for HZ in the UK (OR 3.06 [1.32 7.04]. Furthermore, high CMV IgG titers (exceeding the upper threshold) were less abundant in CMV-seropositive Belgian N2 population samples than in CMV-seropositive UK HZ patients (OR 0.51 [0.31 0.82]. We found CMV-seroprevalence to increase faster with age in the UK than in other countries (P < 0.05). We conclude that CMV IgG seropositivity is associated with HZ. This finding could add to the growing list of risk factors for HZ. PMID:25905443

Survey of congenital cytomegalovirus (cCMV) knowledge among medical students.

PubMed

Baer, H R; McBride, H E; Caviness, A C; Demmler-Harrison, G J

2014-07-01

Congenital cytomegalovirus (cCMV) is a leading cause of congenital infection worldwide and the most common congenital infection in the United States, affecting 30,000-40,000 US newborns each year and causing permanent disabilities in 8000-10,000. In contrast to how commonly it occurs, physicians and medical students have little knowledge of cCMV. To test the hypothesis medical students have little awareness about cCMV infection, and to collect data on medical students' knowledge about cCMV. The long-term goal of this project is to establish medical student awareness of cCMV infection and educate students about available treatments and strategies for prevention in at-risk populations. Medical students at one institution were surveyed by questionnaire to assess their knowledge of cCMV. Responses were described, quantified, and compared between groups. 751 surveys were sent and 422 completed responses were received. Respondents were well distributed over all 4 medical school (MS) class years. Only 34% MS1 had heard of cCMV compared to 100% MS2-4 (P<0.0001). All MS2-4 who reported being "very familiar" with CMV learned about it in medical school, 80% in one lecture. MS1 respondents were significantly less knowledgeable about cCMV than MS2-MS4 respondents. A baseline lack of knowledge about cCMV was documented in first year medical students. A sharp increase in knowledge of cCMV occurred between MS1 and MS2 years, likely due to preclinical medical student curriculum. However, significant knowledge gaps regarding transmission and treatment were observed in all MS years, representing opportunities for medical education. Copyright © 2014 Elsevier B.V. All rights reserved.

Optimized enzyme-linked immunosorbent assay for detecting cytomegalovirus infections during clinical trials of recombinant vaccines.

PubMed

Pagnon, Anke; Piras, Fabienne; Gimenez-Fourage, Sophie; Dubayle, Joseline; Arnaud-Barbe, Nadège; Hessler, Catherine; Caillet, Catherine

2017-11-01

In clinical trials of cytomegalovirus (CMV) glycoprotein B (gB) vaccines, CMV infection is detected by first depleting serum of anti-gB antibodies and then measuring anti-CMV antibodies with a commercially available enzyme-linked immunosorbent assay (ELISA) kit, with confirmation of positive findings by immunoblot. Identification of CMV immunoantigens for the development of an ELISA that detects specifically CMV infection in clinical samples from individuals immunized with gB vaccines. Sensitivity and specificity of ELISAs using antigenic regions of CMV proteins UL83/pp65, UL99/pp28, UL44/pp52, UL80a/pp38, UL57, and UL32/pp150 were measured. An IgG ELISA using a UL32/pp150 [862-1048] capture peptide was the most specific (93.7%) and sensitive (96.4%) for detecting CMV-specific antibodies in sera. The ELISA successfully detected CMV-specific antibodies in 22 of 22 sera of subjects who had been vaccinated with a gB vaccine but who had later been infected with CMV. The ELISA was linear over a wide range of CMV concentrations (57-16,814 ELISA units/mL) and was reproducible as indicated by a 5% intra-day and 7% inter-day coefficients of variation. The signal was specifically competed by UL32/pp150 [862-1048] peptide but not by CMV-gB or herpes simplex virus 2 glycoprotein D. Lipid and hemoglobin matrix did not interfere with the assay. The UL32/pp150 [862-1048] IgG ELISA can be used for the sensitive and specific detection of CMV infection in gB-vaccinated individuals. Copyright © 2017 Elsevier B.V. All rights reserved.

75 FR 8398 - Agency Information Collection Activities; Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-24

... Marilyn R. Abbott, Secretary to the Commission, U.S. International Trade Commission, 500 E Street, SW... complete. By order of the Commission. February 19, 2010. Marilyn R. Abbott, Secretary to the Commission...

Abbott Opinions #1-5.

ERIC Educational Resources Information Center

Education Law Center, Inc., Newark, NJ.

This document contains the following "Abbott Opinions": (1) "Early Childhood Education"; (2) "Adequate School Facilities"; (3) "Supplemental Programs and Whole School Reform in Elementary Schools"; (4) "Supplemental Programs in Middle and High Schools"; and (5) "Planning Programs and Budgets…

Significant IFNγ responses of CD8+ T cells in CMV-seropositive individuals with autoimmune arthritis.

PubMed

Almanzar, Giovanni; Schmalzing, Marc; Trippen, Raimund; Höfner, Kerstin; Weißbrich, Benedikt; Geissinger, Eva; Meyer, Thomas; Liese, Johannes; Tony, Hans-Peter; Prelog, Martina

2016-04-01

Latent Cytomegalovirus (CMV) infection accelerates immunosenescence in elderly with reactivations reported in Rheumatoid Arthritis (RA) and abnormal responses towards CMV in Juvenile Idiopathic Arthritis (JIA). Considering the signs of premature T-cell immunosenescence in arthritis patients, the known effect of CMV latency on speeding up many of these signs in an age-dependent manner and the role of CMV on IFNγ-mediated inflammation in healthy elderly and RA, we hypothesized that latent CMV infection accelerates TCR repertoire restriction, loss of CD28, peripheral T-cell proliferation and aberrant IFNγ responses in arthritis patients. Unspecific and CMVpp65-specific IFNγ responses were investigated in peripheral CD8+ T-cells in RA or JIA patients and healthy, age-matched controls. Despite higher prevalence and concentrations of IgG-anti-CMV, arthritis patients showed lower unspecific IFNγ production, lower CD69-mediated activation and lower CD8+ T-cell proliferation. CMV-seropositive RA patients showed higher intracellular IFNγ production and increased proportions of CD28-CD8+ T-cells after specific CMVpp65 long-term stimulation which was not altered by in vitro blockade of TNFα or IL-6. A skewed TCR repertoire towards oligoclonality and less polyclonality was found in JIA. CMVpp65-specific IFNγ production with expansion of CD28-CD8+ T-cells suggests an efficient control of latent CMV regardless of immunosuppressive therapy or in vitro blockade of TNFα or IL-6 in CMV-seropositive arthritis patients. Increased IgG-anti-CMV antibody concentrations and increased proportions of intracellular IFNγ-producing CMVpp65-specific CD8+ T-cells in long-term cultures propose a possibly role of endogenous CMV reactivations boosting antibody levels and a higher possibly CMV-driven IFNγ-mediated inflammatory potential of CD8+ T-cells in arthritis patients. Copyright © 2016 Elsevier B.V. All rights reserved.

Unique and Highly Selective Anticytomegalovirus Activities of Artemisinin-Derived Dimer Diphenyl Phosphate Stem from Combination of Dimer Unit and a Diphenyl Phosphate Moiety

PubMed Central

He, Ran; Forman, Michael; Mott, Bryan T.; Venkatadri, Rajkumar; Posner, Gary H.

2013-01-01

We report that the artemisinin-derived dimer diphenyl phosphate (DPP; dimer 838) is the most selective inhibitor of human cytomegalovirus (CMV) replication among a series of artemisinin-derived monomers and dimers. Dimer 838 was also unique in being an irreversible CMV inhibitor. The peroxide unit within artemisinins' chemical structures is critical to their activities, and its absence results in loss of anti-CMV activities. Surprisingly, the deoxy dimer of 838 retained modest anti-CMV activity, suggesting that the DPP moiety of dimer 838 contributes to its anti-CMV activities. DPP alone did not inhibit CMV replication, but triphenyl phosphate (TPP) had modest CMV inhibition, although its selectivity index was low. Artemisinin DPP derivatives dimer 838 and monomer diphenyl phosphate (compound 558) showed stronger CMV inhibition and a higher selectivity index than their analogs lacking the DPP unit. An add-on and removal assay revealed that removing DPP derivatives (compounds 558 and 838) but not the non-DPP backbones (artesunate and compound 606) at 24 h postinfection (hpi) already resulted in dominant CMV inhibition. CMV inhibition was fully irreversible with 838 and partially irreversible with 558, while non-DPP artemisinins were reversible inhibitors. While all artemisinin derivatives and TPP reduced the expression of the CMV immediate early 2 (IE2), UL44, and pp65 proteins at or after 48 hpi, only TPP inhibited the expression of both IE1 and IE2. Combination of a non-DPP dimer (compound 606) with TPP was synergistic in CMV inhibition, while ganciclovir and TPP were additive. Although TPP shared structural similarity with monomer DPP (compound 558) and dimer DPP (compound 838), its pattern of CMV inhibition was significantly different from the patterns of the artemisinins. These findings demonstrate that the DPP group contributes to the unique activities of compound 838. PMID:23774439

Dendritic Cells Enhance Polyfunctionality of Adoptively Transferred T Cells That Target Cytomegalovirus in Glioblastoma.

PubMed

Reap, Elizabeth A; Suryadevara, Carter M; Batich, Kristen A; Sanchez-Perez, Luis; Archer, Gary E; Schmittling, Robert J; Norberg, Pamela K; Herndon, James E; Healy, Patrick; Congdon, Kendra L; Gedeon, Patrick C; Campbell, Olivia C; Swartz, Adam M; Riccione, Katherine A; Yi, John S; Hossain-Ibrahim, Mohammed K; Saraswathula, Anirudh; Nair, Smita K; Dunn-Pirio, Anastasie M; Broome, Taylor M; Weinhold, Kent J; Desjardins, Annick; Vlahovic, Gordana; McLendon, Roger E; Friedman, Allan H; Friedman, Henry S; Bigner, Darell D; Fecci, Peter E; Mitchell, Duane A; Sampson, John H

2018-01-01

Median survival for glioblastoma (GBM) remains <15 months. Human cytomegalovirus (CMV) antigens have been identified in GBM but not normal brain, providing an unparalleled opportunity to subvert CMV antigens as tumor-specific immunotherapy targets. A recent trial in recurrent GBM patients demonstrated the potential clinical benefit of adoptive T-cell therapy (ATCT) of CMV phosphoprotein 65 (pp65)-specific T cells. However, ex vivo analyses from this study found no change in the capacity of CMV pp65-specific T cells to gain multiple effector functions or polyfunctionality, which has been associated with superior antitumor efficacy. Previous studies have shown that dendritic cells (DC) could further enhance tumor-specific CD8 + T-cell polyfunctionality in vivo when administered as a vaccine. Therefore, we hypothesized that vaccination with CMV pp65 RNA-loaded DCs would enhance the frequency of polyfunctional CMV pp65-specific CD8 + T cells after ATCT. Here, we report prospective results of a pilot trial in which 22 patients with newly diagnosed GBM were initially enrolled, of which 17 patients were randomized to receive CMV pp65-specific T cells with CMV-DC vaccination (CMV-ATCT-DC) or saline (CMV-ATCT-saline). Patients who received CMV-ATCT-DC vaccination experienced a significant increase in the overall frequencies of IFNγ + , TNFα + , and CCL3 + polyfunctional, CMV-specific CD8 + T cells. These increases in polyfunctional CMV-specific CD8 + T cells correlated ( R = 0.7371, P = 0.0369) with overall survival, although we cannot conclude this was causally related. Our data implicate polyfunctional T-cell responses as a potential biomarker for effective antitumor immunotherapy and support a formal assessment of this combination approach in a larger randomized study. Significance: A randomized pilot trial in patients with GBM implicates polyfunctional T-cell responses as a biomarker for effective antitumor immunotherapy. Cancer Res; 78(1); 256-64. ©2017 AACR . ©2017 American Association for Cancer Research.

The cognate coat protein is required for cell-to-cell movement of a chimeric brome mosaic virus mediated by the cucumber mosaic virus movement protein.

PubMed

Nagano, H; Mise, K; Okuno, T; Furusawa, I

1999-12-20

Cucumber mosaic cucumovirus (CMV) and brome mosaic bromovirus (BMV) have many similarities, including the three-dimensional structure of virions, genome organizations, and requirement of the coat protein (CP) for cell-to-cell movement. We have shown that a chimeric BMV with the CMV 3a movement protein (MP) gene instead of its own cannot move from cell to cell in Chenopodium quinoa, a common permissive host for both BMV and CMV. Another chimeric BMV was constructed by replacing both MP and CP genes of BMV with those of CMV (MP/CP-chimera) and tested for its infectivity in C. quinoa, to determine whether the CMV CP has some functions required for the CMV MP-mediated cell-to-cell movement and to exhibit functional difference between CPs of BMV and CMV. Cell-to-cell movement of the MP/CP-chimera occurred, and small local lesions were induced on the inoculated leaves. A frameshift mutation introduced in the CMV CP gene of the MP/CP-chimera resulted in a lack of cell-to-cell movement of the chimeric virus. These results indicate that the viral movement mediated by the CMV MP requires its cognate CP. Deletion of the amino-terminal region in CMV CP, which is not obligatory for CMV movement, also abolished cell-to-cell movement of the MP/CP-chimera. This may suggest some differences in cell-to-cell movement of the MP/CP-chimera and CMV. On the other hand, the sole replacement of BMV CP gene with that of CMV abolished viral cell-to-cell movement, suggesting a possibility that the viral movement mediated by the BMV MP may also require its cognate CP. Functional compatibility between MP and CP in viral cell-to-cell movement is discussed. Copyright 1999 Academic Press.

Correlation between viral loads of cytomegalovirus in blood and bronchoalveolar lavage specimens from lung transplant recipients determined by histology and immunohistochemistry.

PubMed

Chemaly, Roy F; Yen-Lieberman, Belinda; Castilla, Elias A; Reilly, Amy; Arrigain, Susana; Farver, Carol; Avery, Robin K; Gordon, Steven M; Procop, Gary W

2004-05-01

Cytomegalovirus (CMV) is an important pathogen in lung transplant recipients. Early detection of CMV end-organ disease should help with treatment management. We determined the CMV viral load by hybrid capture in bronchoalveolar lavage (BAL) fluid samples from patients who had undergone lung transplantation. For 39 of these samples (from 25 patients), corresponding transbronchial biopsy samples were available for CMV immunohistochemistry (IHC). The CMV IHC results were interpreted and categorized as positive or negative, and the positive results were subcategorized as typical if cells with both significant nuclear enlargement or Cowdry A-type inclusions and positive staining were present or as atypical if definitive nuclear staining was seen but significant nuclear enlargement was not. Diagnostic CMV viral inclusions were reported in the anatomic diagnosis, based on hematoxylin-eosin staining alone, for three (8%) of the biopsy samples. CMV was detected by IHC in 13 (33%) samples (5 typical, 8 atypical). The median CMV viral load in BAL samples was 0 copies/ml for BAL samples from patients with IHC-negative biopsy samples; 47,678 copies/ml for BAL samples from patients with biopsy samples with positive, atypical staining; and 1,548,827 copies/ml for BAL samples from patients with biopsy samples with positive, typical staining (P < 0.001). Compared to routine pathology of biopsy samples, the use of IHC increased the diagnostic yield of CMV. Also, the CMV viral load in BAL fluid samples increased along with immunoreactivity from negative to positive, atypical staining to positive, typical staining. The CMV viral load determined with the end-organ sample, the BAL fluid sample, was higher than the corresponding viral load determined with blood. Both IHC and determination of the CMV viral load in BAL samples may be useful for the detection of individuals at risk for the development of fulminant invasive CMV disease.

Cytomegalovirus Retinitis in Three Pediatric Cases with Acute Lymphoblastic Leukemia: Case Series and Review of the Literature.

PubMed

Demir, Sevliya Öcal; Çeliker, Hande; Karaaslan, Ayşe; Kadayifci, Eda Kepenekli; Akkoç, Gülşen; Atıcı, Serkan; Yakut, Nurhayat; Şenay, Emel; Kazokoğlu, Haluk; Koç, Ahmet; Bakır, Mustafa; Soysal, Ahmet

2016-11-22

Cytomegalovirus (CMV) retinitis is typically diagnosed in patient with AIDS and those who underwent allogeneic hematopoietic cell transplant. However, it may develop in patients with acute lymphoblastic leukemia (ALL) who have not undergone hematopoietic cell transplantation. To increase awareness of CMV retinitis in this group, we describe 3 patients ages 3, 9, and 12, with ALL who developed CMV retinitis. The diagnosis of CMV retinitis was made on the basis of ophthalmological findings suggesting typical retinal lesions. In 2 cases, CMV DNAemia was present, while in 1 patient CMV DNA was detected only in vitreous fluid using the PCR technique. All cases were treated with intravenous ganciclovir for 2 or 3 weeks as induction therapy, followed by oral valganciclovir prophylaxis. Initially, active retinitis lesions resolved in all cases; however, in 1 patient CMV retinitis relapsed 3 times during follow-up. In this case, by using foscarnet therapy, satisfactory responses were achieved and the progression of CMV retinitis lesions stopped and eventually regressed.

The incidence of cytomegalovirus (CMV) antigenemia and CMV disease is reduced by highly active antiretroviral therapy.

PubMed

Varani, S; Spezzacatena, P; Manfredi, R; Chiodo, F; Mastroianni, A; Ballarini, P; Boschini, A; Lazzarotto, T; Landini, M P

2000-05-01

Cytomegalovirus (CMV) infection was one of the most common opportunistic infections in AIDS patients, leading to blindness or life-threatening disease in about 40% of patients in the later stages of AIDS before highly active antiretroviral therapy (HAART). In a retrospective multicenter study we investigated the incidence of CMV retinitis and organ involvement in Northern Italy before (1995 and 1996) and after the introduction of HAART (1997 and 1998) as well as the data regarding CMV antigenemia. We found a sharp drop in the incidence of CMV disease in AIDS patients as well as a decline in the incidence of relapses of CMV-disease after the widespread introduction of HAART. Moreover, there was a decrease in the incidence of antigenemia-positive cases in AIDS patients in the era of HAART and the median CMV viral load was significantly higher in patients who didn't receive HAART than in patients who received HAART (p = 0.001, t test).

Reversibility of peripheral blood leukocyte phenotypic and functional changes after exposure to and withdrawal from tofacitinib, a Janus kinase inhibitor, in healthy volunteers.

PubMed

Weinhold, Kent J; Bukowski, Jack F; Brennan, Todd V; Noveck, Robert J; Staats, Janet S; Lin, Liwen; Stempora, Linda; Hammond, Constance; Wouters, Ann; Mojcik, Christopher F; Cheng, John; Collinge, Mark; Jesson, Michael I; Hazra, Anasuya; Biswas, Pinaki; Lan, Shuping; Clark, James D; Hodge, Jennifer A

2018-06-01

This study evaluated the short-term effects of tofacitinib treatment on peripheral blood leukocyte phenotype and function, and the reversibility of any such effects following treatment withdrawal in healthy volunteers. Cytomegalovirus (CMV)-seropositive subjects received oral tofacitinib 10 mg twice daily for 4 weeks and were followed for 4 weeks after drug withdrawal. There were slight increases in total lymphocyte and total T-cell counts during tofacitinib treatment, and B-cell counts increased by up to 26%. There were no significant changes in granulocyte or monocyte counts, or granulocyte function. Naïve and central memory T-cell counts increased during treatment, while all subsets of activated T cells were decreased by up to 69%. T-cell subsets other than effector memory cluster of differentiation (CD)4+, activated naïve CD4+ and effector CD8+ T-cell counts and B-cell counts, normalized 4 weeks after withdrawal. Following ex vivo activation, measures of CMV-specific T-cell responses, and antigen non-specific T-cell-mediated cytotoxicity and interferon (IFN)-γ production, decreased slightly. These T-cell functional changes were most pronounced at Day 15, partially normalized while still on tofacitinib and returned to baseline after drug withdrawal. Total natural killer (NK)-cell counts decreased by 33%, returning towards baseline after drug withdrawal. NK-cell function decreased during tofacitinib treatment, but without a consistent time course across measured parameters. However, markers of NK-cell-mediated cytotoxicity, antibody-dependent cellular cytotoxicity and IFN-γ production were decreased up to 42% 1 month after drug withdrawal. CMV DNA was not detectable in whole blood, and there were no cases of herpes zoster reactivation. No new safety concerns arose. In conclusion, the effect of short-term tofacitinib treatment on leukocyte composition and function in healthy CMV+ volunteers is modest and largely reversible 4 weeks after withdrawal. Copyright © 2018 Pfizer Inc. Published by Elsevier Inc. All rights reserved.

Assessment of hydrologic and water quality data collected in Abbotts Lagoon watershed, Point Reyes National Seashore, California, during water years 1999 and 2000

USGS Publications Warehouse

Kratzer, Charles R.; Saleh, Dina K.; Zamora, Celia

2006-01-01

Abbotts Lagoon is part of Point Reyes National Seashore, located about 40 miles northwest of San Francisco and about 20 miles south of Bodega Bay. Water-quality samples were collected quarterly during water year 1999 at a site in each of three connected lagoons that make up Abbotts Lagoon and at a site in its most significant tributary. The quarterly samples were analyzed for major ions, nutrients, and chlorophyll-a. A bed-sediment sample was collected in each lagoon during August 1999 and was analyzed for organic carbon, iron, and total phosphorus. Seven tributaries were sampled during a February 1999 storm and four during an April 1999 storm. These samples were analyzed only for nutrients. One storm sample collected in April 1999 from a tributary downstream of the I Ranch dairy was analyzed for a suite of 47 compounds indicative of wastewater. Continuous water-level recorders were installed in the most significant tributary and the two largest lagoons for portions of the study. A water budget analysis for an April 2000 storm indicated that the main tributary accounted for 85 percent of surface inflows to Abbotts Lagoon. The portion of the surface inflow from the main tributary was lower in the February 1999 storms and is a function of upstream storage and vegetative growth in the tributary basins. Another water budget analysis for a period of no surface inflow (June and July 2000) indicated that the net ground-water contribution was an outflow (seepage) from Abbotts Lagoon of about 0.3 ft3/s. Salinity increased and nutrient concentrations decreased from upstream to downstream in the chain of lagoons. The lower lagoon, nearest the ocean, had less organic carbon and total phosphorus in the bed sediment than the upper lagoons. The two tributaries originating in the I Ranch dairy had the highest concentrations of nutrients in storm runoff, and the highest loading rates and yields of ammonia and phosphorus. These tributaries account for only 10.3 percent of the area drained by the sampled tributaries, but contributed 83 percent of the ammonia load and 79 percent of the orthophosphate load. The basins with the highest nutrient loading rates and yields had the highest percentage of dairy and (or) ranching impacted land use and, to a lesser extent, grazing land use. The ratios of inorganic nitrogen to phosphorus in the lagoons ranged from 0.1 to 9.5 in the upper lagoon, 0.10 to 0.15 in the middle lagoon, and 0.05 to 0.10 in the lower lagoon. Thus, there is an abundance of phosphorus in the lagoons, and nitrogen appears to be limiting the growth of phytoplankton. Two sterols indicative of fecal material were among 11 compounds detected in the sample collected for analysis of wastewater indicators from a tributary downstream of the I Ranch dairy.

Preemptive Therapy Prevents Cytomegalovirus End-Organ Disease in Treatment-Naïve Patients with Advanced HIV-1 Infection in the HAART Era

PubMed Central

Mizushima, Daisuke; Nishijima, Takeshi; Gatanaga, Hiroyuki; Tsukada, Kunihisa; Teruya, Katsuji; Kikuchi, Yoshimi; Oka, Shinichi

2013-01-01

Background The efficacy of preemptive therapy against cytomegalovirus (CMV) infection remains unknown in treatment-naïve patients with advanced HIV-1 infection in the HAART era. Methods The subjects of this single-center observation study were126 treatment-naïve HIV-1 infected patients with positive CMV viremia between January 1, 2000 and December 31, 2006. Inclusion criteria were age more than 17 years, CD4 count less than 100/μl, plasma CMV DNA positive, never having received antiretroviral therapy (ART) and no CMV end-organ disease (EOD) at first visit. The incidence of CMV-EOD was compared in patients with and without preemptive therapy against CMV-EOD. The effects of the CMV preemptive therapy were estimated in uni- and multivariate Cox hazards models. Results CMV-EOD was diagnosed in 30 of the 96 patients of the non-preemptive therapy group (31%, 230.3 per 1000 person-years), compared with 3 of the 30 patients of the preemptive therapy group (10%, 60.9 per 1000 person-years). Univariate (HR = 0.286; 95%CI, 0.087–0.939; p = 0.039) and multivariate (adjusted HR = 0.170; 95%CI, 0.049–0.602; p = 0.005) analyses confirmed that CMV-EOD is significantly prevented by CMV preemptive therapy. Multivariate analysis showed that plasma CMV DNA level correlated significantly with CMV-EOD (per log10/ml, adjusted HR = 1.941; 95%CI, 1.266–2.975; p = 0.002). Among the 30 patients on preemptive therapy, 7 (23.3%) developed grade 3–4 leukopenia. The mortality rate was not significantly different between the two groups (p = 0.193, Log-rank test). Conclusions The results indicate that preemptive therapy lowers the incidence of CMV-EOD by almost 25%. Preemptive therapy for treatment-naïve patients with CMV viremia is effective, although monitoring of potential treatment-related side effects is required. PMID:23724140

Cohort study on maternal cytomegalovirus seroprevalence and prevalence and clinical manifestations of congenital infection in China

PubMed Central

Wang, Shiwen; Wang, Tongzhan; Zhang, Wenqiang; Liu, Xiaolin; Wang, Xiaofang; Wang, Haiyan; He, Xiaozhou; Zhang, Shunxian; Xu, Shuhui; Yu, Yang; Jia, Xingbing; Wang, Maolin; Xu, Aiqiang; Ma, Wei; Amin, Minal M.; Bialek, Stephanie R.; Dollard, Sheila C.; Wang, Chengbin

2017-01-01

Abstract Congenital cytomegalovirus (CMV) infection is the leading viral cause of birth defects and developmental disabilities in developed countries. However, CMV seroprevalence and burden of congenital CMV infection are not well defined in China. Cohort of newborns from 5 birthing hospitals in 2 counties of Shandong Province, China, were enrolled from March 2011 to August 2013. Dried blood spots (DBS) and saliva were collected within 4 days after birth for IgG testing for maternal seroprevalence and real-time PCR testing for congenital CMV infection, respectively. Among 5020 newborns tested for CMV IgG, 4827 were seropositive, resulting in CMV maternal seroprevalence of 96.2% (95% confidence interval [CI]:95.6%–96.7%). Of the 10,933 newborns screened for congenital CMV infection, 75 had CMV detected, resulting in an overall prevalence of 0.7% (95% CI: 0.5%–0.9%), with prevalences of 0.4% (14/3995), 0.6% (66/10,857), and 0.7% (52/7761) for DBS, wet saliva, and dried saliva specimens screened, respectively. Prevalence of congenital CMV infection decreased with increasing maternal age (0.9%, 0.6%, and 0.3% among newborns delivered from mothers aged 16–25, 26–35, and >35 years, respectively; P = 0.03), and was higher among preterm infants than full term infants (1.3% vs 0.6%, P = 0.04), infants with intrauterine growth restriction (IUGR) than those without (1.8% vs 0.7%, P = 0.03), and twins or triplets than singleton pregnancies (2.8% vs 0.7%, P = 0.04). None of the 75 newborns exhibited symptomatic congenital CMV infection, and there was no difference in clinical characteristics and newborn hearing screening results between infants with and without congenital CMV infection at birth. Congenital CMV infection prevalence was lower and the clinical manifestations were milder in this relatively developed region of China compared to populations from other countries with similarly high maternal seroprevalence. Follow-up on children with congenital CMV infection will clarify the burden of disabilities from congenital CMV infection in China. PMID:28151899

Frequent occurrence of therapeutically reversible CMV-associated encephalopathy during radiotherapy of the brain.

PubMed

Goerig, Nicole L; Frey, Benjamin; Korn, Klaus; Fleckenstein, Bernhard; Überla, Klaus; Schmidt, Manuel A; Dörfler, Arnd; Engelhorn, Tobias; Eyüpoglu, Ilker; Rühle, Paul F; Putz, Florian; Semrau, Sabine; Gaipl, Udo S; Fietkau, Rainer

2016-12-01

Neurological decline during radio(chemo)therapy of the brain is often attributed to disease progression or side effects of radiotherapy. Diagnosis of opportunistic neurotropic infections such as cytomegalovirus (CMV) infections is uncommon, even though high-grade gliomas and some brain metastases are known to contain CMV particles. We prospectively examined the frequency of CMV encephalopathy during radiotherapy of the brain. Fifty patients requiring whole-brain radiotherapy for brain metastases (n = 27) or local radio(chemo)therapy of the brain for high-grade gliomas (n = 23) were observed in the prospective observational GLIO-CMV-01 study. MRIs and blood samples were obtained before, halfway through, and at the end of radiotherapy. MRIs were screened for disease progression or increased intracranial pressure. Blood was tested for anti-CMV immunoglobulin (Ig)M, anti-CMV IgG, and CMV DNA. Thirty-two of 50 (64%) patients were positive for anti-CMV IgG before radio(chemo)therapy. Fifteen of those 32 (48%) developed viremia during or up to 28 days after treatment. Thirteen of those 15 (87%) required treatment for CMV-associated encephalopathy. MRIs were negative for disease progression, edema, or bleeding. None of the patients negative for anti-CMV IgG developed viremia, suggesting a reactivation rather than a primary infection.In the group at risk consisting of anti-CMV IgG+ patients, age >65 (P = .004) and the amount of dexamethasone taken during radio(chemo)therapy (P = .004) were associated with an increased risk for CMV-associated encephalopathy. One hundred and fifty days after the start of radio(chemo)therapy, survival was 74% (14/19) (no encephalopathy) versus 54% (7/13) (encephalopathy) (odds ratio, 0.42; 95% CI, 0.03-1.86; P = .25). CMV reactivation frequently causes encephalopathy during radio(chemo)therapy of the brain. The unexpected high incidence of this infection makes it highly clinically relevant for every treating physician. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A case of cytomegalovirus colitis following immunosuppressive treatment for pyoderma gangrenosum.

PubMed

Kikuchi, Hidezumi; Nagamine, Hidehiro; Setoyama, Mitsuru

2005-04-01

We report a case of pyoderma gangrenosum (PG) complicated by cytomegalovirus (CMV)-induced colitis. A 79-year-old woman with PG was treated with corticosteroid and cyclosporin. She had blood in her stool and advancing anemia during the treatment. A colonoscopic biopsy specimen from the colon revealed typical CMV-infected cells with CMV inclusions confirmed by immunohistochemistry. Furthermore, there were many CMV-antigen-positive leukocytes, suggesting an active CMV infection, which is serious in compromised hosts. Although ulcerative colitis and Crohn's disease are well known as complications of PG, CMV enterocolitis should be considered in the differential diagnosis of enterocolitis in immunocompromised patients.

Bilateral intraocular calcification in necrotizing cytomegalovirus retinitis.

PubMed

Tuncer, Samuray; Oray, Merih; Yildirim, Yeliz; Camcioglu, Yildiz; Tugal-Tutkun, Ilknur

2014-10-01

We report a unique case of bilateral intraocular calcification due to necrotizing cytomegalovirus (CMV) retinitis associated with congenital CMV infection. A 7-month-old boy with a history of congenital CMV infection showed bilateral intraocular calcific plaques on computed tomography (CT) and ultrasonography. We reviewed the patient's medical files for the purpose of this report. The patient had a prior medical history of hospitalization for fever and swelling in the neck at 3 months of age. Systemic findings (anemia, neutropenia, hepatosplenomegaly, and reactive lymphadenomegaly) in association with a low CD4 count, high blood CMV viral load, and positivity for urine CMV DNA by polymerase chain reaction led to the diagnosis of bone marrow suppression and congenital CMV infection. At 7 months, he developed horizontal nystagmus and bilateral leukocoria over 20 days. Cranial CT and ultrasonography revealed bilateral intraocular calcific plaques and the patient was referred to rule out retinoblastoma. Fundoscopy was consistent with bilateral hemorrhagic, necrotizing CMV retinitis. Significant resolution of the retinal infiltrations occurred 2 weeks after initiation of systemic treatment with ganciclovir. Intraocular calcification may be a sign of active CMV retinitis. To our knowledge this is the first report of bilateral intraocular calcification serving as the presenting clinical manifestation of necrotizing CMV retinitis.

An overview of the infection of CMV, HSV 1/2 and EBV in Mexican patients with glioblastoma multiforme.

PubMed

Zavala-Vega, Sergio; Castro-Escarpulli, Graciela; Hernández-Santos, Hector; Salinas-Lara, Citlatepetl; Palma, Icela; Mejía-Aranguré, Juan Manuel; Gelista-Herrera, Noemí; Rembao-Bojorquez, Daniel; Ochoa, Sara A; Cruz-Córdova, Ariadnna; Xicohtencatl-Cortes, Juan; Uribe-Gutiérrez, Gabriel; Arellano-Galindo, José

2017-03-01

Several risk factors are involved in glioblastoma, including cytomegalovirus (CMV). This research was carried out to determine the rate of CMV infection, as well as HSV 1/2 and EBV in brain tissue, in patients with glioblastomamultiforme (GBM). The tissues were tested using immunohistochemistry, PCR, in situ hybridization and real-time PCR. At least, one HHV was detected in 21/29 (72%) patients as follows: single infections with HSV-1/2 in 4/21 (19%), EBV in 6/21 (28.6%) and CMV in 1/21 (4.8%). Mixed viral infection, HSV-1/2 and EBV were detected in 4/21 patients (19%), CMV and EBV in 5/21 (23.8%), and HSV-1/2, EBV, and CMV in 1/21. The CMV viral load ranged from 3×10 2 to 4.33×10 5 genome/100ng of tissue. Genotype based on CMV gB was 3/7 where 2/3 was gB1 and 1/3 gB4. HSV, EBV and CMV were frequently found in brain tissues, more in mix in a population reported as highly seropositive. Copyright © 2017 Elsevier GmbH. All rights reserved.

Active CMV infection before lung transplantation: risk factors and clinical implications.

PubMed

Milstone, A P; Brumble, L M; Loyd, J E; Ely, E W; Roberts, J R; Pierson, R N; Dummer, J S

2000-08-01

Cytomegalovirus (CMV) infection is a major cause of morbidity following lung transplantation, but active CMV infection has not been described before transplantation. Since 1990, we have screened all lung-transplant recipients for CMV infection with viral urine cultures on the day of transplantation. We retrospectively reviewed the medical records of all 102 lung-allograft recipients transplanted between March 1990 and September 1998. Patients with positive urine cultures for CMV were compared to culture negative patients for age, gender, pretransplant diagnosis, time from diagnosis to transplantation, CMV serostatus, use of pretransplant immunosuppression, T-lymphocyte subsets, and presence of fever. Posttransplant outcomes assessed were duration of intubation and hospitalization, acute rejection, frequency of CMV disease, duration of Nashville rabbit antithymocyte serum or globulin (N-RATS/G) and ganciclovir, and survival. Five (5%) of 102 patients had positive urine cultures for CMV; none had symptoms of CMV infection. All 5 had idiopathic pulmonary fibrosis (IPF) (5/5 vs 27/97; p = 0.002). The age, gender, and CMV serostatus of these patients did not differ from the 97 patients in the culture negative group. Four (80%) of the 5 patients with positive cultures were receiving treatment with azathioprine or cyclophosphamide vs only 18 (19%) of the 97 patients with negative cultures (p = 0.007), and all 5 (100%) were receiving steroids compared to 50 (52%) of 97 patients with negative cultures (p = 0.06). Culture-positive IPF patients, when compared with the 27 culture-negative IPF patients, did not differ in any demographic variable or in the use of immunosuppression, but culture-positive patients were more likely to have a CD4/CD8 T-cell subset ratio <1.0 (p = 0.02). Following transplantation, 3 (60%) of 5 IPF patients with positive CMV cultures developed CMV disease compared to 3 (11%) of 27 IPF patients with negative cultures (p = 0.03). Patients with positive cultures also received more days of parenteral antiviral therapy (mean 44 +/- 11 days vs 16 +/- 10 days; p < 0.001). Utilizing pretransplant screening, we have discovered that 16% of patients with IPF had active CMV infection, which was associated with both alterations in their T-cell subsets and a greater risk for CMV disease after transplantation. This occurrence of occult CMV infection in patients with IPF has not been previously recognized, and has important implications.

The Performance of the Abbott i2000 for Measuring Serum Markers of Infectious Diseases.

PubMed

Wang, Linchuan; Chen, Wei; Yu, Yan

2017-01-01

To date, there is a trend that the chemiluminescent microparticle immunoassays (CMIA) and electrochemiluminescence immunoassays (ECIA) technology gradually replacing the enzyme-linked immunosorbent assay (ELISA). But the performance such as the limit of quantitation (LOQ), precision, linear range of CMIA, or ECIA for serum markers of infectious diseases has rarely been reported. Using proficiency testing samples and standard materials, we confirmed the LOQ of the ELISA and the precision, linear range, LOQ, and instrument biases of the Abbott i2000 for eight serum markers. We used the Abbott i2000 and ELISAs to assess five HIV samples; the researchers were blinded to the true status of the samples. For the Abbott i2000, the coefficients of variation (CV) for the low, medium, and high concentration samples ranged from 1.06 to 12.74%, which were less than the allowable error; the linear ranges of HBsAg and HBsAb were 0.66-304.11 IU/ml and 8.16-1205.9 mIU/ml, respectively. For the Abbott i2000, the LOQs of HBsAg, HBsAb, HBeAg, HBeAb, HBcAb, anti-HCV, anti-TP, and anti-HIV were 0.026 IU/ml, 4 mIU/ml, 0.14 NCU/ml, 0.56 NCU/ml, 0.99 NCU/ml, 0.5 NCU/ml, 8.8 mIU/ml, and 1.92 NCU/ml, respectively, and these values were 0.16 IU/ml, 6.97 mIU/ml, 1.16 NCU/ml, 1.63 NCU/ml, 1.79 NCU/ml, 1.03 NCU/ml, 8.33 mIU/ml, and 1.3 NCU/ml, respectively, for the ELISA. When five HIV samples were blindly assessed, two cases were missed by the Abbott i2000 and the ELISA results were consistent with the expected results. The Abbott i2000 performed significantly better than the ELISA on HBV and HCV screening; however, for anti-TP and anti-HIV, the ELISA remained the preferred method. © 2016 Wiley Periodicals, Inc.

Evaluation of the Abbott Real Time HCV genotype II assay for Hepatitis C virus genotyping.

PubMed

Sariguzel, Fatma Mutlu; Berk, Elife; Gokahmetoglu, Selma; Ercal, Baris Derya; Celik, Ilhami

2015-01-01

The determination of HCV genotypes and subtypes is very important for the selection of antiviral therapy and epidemiological studies. The aim of this study was to evaluate the performance of Abbott Real Time HCV Genotype II assay in HCV genotyping of HCV infected patients in Kayseri, Turkey. One hundred patients with chronic hepatitis C admitted to our hospital were evaluated between June 2012 and December 2012, HCV RNA levels were determined by the COBAS® AmpliPrep/COBAS® TaqMan® 48 HCV test. HCV genotyping was investigated by the Abbott Real Time HCV Genotype II assay. With the exception of genotype 1, subtypes of HCV genotypes could not be determined by Abbott assay. Sequencing analysis was used as the reference method. Genotypes 1, 2, 3 and 4 were observed in 70, 4, 2 and 24 of the 100 patients, respectively, by two methods. The concordance between the two systems to determine HCV major genotypes was 100%. Of 70 patients with genotype 1, 66 showed infection with subtype 1b and 4 with subtype 1a by Abbott Real Time HCV Genotype II assay. Using sequence analysis, 61 showed infection with subtype 1b and 9 with subtype 1a. In determining of HCV genotype 1 subtypes, the difference between the two methods was not statistically significant (P>0.05). HCV genotype 4 and 3 samples were found to be subtype 4d and 3a, respectively, by sequence analysis. There were four patients with genotype 2. Sequence analysis revealed that two of these patients had type 2a and the other two had type 2b. The Abbott Real Time HCV Genotype II assay yielded results consistent with sequence analysis. However, further optimization of the Abbott Real Time HCV Genotype II assay for subtype identification of HCV is required.

49 CFR 350.105 - What definitions are used in this part?

Code of Federal Regulations, 2013 CFR

2013-10-01

..., Administrative Takedown, and Incentive Funds. Commercial motor vehicle (CMV) means a motor vehicle that has any...) means the document outlining the State's CMV safety objectives, strategies, activities and performance... projects that improve CMV safety and compliance with CMV safety regulations (including activities and...

49 CFR 350.105 - What definitions are used in this part?

Code of Federal Regulations, 2014 CFR

2014-10-01

..., Administrative Takedown, and Incentive Funds. Commercial motor vehicle (CMV) means a motor vehicle that has any...) means the document outlining the State's CMV safety objectives, strategies, activities and performance... projects that improve CMV safety and compliance with CMV safety regulations (including activities and...

49 CFR 350.105 - What definitions are used in this part?

Code of Federal Regulations, 2012 CFR

2012-10-01

..., Administrative Takedown, and Incentive Funds. Commercial motor vehicle (CMV) means a motor vehicle that has any...) means the document outlining the State's CMV safety objectives, strategies, activities and performance... projects that improve CMV safety and compliance with CMV safety regulations (including activities and...

Refractory acute respiratory failure due to Pneumocystis jiroveci (PCP) and Cytomegalovirus (CMV) pneumonitis: A case report and review of literature.

PubMed

Shah, Kairav; Cherabuddi, Kartikeya; Beal, Stacy G; Kalyatanda, Gautam

2017-01-01

Opportunistic infections with Pneumocystis jiroveci pneumonia (PCP) are common in patients with HIV (human immunodeficiency virus) and are encountered once the CD4 count decreases below 200 cells/mm3. Cytomegalovirus (CMV) tends to cause disease once the CD4 count drops below 50 cells/mm3. CMV pneumonitis is not common in this population. However, detecting its presence in broncho-alveolar lavage (BAL) fluid has been associated with increased morbidity and mortality. The role of antiviral therapy against CMV remains unclear. We report a newly diagnosed HIV patient with a CD4 count of 44 cells/mm3 presenting with acute respiratory failure secondary to PCP that failed to respond to 3 weeks of standard therapy with trimethoprim-sulfamethoxazole and corticosteroids. He was later diagnosed to have a CMV co-infection causing pneumonitis with BAL cytology findings showing CMV cytopathic effects and PCP. Plasma CMV DNA PCR was 17,424 copies/mL. He responded well after introduction of intravenous ganciclovir. The presence of histopathologic changes demonstrating viral cytopathic effects on BAL cytology along with a high plasma CMV DNA PCR should raise the specificity for diagnosing CMV pneumonitis. True PCP and CMV pneumonitis can occur, and the addition of antiviral therapy with ganciclovir may benefit such patients in the right clinical scenario.

Evaluation of COBAS AmpliPrep/COBAS TaqMan CMV Test for use in hematopoietic stem cell transplant recipients.

PubMed

Ramanan, Poornima; Razonable, Raymund R

2017-07-01

Cytomegalovirus (CMV) is a common opportunistic infection that contributes to poor outcomes in hematopoietic stem cell transplant (HSCT) recipients. Prevention of CMV end-organ disease in allogeneic HSCT recipients is commonly achieved by preemptive antiviral therapy of asymptomatic CMV reactivation that is detected by serial nucleic acid testing (NAT). However, there was no standardized CMV NAT until the development of the World Health Organization (WHO) International Standard. Areas covered: This article provides a comprehensive review on COBAS AmpliPrep/TaqMan (CAP/CTM) CMV assay (Roche) and emphasizes the limitations in the clinical use of CMV NAT in HSCT recipients. Expert commentary: The CAP/CTM CMV Test is the first US FDA approved commercial quantitative NAT for CMV viral load monitoring of plasma samples in solid organ transplant and HSCT recipients. The CAP/CTM assay has wide linear range of DNA quantification and demonstrates colinearity to the WHO International Standard. Studies of CAP/CTM CMV assay in HSCT recipients are still limited, but are now being reported to define viral thresholds for diagnosis, surveillance and monitoring. Results from these early studies in HSCT recipients suggest that, while the WHO IS has improved the inter-laboratory result variances, there are still important factors that continue to contribute to assay variability. This lack of harmony among NAT highlights the need for further standardization.

Risk factors for treatment failures in patients receiving PCR-based preemptive therapy for CMV infection.

PubMed

Einsele, H; Hebart, H; Kauffmann-Schneider, C; Sinzger, C; Jahn, G; Bader, P; Klingebiel, T; Dietz, K; Löffler, J; Bokemeyer, C; Müller, C A; Kanz, L

2000-04-01

PCR-based preemptive therapy with ganciclovir has been shown to reduce the incidence of CMV disease after BMT. Failures of this treatment strategy are CMV disease and secondary non-viral infections. Eighty-six consecutive patients at high risk for CMV disease who received PCR-based preemptive therapy with ganciclovir were assessed for treatment failures and possible risk factors. Ganciclovir was initiated in 57 of 86 patients (66%). Only 28 of 86 (32%) patients received 4 or more weeks of ganciclovir. Recurrence of CMV infection after successful treatment was more frequent among recipients of a BMT from an unrelated compared to a sibling donor (P = 0.004). Three (3.5%) patients developed non-fatal early onset CMV disease and seven of 68 (10.3 %) late onset CMV disease (>100 days post transplant). Risk factors for late onset CMV disease were cGVHD (P = 0.0017) and duration of prior antiviral therapy >4 weeks (P = 0. 0073). The incidence of secondary non-viral infections was 28% with the duration of antiviral treatment being a significant risk factor for secondary bacterial (P = 0.0045) and invasive fungal infections (P = 0.006). Thus, PCR-based preemptive treatment with ganciclovir reduces early onset CMV disease, but the duration of antiviral therapy prior to day +100 is a significant risk factor for late onset CMV disease as well as secondary non-viral infections.

Recurrence of CMV Infection and the Effect of Prolonged Antivirals in Organ Transplant Recipients.

PubMed

Natori, Yoichiro; Humar, Atul; Husain, Shahid; Rotstein, Coleman; Renner, Eberhard; Singer, Lianne; Kim, S Joseph; Kumar, Deepali

2017-06-01

Although initial therapy for cytomegalovirus (CMV) is usually successful, a significant subset of patients may have recurrent viremia. However, the epidemiology and risk factors for recurrence have not been fully defined, as well as the utility of prolonged antivirals after initial clearance. Solid organ transplant patients with first episode of CMV disease or asymptomatic viremia (≥1000 IU/mL) requiring treatment were identified by chart review. Clinical and virologic data were collected. The primary outcome was recurrence of CMV viremia or disease within 6 months of treatment discontinuation. The first episode of CMV viremia requiring antiviral therapy was assessed in 282 patients (147 CMV disease and 135 asymptomatic viremia). Cytomegalovirus occurred at 5.6 (0.63-27.7) months posttransplant. Recurrent CMV occurred in 30.5% patients at a median of 51 (0-160) days after discontinuation of therapy. Factors predictive of recurrence were treatment phase viral kinetics (P = 0.005), lung transplant (P = 0.002), CMV donor (D)+/recipient (R)- serostatus(P = 0.04) and recent acute rejection(P = 0.02). Prolonged antiviral therapy was given to 226 (80.1%) of 282 patients. Recurrence occurred in 73 (32.3%) of 226 patients that received prolonged antivirals versus 13 (23.2%) of 56 in those with no prolonged antivirals (P = 0.19). Recurrent CMV occurs in a significant percentage of patients after treatment of the first episode of CMV viremia/disease. CMV D+/R- serostatus, lung transplant, and treatment phase viral kinetics were significant predictors of recurrence. Continuation of prolonged antivirals beyond initial clearance was not associated with a reduced risk of recurrence.

Gallium scintigraphic pattern in lung CMV infections

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ganz, W.I.; Cohen, D.; Mallin, W.

1994-05-01

Due to extensive use of prophylactic therapy for Pneumonitis Carinii Pneumonia (PCP), Cytomegalic Viral (CMV) infection may now be the most common lung infection in AIDS patients. This study was performed to determine Gallium-67 patterns in AIDS patients with CMV. Pathology reports were reviewed in AIDS patients who had a dose of 5 to 10 mCi of Gallium-67 citrate. Analysis of images were obtained 48-72 hours later of the entire body was performed. Gallium-67 scans in 14 AIDS patients with biopsy proven CMV, were evaluated for eye, colon, adrenal, lung and renal uptake. These were compared to 40 AIDS patientsmore » without CMV. These controls had infections including PCP, Mycobacterial infections, and lymphocytic interstitial pneumonitis. 100% of CMV patients had bowel uptake greater than or equal to liver. Similar bowel activity was seen in 50% of AIDS patients without CMV. 71% had intense eye uptake which was seen in only 10% of patients without CMV. 50% of CMV patients had renal uptake compared to 5% of non-CMV cases. Adrenal uptake was suggested in 50%, however, SPECT imaging is needed for confirmation. 85% had low grade lung uptake. The low grade lung had perihilar prominence. The remaining 15% had high grade lung uptake (greater than sternum) due to superimposed PCP infection. Colon uptake is very sensitive indicator for CMV infection. However, observing eye, renal, and or adrenal uptake improved the diagnostic specificity. SPECT imaging is needed to confirm renal or adrenal abnormalities due to intense bowel activity present in 100% of cases. When high grade lung uptake is seen superimposed PCP is suggested.« less

Review of cytomegalovirus coinfection in HIV-infected individuals in Africa.

PubMed

Grønborg, Helene Ladefoged; Jespersen, Sanne; Hønge, Bo Langhoff; Jensen-Fangel, Søren; Wejse, Christian

2017-01-01

Cytomegalovirus (CMV) infection among HIV-infected individuals may cause end-organ disease, which is an AIDS-defining condition. Evidence from high-income countries suggests that CMV may alter the outcome of HIV infection, other than causing end-organ diseases. We reviewed literature on HIV and CMV coinfection in Africa. Systematic review of published studies on HIV and CMV coinfection in Africa using the PubMed database. High CMV seroprevalence was found throughout Africa, exceeding 90% in most populations. Retinitis, pneumonia, and colitis were the most commonly reported CMV manifestations in HIV-infected individuals. Among patients with pulmonary symptoms, the prevalence of CMV pneumonitis varied from 20% to over 60%, whereas CMV was found in 0% to 14% of patients with gastrointestinal manifestations. Cytomegalovirus retinitis was found in 0% to 2.6% of examined HIV-infected individuals. The diagnostics of CMV end-organ diseases were found complex and difficult to interpret in African settings. Cytomegalovirus viremia was correlated with significantly lower CD4 cell count and increase in activated and apoptosis vulnerable T-lymphocytes. Also, CMV coinfection was found to be associated with increased transmission and progression of HIV infection. Moreover, detectable CMV DNA was an independent predictor of HIV transmission and mortality among HIV-infected individuals. Cytomegalovirus is highly prevalent in Africa and a common cause of disease manifestations in HIV-infected individuals among all age groups. Cytomegalovirus coinfection in HIV-infected individuals in Africa is associated with increased transmission and mortality of HIV, but it is a neglected area of research. Copyright © 2016 John Wiley & Sons, Ltd.

The cytomegalovirus promoter-driven short hairpin RNA constructs mediate effective RNA interference in zebrafish in vivo.

PubMed

Su, Jianguo; Zhu, Zuoyan; Wang, Yaping; Xiong, Feng; Zou, Jun

2008-01-01

The ability to utilize the RNA interference (RNAi) machinery for silencing target-gene expression has created a lot of excitement in the research community. In the present study, we used a cytomegalovirus (CMV) promoter-driven DNA template approach to induce short hairpin RNA (shRNA) triggered RNAi to block exogenous Enhanced Green Fluorescent Protein (EGFP) and endogenous No Tail (NTL) gene expressions. We constructed three plasmids, pCMV-EGFP-CMV-shGFP-SV40, pCMV-EGFP-CMV-shNTL-SV40, and pCMV-EGFP-CMV-shScrambled-SV40, each containing a CMV promoter driving an EGFP reporter cDNA and DNA coding for one shRNA under the control of another CMV promoter. The three shRNA-generating plasmids and pCMV-EGFP control plasmid were introduced into zebrafish embryos by microinjection. Samples were collected at 48 h after injection. Results were evaluated by phenotype observation and real-time fluorescent quantitative reverse-transcription polymerase chain reaction (Q-PCR). The shGFP-generating plasmid significantly inhibited the EGFP expression viewed under fluorescent microscope and reduced by 70.05 +/- 1.26% of exogenous EGFP gene mRNA levels compared with controls by Q-PCR. The shRNA targeting endogenous NTL gene resulted in obvious NTL phenotype of 30 +/- 4% and decreased the level of their corresponding mRNAs up to 54.52 +/- 2.05% compared with nontargeting control shRNA. These data proved the feasibility of the CMV promoter-driven shRNA expression technique to be used to inhibit exogenous and endogenous gene expressions in zebrafish in vivo.

An Artesunate-Containing Antimalarial Treatment Regimen Did Not Suppress Cytomegalovirus Viremia

PubMed Central

Gantt, Soren; Huang, Meei-Li; Magaret, Amalia; Bunts, Lisa; Selke, Stacy; Wald, Anna; Rosenthal, Philip J.; Dorsey, Grant; Casper, Corey

2014-01-01

Background Additional drugs are needed for the treatment of cytomegalovirus (CMV) infection. Artesunate is an antimalarial drug that has activity against CMV in vitro and in a rodent model. Only a small number of case reports are available describing the clinical effects of artesunate on CMV infection, and these yielded inconsistent results. Objective To evaluate the effect of artesunate on CMV infection, using blood samples collected from children who participated in malaria treatment trials. Study design Quantitative CMV DNA PCR was performed on dried blood spots collected from 494 Ugandan children, who were randomized either to artesunate plus amodiaquine or sulfadoxine-pyrimethamine plus amodiaquine for acute malaria infection. Poisson regression was used to compare treatment regimens with respect to the change in the frequency and quantity of CMV detected that occurred before and after treatment. Results CMV was detected in 11.4% of children immediately prior to treatment and 10.7% 3 days later (p=0.70). The average quantity of CMV was 0.30 log10 copies per million cells higher on day 3 than at treatment initiation (95% CI 0.01 to 0.58, p=0.041). There was no measurable difference in either the frequency or quantity of CMV detected in blood between children randomized to the two treatment arms. Conclusions A standard 3-day artesunate-containing antimalarial regimen had no detectable effect on CMV viremia in children with malaria. Longer treatment courses and/or higher doses of artesunate than those routinely used for malaria may be required for effective treatment of CMV infection. PMID:23827788

Risk of congenital cytomegalovirus infection among HIV-exposed uninfected infants is not decreased by maternal nelfinavir use during pregnancy.

PubMed

Gantt, Soren; Leister, Erin; Jacobsen, Denise L; Boucoiran, Isabelle; Huang, Meei-Li; Jerome, Keith R; Jourdain, Gonzague; Ngo-Giang-Huong, Nicole; Burchett, Sandra; Frenkel, Lisa

2016-06-01

Congenital cytomegalovirus (cCMV) infection is common among infants born to HIV-infected women. Nelfinavir (NFV), an antiretroviral drug that is safe during pregnancy, inhibits CMV replication in vitro at concentrations that standard doses achieve in plasma. We hypothesized that infants born to women receiving NFV for prevention of mother-to-child transmission of HIV (PMTCT) would have a reduced prevalence of cCMV infection. The prevalence of cCMV infection was compared among HIV-uninfected infants whose HIV-infected mothers either received NFV for >4 weeks during pregnancy (NFV-exposed) or did not receive any NFV in pregnancy (NFV-unexposed). CMV PCR was performed on infant blood samples collected at <3 weeks from birth. Of the 1,255 women included, 314 received NFV for >4 weeks during pregnancy and 941 did not receive any NFV during pregnancy. The overall prevalence of cCMV infection in the infants was 2.2%, which did not differ by maternal NFV use. Maternal CD4 T cell counts were inversely correlated with risk of cCMV infection, independent of the time NFV was initiated during gestation. Infants with cCMV infection were born 0.7 weeks earlier (P = 0.010) and weighed 170 g less (P = 0.009) than uninfected infants. Among HIV-exposed uninfected infants, cCMV infection was associated with adverse perinatal outcomes. NFV use in pregnancy was not associated with protection against cCMV. Safe and effective strategies to prevent cCMV infection are needed. © 2015 Wiley Periodicals, Inc.

[Comparison of the CMV antigenemia test and CMV-DNA PCR results in solid organ transplant recipients].

PubMed

Özkarata, Emre; Özkarataş, Emre; Özbek, Ö Alpay; Avkan Oğuz, Vildan; Sayıner, A Arzu

2016-01-01

Cytomegalovirus (CMV) infection is among the most common important viral infections in solid organ transplant (SOT) recipients. Diagnostic tests for detecting CMV replication are widely used for this group of patients, however there is no clear agreement on the cut-off levels for interpretation of clinical decisions especially when the low level of viral load is detected. In this study, CMV pp65 antigenemia test results were compared with plasma CMV-DNA levels detected by quantitative real-time polymerase chain reaction (qPCR) in samples of kidney and liver transplant recipients in the Central Laboratory of Dokuz Eylul University Hospital between 2011 and 2013, and the correlation between these two tests and viral load equivalent to antigenemia positivity were determined. In the study, pp65 antigenemia and CMV-DNA qPCR results were evaluated retrospectively. The samples from the same patients were included if the time between antigenemia and CMV-DNA qPCR tests were less than 48 hours. SPSS v15.0 was used for correlation, regression and ROC curve analysis. The results of the 217 samples collected from 100 patients (59 male, 41 female; age range: 16-71, mean age: 46 ± 13 years), 36 liver and 64 kidney recipients were evaluated in the study. Of the patients 80% were CMV IgM negative, IgG positive; 1% was CMV IgG and IgM positive; 2% were CMV IgM and IgG negative, while for 17 patients serological results could not be reached. CMV pp65 antigenemia and CMV-DNA were both negative in 102 (47%) samples, while both were positive in 37 (17%) samples. The single sample from a case with CMV IgM and IgG positivity yielded negative results for both antigenemia and CMV-DNA tests. In 78 samples antigenemia were negative and CMV-DNA qPCR were positive, while there were no samples with antigenemia positive and qPCR negative. Mean values of antigenemia and qPCR tests were 23 positive cells/200.000 leukocytes (range: 1 to 230 positive cells) and 12.595 copies/ml (range: 180 to 106.311 copies/ml), respectively. There was a significant correlation between antigenemia and qPCR results among the samples that were positive by both assays (r= 0.785). ROC curve analysis showed that CMV viral load of 205 copies/ml in plasma corresponds to ≥ 1 pp65 antigen positive cells per 200.000 leukocytes (sensitivity: 91.7%, specificity: 90.3%). Higher analytical sensitivity of qPCR test can be explained by the results of CMV-DNA PCR positive and antigenemia negative samples. Non-existence of samples with antigen positive and PCR negative results supported this finding. ROC analysis showed that any sample with CMV-DNA qPCR result less than 205 copies/ml, could be accepted as pp65 antigenemia negative. This viral load value is valid only for the studied patient group and assays, therefore could be changed according to study population and tests.

49 CFR 350.319 - What are permissible uses of High Priority Activity Funds?

Code of Federal Regulations, 2010 CFR

2010-10-01

...) Implement, promote, and maintain national programs to improve CMV safety. (2) Increase compliance with CMV safety regulations. (3) Increase public awareness about CMV safety. (4) Provide education on CMV safety and related issues. (5) Demonstrate new safety related technologies. (b) These funds will be allocated...

Cytokine Response to Subclinical Cytomegalovirus Reactivation as a Cause of Severe Fatigue in Women Undergoing Chemotherapy for Breast Cancer

DTIC Science & Technology

2013-09-01

herpesvirus cytomegalovirus (CMV) might contribute to severe cancer treatment related fatigue (CTRF) in women undergoing chemotherapy for breast cancer...reactivation of the latent herpesvirus CMV, which would stimulate inflammatory cytokines. We predicted that women harboring latent CMV (CMV positives) would

Comparison of the Abbott m2000 HIV-1 Real-Time and Roche AMPLICOR Monitor v1.5 HIV-1 assays on plasma specimens from Rakai, Uganda.

PubMed

Ssebugenyi, I; Kizza, A; Mpoza, B; Aluma, G; Boaz, I; Newell, K; Laeyendecker, O; Shott, J P; Serwadda, D; Reynolds, S J

2011-07-01

The need for viral load (VL) monitoring of HIV patients receiving antiretroviral therapy (ART) in resource-limited settings (RLS) has become apparent with studies showing the limitations of immunological monitoring. We compared the Abbott m2000 Real-Time (Abbott) HIV-1 assay with the Roche AMPLICOR Monitor v1.5 (Roche) HIV-1 assay over a range of VL concentrations. Three hundred and eleven plasma samples were tested, including 164 samples from patients on ART ≥ six months and 147 from ART-naïve patients. The Roche assay detected ≥400 copies/mL in 158 (50.8%) samples. Of these, Abbott produced 145 (91.8%) detectable results ≥400 copies/mL; 13 (8.2%) samples produced discrepant results. Concordance between the assays for detecting HIV-1 RNA ≥400 copies/mL was 95.8% (298/311). The sensitivity, specificity, positive predictive value and negative predictive value of Abbott to detect HIV-1 RNA ≥400 copies/mL were 91.8%, 100%, 100% and 92.2%, respectively. For the 151 samples with HIV-1 RNA ≥400 copies/mL for both assays, a good linear correlation was found (r = 0.81, P < 0.0001; mean difference, 0.05). The limits of agreement were -0.97 and 1.07 log(10) copies/mL (mean ± 2 SD). The Abbott assay performed well in our setting, offering an alternative methodology for HIV-1 VL for laboratories with realtime polymerase chain reaction (PCR) capacity.

75 FR 10815 - Notice of Proposed Withdrawal Extension and Opportunity for Public Meeting; Oregon

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-09

... ecological research values at the Abbott Creek Research Natural Area. The withdrawal created by PLO No. 6856... the protection of the unique natural and ecological research values at the Abbott Creek Research...

76 FR 383 - Notice of Receipt of Complaint; Solicitation of Comments Relating to the Public Interest

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-04

... interest issues raised by the complaint. FOR FURTHER INFORMATION CONTACT: Marilyn R. Abbott, Secretary to... Commission. Issued: December 28, 2010. Marilyn R. Abbott, Secretary to the Commission. [FR Doc. 2010-33131...

76 FR 5204 - Notice of Receipt of Complaint; Solicitation of Comments Relating to the Public Interest

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-28

.... Abbott, Secretary to the Commission, U.S. International Trade Commission, 500 E Street, SW., Washington...)(4)). Issued: January 24, 2011. By order of the Commission. Marilyn R. Abbott. Secretary to the...

75 FR 69703 - Notice of Receipt of Complaint; Solicitation of Comments Relating to the Public Interest

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-15

.... Abbott, Secretary to the Commission, U.S. International Trade Commission, 500 E Street, SW., Washington... Commission. Issued: November 5, 2010. Marilyn R. Abbott, Secretary to the Commission. [FR Doc. 2010-28625...

76 FR 4722 - Notice of Receipt of Complaint; Solicitation of Comments Relating to the Public Interest

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-26

... public interest issues raised by the complaint. FOR FURTHER INFORMATION CONTACT: Marilyn R. Abbott...)(4)). By order of the Commission. Issued: January 21, 2011. Marilyn R. Abbott, Secretary to the...

8. DETAIL OF END BEARING CONDITION AT SOUTHWEST CORNER OF ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

8. DETAIL OF END BEARING CONDITION AT SOUTHWEST CORNER OF BRIDGE, SHOWING METAL ENCASED CIRCULAR CONCRETE PILING AND FIXED SHOE - Abbott's Parker Through Truss Bridge, Spanning Sandusky River at Abbott Road (Pleasant Township), Tiffin, Seneca County, OH

Utility of Leflunomide in the Treatment of Drug Resistant Cytomegalovirus Retinitis.

PubMed

Rifkin, Lana M; Minkus, Caroline L; Pursell, Kenneth; Jumroendararasame, Chaisiri; Goldstein, Debra A

2017-02-01

To describe leflunomide use in the treatment of drug resistant cytomegalovirus retinitis. Leflunomide has been shown to be effective in the treatment of systemic CMV viremia. Retrospective chart review of patients with CMV retinitis treated with leflunomide. Two HIV-negative organ transplant recipients with UL 97 mutation resistant-genotype CMV were identified. Patient 1 developed CMV viremia post-kidney transplant and subsequently bilateral CMV retinitis. Retinitis progressed, despite intravitreal injection of ganciclovir and foscarnet, and IV foscarnet and oral valganciclovir. Retinitis control was achieved with the addition of oral leflunomide. Disease remained inactive for 22 months. Patient 2 developed CMV retinitis after lung transplant. Disease progressed despite intravitreal foscarnet injections and oral valganciclovir. Control of retinitis was achieved with addition of oral leflunomide, allowing cessation of intravitreal therapy. Disease remained inactive until his death. Leflunomide may be considered as a treatment option for resistant CMV retinitis.

Intravitreal foscarnet for recurring CMV retinitis in a congenitally infected premature infant.

PubMed

Tawse, Kirstin L; Baumal, Caroline R

2014-02-01

A girl born at 32 weeks' gestational age was diagnosed at birth with congenital cytomegalovirus (CMV) infection without ocular involvement. On day 19 of life, retinal examination requested for retinopathy of prematurity (ROP) identified bilateral CMV retinitis and stage 1 ROP. Treatment of macular threatening CMV infection with intravitreal foscarnet injections and intravenous ganciclovir for 6 weeks led to quiescence of retinitis. Bilateral recurrence of CMV retinitis occurred on day 89 of life, requiring a second course of intravitreal foscarnet injections and intravenous ganciclovir. Both the initial presentation and reactivation of CMV retinitis were identified on examination for ROP and would have gone unrecognized had the infant not met ROP screening criteria. This case demonstrates delayed presentation of CMV retinitis after initial negative retinal examination in a premature infant with congenital infection and concurrent ROP. Copyright © 2014 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.

CMV Infection in Bone Marrow and Solid Organ Transplant Patients in the Era of Antiviral Prophylaxis.

PubMed

Hebart, Holger; Jahn, Gerhard; Sinzger, Christian; Kanz, Lothar; Einsele, Hermann

2000-02-01

Recent developments in the diagnosis and therapy of cytomegalovirus (CMV) infection have helped to reduce CMV-associated morbidity and mortality following allogeneic bone marrow and solid organ transplantation. The clinical symptoms of active CMV infection and the prevalence of life-threatening CMV disease vary widely between different patient populations according to the type of transplant and the intensity of immunosuppression employed. Antiviral prophylaxis with aciclovir, valaciclovir and ganciclovir has been shown to reduce CMV infection and disease following organ transplantation. Antiviral drugs, in particular ganciclovir and foscarnet, have varying sideeffects, however, and antiviral resistance due to prolonged administration of ganciclovir and foscarnet has been reported recently. Short courses of pre-emptive antiviral therapy for documented CMV infection help to reduce the duration and sideeffects of therapy, offering an alternative strategy to antiviral prophylaxis. Studies are required to compare the efficacy and costs of antiviral prophylaxis with pre-emptive therapy.

[Redox-potential of blood and consistence of energoproviding defence system in cytomegalovirus infection in pregnancy].

PubMed

Dzhikiia, I V; Rizhvadze, M A; Dzhangidze, M A

2006-05-01

We have studied the relationship between the hypoxic change and mitochondrial redox-potential disturbances in the mechanism of pheto-placental insufficiency in pregnancy with cytomegalovirus infection (CMV), detected by the positive anti-CMV-IgG titer and more then 4-fold increase of low avid anti-CMV-IgG. It was shown, that chronic CMV infection induces production of active forms of oxygen, peroxidation of structures and concurrently damage of mitochondria with essential decrease of ATP level. Results of the study have shown the important diagnostic value of estimation of hypoxic-oxidative damage induced by CMV infection. The results also revealed important relationships between the activity of the CMV infection and intensity of mitochondrial damage. On the basis of our investigations we suggest the additional diagnostic test (the determination of citozol NADH dependent isocitratdehydrogenaze activity) to evaluate the depth of CMV induced metabolic disturbances.

Health Update: CMV and Child Care Prgrams.

ERIC Educational Resources Information Center

Aronson, Susan S.

1988-01-01

Discusses appropriate steps to be taken in a day care setting to minimize the known risks associated with cytomegalovirus (CMV). Explains what CMV is; why people should worry about CMV; how it is spread; and how it can be treated and prevented. Suggests a number of hygiene practices for use in day care centers. (RWB)

Why CMV is a candidate for elimination and then eradication.

PubMed

Griffiths, Paul D; Mahungu, Tabitha

2016-07-01

Cytomegalovirus (CMV) is well-known for the end organ diseases (EODs) it causes following viraemic dissemination in immunocompromised hosts. These are termed the direct effects of CMV, where a diagnosis can be made in an individual patient. In addition, CMV is associated with indirect effects where populations can be seen to be disadvantaged compared to those without CMV. These indirect effects have been described in solid organ transplants, bone marrow transplants, advanced HIV, people admitted to intensive care units, the elderly and the general population. We summarise the evidence that associates CMV with its direct effects following congenital infection, solid organ transplantation, bone marrow transplantation and advanced HIV as well as its indirect effects in all patient populations. We propose that the greatest worldwide burden of CMV comes from its indirect effects. Control of this infection at the population level is being sought through the development of vaccines to control EODs where cost effectiveness is expected. We propose that the financial case for universal immunisation will be enhanced even further by the potential benefits vaccines may produce against the indirect effects of CMV.

More intensive CMV-infection in chronic heart failure patients contributes to higher T-lymphocyte differentiation degree.

PubMed

Moro-García, Marco Antonio; López-Iglesias, Fernando; Marcos-Fernández, Raquel; Bueno-García, Eva; Díaz-Molina, Beatriz; Lambert, José Luis; Suárez-García, Francisco Manuel; Morís de la Tassa, Cesar; Alonso-Arias, Rebeca

2018-03-30

Immunosenescence in chronic heart failure (CHF) is characterized by a high frequency of differentiated T-lymphocytes, contributing to an inflammatory status and a deficient ability to generate immunocompetent responses. CMV is the best known inducer of T-lymphocyte differentiation, and is associated with the phenomenon of immunosenescence. In this study, we included 58 elderly chronic heart failure patients (ECHF), 60 healthy elderly controls (HEC), 40 young chronic heart failure patients (YCHF) and 40 healthy young controls (HYC). High differentiation of CD8+ T-lymphocytes was found in CMV-seropositive patients; however, the differentiation of CD4+ T-lymphocytes was increased in CMV-seropositive but also in CHF patients. Anti-CMV antibody titers showed positive correlation with more differentiated CD4+ and CD8+ subsets and inverse correlation with CD4/CD8 ratio. Immunosenescence found in CHF patients is mainly due to the dynamics of CMV-infection, since the differentiation of T-lymphocyte subsets is related not only to CMV-infection, but also to anti-CMV antibody titers. Copyright © 2018 Elsevier Inc. All rights reserved.

Rhesus Cytomegalovirus Encodes Seventeen MicroRNAs that are Differentially Expressed in vitro and in vivo

PubMed Central

Hancock, Meaghan H; Tirabassi, Rebecca S; Nelson, Jay A

2013-01-01

Human cytomegalovirus (HCMV) miRNAs are important for regulation of viral infection and evasion of host immune responses. Unfortunately, the importance of HCMV miRNAs cannot be addressed in vivo due to the species specificity of CMVs. Rhesus CMV (RhCMV) infection of rhesus macaques provides an important model system for HCMV pathogenesis due to the genetic similarity between the viruses. In this report, seventeen RhCMV miRNAs were identified using Next Generation Sequencing. In fibroblasts, RhCMV miRNAs associate with Argonaute proteins and display several patterns of expression, including an early peak in expression followed by decline and accumulation throughout infection. Additionally, RhCMV encodes an HCMV miR-US5-2 homologue that targets the 3’ UTR of RhCMV US7. Finally, examination of salivary gland tissue from infected animals revealed the presence of a subset of viral miRNAs. This study highlights the importance of the RhCMV model system for evaluating the roles of CMV miRNAs during viral infection. PMID:22305624

Rhesus cytomegalovirus encodes seventeen microRNAs that are differentially expressed in vitro and in vivo.

PubMed

Hancock, Meaghan H; Tirabassi, Rebecca S; Nelson, Jay A

2012-04-10

Human cytomegalovirus (HCMV) miRNAs are important for regulation of viral infection and evasion of host immune responses. Unfortunately, the importance of HCMV miRNAs cannot be addressed in vivo due to the species specificity of CMVs. Rhesus CMV (RhCMV) infection of rhesus macaques provides an important model system for HCMV pathogenesis due to the genetic similarity between the viruses. In this report, seventeen RhCMV miRNAs were identified using Next Generation Sequencing. In fibroblasts, RhCMV miRNAs associate with Argonaute proteins and display several patterns of expression, including an early peak in expression followed by decline and accumulation throughout infection. Additionally, RhCMV encodes an HCMV miR-US5-2 homologue that targets the 3' UTR of RhCMV US7. Finally, examination of salivary gland tissue from infected animals revealed the presence of a subset of viral miRNAs. This study highlights the importance of the RhCMV model system for evaluating the roles of CMV miRNAs during viral infection. Copyright © 2012 Elsevier Inc. All rights reserved.

Treatment of CMV infection after allogeneic hematopoietic stem cell transplantation.

PubMed

Maffini, Enrico; Giaccone, Luisa; Festuccia, Moreno; Brunello, Lucia; Busca, Alessandro; Bruno, Benedetto

2016-06-01

Despite a remarkable reduction in the past decades, cytomegalovirus (CMV) disease in allogeneic hematopoietic stem cell transplant (HSCT) recipients remains a feared complication, still associated with significant morbidity and mortality. Today, first line treatment of CMV infection/reactivation is still based on dated antiviral compounds Ganciclovir (GCV), Foscarnet (FOS) and Cidofovir (CDF) with their burdensome weight of side effects. Maribavir (MBV), Letermovir (LMV) and Brincidofovir (BDF) are three new promising anti-CMV drugs without myelosuppressive properties or renal toxic effects that are under investigation in randomized phase II and III trials. Adoptive T-cell therapy (ATCT) in CMV infection possesses a strong rationale, demonstrated by several proof of concept studies; its feasibility is currently under investigation by clinical trials. ATCT from third-party and naïve donors could meet the needs of HSCT recipients of seronegative donors and cord blood grafts. In selected patients such as recipients of T-cell depleted grafts, ATCT, based on CMV-specific host T-cells reconstitution kinetics, would be of value in the prophylactic and/or preemptive CMV treatment. Vaccine-immunotherapy has the difficult task to reduce the incidence of CMV reactivation/infection in highly immunocompromised HSCT patients. Newer notions on CMV biology may represent the base to flush out the Troll of transplantation.

Impact of Early Cytomegalovirus Reactivation in Cord Blood Stem Cell Recipients in the Current Era

PubMed Central

Ramanathan, Muthalagu; Teira, Pierre; Battiwalla, Minoo; Barrett, John; Ahn, Kwang Woo; Chen, Min; Green, Jamie; Laughlin, Mary; Lazarus, Hillard M.; Marks, David; Saad, Ayman; Seftel, Matthew; Saber, Wael; Savani, Bipin; Waller, Edmund; Wingard, John; Auletta, Jeffery J.; Lindemans, Caroline A.; Boeckh, Michael; Riches, Marcie L.

2016-01-01

Several studies have reported an association between cytomegalovirus (CMV) reactivation and a decreased incidence of relapse for acute myeloid leukemia (AML) after adult donor allogeneic hematopoietic cell transplantation (HCT). Limited data, however, are available on the impact of CMV reactivation on relapse after cord blood stem cell (CB) transplantation. The unique combination of higher incidence of CMV reactivation in the seropositive recipient and lower incidence of graft versus host disease (GvHD) in CB HCT allows for a valuable design to analyze the impact of CMV reactivation. Data from 1684 patients transplanted with cord blood (CB) between 2003 and 2010 for AML and acute lymphoblastic leukemia (ALL) were analyzed. The median time to CMV reactivation was 34 days (range: 2 – 287). CMV reactivation and positive CMV serology were associated with increased non-relapse mortality (NRM) amongst both AML and ALL CB recipients [Reactivation, AML: RR 1.41 (1.07–1.85); ALL: 1.60 (1.14 – 2.23); Serology, AML: RR 1.39 (1.05 – 1.85), ALL: RR 1.61 (1.18 – 2.19)]. For patients with ALL, but not those with AML, this yielded inferior overall survival (p<0.005). Risk of relapse was not impacted by CMV reactivation or positive CMV serostatus for either disease. PMID:27042847

Cross-reactive antibodies against GM2 and CMV-infected fibroblasts in Guillain-Barré syndrome.

PubMed

Ang, C W; Jacobs, B C; Brandenburg, A H; Laman, J D; van der Meché, F G; Osterhaus, A D; van Doorn, P A

2000-04-11

To investigate whether anti-GM2 antibodies in patients with Guillain-Barré syndrome (GBS) are induced by molecular mimicry with cytomegalovirus (CMV). Antibodies against ganglioside GM2 are frequently present in the serum from GBS patients with an antecedent infection with CMV. The authors detected inhibition of anti-GM2 reactivity after incubation of GM2-reactive serum samples with fibroblasts infected with a GBS-associated CMV strain. Control sera consisted of GQ1b-reactive samples, and control antigens included uninfected fibroblasts and fibroblasts that were infected with other herpes viruses. Serum immunoglobulin M reactivity with GM2 was decreased in a dose-dependent manner after incubation with CMV-infected fibroblasts. Incubation of anti-GM2-positive serum samples with uninfected fibroblasts and fibroblasts infected with varicella zoster virus did not inhibit anti-GM2 reactivity, whereas this reactivity was slightly decreased after incubation with herpes simplex virus type 1 in one patient. Antibodies against ganglioside GQ1b did not react with CMV-infected fibroblasts. CMV-infected fibroblasts express gangliosidelike epitopes that recognize specifically anti-GM2 antibodies. These results support the hypothesis that antiganglioside antibodies in CMV-infected GBS patients are induced by molecular mimicry between GM2 and antigens that are induced by a CMV infection.

Seroepidemiology of Epstein-Barr virus and cytomegalovirus among Israeli male young adults.

PubMed

Levine, Hagai; Balicer, Ran D; Rozhavski, Vladi; Halperin, Tamar; Shreberk, Michal; Davidovitch, Nadav; Huerta-Hartal, Michael; Ankol, Omer E

2012-11-01

To assess the seroprevalence and seroconversion of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) Immunoglobulin G (IgG) antibodies and identify associated socioeconomic and smoking variables among male young adults in Israel, to explore health disparities and aid prevention efforts. A population-based seroprevalence study of EBV and CMV IgG antibodies in a systematic sample of Israeli males upon recruitment to mandatory military service during 1994-2004. Associations between socioeconomic and smoking variables and the seroprevalence of EBV/CMV were evaluated, controlling for possible confounders. A subset of seronegative subjects was assessed for seroconversion upon discharge from military service. Overall seroprevalence rates were 87% for EBV and 59% for CMV. An association between the seroprevalence of EBV and CMV was observed. Seroconversion was 56% for EBV as compared with 31% for CMV. Lower paternal education was found to be associated with both EBV and CMV seroprevalence. Lower socioeconomic status, North African origin, and urban residence were found to be associated with CMV seropositivity, as was smoking for EBV seropositivity. Socioeconomic disparities exist in the seroprevalence rates of CMV and EBV among Israeli male young adults. The results of the study could aid public health efforts and determine target populations when a vaccine becomes available. Copyright © 2012 Elsevier Inc. All rights reserved.

Impairment of short-term memory and Korsakoff syndrome are common in AIDS patients with cytomegalovirus encephalitis.

PubMed

Pirskanen-Matell, R; Grützmeier, S; Nennesmo, I; Sandström, E; Ehrnst, A

2009-01-01

The diagnosis of cytomegalovirus encephalitis (CMV-E) in AIDS patients is challenging as other illnesses may obscure the symptoms. Here, we characterize the clinical symptoms of CMV-E and link them to post-mortem findings. Patients and methods In 254 homosexual men with AIDS, followed from HIV diagnosis to death before the antiretroviral combination therapy era, CMV-E was suspected in 93 cases. All were CMV-positive in blood. Neurological examination, including cognitive testing was performed in 34 of them within 6 months before death. CMV-E was diagnosed by CMV-PCR in cerebrospinal fluid (n = 24) or by post-mortem (n = 24). The majority complained of forgetfulness (91%), balance difficulties (85%) and impotence (85%). Impaired short-term memory was present in 29 patients. It was extreme in 17, justifying the diagnosis of Korsakoff's syndrome. This was often associated with infectious CMV in blood (P = 0.01). Brainstem symptoms were found in 19 patients. Post-mortem examination often revealed ventriculoencephalitis. CMV was found primarily around the ventricles and in other structures, described in Korsakoff's syndrome. The location of CMV in the brain corresponded well to the clinical findings, demonstrating the close relationship between the neurological symptoms and the neuroanatomical lesions.

Pneumonia relevant to lung transplantation and pathogen distribution.

PubMed

He, Xuan; Dai, Hua-Ping; Chen, Qi-Rui; Miao, Jin-Bai; Sun, Bing; Bao, Na; Hu, Bin; Li, Hui; Wu, An-Shi; Ban, Cheng-Jun; Ge, Su-Juan; Wang, Chen; Hou, Sheng-Cai

2013-01-01

Pneumonia is the most common cause of morbidity and mortality in lung transplant (LT) recipients. The aim of the present study was to evaluate the incidence, etiology, risk factors and prognosis of pneumonia in LT recipients. The LT cohort consisted of 28 recipients receiving LT in Beijing Chao-Yang Hospital from August 2005 to April 2011. Data collected included demographic data, underlying disorders, time and type of transplant, follow-up information, date of last follow-up, and patient status. A retrospective analysis was made of observational data that were prospectively collected. Twenty-two patients of 28 LT recipients had 47 episodes of pneumonia throughout the study period. Thirtyeight episodes of pneumonia in 19 recipients occurred post-LT with a median follow-up of 257.5 days (1-2104 days), the incidence of pneumonia was 192.4 episodes per 100 LT/year and its median time of onset was 100.5 days (0-946 days) post-transplantation. Bacteria, virus and fungi accounted for 62%, 16% and 15% of the microbial pathogens, respectively. The most frequent were Pseudomonas aeruginosa (20%), cytomegalovirus (CMV) (15%), and Aspergillus fumigatus (10%). A total of 29% (11/38) of pneumonias occurred in the first month post-LT, and then the incidence decreased gradually. The incidence of CMV pneumonia was 25% (7/28) with a median time of 97 days (10-971 days). More than one bacterial infection and CMV infection were independent risk factors for aspergillus infection. The incidence of pulmonary tuberculosis (TB) was 18% (5/28), and the history of TB was a risk factor for TB relapse. There were 58% (7/12) of recipients who died of infection, and 71% (5/7) of these died in the first year after LT. Pneumonia is still a major cause of morbidity and mortality in LT recipients. The most frequent microorganisms were Pseudomonas aeruginosa, CMV, and Aspergillus fumigates. The incidence of CMV pneumonia decreases with a delayed median time of onset. More than one incidence of bacterial infection and CMV infection are independent risk factors for aspergillus infection. LT recipients are at high risk for TB, and the history of TB is a risk factor for TB relapse.

How Do Donor-Recipient CMV Serostatus and Post-Hematopoietic Stem Cell Transplantation CMV Reactivation Affect Outcomes in Acute Leukemia Patients?

PubMed

Vaezi, Mohammad; Kasaeian, Amir; Souri, Maryam; Soufiyan, Faeze; Shokri Boosjin, Amir; Setarehdan, Seyed Amin; Alimoghaddam, Kamran; Ghavamzadeh, Ardeshir

2017-07-01

Background : This study evaluated CMV serostatus in donors and recipients of hematopoietic stem cell transplantation (HSCT) and its effects on CMV reactivation of patients and all aspects of CMV on HSCT outcomes. Materials and Methods : Seven hundred and five adult acute leukemia patients (AML=408 and AML=297) who had undergone HSCT were included in this retrospective study. We categorized donor-recipient pairs in three risk groups: positive donors (D+) were studied as high-risk group, including either R+ or R-(n=485), R-D- as low-risk group (n=32) and R+D- as intermediate group (n=15). Results: There was no statistically difference in CMV reactivation among these risk groups (P=0.14).CMV infection rate was lower in R+D+ than R+D-(p=0.050). Multivariate analysis showed that patients developing CMV infection had lower overall survival (p=0.04, HR: 1.43, CI=1.00- 2.05) and higher non- relapse mortality (P=0.01, HR: 1.62, CI=1.11-2.38). Relapse rate did not change in CMV reactivated patients (P=0.94). Conclusion: The results of the study indicated that asCMV reactivation occurred more in R+D- patients compared to R+D+ ones, and was associated with inferior OS and higher NRM it could be suggested that in contrast to general belief, if the recipient is seropositive , seropositive donor is preferred to a seronegative one.

Comparison of the efficacy and cost effectiveness of pre-emptive therapy as directed by CMV antigenemia and prophylaxis with ganciclovir in lung transplant recipients.

PubMed

Kelly, J; Hurley, D; Raghu, G

2000-04-01

CMV disease remains a major complication of lung transplantation and attempts to prevent it have met with marginal success. In a previous study we documented that universal prophylaxis did not prevent CMV disease but merely delayed it, and was very costly. We compared the efficacy and cost of pre-emptive therapy with ganciclovir, guided by CMV antigenemia, to that of historic controls that received universal prophylaxis with ganciclovir. CMV antigenemia assay was done routinely and pre-emptive therapy was initiated if greater than 25 CMV positive cells per 100,000 polymorphonuclear cells were found. Nineteen patients were enrolled; 6 of of whom received 12 courses of pre-emptive therapy. The incidence of CMV disease was 26% compared to 38% for the historical controls (p = 0.51). None of the patients that received pre-emptive therapy developed CMV disease following that therapy. Antigenemia failed to predict disease in 5 patients that developed it, and thus it is unknown if pre-emptive therapy could have prevented it. There was no mortality in either the study patients or historic controls directly related to CMV. The net savings with pre-emptive therapy was $2569 per patient. We conclude that pre-emptive therapy with ganciclovir is as safe and effective as universal prophylaxis in preventing CMV disease in lung transplant recipients, and is less expensive. The appropriate surveillance technique and timing remain to be determine to optimize the efficacy of pre-emptive therapy.

Progress toward Development of a Vaccine against Congenital Cytomegalovirus Infection

PubMed Central

Permar, Sallie R.; Plotkin, Stanley A.

2017-01-01

ABSTRACT A vaccine against congenital human cytomegalovirus (CMV) infection is a major public health priority. Congenital CMV causes substantial long-term morbidity, particularly sensorineural hearing loss (SNHL), in newborns, and the public health impact of this infection on maternal and child health is underrecognized. Although progress toward development of a vaccine has been limited by an incomplete understanding of the correlates of protective immunity for the fetus, knowledge about some of the key components of the maternal immune response necessary for preventing transplacental transmission is accumulating. Moreover, although there have been concerns raised about observations indicating that maternal seropositivity does not fully prevent recurrent maternal CMV infections during pregnancy, it is becoming increasing clear that preconception immunity does confer some measure of protection against both CMV transmission and CMV disease (if transmission occurs) in the newborn infant. Although the immunity to CMV conferred by both infection and vaccination is imperfect, there are encouraging data emerging from clinical trials demonstrating the immunogenicity and potential efficacy of candidate CMV vaccines. In the face of the knowledge that between 20,000 and 30,000 infants are born with congenital CMV in the United States every year, there is an urgent and compelling need to accelerate the pace of vaccine trials. In this minireview, we summarize the status of CMV vaccines in clinical trials and provide a perspective on what would be required for a CMV immunization program to become incorporated into clinical practice. PMID:29046308

Sequence homology between HLA-bound cytomegalovirus and human peptides: A potential trigger for alloreactivity

PubMed Central

Koparde, Vishal N.; Jameson-Lee, Maximilian; Elnasseh, Abdelrhman G.; Scalora, Allison F.; Kobulnicky, David J.; Serrano, Myrna G.; Roberts, Catherine H.; Buck, Gregory A.; Neale, Michael C.; Nixon, Daniel E.; Toor, Amir A.

2017-01-01

Human cytomegalovirus (hCMV) reactivation may often coincide with the development of graft-versus-host-disease (GVHD) in stem cell transplantation (SCT). Seventy seven SCT donor-recipient pairs (DRP) (HLA matched unrelated donor (MUD), n = 50; matched related donor (MRD), n = 27) underwent whole exome sequencing to identify single nucleotide polymorphisms (SNPs) generating alloreactive peptide libraries for each DRP (9-mer peptide-HLA complexes); Human CMV CROSS (Cross-Reactive Open Source Sequence) database was compiled from NCBI; HLA class I binding affinity for each DRPs HLA was calculated by NetMHCpan 2.8 and hCMV- derived 9-mers algorithmically compared to the alloreactive peptide-HLA complex libraries. Short consecutive (≥6) amino acid (AA) sequence homology matching hCMV to recipient peptides was considered for HLA-bound-peptide (IC50<500nM) cross reactivity. Of the 70,686 hCMV 9-mers contained within the hCMV CROSS database, an average of 29,658 matched the MRD DRP alloreactive peptides and 52,910 matched MUD DRP peptides (p<0.001). In silico analysis revealed multiple high affinity, immunogenic CMV-Human peptide matches (IC50<500 nM) expressed in GVHD-affected tissue-specific manner. hCMV+GVHD was found in 18 patients, 13 developing hCMV viremia before GVHD onset. Analysis of patients with GVHD identified potential cross reactive peptide expression within affected organs. We propose that hCMV peptide sequence homology with human alloreactive peptides may contribute to the pathophysiology of GVHD. PMID:28800601

Sequence homology between HLA-bound cytomegalovirus and human peptides: A potential trigger for alloreactivity.

PubMed

Hall, Charles E; Koparde, Vishal N; Jameson-Lee, Maximilian; Elnasseh, Abdelrhman G; Scalora, Allison F; Kobulnicky, David J; Serrano, Myrna G; Roberts, Catherine H; Buck, Gregory A; Neale, Michael C; Nixon, Daniel E; Toor, Amir A

2017-01-01

Human cytomegalovirus (hCMV) reactivation may often coincide with the development of graft-versus-host-disease (GVHD) in stem cell transplantation (SCT). Seventy seven SCT donor-recipient pairs (DRP) (HLA matched unrelated donor (MUD), n = 50; matched related donor (MRD), n = 27) underwent whole exome sequencing to identify single nucleotide polymorphisms (SNPs) generating alloreactive peptide libraries for each DRP (9-mer peptide-HLA complexes); Human CMV CROSS (Cross-Reactive Open Source Sequence) database was compiled from NCBI; HLA class I binding affinity for each DRPs HLA was calculated by NetMHCpan 2.8 and hCMV- derived 9-mers algorithmically compared to the alloreactive peptide-HLA complex libraries. Short consecutive (≥6) amino acid (AA) sequence homology matching hCMV to recipient peptides was considered for HLA-bound-peptide (IC50<500nM) cross reactivity. Of the 70,686 hCMV 9-mers contained within the hCMV CROSS database, an average of 29,658 matched the MRD DRP alloreactive peptides and 52,910 matched MUD DRP peptides (p<0.001). In silico analysis revealed multiple high affinity, immunogenic CMV-Human peptide matches (IC50<500 nM) expressed in GVHD-affected tissue-specific manner. hCMV+GVHD was found in 18 patients, 13 developing hCMV viremia before GVHD onset. Analysis of patients with GVHD identified potential cross reactive peptide expression within affected organs. We propose that hCMV peptide sequence homology with human alloreactive peptides may contribute to the pathophysiology of GVHD.

Rapid reconstitution of CMV-specific T-cells after stem-cell transplantation.

PubMed

Widmann, Thomas; Sester, Urban; Schmidt, Tina; Gärtner, Barbara C; Schubert, Jörg; Pfreundschuh, Michael; Sester, Martina

2018-04-13

As reconstitution of virus-specific T-cells is critical to control cytomegalovirus (CMV)-viremia following stem-cell transplantation (SCT), we characterized the dynamics in CMV-specific T-cell reconstitution after SCT. Cytomegalovirus-specific T-cells from 51 SCT-recipients were prospectively quantified and phenotypically characterised by intracellular cytokine-staining after specific stimulation and HLA class-I-specific pentamers using flow cytometry. Cytomegalovirus-specific CD4 T-cells reconstituted after a median of 2.3 (IQR, 2.0-3.0) weeks following autografting, and 4.0 (IQR, 3.0-5.6) weeks after allografting, with CMV-specific T-cells originating from donors and/or recipients. The time for reconstitution of CMV-specific CD4 and CD8 T-cells did not differ (P = .58). Factors delaying the time to initial reconstitution of CMV-specific CD4 T-cells included a negative recipient serostatus (P = .016) and CMV-viremia (P = .026). Percentages of CMV-specific CD4 T-cells significantly increased over time and reached a plateau after 90 days (P = .043). Relative CMV-specific CD4 T-cell levels remained higher in long-term transplant recipients compared with those in controls (P < .0001). However, due to persisting lymphopenia, absolute numbers of CMV-specific T-cells were similar as in controls. Cytomegalovirus-specific T-cells rapidly reconstitute after SCT and their percentages remain high in the long term. In the face of persistent lymphopenia, this results in similar absolute numbers of CMV-specific T-cells as in controls to ensure sufficient pathogen control. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cytomegalovirus (CMV) Shedding in Seropositive Pregnant Women from a High Seroprevalence Population: "The Brazilian Cytomegalovirus Hearing and Maternal Secondary Infection Study" (BraCHS).

PubMed

Barbosa, Nayara G; Yamamoto, Aparecida Y; Duarte, Geraldo; Aragon, Davi C; Fowler, Karen B; Boppana, Suresh; Britt, William J; Mussi-Pinhata, Marisa M

2018-02-27

Most congenital CMV infections in highly seropositive populations occur in infants born to women with preexisting CMV seroimmunity. Although essential for developing prevention strategies, CMV shedding patterns in pregnant women with non-primary infections have not been characterized. We investigated correlates of CMV shedding in a cohort of seropositive pregnant women. In a prospective study, saliva, urine, vaginal swabs, and blood were collected from 120 CMV seropositive women in the 1st, 2nd, and 3rd trimesters and one month postpartum. Specimens were tested for CMV-DNA by PCR. We analyzed the contribution of the specific maternal characteristics to viral shedding. Overall, 2,512 samples were assayed. CMV shedding was detected at least once in 42 (35%) women. Maternal age, race, education, parity and marital status were not associated with viral shedding. Mothers living with or providing daily care to young children (3-6 years) were twice as likely to shed CMV at least once compared to women with less exposure to young children (58% vs. 26%; aRR=2.21; 95%CI=1.37-3.56). Living in crowded households (≥2 people per room) was associated with viral shedding (64% vs. 31%; aRR=1.99; 95%CI=1.26-3.13). Sexual activity as indicated by the number of sexual partners per year or condom use was not found to be a correlate of viral shedding. CMV shedding is relatively frequent in seropositive pregnant women. The association between virus shedding and caring for young children as well as crowded living conditions may provide opportunies for increased exposures that could lead to CMV reinfections in seropositive women.

Differences in immune responses between CMV-seronegative and -seropositive patients with myocardial ischemia and reperfusion

PubMed Central

Shmeleva, Evgeniya V; Boag, Stephen E; Murali, Santosh; Bennaceur, Karim; Das, Rajiv; Egred, Mohaned; Purcell, Ian; Edwards, Richard; Todryk, Stephen; Spyridopoulos, Ioakim

2015-01-01

CMV infection is responsible for acceleration of immune senescence and linked to systemic pathologies, including cardiovascular diseases. In this study, we investigated differences in the immune response between CMV-seropositive and seronegative patients undergoing primary percutaneous coronary intervention (PPCI) for acute myocardial infarction (MI). Peripheral blood samples were taken at six different time points: pre-, 15, 30, 90 min, 24 h after PPCI and at 3 months after MI. Absolute counts of lymphocyte subpopulations, immune response to specific and nonspecific stimulation, serum cytokines and levels of CMV-IgG, cardiolipin-IgG, and anti-endothelial cell antibodies were assessed. CMV-seropositive patients with MI showed a twofold higher IFN-γ production to PHA-stimulation, up to 2.5-fold higher levels of IP-10 in serum and up to 30% lower serum levels of IL-16 compared to CMV-seronegative individuals. CMV-seropositive patients could be divided into two subgroups with high (IL-10Hi) and low (IL-10Lo) IL-10 serum levels during the acute stage of MI. The IL-10Hi CMV-seropositive subgroup showed an increased exit of late-differentiated T lymphocytes, NK and NKT-like cells from the circulation, which may potentially enhance cytotoxic damage in the ischemic myocardium. Finally, we did not observe an acceleration of autoimmunity by MI in CMV-seropositive individuals. The immune response during acute MI showed characteristic differences between CMV seronegative and seropositive patients, with a stronger pro-inflammatory response in seropositive patients. The effects of IP-10, IL-16, and IL-10 on characteristics of acute immune responses and formation of different immune profiles in CMV-seropositive individuals require further investigation. PMID:26029366

Antiganglioside antibodies in Guillain-Barré syndrome after a recent cytomegalovirus infection.

PubMed

Khalili-Shirazi, A; Gregson, N; Gray, I; Rees, J; Winer, J; Hughes, R

1999-03-01

To study the association between anti-ganglioside antibody responses and Guillan-Barré syndrome (GBS) after a recent cytomegalovirus (CMV) infection. Enzyme linked immunosorbant assay (ELISA) was undertaken on serum samples from 14 patients with GBS with recent cytomegalovirus (CMV) infection (CMV+GBS) and 12 without (CMV-GBS), 17 patients with other neurological diseases (OND), 11 patients with a recent CMV infection but without neurological involvement, 11 patients with recent Epstein-Barr virus (EBV) infection but without neurological involvement, and 20 normal control (NC) subjects. IgM antibodies were found at 1:100 serum dilution to gangliosides GM2 (six of 14 patients), GM1 (four of 14), GD1a (three of 14) and GD1b (two of 14) in the serum samples of the CMV+GBS patients, but not in those of any of the CMV-GBS patients. IgM antibodies were also found to gangliosides GM1, GD1a, and GD1b in one of 11 OND patients, to ganglioside GM1 in one of 11 non- neurological CMV patients, and to ganglioside GD1b in one of 20 NC subjects. Some patients with EBV infection had IgM antibodies to gangliosides GM1 (five of 11), GM2 (three of 11), and GD1a (two of 11). However, the antibodies to ganglioside GM2 had a low titre, none being positive at 1:200 dilution, whereas five of the CMV+GBS serum samples remained positive at this dilution. Antibodies to ganglioside GM2 are often associated with GBS after CMV infection, but their relevance is not known. It is unlikely that CMV infection and anti-ganglioside GM2 antibodies are solely responsible and an additional factor is required to elicit GBS.

Cribriform-morular variant of papillary thyroid carcinoma: an indication to screen for occult FAP.

PubMed

Levy, Rachel A; Hui, Vanessa W; Sood, Rupa; Fish, Stephanie; Markowitz, Arnold J; Wong, Richard J; Guillem, José G

2014-12-01

Cribriform-morular variant (CMV) is a rare subtype of papillary thyroid carcinoma (PTC) that is associated with familial adenomatous polyposis (FAP). Given the high likelihood for multi-organ malignancies in FAP patients, this study explores the yield of diagnosing occult FAP among CMV-PTC patients. Institutional database was searched in order to identify patients with pathologically-confirmed CMV-PTC from 2000 to 2012. Medical records were reviewed, and clinical and pathological features were analyzed. Eleven cases of CMV were identified from 6,901 patients with PTC, for a prevalence of 0.16 %. All 11 patients were female. The median age at CMV-PTC diagnosis was 36 years (range 18-46). Two patients had pre-existing FAP at the time of PTC diagnosis. The other nine patients were referred for colonoscopy and/or genetic testing. Six patients underwent colonoscopy and one (17 %) was diagnosed with FAP based on polyposis phenotype and genetic testing. The mean age of patients at the time of CMV-PTC diagnosis was younger in the FAP group (23 years, range 18-34) than in the sporadic group (37 years, range 25-46). All three patients with FAP-associated CMV-PTC had multicentric tumors, while all five sporadic patients did not. Our study found that approximately one-sixth of patients with CMV-PTC may have occult FAP. Patients with FAP-associated CMV-PTC appear to be younger and more likely to have multicentric tumors than those with sporadic CMV-PTC. Due to the increased risk of malignancy in patients with FAP, patients with CMV-PTC should be referred for colonoscopy and/or genetic evaluation for FAP.

Regulation of adaptive NK cells and CD8 T cells by HLA-C correlates with allogeneic hematopoietic cell transplantation and with CMV reactivation1

PubMed Central

Horowitz, Amir; Guethlein, Lisbeth A.; Nemat-Gorgani, Neda; Norman, Paul J.; Cooley, Sarah; Miller, Jeffrey S.; Parham, Peter

2015-01-01

Mass cytometry was used to investigate the effect of CMV reactivation on lymphocyte reconstitution in hematopoietic cell transplant patients. For eight transplant recipients, four CMV negative and four CMV positive, we studied peripheral blood mononuclear cells (PBMC) obtained six months after unrelated donor hematopoietic cell transplantation (HCT). Forty cell-surface markers, distinguishing all major leukocyte populations in PBMC, were analyzed by mass cytometry. These included 34 NK cell markers. Compared to healthy controls, transplant recipients had higher HLA-C expression on CD56−CD16+ NK cells, B cells, CD33bright myeloid cells and CD4CD8 T cells. The increase in HLA-C expression was greater for CMV-positive HCT recipients than CMV negative recipients. Present in CMV-positive HCT recipients, but not in CMV-negative HCT recipients or controls, is a population of KIR-expressing CD8 T cells not previously described. These CD8 T cells co-express CD56, CD57 and NKG2C. The HCT recipients also have a population of CD57+NKG2A+ NK cells that preferentially express KIR2DL1. An inverse correlation was observed between the frequencies of CD57+NKG2C+ NK cells and CD57+NKG2A+ NK cells. Although CD57+NKG2A+ NK cells are less abundant in CMV-positive recipients, their phenotype is of a more activated cell than the CD57+NKG2A+ NK cells of controls and CMV-negative HCT recipients. These data demonstrate that HCT and CMV reactivation are associated with an increased expression of HLA-C. This could influence NK cell education during lymphocyte reconstitution. The increased inhibitory KIR expression by proliferating CMV-specific CD8 T cells suggests regulatory interactions between HLA-C and KIR might promote GVL effects following transplantation. PMID:26416275

Valganciclovir Use Among Commercially and Medicaid-insured Infants With Congenital CMV Infection in the United States, 2009-2015.

PubMed

Leung, Jessica; Dollard, Sheila C; Grosse, Scott D; Chung, Winnie; Do, ThuyQuynh; Patel, Manisha; Lanzieri, Tatiana M

2018-03-01

The aim of this study was to assess the clinical characteristics and trends in valganciclovir use among infants diagnosed with congenital cytomegalovirus (CMV) disease in the United States. We analyzed data from medical claims dated 2009-2015 from the Truven Health MarketScan ® Commercial Claims and Encounters and Medicaid databases. We identified infants with a live birth code in the first claim who were continuously enrolled for at least 45 days. Among infants diagnosed with congenital CMV disease, identified by an ICD-9-CM or ICD-10-CM code for congenital CMV infection or CMV disease within 45 days of birth, we assessed data from claims containing codes for any CMV-associated clinical condition within the same period, and data from claims for hearing loss and/or valganciclovir within the first 180 days of life. In the commercial and Medicaid databases, we identified 257 (2.5/10,000) and 445 (3.3/10,000) infants, respectively, diagnosed with congenital CMV disease, among whom 135 (53%) and 282 (63%) had ≥1 CMV-associated condition, 30 (12%) and 32 (7%) had hearing loss, and 41 (16%) and 78 (18%) had a claim for valganciclovir. Among infants with congenital CMV disease who had a claim for valganciclovir, 37 (90%) among commercially insured infants and 68 (87%) among Medicaid-insured infants had ≥1 CMV-associated condition and/or hearing loss. From 2009 to 2015, the percentages with a claim for valganciclovir increased from 0% to 29% among commercially insured infants and from 4% to 37% among Medicaid-insured infants (P < 0.0001). During 2009-2015, there was a strong upward trend in valganciclovir claims among insured infants who were diagnosed with congenital CMV disease, the majority of whom had CMV-associated conditions and/or hearing loss. Published by Elsevier Inc.

[Quantitative real-time PCR--usefulness in detection and monitoring of CMV infection after hematopeietic stem cells transplant].

PubMed

Grabarczyk, Piotr; Brojer, Ewa; Nasiłowska, Barbara; Mariańska, Bozena

2006-09-01

It is recommended that all patients after allogeneic hematopoietic stem cell transplantation (alloHSCT) should be monitored for CMV infection markers. The aim of the study was to check the usefulness of quantitative DNA CMV monitoring after alloHSCT. DNA CMV was tested by real-time PCR in sera and blood samples twice a week until 30th day after alloHSCT thereafter, once a week until 100th day and then, once every 2-3 weeks. 832 samples from 16 patients were tested. All patients were anti-CMV positive or/and received stem cells from seropositive donors. Introduction of antiviral treatment was based on initial viral load and its rate of increase. DNA CMV was detected in 13/16 patients; in 3 before 30h day after allo HSCT (group I) and in 10 (group II) after 30th day. In all patients from group I clinical symptoms were observed and DNA CMV was detected in sera and blood samples. Peak viral load was 2490-34 620 geq/ml. Although antiviral treatment was applied, reinfection was observed and infection lasted from 28 to 91 days. In 6 group II patients, clinical symptoms were observed and DNA CMV in sera and blood was detected for 16-56 days, DNA CMV peak load was 100-8950 geq/ml. In the remaining 4 patients, no clinical symptoms were observed--DNA CMV was detected in blood only for 7 to 14 days. In one patient with peak viral load 10,540 geq/ml, antiviral treatment was applied. In 3 with viral load of 400-2000 geq/ml, treatment was not introduced. The quantitative DNA CMV results were taken into account before the change of antiviral drugs for more effective drugs and the decrease of drug dose due to side effects. Application of quantititative DNA CMV testing allowed to optimise antiviral drug administration in immunosupressed patients after alloHSCT

Reevaluation of the Coding Potential and Proteomic Analysis of the BAC Derived Rhesus Cytomegalovirus Strain 68-1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Malouli, Daniel; Nakayasu, Ernesto S.; Viswanathan, Kasinath

2012-09-01

Cytomegaloviruses are highly host restricted resulting in co-speciation with their hosts. As a natural pathogen of rhesus macaques (RM), Rhesus Cytomegalovirus (RhCMV) has therefore emerged as a highly relevant experimental model for pathogenesis and vaccine development due to its close evolutionary relationship to human CMV (HCMV). To date, most in vivo experiments performed with RhCMV employed strain 68-1 cloned as bacterial artificial chromosome (BAC). However, the complete genome sequence of the 68-1 BAC has not been determined. Furthermore, the gene content of the RhCMV genome is unknown and previous open reading frame (ORF) predictions relied solely on uninterrupted ORFs withmore » an arbitrary cutoff of 300bp. To obtain a more precise picture of the actual proteins encoded by the most commonly used molecular clone of RhCMV we re-evaluated the RhCMV 68-1 BAC-genome by whole genome shotgun sequencing and determined the protein content of the resulting RhCMV virions by proteomics. By additionally comparing the RhCMV genome to that of several closely related Old World Monkey (OWM) CMVs we were able to filter out many unlikely ORFs and obtain a simplified map of the RhCMV genome. This comparative genomics analysis eliminated many genes previously characterized as RhCMV-specific while consolidating a high conservation of ORFs among OWM-CMVs and between RhCMV and HCMV. Moreover, virion proteomics independently validated the revised ORF predictions since only proteins encoded by predicted ORFs could be detected. Taken together these data suggest a much higher conservation of genome and virion structure between CMVs of humans, apes and OWMs than previously assumed. Remarkably, BAC-derived RhCMV is able to establish and maintain persistent infection despite the lack of multiple genes homologous to HCMV genes involved in tissue tropism.« less

Cytomegalovirus infection in living-donor and cadaveric lung transplantations.

PubMed

Ohata, Keiji; Chen-Yoshikawa, Toyofumi F; Takahashi, Koji; Aoyama, Akihiro; Motoyama, Hideki; Hijiya, Kyoko; Hamaji, Masatsugu; Menju, Toshi; Sato, Toshihiko; Sonobe, Makoto; Takakura, Shunji; Date, Hiroshi

2017-11-01

Cytomegalovirus (CMV) infection remains a major cause of morbidity after lung transplantation. Some studies have reported prognostic factors for the postoperative development of CMV infection in cadaveric lung transplantation (CLT), but no research has been performed in living-donor lobar lung transplantation (LDLLT). Therefore, we analysed the possible risk factors of post-transplant CMV infection and the differences between LDLLT and CLT. The development of CMV disease and viraemia in 110 patients undergoing lung transplantation at Kyoto University Hospital in 2008-2015 were retrospectively assessed. The prognostic factors in the development of CMV infection and the differences between LDLLT and CLT were analysed. Among 110 patients, 58 LDLLTs and 52 CLTs were performed. The 3-year freedom rates from CMV disease and viraemia were 92.0% and 58.5%, respectively. There was no difference in the development of CMV infection between LDLLT and CLT (disease: 94.6% vs 91.0%, P = 0.58 and viraemia: 59.3% vs 57.2%, P = 0.76). In preoperative anti-CMV immunoglobulin status, R-D+ recipients (recipient: negative, donor: positive) and R-D- recipients (recipient: negative, donor: negative) tended to have higher and lower cumulative incidences, respectively, of CMV infection (disease: P = 0.34 and viraemia: P = 0.24) than that with R+ recipients (recipient: seropositive). Significantly lower cumulative incidence of CMV viraemia was observed in patients receiving 12-month prophylactic medication (70.6% vs 36.8%, P < 0.001). Twenty-eight patients (25.5%) had early cessation of anti-CMV prophylaxis due to toxicity; however, the extended prophylaxis duration did not increase the incidence of early cessation (P = 0.88). These trends were seen in both LDLLT and CLT. We found that there was no difference in the development of CMV infection between LDLLT and CLT. Twelve-month prophylaxis protocol provides beneficial effect without increased toxicity also in LDLLT. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Expression of Activating KIR2DS2 and KIR2DS4 genes following hematopoietic cell transplant (HCT): relevance to cytomegalovirus (CMV) infection

PubMed Central

Gallez-Hawkins, Ghislaine M.; Franck, Anne E.; Li, Xiuli; Thao, Lia; Oki, Arisa; Gendzekhadze, Ketevan; Dagis, Andrew; Palmer, Joycelynne; Nakamura, Ryotaro; Forman, Stephen J.; Senitzer, David; Zaia, John A.

2011-01-01

The important role of activating Killer Immunoglobulin-like Receptors (aKIR) in protecting against cytomegalovirus (CMV) reactivation has been described previously in hematopoietic cell transplantation (HCT). More specifically, the presence of multiple aKIR and the presence of at least KIR2DS2 and KIR2DS4 in the donor genotype identified a group of HCT patients that were at low risk for CMV reactivation. However, CMV infection still occurs in patients with KIR protective genotype and the question was raised as to whether this was due to the lack of KIR expression. In this report, the expression of KIR2DS2 and 2DS4 gene, as measured by mRNA-based Q-PCR both in the donor cells and in the HCT recipient cells was studied relative to CMV reactivation. In the control samples from healthy HCT donors, the median range of for KIR2DS2 and KIR2DS4 expression was low with 35% considered null-expressers. Interestingly, KIR2DS2 and KIR2DS4 expression was elevated after HCT when compared to donor expression prior to transplant, and significantly elevated in the CMV viremic (V) compared to non-viremic (NV) HCT recipients. CMV seropositivity of donors was not associated with aKIR expression, and donor null-expression in those with KIR2DS2 or KIR2DS4 genotype did not predict for CMV reactivation in the recipient. After controlling for other transplant factors that included donor type (sibling or unrelated), transplant source -bone marrow (BM) or peripheral blood stem cells (PB) and acute GVHD grade, the result of the regression analysis of elevated KIR gene expression was found to be associated for both KIR2DS2 and KIR2DS4, with seven fold increase in risk for CMV reactivation. We speculate that the elevated aKIR expression in CMV viremic HCT recipients is either coincidental with factors that activate CMV or is initiated by CMV or cellular processes responsive to such CMV infection reactivation. PMID:21596150

Rapid identification of QTLs underlying resistance to Cucumber mosaic virus in pepper (Capsicum frutescens).

PubMed

Guo, Guangjun; Wang, Shubin; Liu, Jinbing; Pan, Baogui; Diao, Weiping; Ge, Wei; Gao, Changzhou; Snyder, John C

2017-01-01

Next-generation sequencing enabled a fast discovery of QTLs controlling CMV resistant in pepper. The gene CA02g19570 as a possible candidate gene of qCmr2.1 was identified for resistance to CMV in pepper. Cucumber mosaic virus (CMV) is one of the most important viruses infecting pepper, but the genetic basis of CMV resistance in pepper is elusive. In this study, we identified a candidate gene for CMV resistance QTL, qCmr2.1 through SLAF-seq. Segregation analysis in F 2 , BC 1 and F 2:3 populations derived from a cross between two inbred lines 'PBC688' (CMV-resistant) and 'G29' (CMV-susceptible) suggested quantitative inheritance of resistance to CMV in pepper. Genome-wide comparison of SNP profiles between the CMV-resistant and CMV-susceptible bulks constructed from an F 2 population identified two QTLs, designated as qCmr2.1 on chromosome 2 and qCmr11.1 on chromosome 11 for resistance to CMV in PBC688, which were confirmed by InDel marker-based classical QTL mapping in the F 2 population. As a major QTL, joint SLAF-seq and traditional QTL analysis delimited qCmr2.1 to a 330 kb genomic region. Two pepper genes, CA02g19570 and CA02g19600, were identified in this region, which are homologous with the genes LOC104113703, LOC104248995, LOC102603934 and LOC101248357, which were predicted to encode N-like protein associated with TMV-resistant in Solanum crops. Quantitative RT-PCR revealed higher expression levels of CA02g19570 in CMV resistance genotypes. The CA02g19600 did not exhibit obvious regularity in expression patterns. Higher relative expression levels of CA02g19570 in PBC688 and F 1 were compared with those in G29 during days after inoculation. These results provide support for CA02g19570 as a possible candidate gene of qCmr2.1 for resistance to CMV in pepper.

75 FR 48724 - Notice of Receipt of Complaint; Solicitation of Comments Relating to the Public Interest

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-11

... any public interest issues raised by the complaint. FOR FURTHER INFORMATION CONTACT: Marilyn Abbott... Commission. Marilyn R. Abbott, Secretary to the Commission. [FR Doc. 2010-19763 Filed 8-10-10; 8:45 am...

75 FR 53710 - Notice of Receipt of Complaint; Solicitation of Comments Relating to the Public Interest

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-01

...: Marilyn R. Abbott, Secretary to the Commission, U.S. International Trade Commission, 500 E Street, SW... Commission. Issued: August 26, 2010. Marilyn R. Abbott, Secretary to the Commission. [FR Doc. 2010-21789...

A checklist of the vascular plants in Abbott Creek Research Natural Area, Oregon.

Treesearch

Rod Mitchell

1979-01-01

This paper is a checklist of 277 vascular plant taxa that have been collected or encountered in Abbott Creek Research Natural Area, Oregon; a brief description of five forested and two nonforested vegetation types is included.

Cytomegalovirus Replication in Semen Is Associated with Higher Levels of Proviral HIV DNA and CD4+ T Cell Activation during Antiretroviral Treatment

PubMed Central

Massanella, Marta; Richman, Douglas D.; Little, Susan J.; Spina, Celsa A.; Vargas, Milenka V.; Lada, Steven M.; Daar, Eric S.; Dube, Michael P.; Haubrich, Richard H.; Morris, Sheldon R.; Smith, Davey M.

2014-01-01

ABSTRACT Asymptomatic cytomegalovirus (CMV) replication occurs frequently in the genital tract in untreated HIV-infected men and is associated with increased immune activation and HIV disease progression. To determine the connections between CMV-associated immune activation and the size of the viral reservoir, we evaluated the interactions between (i) asymptomatic seminal CMV replication, (ii) levels of T cell activation and proliferation in blood, and (iii) the size and transcriptional activity of the HIV DNA reservoir in blood from 53 HIV-infected men on long-term antiretroviral therapy (ART) with suppressed HIV RNA in blood plasma. We found that asymptomatic CMV shedding in semen was associated with significantly higher levels of proliferating and activated CD4+ T cells in blood (P < 0.01). Subjects with detectable CMV in semen had approximately five times higher average levels of HIV DNA in blood CD4+ T cells than subjects with no CMV. There was also a trend for CMV shedders to have increased cellular (multiply spliced) HIV RNA transcription (P = 0.068) compared to participants without CMV, but it is unclear if this transcription pattern is associated with residual HIV replication. In multivariate analysis, the presence of seminal plasma CMV (P = 0.04), detectable 2-long terminal repeat (2-LTR), and lower nadir CD4+ (P < 0.01) were independent predictors of higher levels of proviral HIV DNA in blood. Interventions aimed at reducing seminal CMV and associated immune activation may be important for HIV curative strategies. Future studies of anti-CMV therapeutics will help to establish causality and determine the mechanisms underlying these described associations. IMPORTANCE Almost all individuals infected with HIV are also infected with cytomegalovirus (CMV), and the replication dynamics of the two viruses likely influence each other. This study investigated interactions between asymptomatic CMV replication within the male genital tract, levels of inflammation in blood, and the size of the HIV DNA reservoir in 53 HIV-infected men on long-term antiretroviral therapy (ART) with suppressed HIV RNA in blood plasma. In support of our primary hypothesis, shedding of CMV DNA in semen was associated with increased activation and proliferation of T cells in blood and also significantly higher levels of HIV DNA in blood cells. These results suggest that CMV reactivation might play a role in the maintenance of the HIV DNA reservoir during suppressive ART and that it could be a target of pharmacologic intervention in future studies. PMID:24789781

“Targeted” Screening for Cytomegalovirus (CMV)-Related Hearing Loss: It’s Time for Universal CMV Screening in the NICU!

PubMed Central

Medoro, Alexandra; Malhotra, Prashant; Shimamura, Masako; Hounam, Gina; Findlen, Ursula; Wozniak, Phillip; Foor, Nicholas; Adunka, Oliver; Sanchez, Pablo J

2017-01-01

Abstract Background Congenital CMV infection is the leading cause of non-genetic sensorineural hearing loss in infancy. Antiviral therapy has been shown to improve hearing outcomes, and thus “targeted” CMV screening for newborns who do not pass the hearing screen has been recommended. Diagnosis of congenital CMV infection requires that the infant be tested for CMV in the first 3 weeks of age. Our objective was to determine when infants in the neonatal intensive care unit (NICU) have their first hearing screen performed and thus inform the practice of targeted screening for determination of CMV-related hearing loss. Methods Retrospective review of the electronic health records of all infants admitted to the Level 4 outborn NICU at Nationwide Children’s Hospital, Columbus, OH from August 2016 to May 2017. Demographic and clinical data were obtained, and the age that the first hearing screen was performed was assessed. Results During the 10 month study period, 362 infants were admitted to the NICU and had a first hearing screen performed. The majority of neonates (204, 56%) had a first hearing screen performed in the first 3 weeks of age. However, 158 (44%; median birth weight [IQR], 1072 g [747–1766]; median gestational age [IQR], 28 weeks [25–32]) infants received the first hearing screen at >3 weeks of age when a positive CMV PCR or culture cannot distinguish congenital infection from intrapartum/postnatal acquisition of CMV. Of the 158 infants, 20 (13%) did not pass the first hearing screen (13, unilateral; 7, bilateral), and subsequently, 9 of them did pass a second hearing screen. However, 11 of the 20 infants did not pass a second hearing screen and had urine CMV PCR testing, and 1 (9%) was positive. This latter infant’s newborn dried blood spot CMV DNA PCR was negative so a diagnosis of congenital CMV infection was not possible. Conclusion Targeted screening in the NICU for CMV-related hearing loss is problematic as a substantial number of infants do not have a hearing screen performed until after 21 days of age, thus representing a missed opportunity for diagnosis of congenital CMV infection and institution of antiviral therapy if indicated. Our findings support universal CMV screening of neonates on admission to the NICU. Disclosures O. Adunka, MED-EL Corporation: Consultant, Consulting fee, Educational grant and Research support; Advanced Bionics: Consultant, Consulting fee and Licensing agreement or royalty; Advanced Cochlear Diagnostics: President, Ownership interest; AGTC Corporation: Consultant, Consulting fee

A phase I-II trial to examine the toxicity of CMV- and EBV-specific cytotoxic T lymphocytes when used for prophylaxis against EBV and CMV disease in recipients of CD34-selected/T cell-depleted stem cell transplants.

PubMed

Lucas, K G; Sun, Q; Burton, R L; Tilden, A; Vaughan, W P; Carabasi, M; Salzman, D; Ship, A

2000-07-01

Epstein-Barr virus (EBV)-induced lymphoproliferative disease and cytomegalovirus (CMV) infection are major causes of morbidity and mortality in individuals with compromised cellular immunity. Although anti-viral pharmacological agents exist, severe side effects such as myelosuppression often limit the application of these medications. Infusion of ex vivo-expanded, virus-specific cytotoxic T-lymphocytes (CTL) has been proven to be safe and efficacious for the prophylaxis and treatment of EBV and CMV complications. While EBV-specific CTL can be readily and reliably produced with EBV-immortalized B-lymphoblastoid cell lines (BLCL) as stimulators, current protocols for CMV-specific CTL, which use CMV-infected fibroblasts as stimulators, may be associated with alloreactivity and the need for cloning, as well as the potential for exposure to human blood-born infectious agents. Our laboratory has developed a novel system to generate EBV/CMV-bi-specific CTL by co-culturing PBMC with autologous BLCL expressing a CMV protein pp65 (BLCLpp65) (Sun et al., 1999). pp65, an immunodominant CMV antigen, is transduced into BLCL by a recombinant retrovirus MSCVpp65. While low in alloreactivity, BLCLpp65-stimulated CTL are cytolytic to autologous cells infected with EBV or CMV, and this cytotoxicity is mediated by polyclonal, CD8+, MHC Class I-restricted T-cells. Further experiments revealed that retroviral transduction and expression of pp65 do not compromise the capacity of presenting EBV antigens, and T cells stimulated by BLCLpp65 recognize clinical strains of CMV (Sun et al., 2000). These data indicated that BLCLpp65 could substitute for BLCL as antigen presenting cells in adoptive immunotherapy against EBV-LPD, with the benefit of providing protection against CMV reactivation. This protocol is a Phase I/II study to examine the toxicity associated with and the immunologic effects of ex vivo simultaneously expanded EBV- and CMV-specific CTL for prophylaxis against EBV and CMV complications in recipients of CD34 selected/T-cell depleted stem cell transplants (SCT). EBV/CMV-specific CTL will be generated from peripheral blood mononuclear cells (PBMC) of EBV/CMV-seropositive donors in a course of from 21-28 days by weekly stimulation with autologous BLCLpp65. Qualified CTL will be administered to consenting patients at 40, 60, and 80 days post-transpOFF criteria of molecular virology and immunological reconstitution, which include blood levels of pp65 antigen and EBV viral DNA, and virus-specific CTL precursor frequency. Patients will also be tested for replication-competent retrovirus at 3, 6, and 12 month intervals post-transplant to ensure bio-safety.

The distribution of Abbott high-sensitivity troponin I levels in Korean patients with chest pain.

PubMed

Lee, Kyunghoon; Lee, Soo-Youn; Choi, Jin-Oh; Jeon, Eun-Seok; Park, Hyung-Doo

2015-01-01

Troponin is considered a primary biomarker for coronary heart disease. We investigated the clinical utility of the Abbott high-sensitivity cardiac troponin I (hs-TnI) assay in patients with various cardiac problems. Precision was investigated by ten levels of pooled sera and three levels of control materials. We determined Abbott hs-TnI levels in a total of 3314 Korean patients with chest pain, including acute myocardial infarction (n=381), unstable angina (n=327), stable angina (n=1361), variant angina (n=189), non-coronary artery diseases (n=236), and nonspecific chest pain (n=820). The 99(th) percentile cutoff was established by the plasma from the cardio-healthy subgroup and validated by 118 healthy individuals. The total coefficient of variation in patient pooled sera and controls ranged from 3.93-6.35% and 4.81-9.73%, respectively. There was a significant difference in hs-TnI among various cardiac problems: subjects with non-cardiac chest pain (median 1.7 pg/mL, 25%/75% quartile 1.1/2.8 pg/mL), variant angina (2.4 pg/mL,1.4/5.6 pg/mL), stable angina (3.7 pg/mL, 2.1/8.9 pg/mL), unstable angina (10.7 pg/mL, 3.7/61.7 pg/mL), and non-coronary artery diseases (9.3 pg/mL, 4.3/37.4 pg/mL). However, the median levels of hs-TnI were not statistically different (p=0.921) between unstable angina and non-coronary artery diseases. The overall 99(th) percentile cutoff was 19.3 pg/mL (range 0.2-30.6 pg/mL). This new hs-TnI assay may be helpful in determining a differential diagnosis in patients with chest pain. © 2015 by the Association of Clinical Scientists, Inc.

49 CFR 383.37 - Employer responsibilities.

Code of Federal Regulations, 2011 CFR

2011-10-01

... operate a CMV in the United States in any of the following circumstances: (a) During any period in which... endorsements. An employer may not use a driver to operate a CMV who violates any restriction on the driver's... lost the right to operate a CMV in a State, or has been disqualified from operating a CMV. (c) During...

49 CFR 383.37 - Employer responsibilities.

Code of Federal Regulations, 2012 CFR

2012-10-01

... operate a CMV in the United States in any of the following circumstances: (a) During any period in which... endorsements. An employer may not use a driver to operate a CMV who violates any restriction on the driver's... lost the right to operate a CMV in a State, or has been disqualified from operating a CMV. (c) During...

Detection of Human Cytomegalovirus DNA by Real-Time Quantitative PCR

PubMed Central

Nitsche, Andreas; Steuer, Nina; Schmidt, Christian Andreas; Landt, Olfert; Ellerbrok, Heinz; Pauli, Georg; Siegert, Wolfgang

2000-01-01

A real-time PCR assay was developed to quantify human cytomegalovirus (CMV) DNA. This assay was used to demonstrate a higher CMV DNA load in plasma of bone marrow transplant patients than in that of blood donors. The CMV load was higher in CMV antigen-positive patients than in antigen-negative patients. PMID:10878073

CMV colitis in early HIV infection.

PubMed

Smith, P R; Glynn, M; Sheaff, M; Aitken, C

2000-11-01

Cytomegalovirus (CMV) colitis is a well recognized complication of advanced HIV disease and is only rarely diagnosed in patients with normal immune function. A case of CMV colitis occurring in early HIV infection is described. Although CMV infection is normally confined to patients with advanced HIV disease, it is possible that a number of contributing factors may have led to clinical disease in this patient. CMV colitis is an important diagnosis to consider in all patients who present with a diarrhoeal illness associated with systemic features, regardless of underlying immunosuppression.

Reactivation and shedding of cytomegalovirus in astronauts during spaceflight

NASA Technical Reports Server (NTRS)

Mehta, S. K.; Stowe, R. P.; Feiveson, A. H.; Tyring, S. K.; Pierson, D. L.

2000-01-01

The reactivation of cytomegalovirus (CMV) in 71 astronauts was investigated, using polymerase chain reaction. A significantly greater (P<.0001) shedding frequency was found in urine samples from astronauts before spaceflight (10.6%) than in urine from the healthy control subject group (1.2%). Two of 4 astronauts studied during spaceflight shed CMV in urine. A significant increase (P<.0001) in CMV antibody titer, compared with baseline values, was also found 10 days before spaceflight. CMV antibody titer was further increased (P<.001) 3 days after landing, compared with 10 days before the mission. Significant increases in stress hormones were also found after landing. These results demonstrate that CMV reactivation occurred in astronauts before spaceflight and indicate that CMV may further reactivate during spaceflight.

Pulmonary cytomegalovirus infection: detection by Gallium-67 imaging in the transplant patient

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hamed, I.A.; Wenzl, J.E.; Leonard, J.C.

1979-03-01

Cytomegalovirus (CMV) infection is a frequent complication during the first few months following renal transplantation. The diagnosis is sometimes difficult but may be made by viral culture, a fourfold rise in the CMV antibody titer, or by demonstration of the CMV inclusions in the affected tissue. An increased pulmonary uptake of gallium citrate Ga 67 has been demonstrated following renal transplantation in two patients, each of whom had a fourfold rise in CMV complement fixing antibody titer, one of whom additionally had CMV inclusion bodies in a lung biopsy specimen prior to clinical or radiological demonstration of the pulmonary involvement.more » Gallium imaging, therefore, appears to be a valuable noninvasive test for early diagnosis of CMV pulmonary infections.« less

Commercial Motor Vehicle (CMV) Driver Restart Study: Final Report

DOT National Transportation Integrated Search

2017-03-01

A congressionally-mandated naturalistic study was conducted to evaluate the operational, safety, fatigue, and health impacts of the restart provisions in Sections 395.3(c) and 395.3(d) of Title 49, Code of Federal Regulations. A total of 235 commerci...

Correlation between viral load of cytomegalovirus and tacrolimus and sirolimus levels in transplanted pediatric patients.

PubMed

Reyes-Pérez, Herlinda; Sánchez-Huerta, José Luis; Varela-Fascinetto, Gustavo; Romo-Vázquez, José Carlos; Morales-Sánchez, Abigail; Fuentes-Pananá, Ezequiel M; Parra-Ortega, Israel; Ramírez-Ramírez, Graciela; López-Martínez, Briceida

Survival of transplant patients and grafts depends largely on the use of immunosuppressive drugs. However, a balance remains to be established among immunosuppression, transplant rejection and cytomegalovirus (CMV) infection, which results in a high rate of morbidity and mortality. The aim of this study was to define a better strategy for monitoring transplanted patients based on the analysis of the blood concentration of sirolimus and tacrolimus and the burden of CMV. Fifty five post-transplant (kidney and liver) pediatric patients, nine treated with sirolimus and 46 treated with tacrolimus, were included. A total of 541 measurements were obtained. In each measurement the concentration of immunosuppressant in whole blood and CMV viral load in plasma and whole blood was quantified by real-time PCR. Pearson correlation coefficient (r) was estimated. Values of r ≤0.0747 were found for the relationship between dose and concentration of immunosuppressant; r = 0.9406 for the relationship between viral load in whole blood and plasma, and r ≤0.4616 for the relationship between concentration of immunosuppressant and viral load. These data support that the doses of immunosuppressive drugs do not correlate with the levels of the same in whole blood. Therefore, systemic levels of immunosuppressant should be constantly monitored together with CMV load. Meanwhile, a high correlation between viral load measured in whole blood and plasma was found. Copyright © 2016 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

The impact of change in albumin assay on reference intervals, prevalence of 'hypoalbuminaemia' and albumin prescriptions.

PubMed

Coley-Grant, Deon; Herbert, Mike; Cornes, Michael P; Barlow, Ian M; Ford, Clare; Gama, Rousseau

2016-01-01

We studied the impact on reference intervals, classification of patients with hypoalbuminaemia and albumin infusion prescriptions on changing from a bromocresol green (BCG) to a bromocresol purple (BCP) serum albumin assay. Passing-Bablok regression analysis and Bland-Altman plot were used to compare Abbott BCP and Roche BCG methods. Linear regression analysis was used to compare in-house and an external laboratory Abbott BCP serum albumin results. Reference intervals for Abbott BCP serum albumin were derived in two different laboratories using pathology data from adult patients in primary care. Prescriptions for 20% albumin infusions were compared one year before and one year after changing the albumin method. Abbott BCP assay had a negative bias of approximately 6 g/L compared with Roche BCG method.There was good agreement (y = 1.04 x - 1.03; R(2 )= 0.9933) between in-house and external laboratory Abbott BCP results. Reference intervals for the serum albumin Abbott BCP assay were 31-45 g/L, different to those recommended by Pathology Harmony and the manufacturers (35-50 g/L). Following the change in method there was a large increase in the number of patients classified as hypoalbuminaemic using Pathology Harmony references intervals (32%) but not when retrospectively compared to locally derived reference intervals (16%) compared with the previous year (12%). The method change was associated with a 44.6% increase in albumin prescriptions. This equated to an annual increase in expenditure of £35,234. We suggest that serum albumin reference intervals be method specific to prevent misclassification of albumin status in patients. Change in albumin methodology may have significant impact on hospital resources. © The Author(s) 2015.

Evaluation of the clinical performance of the Abbott RealTime High-Risk HPV for carcinogenic HPV detection.

PubMed

Halfon, Philippe; Benmoura, Dominique; Agostini, Aubert; Khiri, Hacene; Penaranda, Guillaume; Martineau, Agnes; Blanc, Bernard

2010-08-01

Abbott RealTime (RT) High-Risk (HR) HPV assay is a new qualitative real-time polymerase chain reaction (PCR) based assay for the detection of 14 HR HPV DNA. The assay can differentiate between the infection by HPV 16, HPV 18 and non-HPV 16/18 types through the distinct fluorescent labels on the type specific probes. To evaluate the clinical performance of the Abbott RT HR HPV test, in comparison with biopsy, Hybrid Capture II (HCII), and Linear Array (LA), for detection of high-grade disease (CIN2+). The study population consisted of 143 women who were included in three referral gynecology clinics in Marseilles (France) between March 2007 and June 2008. The clinical performance of the RT HR HPV assay, performed on the fully automated m2000 system, was compared with HCII and LA. HR HPV positivity rate was similar for all tests (Abbott RT HR HPV and HCII, 62%, and LA 63%). All tests had high sensitivities and negative predictive values for CIN2+ detection (>90%). The agreement between HCII and Abbott RT HR HPV, and between HCII and LA were 93% (k=0.85) and 96% (k=0.91) respectively. As expected, HPV16 or HPV18 positivity was greater in advanced grades of disease, especially in CIN2+ patients: 85% in CIN2+ vs. 33% in

Comparison of the Chiron Quantiplex branched DNA (bDNA) assay and the Abbott Genostics solution hybridization assay for quantification of hepatitis B viral DNA.

PubMed

Kapke, G E; Watson, G; Sheffler, S; Hunt, D; Frederick, C

1997-01-01

Several assays for quantification of DNA have been developed and are currently used in research and clinical laboratories. However, comparison of assay results has been difficult owing to the use of different standards and units of measurements as well as differences between assays in dynamic range and quantification limits. Although a few studies have compared results generated by different assays, there has been no consensus on conversion factors and thorough analysis has been precluded by small sample size and limited dynamic range studied. In this study, we have compared the Chiron branched DNA (bDNA) and Abbott liquid hybridization assays for quantification of hepatitis B virus (HBV) DNA in clinical specimens and have derived conversion factors to facilitate comparison of assay results. Additivity and variance stabilizing (AVAS) regression, a form of non-linear regression analysis, was performed on assay results for specimens from HBV clinical trials. Our results show that there is a strong linear relationship (R2 = 0.96) between log Chiron and log Abbott assay results. Conversion factors derived from regression analyses were found to be non-constant and ranged from 6-40. Analysis of paired assay results below and above each assay's limit of quantification (LOQ) indicated that a significantly (P < 0.01) larger proportion of observations were below the Abbott assay LOQ but above the Chiron assay LOQ, indicating that the Chiron assay is significantly more sensitive than the Abbott assay. Testing of replicate specimens showed that the Chiron assay consistently yielded lower per cent coefficients of variance (% CVs) than the Abbott assay, indicating that the Chiron assay provides superior precision.

A randomized, phase 2 study of ASP0113, a DNA-based vaccine, for the prevention of CMV in CMV-seronegative kidney transplant recipients receiving a kidney from a CMV-seropositive donor.

PubMed

Vincenti, Flavio; Budde, Klemens; Merville, Pierre; Shihab, Fuad; Peddi, V Ram; Shah, Malay; Wyburn, Kate; Cassuto-Viguier, Elisabeth; Weidemann, Alexander; Lee, Misun; Flegel, Teresa; Erdman, Jay; Wang, Xuegong; Lademacher, Christopher

2018-05-09

Cytomegalovirus (CMV) is a latent infection in most infected individuals, but can be pathogenic in immunocompromised kidney transplant recipients. ASP0113 is a DNA-based vaccine for the prevention of CMV-related mortality and end-organ disease in transplant recipients. The efficacy, safety, and immunogenicity of ASP0113 was assessed in a phase 2, double-blind, placebo-controlled study in CMV-seronegative kidney transplant recipients receiving a kidney from a CMV-seropositive donor. Transplant recipients were randomized (1:1) to receive five doses of ASP0113 (5 mg; n=75) or placebo (n=74) on Days 30/60/90/120/180 post transplant, and received prophylactic valganciclovir/ganciclovir 10-100 days post transplant. The primary endpoint was the proportion of transplant recipients with CMV viremia ≥1000 IU/mL from Day 100 through to 1 year after first study vaccine injection. There was no statistically significant difference in the primary endpoint between the ASP0113 and placebo groups (odds ratio 0.79, 95% confidence interval 0.43-1.47; p=0.307). There were similar numbers of transplant recipients with treatment-emergent adverse events between groups; however, more transplant recipients reported injection site pain in the ASP0113 group compared with placebo. ASP0113 did not demonstrate efficacy in the prevention of CMV viremia in this CMV-seronegative kidney transplant population, but demonstrated a safety profile similar to placebo. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Hypoxia-response plasmid vector producing bcl-2 shRNA enhances the apoptotic cell death of mouse rectum carcinoma.

PubMed

Fujioka, Takashi; Matsunaga, Naoya; Okazaki, Hiroyuki; Koyanagi, Satoru; Ohdo, Shigehiro

2010-01-01

Hypoxia-induced gene expression frequently occurs in malignant solid tumors because they often have hypoxic areas in which circulation is compromised due to structurally disorganized blood vessels. Hypoxia-response elements (HREs) are responsible for activating gene transcription in response to hypoxia. In this study, we constructed a hypoxia-response plasmid vector producing short hairpin RNA (shRNA) against B-cell leukemia/lymphoma-2 (bcl-2), an anti-apoptotic factor. The hypoxia-response promoter was made by inserting tandem repeats of HREs upstream of cytomegalovirus (CMV) promoter (HRE-CMV). HRE-CMV shbcl-2 vector consisted of bcl-2 shRNA under the control of HRE-CMV promoter. In hypoxic mouse rectum carcinoma cells (colon-26), the production of bcl-2 shRNA driven by HRE-CMV promoter was approximately 2-fold greater than that driven by CMV promoter. A single intratumoral (i.t.) injection of 40 microg HRE-CMV shbcl-2 to colon-26 tumor-bearing mice caused apoptotic cell death, and repetitive treatment with HRE-CMV shbcl-2 (40 microg/mouse, i.t.) also significantly suppressed the growth of colon-26 tumor cells implanted in mice. Apoptotic and anti-tumor effects were not observed in tumor-bearing mice treated with CMV shbcl-2. These results reveal the ability of HRE-CMV shbcl-2 vector to suppress the expression of bcl-2 in hypoxic tumor cells and suggest the usefulness of our constructed hypoxia-response plasmid vector to treat malignant tumors. [Supplementary Figures: available only at http://dx.doi.org/10.1254/jphs.10054FP].

Cytomegalovirus survival and transferability and the effectiveness of common hand-washing agents against cytomegalovirus on live human hands.

PubMed

Stowell, Jennifer D; Forlin-Passoni, Daniela; Radford, Kay; Bate, Sheri L; Dollard, Sheila C; Bialek, Stephanie R; Cannon, Michael J; Schmid, D Scott

2014-01-01

Congenital cytomegalovirus (CMV) transmission can occur when women acquire CMV while pregnant. Infection control guidelines may reduce risk for transmission. We studied the duration of CMV survival after application of bacteria to the hands and after transfer from the hands to surfaces and the effectiveness of cleansing with water, regular and antibacterial soaps, sanitizer, and diaper wipes. Experiments used CMV AD169 in saliva at initial titers of 1 × 10(5) infectious particles/ml. Samples from hands or surfaces (points between 0 and 15 min) were placed in culture and observed for at least 2 weeks. Samples were also tested using CMV real-time PCR. After application of bacteria to the hands, viable CMV was recovered from 17/20 swabs at 0 min, 18/20 swabs at 1 min, 5/20 swabs at 5 min, and 4/20 swabs at 15 min. After transfer, duration of survival was at least 15 min on plastic (1/2 swabs), 5 min on crackers and glass (3/4 swabs), and 1 min or less on metal and cloth (3/4 swabs); no viable virus was collected from wood, rubber, or hands. After cleansing, no viable virus was recovered using water (0/22), plain soap (0/20), antibacterial soap (0/20), or sanitizer (0/22). Viable CMV was recovered from 4/20 hands 10 min after diaper wipe cleansing. CMV remains viable on hands for sufficient times to allow transmission. CMV may be transferred to surfaces with reduced viability. Hand-cleansing methods were effective at eliminating viable CMV from hands.

AABB Committee Report: reducing transfusion-transmitted cytomegalovirus infections.

PubMed

Heddle, Nancy M; Boeckh, Michael; Grossman, Brenda; Jacobson, Jessica; Kleinman, Steven; Tobian, Aaron A R; Webert, Kathryn; Wong, Edward C C; Roback, John D

2016-06-01

Transfusion-transmitted cytomegalovirus (TT-CMV) is often asymptomatic, but certain patient populations, such as very low birth weight neonates, fetuses requiring intrauterine transfusion, pregnant women, patients with primary immunodeficiencies, transplant recipients, and patients receiving chemotherapy or transplantation for malignant disease, may be at risk of life-threatening CMV infection. It is unclear whether leukoreduction of cellular blood components is sufficient to reduce TT-CMV or whether CMV serological testing adds additional benefit to leukoreduction. The AABB CMV Prevention Work Group commissioned a systematic review to address these issues and subsequently develop clinical practice guidelines. However, the data were of poor quality, and no studies of significant size have been performed for over a decade. Rather than creating guidelines of questionable utility, the Work Group (with approval of the AABB Board of Directors) voted to prepare this Committee Report. There is wide variation in practices of using leukoreduced components alone or combining CMV-serology and leukoreduction to prevent TT-CMV for at-risk patients. Other approaches may also be feasible to prevent TT-CMV, including plasma nucleic acid testing, pathogen inactivation, and patient blood management programs to reduce the frequency of inappropriate transfusions. It is unlikely that future large-scale clinical trials will be performed to determine whether leukoreduction, CMV-serology, or a combination of both is superior. Consequently, alternative strategies including pragmatic randomized controlled trials, registries, and collaborations for electronic data merging, nontraditional approaches to inform evidence, or development of a systematic approach to inform expert opinion may help to address the issue of CMV-safe blood components. © 2016 AABB.

Cytomegalovirus Survival and Transferability and the Effectiveness of Common Hand-Washing Agents against Cytomegalovirus on Live Human Hands

PubMed Central

Stowell, Jennifer D.; Forlin-Passoni, Daniela; Radford, Kay; Bate, Sheri L.; Dollard, Sheila C.; Bialek, Stephanie R.; Cannon, Michael J.

2014-01-01

Congenital cytomegalovirus (CMV) transmission can occur when women acquire CMV while pregnant. Infection control guidelines may reduce risk for transmission. We studied the duration of CMV survival after application of bacteria to the hands and after transfer from the hands to surfaces and the effectiveness of cleansing with water, regular and antibacterial soaps, sanitizer, and diaper wipes. Experiments used CMV AD169 in saliva at initial titers of 1 × 105 infectious particles/ml. Samples from hands or surfaces (points between 0 and 15 min) were placed in culture and observed for at least 2 weeks. Samples were also tested using CMV real-time PCR. After application of bacteria to the hands, viable CMV was recovered from 17/20 swabs at 0 min, 18/20 swabs at 1 min, 5/20 swabs at 5 min, and 4/20 swabs at 15 min. After transfer, duration of survival was at least 15 min on plastic (1/2 swabs), 5 min on crackers and glass (3/4 swabs), and 1 min or less on metal and cloth (3/4 swabs); no viable virus was collected from wood, rubber, or hands. After cleansing, no viable virus was recovered using water (0/22), plain soap (0/20), antibacterial soap (0/20), or sanitizer (0/22). Viable CMV was recovered from 4/20 hands 10 min after diaper wipe cleansing. CMV remains viable on hands for sufficient times to allow transmission. CMV may be transferred to surfaces with reduced viability. Hand-cleansing methods were effective at eliminating viable CMV from hands. PMID:24185855

The movement protein of cucumber mosaic virus traffics into sieve elements in minor veins of nicotiana clevelandii

PubMed Central

Blackman, LM; Boevink, P; Cruz, SS; Palukaitis, P; Oparka, KJ

1998-01-01

The location of the 3a movement protein (MP) of cucumber mosaic virus (CMV) was studied by quantitative immunogold labeling of the wild-type 3a MP in leaves of Nicotiana clevelandii infected by CMV as well as by using a 3a-green fluorescent protein (GFP) fusion expressed from a potato virus X (PVX) vector. Whether expressed from CMV or PVX, the 3a MP targeted plasmodesmata and accumulated in the central cavity of the pore. Within minor veins, the most extensively labeled plasmodesmata were those connecting sieve elements and companion cells. In addition to targeting plasmodesmata, the 3a MP accumulated in the parietal layer of mature sieve elements. Confocal imaging of cells expressing the 3a-GFP fusion protein showed that the 3a MP assembled into elaborate fibrillar formations in the sieve element parietal layer. The ability of 3a-GFP, expressed from PVX rather than CMV, to enter sieve elements demonstrates that neither the CMV RNA nor the CMV coat protein is required for trafficking of the 3a MP into sieve elements. CMV virions were not detected in plasmodesmata from CMV-infected tissue, although large CMV aggregates were often found in the parietal layer of sieve elements and were usually surrounded by 3a MP. These data suggest that CMV traffics into minor vein sieve elements as a ribonucleoprotein complex that contains the viral RNA, coat protein, and 3a MP, with subsequent viral assembly occurring in the sieve element parietal layer. PMID:9548980

Evaluation of CMV/human herpes virus-6 positivity in bronchoalveolar lavage fluids as early detection of acute GVHD following BMT: evidence of a significant relationship.

PubMed

Takemoto, Y; Takatsuka, H; Wada, H; Mori, A; Saheki, K; Okada, M; Tamura, S; Fujimori, Y; Okamoto, T; Kakishita, E; Kanamaru, A

2000-07-01

We evaluated the relationship between CMV and human herpes virus-6 (HHV-6) reactivation and the incidence of grades 2 to 4 acute GVHD post BMT. Bronchoalveolar lavage fluid (BALF) samples extracted from 54 BMT recipients on post-BMT day 35 were analyzed by PCR for detection of CMV DNA, HHV-6 DNA and CMV plus HHV-6 DNA. CMV DNA was detected in 26 patients and 13 (50%) developed grades 2 to 4 acute GVHD. Of the 28 who were CMV negative, only six (21.4%) developed grades 2 to 4 acute GVHD. HHV-6 was detected in 18 patients, and 11 (61.1%) developed grades 2 to 4 acute GVHD. Of the 36 who were HHV-6 negative, only eight (22.2%) developed grades 2 to 4 acute GVHD. CMV and HHV-6 were detected in 13 patients, and eight (61.5%) developed grades 2 to 4 acute GVHD. Of the 23 who were negative for both CMV and HHV-6, only three (13%) developed grades 2 to 4 acute GVHD. In all experiments, the difference between the groups was significant (P<0.05, P<0.05 and P<0.01, respectively). We conclude that herpes virus infection, in particular CMV concurrent with HHV-6 reactivation, is predictive of moderate to severe acute GVHD.

Cochlear implantation in children with congenital cytomegalovirus infection accompanied by psycho-neurological disorders.

PubMed

Yamazaki, Hiroshi; Yamamoto, Rinko; Moroto, Saburo; Yamazaki, Tomoko; Fujiwara, Keizo; Nakai, Masako; Ito, Juichi; Naito, Yasushi

2012-04-01

Cochlear implantation was effective for deaf children with congenital cytomegalovirus (CMV) infection, but their cochlear implant (CI) outcomes were often impaired, depending on the types of CMV-associated psycho-neurological disorders. Evaluation of cognitive development and autistic tendency of implantees might be useful to predict their CI outcomes. To reveal the influence of CMV-associated psycho-neurological disorders on CI outcomes. This was a retrospective evaluation of 11 implantees with congenital CMV infection (CMV-CIs) and 14 implantees with autosomal recessive hearing loss (genetic-CIs). Nine of 11 CMV-CIs suffered from psycho-neurological disorders; one from attention deficit hyperactivity disorder, two from pervasive developmental disorder, and six from mental retardation. Aided hearing thresholds with CIs in the two groups did not differ, but two autistic and two mentally retarded CMV-CIs showed significantly low scores in speech discrimination tests. Language-Social (L-S) developmental quotients (DQs) evaluated by the Kyoto Scale of Psychological development were improved after the implantation in both groups, but the postoperative increase of L-S DQs was significantly smaller in the CMV-CIs than that of genetic-CIs. Interestingly, the postoperative L-S and Cognitive-Adaptive (C-A) DQs showed statistically significant correlation in all cases except for two autistic CMV-CIs whose L-S DQs were much lower than those expected from their C-A DQs.

Seroprevalence of cytomegalovirus infection in France in 2010.

PubMed

Antona, D; Lepoutre, A; Fonteneau, L; Baudon, C; Halftermeyer-Zhou, F; LE Strat, Y; Lévy-Bruhl, D

2017-05-01

Cytomegalovirus (CMV) infection remains the leading cause of congenital virus infection in developed countries. Measuring the national prevalence of this infection, especially among women of childbearing age, is of great value to estimate the risk of congenital CMV infection, as well as to identify risk groups that should be targeted for behavioural interventions and/or vaccination once a CMV vaccine finally becomes available. In order to fulfil these objectives, a seroprevalence survey was conducted in 2010, using a nationally representative, population-based sample of 2536 people aged between 15 and 49 years, living in metropolitan France and attending private microbiological laboratories for blood testing. All blood samples were analysed in the same laboratory and screened for CMV-specific IgG using an enzyme-linked immunoassay technique (Elisa PKS Medac Enzyme immunoassay). The overall point estimate of CMV infection seroprevalence for individuals aged 15-49 years was 41.9%. The estimates were higher in women than in men (respectively 45.6% and 39.3%), and people born in a non-Western country were more likely to be CMV seropositive than those born in France or in another Western country (93.7% vs. 37.7%). Our results showed that a substantial percentage of women of childbearing age in France are CMV seronegative and therefore at risk of primary CMV infection during pregnancy. Educational measures and future vaccine are key issues to prevent infection in pregnant women and congenital CMV disease.

Purely Singular Continuous Spectrum for CMV Operators Generated by Subshifts

NASA Astrophysics Data System (ADS)

Ong, Darren C.

2014-03-01

We prove uniform absence of point spectrum for CMV operators corresponding to the period doubling subshift. We also prove almost sure absence of point spectrum for CMV operators corresponding to a class of Sturmian subshifts. Lastly, we prove almost sure absence of point spectrum for CMV operators corresponding to some subshifts generated by a coding of a rotation.

49 CFR 383.51 - Disqualification of drivers.

Code of Federal Regulations, 2011 CFR

2011-10-01

... drivers. (a) General. (1) A person required to have a CLP or CDL who is disqualified must not drive a CMV... to drive a CMV. (3) A holder of a CLP or CDL is subject to disqualification sanctions designated in paragraphs (b) and (c) of this section, if the holder drives a CMV or non-CMV and is convicted of the...

Association of a cucumber mosaic virus strain with mosaic disease of banana, Musa paradisiaca--an evidence using immuno/nucleic acid probe.

PubMed

Srivastava, A; Raj, S K; Haq, Q M; Srivastava, K M; Singh, B P; Sane, P V

1995-12-01

Virus causing severe chlorosis/mosaic disease of banana was identified as a strain of cucumber mosaic virus (CMV). Association of CMV with the disease was established by Western immunoblot using polyclonal antibodies to CMV-T and slot blot hybridization with nucleic acid probe of CMV-P genome.

Dalmatian toadflax (Linaria dalmatica): New host for cucumber mosaic virus

Treesearch

Courtney L. Pariera Dinkins; Sue K. Brumfield; Robert K. D. Peterson; William E. Grey; Sharlene E. Sing

2007-01-01

To date, there have been no reports of Dalmatian toadflax serving as a host for cucumber mosaic virus (CMV). Infestations of Dalmatian toadflax may serve as a reservoir of CMV, thereby facilitating aphid transmission of CMV to both agricultural crops and native plants. The goal of this study was to determine whether Dalmatian toadflax is a host for CMV. Dalmatian...

Cytomegalovirus-associated cutaneous vasculopathy and scleroderma sans inclusion body change.

PubMed

Magro, Cynthia M; Crowson, A Neil; Ferri, Clodoveo

2007-01-01

Viruses have long been held to be of pathogenetic importance in the evolution of autoimmune connective tissue disease. We describe 7 adults who developed cutaneous connective tissue disease stigmata in temporal association with recent cytomegalovirus (CMV) infection but without the classic cytopathic changes of CMV infection. We examined 7 adults with clinical presentations encompassing cutaneous vasculitis in 4 and scleroderma in 3. In all 7 patients, there was either IgM seropositivity for CMV and/or CMV DNA isolation from peripheral blood. Although no CMV inclusions were seen, in situ hybridization studies revealed very focal CMV RNA transcript expression with localization mainly to the endothelium. The patients with vasculitis treated with ganciclovir had improvement or resolution of symptoms, whereas only 1 patient with scleroderma received antiviral therapy, without benefit. Another scleroderma patient responded to infliximab therapy. Abortive/partial CMV reactivation can be associated with a syndrome complex mimicking and/or triggering a primary immune-based cutaneous microvascular injury syndrome. Antiviral therapy appears to be of therapeutic value in those cases associated with active necrotizing vasculitic changes. The role of tumor necrosis factor alpha blockers in scleroderma cases temporally associated with CMV infection requires further evaluation.

[Cytomegalovirus retinitis in immunocompetent patients].

PubMed

Yoshinaga, Wakako; Mizushima, Yuka; Abematsu, Noriko; Nakao, Kumiko; Sakamoto, Taiji

2008-08-01

Cytomegalovirus (CMV) retinitis usually affects severely immunosuppressed individuals. We report two immunocompetent patients who developed CMV retinitis. Case 1 was a 65-year-old man who was referred to us with blurred vision and floaters of 2 weeks duration in his left eye. Slit-lamp biomicroscopy showed keratic precipitates, aqueous cells, and vitreous opacity in his left eye. Funduscopic examination revealed yellow-white retinal lesions with arterial sheathing in the superotemporal midperiphery. Case 2 was a 63-year-old man who presented with a 2-week history of blurred vision in his left eye. Ophthalmologic examination of the left eye showed keratic precipitates, aqueous cells, vitreous opacity, and yellow-white lesions in the superotemporal peripheral retina. In both cases, CMV DNA was detected in the aqueous humor and therefore the diagnosis was CMV retinitis. CMV retinitis in both cases was indolent and was resolved in one month without treatment with antiviral drugs. Although both patients had diabetes mellitus, the results of their laboratory examinations were unremarkable and they were immunocompetent. Unlike CMV retinitis in immunocompromised patients, CMV retinitis in immunocompetent patients had significant anterior and vitreous inflammation but did not require antiviral treatment. A possible association between CMV retinitis and diabetes mellitus was suggested.

Cytomegalovirus and ulcerative colitis: Place of antiviral therapy

PubMed Central

Pillet, Sylvie; Pozzetto, Bruno; Roblin, Xavier

2016-01-01

The link between cytomegalovirus (CMV) infection and inflammatory bowel diseases remains an important subject of debate. CMV infection is frequent in ulcerative colitis (UC) and has been shown to be potentially harmful. CMV reactivation needs to be diagnosed using methods that include in situ detection of viral markers by immunohistochemistry or by nucleic acid amplification techniques. Determination of the density of infection using quantitative tools (numbers of infected cells or copies of the genome) is particularly important. Although CMV reactivation can be considered as an innocent bystander in active flare-ups of refractory UC, an increasing number of studies suggest a deleterious role of CMV in this situation. The presence of colonic CMV infection is possibly linked to a decreased response to steroids and other immunosuppressive agents. Some treatments, notably steroids and cyclosporine A, have been shown to favor CMV reactivation, which seems not to be the case for therapies using anti-tumor necrosis factor drugs. According to these findings, in flare-ups of refractory UC, it is now recommended to look for the presence of CMV reactivation by using quantitative tools in colonic biopsies and to treat them with ganciclovir in cases of high viral load or severe disease. PMID:26877608

Sepsis and cytomegalovirus: foes or conspirators?

PubMed

Mansfield, Sara; Grießl, Marion; Gutknecht, Michael; Cook, Charles H

2015-06-01

Cytomegalovirus (CMV) reactivation in non-immune-suppressed critically ill patients is an area of increasing interest. CMV has long been appreciated as a pathogen in immunocompromised hosts. CMV reactivates in approximately one-third of latently infected non-immune-suppressed hosts during critical illness; however, its role as a pathogen in these patients remains unclear. CMV reactivation has been linked to bacterial sepsis and likely results from inflammation, transient immune compromise, and viral epigenetic changes. While CMV may improve immune response to some bacterial infections, other data suggest that CMV induces exaggerated responses to severe infections that may be harmful to latently infected hosts. These results also suggest that previous infection history may explain significant differences seen between human septic responses and murine models of sepsis. While critically ill human hosts clearly have worse outcomes associated with CMV reactivation, determining causality remains an area of investigation, with randomized control trials currently being performed. Here we review the current literature and highlight areas for future investigation.

Development of CMV retinitis in an antigenemia-negative infant after cord blood transplantation.

PubMed

Matsumoto, Akane; Umeda, Katsutsugu; Kawaguchi, Koji; Kawada, Koji; Maeda, Sayaka; Kinehara, Takako; Saida, Satoshi; Kato, Itaru; Hiramatsu, Hidefumi; Watanabe, Ken-Ichiro; Yasumi, Takahiro; Heike, Toshio; Tsujikawa, Akitaka; Uji, Akito; Usami, Ikuya; Ito, Kiminari; Adachi, Souichi

2015-05-01

A five-month-old male infant with familial hemophagocytic lymphohistiocytosis underwent cord blood transplantation using reduced-intensity conditioning. Methylprednisolone (mPSL) pulse administration was performed for marked pulmonary edema during the early phase of transplantation, followed by GVHD treatment with mPSL until day 100. CMV antigenemia was detected on days 27 and 55, but serum became negative with 2- to 3-week ganciclovir (GCV) treatment on both occasions. On day 120, ophthalmological findings included multiple bilateral white spots and a positive PCR study using anterior chamber fluid confirmed the diagnosis of CMV retinitis affecting both eyes, although CMV antigenemia was negative. Re-treatment with GCV had a minimal effect on the ophthalmological findings, while foscarnet administration markedly improved the retinitis and decreased the CMV-DNA level. Considering that a substantial proportion of patients develop CMV retinitis even when CMV antigenemia is not present, routine monitoring involving ophthalmological examinations should be conducted for hematopoietic transplant patients, especially infants, who cannot complain of ocular symptoms.

[Monitoring AIDS patients for the development of cytomegalovirus (CMV) disease using multiplex PCR].

PubMed

Terra, A P; Silva-Vergara, M L; Gomes, R A; Pereira, C L; Simpson, A J; Caballero, O L

2000-01-01

The human cytomegalovirus is an important pathogen in patients infected with the human immunodeficiency virus (HIV). The CMV viral load seems to be predictor of the development of the CMV disease in these patients. We used a multiplex PCR protocol that also provides quantitative information in those samples from which a single band is amplified and contains fewer viral genomes than those from which both targets are amplified. Monthly blood samples were collected from 270 AIDS patients. From twenty patients, two CMV targets were amplified three or more consecutive times and these patients developed CMV related disease during the study. In contrast, patients who did not result positive for both viral targets, for three or more consecutive times, or who had alternating positive and negative samples during the follow up did not present CMV related disease. The results suggest that the PCR multiplex can be used for the identification of HIV positive patients with higher risk of development of CMV disease.

Cytomegalovirus prevalence and transmission after islet allograft transplant in patients with type 1 diabetes mellitus.

PubMed

Hafiz, Muhammad M; Poggioli, Raffaella; Caulfield, Aileen; Messinger, Shari; Geiger, Milene C; Baidal, David A; Froud, Tatiana; Ferreira, Jacqueline V; Tzakis, Andreas G; Ricordi, Camillo; Alejandro, Rodolfo

2004-10-01

Cytomegalovirus (CMV) serological status of transplant donors and recipients has important implications on antiviral prophylaxis, morbidity/mortality, donor selection and hospital stay. We evaluated CMV prevalence in our islet transplant candidates (ITC) in comparison with organ donors. We correlated the CMV serological status of our ITC with serology for Epstein-Barr virus and Parvovirus B19, auto-antibodies, patient's age, age at DM onset, duration of DM, gender, race, ABO group, HLA haplotype and C-peptide levels. Cytomegalovirus transmission after islet transplant using the Edmonton regimen was also evaluated. Cytomegalovirus seropositivity varied according to patient group, age, gender and race. Type 1 DM patients had reduced odds of CMV seropositivity when compared with organ donors. In all groups studied, older patients, females, and non-Caucasians were more likely to be CMV seropositive. In addition, no CMV reactivation, infection or disease was observed among our transplanted patients using this steroid-free regimen even after donor/recipient CMV mismatch.