WorldWideScience

Sample records for cytomegalovirus cmv disease

  1. Cytomegalovirus (CMV) and Pregnancy

    Science.gov (United States)

    ... Close contact includes activities like changing diapers and kissing. What is congenital cytomegalovirus (congenital CMV)? Pregnant women ... or saliva. Try to avoid mouth-to-mouth kissing with children in day-care. Do not share ...

  2. Quantitation of cytomegalovirus (CMV) DNA in leukocytes of human immunodeficiency virus-infected subjects with and without CMV disease by using PCR and the SHARP Signal Detection System.

    Science.gov (United States)

    Boivin, G; Handfield, J; Murray, G; Toma, E; Lalonde, R; Lazar, J G; Bergeron, M G

    1997-02-01

    We report the development of a simple and rapid PCR assay for quantitation of the cytomegalovirus (CMV) DNA load in polymorphonuclear leukocytes. Using this system, a very good correlation was found between a high number of CMV copies in the blood and the presence of CMV disease in subjects with AIDS.

  3. Resolution of Mild Ganciclovir-Resistant Cytomegalovirus Disease with Reduced-Dose Cidofovir and CMV-Hyperimmune Globulin

    Directory of Open Access Journals (Sweden)

    Samir J. Patel

    2014-01-01

    Full Text Available 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.

  4. Development of cytomegalovirus (CMV) disease may be predicted in HIV-infected patients by CMV polymerase chain reaction and the antigenemia test

    DEFF Research Database (Denmark)

    Dodt, K K; Jacobsen, P H; Hofmann, B;

    1997-01-01

    evaluated PCR and the antigenemia tests as methods for early detection of CMV disease. METHODS: Two-hundred HIV-seropositive subjects with CD4 T-cell counts below 100 x 10(6)/l were monitored with CMV polymerase chain reaction (PCR), the antigenemia test, blood cultures and CMV immunoglobulin (Ig) G and Ig...

  5. CMV - gastroenteritis/colitis

    Science.gov (United States)

    Colitis - cytomegalovirus; Gastroenteritis - cytomegalovirus; Gastrointestinal CMV disease ... or after bone marrow or organ transplant Ulcerative colitis or Crohn disease Rarely, serious CMV infection involving ...

  6. Late-onset CMV disease following CMV prophylaxis.

    LENUS (Irish Health Repository)

    Donnelly, C

    2012-02-01

    BACKGROUND: Cytomegalovirus (CMV) is the most common opportunistic infection after solid-organ transplantation, increasing morbidity and mortality. Three months of oral valganciclovir have been shown to provide effective prophylaxis. Late-onset CMV disease, occurring after the discontinuation of prophylaxis, is now increasingly recognised. AIMS: To investigate the incidence and the time of detection of CMV infections in liver transplant recipients who received CMV prophylaxis. METHODS: Retrospective review of 64 high- and moderate-risk patients with 1 year of follow-up. RESULTS: The incidence of CMV infection was 12.5%, with 4.7% disease. All cases of symptomatic CMV disease were of late-onset. CONCLUSIONS: The incidence of CMV infections in this study was low compared with literature reports; however, the late-onset disease is an emerging problem. Detection of late-onset disease may be delayed because of less frequent clinic follow-up visits. Increased regular laboratory monitoring may allow earlier detection at the asymptomatic infection stage.

  7. Circulating cytomegalovirus (cmv)-infected endothelial-cells in patients with an active cmv infection

    NARCIS (Netherlands)

    Grefte, A.; van der Giessen, M.; van Son, W.; The, T. Hauw

    1993-01-01

    In 10 of 14 patients with an active cytomegalovirus (CMV) infection, distinctive large cells (35-45 mum in diameter) were present in the peripheral blood. Morphologically these cells closely resembled the classic cytomegalic inclusion cells, generally regarded as a diagnostic hallmark of CMV infecti

  8. Cytomegalovirus (CMV) Infection: A Guide for Patients and Families After Stem Cell Transplant

    Science.gov (United States)

    ... Infection: A Guide for Patients and Families after Stem Cell Transplant What is cytomegalovirus (CMV)? Cytomegalovirus (CMV), a ... weakened by medicines that you must take after stem cell transplant and by the transplant itself. Your body ...

  9. Prevalence and associated characteristics of cytomegalovirus (CMV ...

    African Journals Online (AJOL)

    Objective: To determine the prevalence of IgG and IgM specific antibodies and ... for human immunodeficiency virus, hepatitis B and C viruses and syphilis were ... the immuno-compromised and adoption of a national policy on CMV infected ...

  10. Highly quantitative serological detection of anti-cytomegalovirus (CMV antibodies

    Directory of Open Access Journals (Sweden)

    Alter Harvey J

    2009-05-01

    Full Text Available Abstract Background Human cytomegalovirus infection is associated with a variety of pathological conditions including retinitis, pneumonia, hepatitis and encephalitis that may be transmitted congenitally, horizontally and parenterally and occurs both as a primary infection and as reactivation in immunocompromised individuals. Currently, there is a need for improved quantitative serological tests to document seropositivity with high sensitivity and specificity. Methods Here we investigated whether luciferase immunoprecipitation systems (LIPS would provide a more quantitative and sensitive method for detecting anti-CMV antibodies. Four protein fragments of immunodominant regions of CMV antigens pp150 and pp65 were generated as Renilla luciferase (Ruc fusion proteins and used in LIPS with two cohorts of CMV positive and negative sera samples previously tested by ELISA. Results Analysis of the antibody responses to two of these antigen fragments, pp150-d1 and pp150-d2, revealed geometric mean antibody titers in the first cohort that were 100–1000 fold higher in the CMV positive sera compared to the CMV negative samples (p rs = 0.93, p Conclusion These results suggest that LIPS provides a highly robust and quantitative method for studying anti-CMV antibodies and has the potential to more accurately document CMV infection than standard ELISA.

  11. Characterization of specific antibodies against cytomegalovirus (CMV)-encoded interleukin 10 produced by 28 % of CMV-seropositive blood donors

    DEFF Research Database (Denmark)

    de Lemos Rieper, Carina; Galle, Pia Søndergaard; Pedersen, Bente Klarlund

    2011-01-01

    Cytomegalovirus (CMV) has evolved multiple immunological evasion strategies, including the encoding of viral interleukin (IL)-10 homologues (cmvIL-10). In this study, cmvIL-10 bound avidly to the same receptors on blood mononuclear cells and was as bio-potent as native human IL-10. Seventeen...

  12. A Modified Peptide Stimulation Method for Efficient Amplification of Cytomegalovirus (CMV)-Specific CTLs

    Institute of Scientific and Technical Information of China (English)

    Guangping Ruan; Li Ma; Qian Wen; Wei Luo; Mingqian Zhou; Xiaoning Wang

    2008-01-01

    CMV-specific immunity is essential for control of human cytomegalovirus (HCMV) infection. Stem cell trans- plantation is used widely in the management of a range of diseases of the hemopoietic system. Patients are immunosuppressed profoundly in the early posttransplant period, and reactivation of cytomegalovirus (CMV) remains a significant cause of morbidity and mortality. Adoptive transfer of CMV-specific CD8+ T cell clones has been shown to reduce the rate of viral reactivation; however, the ex vivo production of cells for adoptive transfer is labor intensive and expensive. We report here a modified peptide stimulation method using CMV-specific epitope peptides to stimulate PBMCs for generation of CMV-specific CTLs. This method permits efficient amplification of CMV-specific CTLs and provides a large number of cells for FACS analysis from a single blood sample. Significantly, it achieves high frequencies of tetramer staining of CD8+ T cells allowing the data of different individuals to be easily compared and sequentially evaluated. Thus, this approach expands and selects HLA- restricted CMV-pp65-reactive T-cell lines of high specificity for potential adoptive immunotherapy. Cellular & Molecular Immunology. 2008;5(3):197-201.

  13. [Detection of DNA human cytomegalovirus of a molecular methods: hybrid capture DNA CMV by immunocompromised].

    Science.gov (United States)

    Mhiri, Leila; Arrouji, Zakia; Slim, Amine; Ben Redjeb, Saida

    2006-10-01

    Human cytomegalovirus (HCMV), a member of the beta-virus herpes family, is a ubiquitous human pathogen. After a primary infection, HCMV establishes life latency. HCMV rarely causes symptomatic disease in an immunocompetent host, however, it is a major cause of infectious morbidity and mortality in immunocompromised individuals and developing fetuses. The HCMV genome consists of 240 kbp of double stranded DNA. Early diagnosis molecular of CMV infection is important. The objective of this study was to develop a molecular methods: Quantitative Hybrid capture for the detection of DNA CMV. We present results for 200 immunocompromised collected from 1999 to 2003 (122 men and 78 women, whom mean age was 35 years). Our results showed that 25% of women and 36% of men were positif for hybrid capture DNA CMV. This simple test (cold probe) provide quantitative and fast results. Also the efficacity of anti-CMV therapy can be followed. More over, in contrary with pp65-antigenemia assay and CMV PCR, this test can be managed on biopsy sample.

  14. A case of ganciclovir-resistant cytomegalovirus (CMV) retinitis in a patient with AIDS: longitudinal molecular analysis of the CMV viral load and viral mutations in blood compartments.

    Science.gov (United States)

    Boivin, G; Gilbert, C; Morissette, M; Handfield, J; Goyette, N; Bergeron, M G

    1997-06-01

    To study the temporal relationships between cytomegalovirus (CMV) viral load and specific UL97 mutations in polymorphonuclear leukocytes (PMNL) and plasma samples from a patient with AIDS who developed ganciclovir-resistant CMV retinitis. Sequential PMNL and plasma samples were analysed for determination of the CMV viral load using non-molecular methods and a quantitative polymerase chain reaction (PCR) assay. Screening of the same samples for the most common mutations conferring ganciclovir resistance was performed using nested PCR and restriction enzyme analysis. At the time of progression of CMV retinitis (after 6 months of ganciclovir), a rapid increase in the CMV DNA load was found in both PMNL and plasma samples. This increase paralleled the emergence of a specific mutation (V594) in the same samples and recovery of ganciclovir-resistant blood isolates. In this patient, however, the only tests that substantially predicted the progression of CMV disease were the quantitative PCR assay using PMNL and to a lesser extent the pp65 antigenemia assay. Quantitative evaluation of the CMV viral load in PMNL using sensitive assays such as PCR appears to be a promising approach for monitoring antiviral therapy in subjects with AIDS. In addition, common mutations conferring ganciclovir resistance can be detected directly in PMNL and plasma samples.

  15. Refractory acute respiratory failure due to Pneumocystis jiroveci (PCP) and Cytomegalovirus (CMV) pneumonitis: A case report and review of literature.

    Science.gov (United States)

    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.

  16. Performance Evaluation of the Real-Q Cytomegalovirus (CMV) Quantification Kit Using Two Real-Time PCR Systems for Quantifying CMV DNA in Whole Blood.

    Science.gov (United States)

    Park, Jong Eun; Kim, Ji Youn; Yun, Sun Ae; Lee, Myoung Keun; Huh, Hee Jae; Kim, Jong Won; Ki, Chang Seok

    2016-11-01

    Standardized cytomegalovirus (CMV) DNA quantification is important for managing CMV disease. We evaluated the performance of the Real-Q CMV Quantification Kit (Real-Q assay; BioSewoom, Korea) using whole blood (WB), with nucleic acid extraction using MagNA Pure 96 (Roche Diagnostics, Germany). Real-time PCR was performed on two platforms: the 7500 Fast real-time PCR (7500 Fast; Applied Biosystems, USA) and CFX96 real-time PCR detection (CFX96; Bio-Rad, USA) systems. The WHO international standard, diluted with CMV-negative WB, was used to validate the analytical performance. We used 90 WB clinical samples for comparison with the artus CMV RG PCR kit (artus assay; Qiagen, Germany). Limits of detections (LODs) in 7500 Fast and CFX96 were 367 and 479 IU/mL, respectively. The assay was linear from the LOD to 10⁶ IU/mL (R² ≥0.9886). The conversion factors from copies to IU in 7500 Fast and CFX96 were 0.95 and 1.06, respectively. Compared with the artus assay, for values 1,000 copies/mL, 73.3% and 80.6% of samples in 7500 Fast and CFX96, respectively, had real-time PCR platforms.

  17. Expression of the late cytomegalovirus (CMV) pp150 transcript in leukocytes of AIDS patients is associated with a high viral DNA load in leukocytes and presence of CMV DNA in plasma.

    Science.gov (United States)

    Boivin, G; Handfield, J; Toma, E; Lalonde, R; Bergeron, M G

    1999-05-01

    The expression of a late cytomegalovirus (CMV) transcript (pp150) was sought in peripheral blood leukocytes (PBL) of subjects with AIDS and correlated with the amounts of CMV DNA in PBL and plasma, by means of quantitative polymerase chain reaction (PCR). The detection of the late CMV transcript was associated with a high number of CMV DNA copies in PBL (P=.0015) and with a positive CMV PCR assay in plasma (P<.001). Expression of CMV pp150 mRNA was best predicted by viral DNA thresholds corresponding to 7058 and 30 copies in PBL and plasma, respectively. The detection of CMV pp150 mRNA was associated with the presence of CMV disease in a univariate analysis but not in a multivariate analysis after controlling for the viral DNA load in PBL. Thus, active viral replication as determined by a high CMV DNA load in PBL is reflected by expression of the late CMV transcript in the same cells and by the presence of CMV DNA in plasma.

  18. Treatment of Cytomegalovirus Infection with Cidofovir and CMV Immune Globulin in a Lung Transplant Recipient

    Directory of Open Access Journals (Sweden)

    Heinrike Wilkens

    2016-01-01

    Full Text Available Cytomegalovirus (CMV infection after lung transplantation is associated with increased risk for pneumonitis and bronchiolitis obliterans as well as allograft rejection and opportunistic infections. Ganciclovir is the mainstay of prophylaxis and treatment but CMV infections can be unresponsive. Apart from direct antiviral drugs, CMV immunoglobulin (CMVIG preparations may be considered but are only licensed for prophylaxis. A CMV-seronegative 42-year-old man with cystic fibrosis received a lung from a CMV-seropositive donor. Intravenous ganciclovir prophylaxis was delayed until day 12 due to acute postoperative renal failure and was accompanied by five doses of CMVIG (10 g. By day 16, CMV-DNA was detectable and rising; CMV-specific T-cells were undetectable. Switch from ganciclovir to foscarnet prompted a transient decrease in CMV viral load, but after increasing again to reach 3600 copies/mL foscarnet was changed to intravenous cidofovir and CMVIG was restarted. CMV load continued to fluctuate and declined slowly, whereas CMV-specific T-cells were detected five months later and increased thereafter. At last follow-up, the patient was in very good clinical condition with no evidence of bronchiolitis obliterans. No side effects of this treatment were observed. In this hard-to-treat case, the combination of cidofovir with off-label use of CMVIG contributed to a successful outcome.

  19. [Analytical performances of real-time PCR by Abbott RealTime CMV with m2000 for the detection of cytomegalovirus in urine].

    Science.gov (United States)

    De Monte, Anne; Cannavo, Isabelle; Caramella, Anne; Ollier, Laurence; Giordanengo, Valérie

    2016-01-01

    Congenital cytomegalovirus (CMV) infection is the leading cause of sensoneurinal disability due to infectious congenital disease. The diagnosis of congenital CMV infection is based on the search of CMV in the urine within the first two weeks of life. Viral culture of urine is the gold standard. However, the PCR is highly sensitive and faster. It is becoming an alternative choice. The objective of this study is the validation of real-time PCR by Abbott RealTime CMV with m2000 for the detection of cytomegalovirus in urine. Repeatability, reproducibility, detection limit and inter-sample contamination were evaluated. Urine samples from patients (n=141) were collected and analyzed simultaneously in culture and PCR in order to assess the correlation of these two methods. The sensitivity and specificity of PCR were also calculated. The Abbott RealTime CMV PCR in urine is an automated and sensitive method (detection limit 200 UI/mL). Fidelity is very good (standard deviation of repeatability: 0.08 to 0.15 LogUI/mL and reproducibility 0.18 LogUI/mL). We can note a good correlation between culture and Abbott RealTime CMV PCR (kappa 96%). When considering rapid culture as reference, real-time PCR was highly sensitive (100%) and specific (98.2%). The real-time PCR by Abbott RealTime CMV with m2000 is optimal for CMV detection in urine.

  20. Examining the species-specificity of rhesus macaque cytomegalovirus (RhCMV in cynomolgus macaques.

    Directory of Open Access Journals (Sweden)

    Angie K Marsh

    Full Text Available Cytomegalovirus (CMV is a highly species-specific virus that has co-evolved with its host over millions of years and thus restricting cross-species infection. To examine the extent to which host restriction may prevent cross-species research between closely related non-human primates, we evaluated experimental infection of cynomolgus macaques with a recombinant rhesus macaque-derived CMV (RhCMV-eGFP. Twelve cynomolgus macaques were randomly allocated to three groups: one experimental group (RhCMV-eGFP and two control groups (UV-inactivated RhCMV-eGFP or media alone. The animals were given two subcutaneous inoculations at week 0 and week 8, and a subset of animals received an intravenous inoculation at week 23. No overt clinical or haematological changes were observed and PBMCs isolated from RhCMV-eGFP inoculated animals had comparable eGFP- and IE-1-specific cellular responses to the control animals. Following inoculation with RhCMV-eGFP, we were unable to detect evidence of infection in any blood or tissue samples up to 4 years post-inoculation, using sensitive viral co-culture, qPCR, and Western blot assays. Co-culture of urine and saliva samples demonstrated the presence of endogenous cynomolgus CMV (CyCMV cytopathic effect, however no concomitant eGFP expression was observed. The absence of detectable RhCMV-eGFP suggests that the CyCMV-seropositive cynomolgus macaques were not productively infected with RhCMV-eGFP under these inoculation conditions. In a continued effort to develop CMV as a viral vector for an HIV/SIV vaccine, these studies demonstrate that CMV is highly restricted to its host species and can be highly affected by laboratory cell culture. Consideration of the differences between lab-adapted and primary viruses with respect to species range and cell tropism should be a priority in evaluating CMV as vaccine vector for HIV or other pathogens at the preclinical development stage.

  1. Effect of a 14-day course of foscarnet on cytomegalovirus (CMV) blood markers in a randomized study of human immunodeficiency virus-infected patients with persistent CMV viremia. Agence National de Recherche du SIDA 023 Study Group.

    Science.gov (United States)

    Salmon-Céron, D; Fillet, A M; Aboulker, J P; Gérard, L; Houhou, N; Carrière, I; Ostinelli, J; Vildé, J L; Brun-Vézinet, F; Leport, C

    1999-04-01

    A randomized open-label phase 2 trial compared the virological and clinical effects on cytomegalovirus (CMV) infection of a 14-day course of intravenous foscarnet (100 mg/[kg x 12 h]) or no treatment in 42 HIV-infected patients with virus load rapidly increased. The probability of CMV disease at 6 months was 43% in both groups. Patients who had or who achieved a negative blood culture at any time had a reduced risk of CMV disease (RR = 2.64; 95% CI = 1.24-5.62; P = .02). This study suggests that sequential courses of intravenous foscarnet might not be a good strategy for preemptive therapy in this population and that in patients with a positive blood marker, treatment able to induce and maintain negative CMV blood cultures could constitute an effective intervention.

  2. Case report: persistent cytomegalovirus (CMV) infection after haploidentical hematopoietic stem cell transplantation using in vivo alemtuzumab: emergence of resistant CMV due to mutations in the UL97 and UL54 genes.

    Science.gov (United States)

    Oshima, Kumi; Kanda, Yoshinobu; Kako, Shinichi; Asano-Mori, Yuki; Watanabe, Takuro; Motokura, Toru; Chiba, Shigeru; Shiraki, Kimiyasu; Kurokawa, Mineo

    2008-10-01

    Addition of in vivo alemtuzumab to the conditioning regimen enabled 2- or 3-locus-mismatched hematopoietic stem cell transplantation with an acceptable incidence of graft-versus-host-disease. However, the procedure was associated with a high incidence of cytomegalovirus (CMV) reactivation. Although preemptive therapy with ganciclovir prevented successfully severe CMV diseases and CMV-related mortality, a patient developed persistent positive CMV antigenemia for more than 1 year after transplantation and CMV disease, despite the use of ganciclovir and foscarnet. The in vitro susceptibility assay showed that the clinical isolate was resistant to foscarnet, moderately resistant to ganciclovir, but sensitive to cidofovir. Therefore, cidofovir was administered. CMV antigenemia became negative within 2 weeks and never developed again. Nucleotide sequence of the UL54 and UL97 of the clinical isolate showed 4 amino acid substitutions (V11L, Q578H, S655L, and G874R) in UL54 and 2 mutations (A140V and A594V) in UL97 compared with the Towne and AD169 strains. Ganciclovir resistance was suspected to be caused by both A594V of UL97 and Q578H of UL54, whereas foscarnet resistance was due mainly to Q578H of UL54. In conclusion, the in vitro susceptibility assay as well as nucleotide sequence of clinical isolate is important to choose appropriate antiviral agents for patients who have persistent CMV reactivation after stem cell transplantation.

  3. Retinite por citomegalovirus (CMV após terapia imunossupressora para vasculite leucocitoclástica Cytomegalovirus (CMV retinitis after immunossupressive therapy for leukocytoclastic vasculitis

    Directory of Open Access Journals (Sweden)

    Carlos Ewerton Maia Rodrigues

    2009-02-01

    Full Text Available A retinite por citomegalovírus (CMV é uma doença rara que acomete principalmente pacientes com a síndrome da imunodeficiência adquirida (AIDS. No entanto, outros pacientes imunossuprimidos, como os transplantados, os que estão em uso de quimioterápicos, pacientes com lúpus eritematoso sistêmico (LES ou em tratamento com drogas imunossupressoras também podem ser acometidos. O quadro clínico caracteriza-se por visão turva, diminuição da acuidade ou alterações de campo visual, geralmente unilateral, podendo ocorrer deslocamento de retina. A perda visual é progressiva, evolui em ritmo variável até a completa amaurose do olho acometido. O presente relato de caso descreve um paciente com vasculite leucocitoclástica grave submetido à terapia com corticoide em dose imunossupressora que evoluiu com glaucoma, panuveíte por CMV, perda da acuidade visual e infecção bacteriana secundária.Cytomegalovirus (CMV retinitis is a rare disease which mainly affects patients with acquired immunodeficiency syndrome (AIDS. Nevertheless, other immunosuppressed patients, such as the organ transplant recipients, the ones using chemotherapy, patients with systemic lupus erythematosus (SLE or in treatment with immunosuppressive drugs can also be attacked. The clinical characteristics are blurred vision, decrease of the visual acuity or visual field alterations, generally unilateral, with the possibility of retinal detachment. The visual loss is progressive, evolving in a variable rate until complete amaurosis of the attacked eye. The present case report describes a patient with severe leukocytoclastic vasculitis, submitted to corticosteroid therapy in immunosuppressive doses that evolved with glaucoma, panuveitis by CMV, loss of visual acuity and secondary bacterial infection.

  4. Cytomegalovirus (CMV) IE1- and pp65-specific CD8+ T cell responses broaden over time after primary CMV infection in infants.

    Science.gov (United States)

    Gibson, Laura; Dooley, Sheryl; Trzmielina, Sonia; Somasundaran, Mohan; Fisher, Donna; Revello, Maria Grazia; Luzuriaga, Katherine

    2007-06-15

    Cytomegalovirus (CMV) infection remains a significant cause of morbidity and mortality in young children. We have previously shown that CD8+ T cell responses to CMV pp65 or IE1 protein were readily detectable in children with congenital or postnatal CMV infection. Here, we have further characterized the evolution of the peptide specificity of these responses in 7 infants<6 months of age at the start of the study. Thirteen pp65 and 15 IE1 peptides (median, 5 peptides/infant) were targeted, and most (61%) represented sequences not previously reported. Peptide specificity remained stable or broadened over time despite the clearance of CMV viremia. Loss of peptide recognition was not observed. Responses with the highest functional peptide avidity were not necessarily detected earliest. These data provide additional evidence that young infants can generate diverse CMV-specific CD8+ T cell responses but show that early responses may exhibit relatively focused peptide specificity and lower peptide avidity.

  5. Low predictive value of polymerase chain reaction for diagnosis of cytomegalovirus disease in liver transplant recipients.

    Science.gov (United States)

    Delgado, R; Lumbreras, C; Alba, C; Pedraza, M A; Otero, J R; Gómez, R; Moreno, E; Noriega, A R; Payá, C V

    1992-07-01

    The polymerase chain reaction (PCR) and viral culture techniques were prospectively compared for the detection of cytomegalovirus (CMV) in blood samples from 24 liver transplant recipients. Nine patients had one or more episodes of viremia, seven of which were clinically symptomatic infections. All samples in which CMV was isolated by culture were positive by the PCR. However, the PCR result was also positive for one or more samples from 11 patients who never developed CMV-related symptoms. Although the PCR is a very sensitive technique for CMV detection in blood samples from liver transplant recipients, it is not useful as a marker of symptomatic CMV disease.

  6. The Role of The Cytomegalovirus Antigenemia Assay in the Detection and Prevention of Cytomegalovirus Syndrome and Disease in Solid Organ Transplant Recipients: A Review of the British Columbia Experience

    Directory of Open Access Journals (Sweden)

    Erica D Greanya

    2005-01-01

    Full Text Available BACKGROUND: The pp65 cytomegalovirus (CMV antigenemia assay has been used as a means of guiding the pre-emptive therapy of CMV disease in solid organ transplant (SOT recipients. Recently, concerns have been raised regarding the utility of the test to accurately and precisely detect viral activity early enough to reduce the morbidity and mortality associated with CMV.

  7. An artemisinin-derived dimer has highly potent anti-cytomegalovirus (CMV and anti-cancer activities.

    Directory of Open Access Journals (Sweden)

    Ran He

    Full Text Available We recently reported that two artemisinin-derived dimers (dimer primary alcohol 606 and dimer sulfone 4-carbamate 832-4 are significantly more potent in inhibiting human cytomegalovirus (CMV replication than artemisinin-derived monomers. In our continued evaluation of the activities of artemisinins in CMV inhibition, twelve artemisinin-derived dimers and five artemisinin-derived monomers were used. Dimers as a group were found to be potent inhibitors of CMV replication. Comparison of CMV inhibition and the slope parameter of dimers and monomers suggest that dimers are distinct in their anti-CMV activities. A deoxy dimer (574, lacking the endoperoxide bridge, did not have any effect on CMV replication, suggesting a role for the endoperoxide bridge in CMV inhibition. Differences in anti-CMV activity were observed among three structural analogs of dimer sulfone 4-carbamate 832-4 indicating that the exact placement and oxidation state of the sulfur atom may contribute to its anti-CMV activity. Of all tested dimers, artemisinin-derived diphenyl phosphate dimer 838 proved to be the most potent inhibitor of CMV replication, with a selectivity index of approximately 1500, compared to our previously reported dimer sulfone 4-carbamate 832-4 with a selectivity index of about 900. Diphenyl phosphate dimer 838 was highly active against a Ganciclovir-resistant CMV strain and was also the most active dimer in inhibition of cancer cell growth. Thus, diphenyl phosphate dimer 838 may represent a lead for development of a highly potent and safe anti-CMV compound.

  8. Cytomegalovirus and inflammatory bowel disease: Is there a link?

    Institute of Scientific and Technical Information of China (English)

    Valeria Criscuoli; Maria Rosa Rizzuto; Mario Cottone

    2006-01-01

    The objective of this report is to give an overall view of the epidemiological, clinical, diagnostic and therapeutic features of Cytomegalovirus (CMV) infection in inflammatory bowel disease (IBD). A review of published reports on this topic was carried out, with particular attention paid to the selection of patients included in studies and the diagnostic methods employed. CMV is frequently associated with IBD. In some cases, CMV infection is as sociated with a poor outcome but it is not clear which patients are more likely to be affected and in which stage of the disease. The use of anti-viral therapy in IBD is controversial and an empirical study with controls is needed. The natural history of CMV infection related to the development and treatment of IBD has not been clarified but it is important to take it in consideration because of the possibility of viral persistence in the immunocompromised host and viral interaction with the immune system.

  9. Evaluation of different cytomegalovirus (CMV) DNA PCR protocols for analysis of dried blood spots from consecutive cases of neonates with congenital CMV infections.

    Science.gov (United States)

    Soetens, Oriane; Vauloup-Fellous, Christelle; Foulon, Ina; Dubreuil, Pascal; De Saeger, Ben; Grangeot-Keros, Liliane; Naessens, Anne

    2008-03-01

    Two protocols for the extraction of cytomegalovirus (CMV) DNA and two methods for the amplification of CMV DNA in dried blood spots were evaluated for the retrospective diagnosis of congenital CMV infection. During the period from 1996 to 2006, a urine screening program detected 76 congenitally infected neonates. Stored Guthrie cards with blood from 55 cases and 12 controls were tested. Two spots of dried blood were cut from each card and evaluated in two centers. CMV DNA was extracted from a whole single spot. Center 1 used phenol-chloroform extraction and ethanol precipitation followed by a conventional PCR. Center 2 used the NucliSens easyMAG automated DNA/RNA extraction platform (bioMérieux) followed by a real-time PCR. For evaluation of the extraction method, DNA extracted from each blood spot was evaluated by the amplification method used by the collaborating center. The sensitivities were 66% for center 1 and 73% for center 2. None of the controls were positive. A sensitivity as high as 82% could be obtained by combining the most sensitive extraction method (the phenol-chloroform procedure) with the most sensitive PCR method (real-time PCR). The detection rate was not influenced by the duration of storage of the spots. The sensitivity was higher with blood from congenitally infected cases due to a primary maternal CMV infection, regardless of the protocol used. However, the difference reached significance only for the least-sensitive protocol (P = 0.036).

  10. Washing our hands of the congenital cytomegalovirus disease epidemic

    Directory of Open Access Journals (Sweden)

    Cannon Michael J

    2005-06-01

    Full Text Available Abstract Background Each year in the United States, an estimated 40,000 children are born with congenital cytomegalovirus (CMV infection, causing an estimated 400 deaths and leaving approximately 8000 children with permanent disabilities such as hearing or vision loss, or mental retardation. More children are affected by serious CMV-related disabilities than by several better-known childhood maladies, including Down syndrome, fetal alcohol syndrome, and spina bifida. Discussion Congenital CMV is a prime target for prevention not only because of its substantial disease burden but also because the biology and epidemiology of CMV suggest that there are ways to reduce viral transmission. Because exposure to the saliva or urine of young children is a major cause of CMV infection among pregnant women, it is likely that good personal hygiene, especially hand-washing, can reduce the risk of CMV acquisition. Experts agree that such measures are likely to be efficacious (i.e., they will work if consistently followed and the American College of Obstetricians and Gynecologists recommends that physicians counsel pregnant women about preventing CMV acquisition through careful attention to hygiene. However, because of concerns about effectiveness (i.e., Will women consistently follow hygienic practices as the result of interventions?, the medical and public health communities appear reluctant to embrace primary CMV prevention via improved hygienic practices, and educational interventions are rare. Current data on the effectiveness of such measures in preventing CMV infection are promising, but limited. There is strong evidence, however, that educational interventions can prevent other infectious diseases with similar transmission modes, suggesting that effective interventions can also be found for CMV. Until a CMV vaccine becomes available, effective educational interventions are needed to inform women about congenital CMV prevention. Summary Perhaps no single

  11. Cytomegalovirus infection in inflammatory bowel disease patients undergoing anti-TNFalpha therapy.

    Science.gov (United States)

    D'Ovidio, Valeria; Vernia, Piero; Gentile, Giuseppe; Capobianchi, Angela; Marcheggiano, Adriana; Viscido, Angelo; Martino, Pietro; Caprilli, Renzo

    2008-10-01

    Cytomegalovirus infection and disease is associated with poor prognosis and steroid refractoriness in inflammatory bowel disease patients. The unfavourable effect of steroids and immunosuppressive therapy on CMV infection is well known but few data are available concerning anti-TNFalpha therapy (Infliximab). Aim of the study was to evaluate the presence and severity of CMV infection and disease in Infliximab-treated IBD patients. The severity of active CMV infection and disease was assessed in 11 consecutive patients with ileocolonic/colonic disease and 4 patients with ulcerative colitis before and after a standard 3-infusion course of Infliximab. Active CMV infection was evaluated by serology and diagnosed by means of pp65-antigenemia (pp65 AG), and quantification of CMV DNA isolated from biopsy specimens of colonic tissue. CMV disease was assessed on haematoxylin/eosin-stained colonic biopsies and immunohistochemical stains. Of the 11 patients, nine were CMV seropositive. As far as concerns CMV infection, only one patient had positive pp65 AG, before and after Infliximab. CMV DNA was detected in the colonic biopsies of three patients. In 2, CMV DNA persisted also after therapy with 410 and 1300 copies/microg of DNA, respectively, albeit with no evidence of worsening of the colonic disease. In the remaining patient, CMV DNA load became undetectable. Conventional histology and immunohistochemical stains were negative for CMV in all the patients, without evidence of CMV disease. Active CMV infection did not progress to disease following Infliximab therapy. Although these preliminary observations require confirmation, the response to Infliximab therapy does not appear to be influenced by, or influence the course of, CMV infection/disease.

  12. Ongoing burden of disease and mortality from HIV/CMV coinfection in Africa in the antiretroviral therapy era

    Directory of Open Access Journals (Sweden)

    Emily eAdland

    2015-09-01

    Full Text Available Human Cytomegalovirus (CMV is a well recognised pathogen in the context of HIV infection, but since the roll out of ART, clinical and scientific interest in the problem of HIV/CMV coinfection has diminished. However, CMV remains a significant cofactor in HIV disease, with an influence on HIV acquisition, disease progression, morbidity and mortality. Disease manifestations may be a result of direct interplay between the two viruses, or may arise as a secondary consequence of immune dysregulation and systemic inflammation. The problem is most relevant when the rates of coinfection are high, most notably in sub-Saharan Africa, and in children at risk of acquiring both infections early in life. Understanding the interplay between these viruses and developing strategies to diagnose, treat and prevent CMV should be a priority.

  13. Diagnosis of cytomegalovirus infections by qualitative and quantitative PCR in HIV infected patients Diagnóstico de infecção por CMV em pacientes infectados pelo HIV utilizando PCR qualitativa e quantitativa

    Directory of Open Access Journals (Sweden)

    Aldo de Albuquerque CUNHA

    2002-01-01

    Full Text Available A high incidence of cytomegalovirus (CMV infections is observed in Brazil. These viruses are causatives of significant morbidity and mortality among patients with advanced human immunodeficiency virus (HIV infection. This work, shows the application of a PCR on determination of CMV load in the buffy coat and plasma. We analyzed the samples of 247 HIV infected patients in order to diagnose CMV infection and disease. We developed a semi-quantitative PCR that amplifies part of the glycoprotein B (gB gene of CMV. The semi-quantitative PCR was carried out only in positive clinical samples in a qualitative PCR confirmed by a nested-PCR. CD4 lymphocyte count, HIV viral load and CMV disease symptom were correlated with CMV load. CMV genome was detected in the buffy coat of 82 of 237 (34.6% patients, in 10 of these the CMV load was determined varying between 928 and 332 880 viral copies/mug DNA. None of these 237 patients developed any suggestive manifestation of CMV disease. For the other 10 HIV infected patients selected based on the suspicion of CMV disease, CMV genome was detected in only one case. This patient presented a high CMV load, 8 000 000 copies/mug DNA, and developed a disseminated form of CMV disease including hepatitis and retinitis. Our results were greatly influenced by the impact of the highly active antiretroviral therapy that reduced incidence of CMV viremia and occurrence of CMV disease in the HIV infected patients.Uma alta incidência de infecção pelo citomegalovirus (CMV é observada no Brasil. Este vírus é responsável por significante morbi-mortalidade entre pacientes infectados pelo vírus da imunodeficiência humana (HIV. Neste estudo, mostramos a aplicação de uma PCR quantitativa para determinar a carga de CMV nos leucócitos do sangue periférico e no plasma de 247 pacientes infectados pelo HIV. As amostras clínicas foram previamente testadas por uma PCR qualitativa e confirmadas por uma nested-PCR para posteriormente

  14. Cytomegalovirus infection in inflammatory bowel disease is not associated with worsening of intestinal inflammatory activity.

    Directory of Open Access Journals (Sweden)

    Alexandre Medeiros do Carmo

    Full Text Available Cytomegalovirus is highly prevalent virus and usually occurs in immunocompromised patients. The pathophysiology and treatment of inflammatory bowel disease often induce a state of immunosuppression. Because this, there are still doubts and controversies about the relationship between inflammatory bowel disease and cytomegalovirus.Evaluate the frequency of cytomegalovirus in patients with inflammatory bowel disease and identify correlations.Patients with inflammatory bowel disease underwent an interview, review of records and collection of blood and fecal samples. The search for cytomegalovirus was performed by IgG and IgM blood serology, by real-time PCR in the blood and by qualitative PCR in feces. Results were correlated with red blood cell levels, C-reactive protein levels, erythrocyte sedimentation rates and fecal calprotectin levels for each patient.Among the 400 eligible patients, 249 had Crohn's disease, and 151 had ulcerative colitis. In the group of Crohn's disease, 67 of the patients had moderate or severe disease, but 126 patients presented with active disease, based on the evaluation of the fecal calprotectin. In patients with ulcerative colitis, only 21 patients had moderate disease, but 76 patients presented with active disease, based on the evaluation of the fecal calprotectin. A large majority of patients had positive CMV IgG. Overall, 10 patients had positive CMV IgM, and 9 patients had a positive qualitative detection of CMV DNA by PCR in the feces. All 400 patients returned negative results after the quantitative detection of CMV DNA in blood by real-time PCR. Analyzing the 19 patients with active infections, we only found that such an association occurred with the use of combined therapy (anti-TNF-alpha + azathioprine.The findings show that latent cytomegalovirus infections are frequent and active cytomegalovirus infection is rare. We did not find any association between an active infection of CMV and inflammatory bowel

  15. Lymphocyte subpopulations during cytomegalovirus disease in renal transplant recipients

    Directory of Open Access Journals (Sweden)

    S.M. Castro

    2003-06-01

    Full Text Available We have determined the number of circulating T, B and natural killer cells in renal transplant recipients in order to detect changes during cytomegalovirus (CMV infections. Serial blood samples were taken from 61 patients on standard triple immunosuppression therapy (cyclosporin A, azathioprine and prednisone. Using two-color flow cytometry analysis, the absolute number of CD3+, CD4+, CD8+, CD19+, CD3+HLA-DR+ and CD16+56+ cells was determined. Forty-eight patients (78.7% developed active CMV infection, and all of them subsequently recovered. Twenty of the infected patients (32.8% presented symptoms compatible with CMV disease during the infectious process. The number of lymphocytes and their main subpopulations were normal before the onset of CMV disease. During the disease there was a decrease followed by a significant increase (P<0.005 in the number of CD3+, CD4+, CD8+ and CD3+HLA-DR+ cells. No significant changes were observed in natural killer cells or B lymphocytes during the disease. We conclude, as observed in all viremic patients recovering from infection, that recovery is associated with an increase in the number of T cell subsets. The monitoring of different lymphocyte subsets along with antigenemia can be extremely useful in the detection of patients at high risk of developing CMV symptoms, allowing the early introduction of antiviral therapy or the reduction of immunosuppression therapy.

  16. Breastfeeding and transmission of cytomegalovirus to preterm infants. Case report and kinetic of CMV-DNA in breast milk

    Directory of Open Access Journals (Sweden)

    Rossi Marta J

    2011-01-01

    Full Text Available Abstract Background Breastfeeding has a major impact on CMV epidemiology. Postnatal CMV reactivation's incidence during lactation is nearby the maternal seroprevalence. Although perinatal CMV infection has practically no consequences in term newborn, it may cause, in some cases, a severe symptomatic disease in preterm newborns. The aims of the present study are to evaluate the rate and clinical expression of CMV infection breast milk transmitted in preterm infants and to check the safety of the freezing treated breast milk. Methods The study included fifty-seven preterm infants and their CMV seropositive mothers. Fresh breast milk samples have been collected from 1st to 9th postpartum week. Both fresh breast milk and 72, 96, 120 hours frozen samples have been examined, checking the presence of CMV; urine samples have been tested too. Results 70.2% of tested mothers showed reactivation of the infection, and CMV-positive breast milk during the six weeks postpartum has been found. However, only one infant was infected by CMV, developing hepatic affection concomitantly with a multi-system involvement, as shown CMV DNA detection in urine, saliva, blood, gastric aspirate, and stools. Conclusion Freezing breast milk at -20°C and pasteurization may respectively reduce or eliminate the viral load.

  17. Effect of Cytomegalovirus (CMV) and Ageing on T-Bet and Eomes Expression on T-Cell Subsets

    Science.gov (United States)

    Hassouneh, Fakhri; Lopez-Sejas, Nelson; Campos, Carmen; Sanchez-Correa, Beatriz; Tarazona, Raquel; Pera, Alejandra; Solana, Rafael

    2017-01-01

    The differential impact of ageing and cytomegalovirus (CMV) latent infection on human T-cell subsets remains to some extent controversial. The purpose of this study was to analyse the expression of the transcription factors T-bet and Eomes and CD57 on CD4+, CD4hiCD8lo and CD8+ T-cell subsets in healthy individuals, stratified by age and CMV serostatus. The percentage of CD4+ T-cells expressing T-bet or Eomes was very low, in particular in CD4+ T-cells from young CMV-seronegative individuals, and were higher in CMV-seropositive older individuals, in both CD57− and CD57+ CD4+ T-cells. The study of the minor peripheral blood double-positive CD4hiCD8lo T-cells showed that the percentage of these T-cells expressing both Eomes and T-bet was higher compared to CD4+ T-cells. The percentage of CD4hiCD8lo T-cells expressing T-bet was also associated with CMV seropositivity and the coexpression of Eomes, T-bet and CD57 on CD4hiCD8lo T-cells was only observed in CMV-seropositive donors, supporting the hypothesis that these cells are mature effector memory cells. The percentage of T-cells expressing Eomes and T-bet was higher in CD8+ T-cells than in CD4+ T-cells. The percentages of CD8+ T-cells expressing Eomes and T-bet increased with age in CMV-seronegative and -seropositive individuals and the percentages of CD57− CD8+ and CD57+ CD8+ T-cells coexpressing both transcription factors were similar in the different groups studied. These results support that CMV chronic infection and/or ageing are associated to the expansion of highly differentiated CD4+, CD4hiCD8lo and CD8+ T-cells that differentially express T-bet and Eomes suggesting that the expression of these transcription factors is essential for the generation and development of an effector-memory and effector T lymphocytes involved in conferring protection against chronic CMV infection. PMID:28661443

  18. Cytomegalovirus colitis in hospitalized inflammatory bowel disease patients in Taiwan: a referral center study.

    Science.gov (United States)

    Weng, Meng-Tzu; Tung, Chien-Chih; Lee, Yi-Shuan; Leong, Yew-Loong; Shieh, Ming-Jium; Shun, Chia-Tung; Wang, Cheng-Yi; Wong, Jau-Min; Wei, Shu-Chen

    2017-02-13

    Colitis is exacerbated in patients with concurrent cytomegalovirus (CMV) infection and inflammatory bowel disease (IBD). We assessed the prevalence and clinical features of CMV colitis in hospitalized IBD patients. A retrospective study reviewed the data from January 1, 1998 through December 31, 2013 compiled at the National Taiwan University Hospital. The CMV colitis patients' demographic data, clinical information, treatment regimens, pathologic findings, and outcome were analyzed. A total of 673 IBD patients were hospitalized during the study period. There were 312 patients diagnosed with Crohn's disease (CD) and 361 with ulcerative colitis (UC). CMV colitis was diagnosed as having positive inclusion bodies in colonic tissue. Six of the 312 CD patients (1.9%) and five of the 361 UC patients (1.4%) were diagnosed with CMV colitis. Compared to CD patients without CMV colitis, patients with CMV colitis were more often older (p colitis flare-ups after the index admission. The prevalence of CMV colitis in hospitalized IBD inpatients was 1.6% in Taiwan. Two associated factors for CMV colitis in hospitalized IBD patients were that they were elderly in CD and were on higher doses of steroids. Routine histopathology studies and/or PCR for refractory colitis patients are suggested to diagnose CMV colitis. Once the diagnosis is made, antiviral treatment is recommended to decrease the colitis relapse rate.

  19. Evaluation of cytomegalovirus (CMV)-specific T-cell immunity for the assessment of the risk of active CMV infection in non-immunosuppressed surgical and trauma intensive care unit patients.

    Science.gov (United States)

    Clari, María A; Aguilar, Gerardo; Benet, Isabel; Belda, Javier; Giménez, Estela; Bravo, Dayana; Carbonell, José A; Henao, Liliana; Navarro, David

    2013-10-01

    The current study was designed to assess the predictive value of the evaluation of cytomegalovirus (CMV)-specific T-cell immunity early following admission to the intensive care unit for inferring the risk of active CMV infection in non-immunosuppressed surgical and trauma patients. A total of 31 CMV-seropositive patients were included. Patients were screened for the presence of CMV DNA in plasma and in tracheal aspirates by real-time PCR. Enumeration of CMV pp65 and IE-1-specific IFN-γ CD8(+) and CD4(+) T cells was performed by flow cytometry for intracellular cytokine staining. Virological and immunological monitoring was conducted once or twice a week. Active CMV infection occurred in 17 out of 31 patients. Undetectable levels of pp65 and IE-1-specific IFN-γ CD8(+) and CD4(+) T-cell subsets cells were observed in 10 patients who developed active CMV infection and in one who did not (at a median of 2 days following ICU admission). Peak CMV DNA loads in both tracheal aspirates and plasma were substantially higher (P = 0.018 and P = 0.091, respectively) in patients with undetectable IFN-γ T-cell responses than in patients with detectable responses. The expansion of both CMV-specific T-cell subsets following detection of active CMV infection was demonstrated in 9 out of 14 patients with active CMV infection. In conclusion, the evaluation of CMV pp65 and IE-1-specific IFN-γ-producing CD8(+) and CD4(+) T cells early following ICU admission may allow the identification of patients most at risk of either having or developing an episode of active CMV infection, particularly those associated with high-level virus replication.

  20. Child Care Provider Awareness and Prevention of Cytomegalovirus and Other Infectious Diseases

    Science.gov (United States)

    Thackeray, Rosemary; Magnusson, Brianna M.

    2016-01-01

    Background: Child care facilities are prime locations for the transmission of infectious and communicable diseases. Children and child care providers are at high risk for cytomegalovirus (CMV) infection which causes severe birth defects and developmental delays. Objective: The goals of study were: (1) to determine the level of cytomegalovirus…

  1. Inflammatory bowel disease after liver transplantation : a role for cytomegalovirus infection

    NARCIS (Netherlands)

    Verdonk, Robert C; Haagsma, Elizabeth B; Van Den Berg, Aad P; Karrenbeld, Arend; Slooff, Maarten J H; Kleibeuker, Jan H; Dijkstra, Gerard

    2006-01-01

    OBJECTIVE: Despite the use of immunosuppressive drugs, recurrent and de novo inflammatory bowel disease (IBD) can develop after orthotopic liver transplantation (OLT). Cytomegalovirus (CMV) infection has been suggested to play a role in the pathogenesis of IBD. The aim of this study was to investiga

  2. Child Care Provider Awareness and Prevention of Cytomegalovirus and Other Infectious Diseases

    Science.gov (United States)

    Thackeray, Rosemary; Magnusson, Brianna M.

    2016-01-01

    Background: Child care facilities are prime locations for the transmission of infectious and communicable diseases. Children and child care providers are at high risk for cytomegalovirus (CMV) infection which causes severe birth defects and developmental delays. Objective: The goals of study were: (1) to determine the level of cytomegalovirus…

  3. DETECTION OF CYTOMEGALOVIRUS(CMV) IMMEDIATE EARLY ANTIGEN IN KIDNEY BIOPSIES AND TRANSPLANT NEPHRECTOMIES

    Institute of Scientific and Technical Information of China (English)

    燕航; 薛武军; 田普训; 郭奇; 何晓丽

    2004-01-01

    Objective To investigate the relationship between CMV infection and renal allograft rejection. Methods 39 kidney biopsies and transplant nephrectomies were collected and investigated for CMV immediate early antigen by immunohistochemistry. Results In 14 out of 39 tissue specimens CMV immediate early antigen were found. 8 biopsies from normal donor kidneys were negative; only 1 (10%) in 10 tissue specimens with early stage acute rejection was positive; 5(55.6%) in 9 biopsies with late stage acute rejection and 8 (66.7%) in 12 tissue blocks with chronic rejection were positive. Compared with normal kidney tissues, the infections in tissues with early stage acute rejection didn't increase obviously, but increased obviously in kidney tissue specimens with late stage rejection and with chronic rejection (P<0.05). Conclusion CMV infection appears to contribute to late stage acute rejection and chronic rejection after renal transplantation.

  4. Cytomegalovirus retinitis after central retinal vein occlusion in a patient on systemic immunosuppression: does venooclusive disease predispose to cytomegalovirus retinitis in patients already at risk?

    Directory of Open Access Journals (Sweden)

    Welling JD

    2012-04-01

    Full Text Available John D Welling, Ahmad B Tarabishy, John ChristoforidisDepartment of Ophthalmology, Havener Eye Institute, Ohio State University, Columbus, OH, USAAbstract: Cytomegalovirus (CMV retinitis remains the most common opportunistic ocular infection in immunocompromised patients. Patients with immunocompromising diseases, such as acquired immunodeficiency syndrome, inherited immunodeficiency states, malignancies, and those on systemic immunosuppressive therapy, are known to be at risk. Recently, it has been suggested that patients undergoing intravitreal injection of immunosuppressive agents may also be predisposed. One previous case report speculated that there may be an additional risk for CMV retinitis in acquired immunodeficiency syndrome patients with venoocclusive disease. This case study presents a case of CMV retinitis following central retinal vein occlusion in a patient on systemic immunosuppressants.Keywords: cytomegalovirus retinitis, central retinal vein occlusion, immunosuppression, solid organ transplant, venous stasis, risk factor

  5. Monitoring of trough plasma ganciclovir levels and peripheral blood cytomegalovirus (CMV)-specific CD8+ T cells to predict CMV DNAemia clearance in preemptively treated allogeneic stem cell transplant recipients.

    Science.gov (United States)

    Giménez, Estela; Solano, Carlos; Azanza, José Ramón; Amat, Paula; Navarro, David

    2014-09-01

    It is uncertain whether monitoring plasma ganciclovir (GCV) levels is useful in predicting cytomegalovirus (CMV) DNAemia clearance in preemptively treated allogeneic stem cell transplant recipients. In this observational study, including 13 episodes of CMV DNAemia treated with intravenous (i.v.) GCV or oral valganciclovir, we showed that monitoring trough plasma GCV levels does not reliably predict response to therapy. Rather, immunological monitoring (pp65 and immediate-early [IE]-1-specific gamma interferon [IFN-γ]-producing CD8+ T cells) appeared to perform better for this purpose.

  6. Fatal Cytomegalovirus Gastrointestinal Disease in an Infant with Wiskott-Aldrich Syndrome

    Directory of Open Access Journals (Sweden)

    Kuan-Ying Huang

    2008-01-01

    Full Text Available Although most cytomegalovirus (CMV infections are asymptomatic or cause only mild disease, the virus can cause serious disease and even mortality in immunocompromised children. In patients with WiskottAldrich syndrome (WAS, recurrent CMV infection is infrequently seen. A 3-month-old male infant was referred to Chang Gung Children's Hospital due to persistent thrombocytopenia and intermittent tachypnea. WAS complicated with CMV pneumonitis was diagnosed subsequently. He was discharged at the age of 7 months after a complete course of antiviral treatment. Unfortunately, refractory hemorrhagic gastritis developed later and recurred in spite of antiviral treatment and intravenous immunoglobulin. The patient died of recurrent gastrointestinal bleeding at the age of 23 months. This observation indicates that a case of WAS complicated with CMV gastrointestinal disease may need more vigorous treatment.

  7. Cytomegalovirus infection associated with inflammatory bowel disease.

    Science.gov (United States)

    Siegmund, Britta

    2017-05-01

    Refractory colitis in patients with inflammatory bowel disease is a complicated clinical disorder that might, in some patients, even necessitate surgery. Hence the diagnosis of additional complications is of utmost importance. Colitis mediated by cytomegalovirus is one such complication. The high seroprevalence and latent nature of cytomegalovirus, with the possibility of viral replication without mediating disease, poses a real challenge for the diagnosis of cytomegalovirus-mediated colitis. The challenge in daily clinical practice is to distinguish cytomegalovirus replication from cytomegalovirus-mediated colitis in patients with inflammatory bowel disease who have refractory colitis. This Review discusses the scientific literature and provides a diagnostic and therapeutic algorithm for clinical practice. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Antenatal interventions for preventing the transmission of cytomegalovirus (CMV) from the mother to fetus during pregnancy and adverse outcomes in the congenitally infected infant.

    LENUS (Irish Health Repository)

    McCarthy, Fergus P

    2012-01-31

    BACKGROUND: Cytomegalovirus (CMV) is a herpesvirus and the most common cause of congenital infection in developed countries. Congenital CMV infection can have devastating consequences to the fetus. The high incidence and the serious morbidity associated with congenital CMV infection emphasise the need for effective interventions to prevent the antenatal transmission of CMV infection. OBJECTIVES: The aim of this review was to assess the benefits and harms of interventions used during pregnancy to prevent mother to fetus transmission of CMV infection. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group\\'s Trials Register (31 December 2010). SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi RCTs investigating antenatal interventions for preventing the transmission of CMV from the mother to fetus during pregnancy and adverse outcomes in the congenitally infected infant. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion. MAIN RESULTS: We identified six studies from the search. None of these studies met the pre-defined criteria for inclusion in this review. AUTHORS\\' CONCLUSIONS: To date, no RCTs are available that examine antenatal interventions for preventing the transmission of CMV from the infected mother to fetus during pregnancy and adverse outcomes in the congenitally infected infant. Further research is needed to assess the efficacy of interventions aimed at preventing the transmission of CMV from the mother to fetus during pregnancy including a long-term follow-up of exposed infants and a cost effective analysis.

  9. Virological and immunological characteristics of human cytomegalovirus infection associated with Alzheimer disease.

    Science.gov (United States)

    Lurain, Nell S; Hanson, Barbara A; Martinson, Jeffrey; Leurgans, Sue E; Landay, Alan L; Bennett, David A; Schneider, Julie A

    2013-08-15

    Serum, cerebrospinal fluid (CSF), and cryopreserved lymphocytes from subjects in the Rush Alzheimer's Disease Center Religious Orders Study were analyzed for associations between cytomegalovirus (CMV) infection and clinical and pathological markers of Alzheimer disease. CMV antibody levels were associated with neurofibrillary tangles (NFTs). CSF interferon γ was only detected in seropositive subjects and was significantly associated with NFTs. The percentage of senescent T cells (CD4+ or CD8+CD28-CD57+) was significantly higher for CMV-seropositive as compared to CMV-seronegative subjects and was marginally associated with the pathologic diagnosis of Alzheimer disease (CD4+) or amyloid-β (CD8+). Immunocytochemical analysis showed induction of amyloid-β in human foreskin fibroblasts (HFFs) infected with each of 3 clinical CMV strains. In the same subjects, there was no association of herpes simplex virus type 1 (HSV-1) antibody levels with CMV antibody levels or clinical or pathological markers of Alzheimer disease. HSV-1 infection of HFFs did not induce amyloid-β. These data support an association between CMV and the development of Alzheimer disease.

  10. Hearing impairment in children with congenital cytomegalovirus (CMV) infection based on distortion product otoacoustic emissions (DPOAE) and brain evoked response audiometry stimulus click (BERA Click) examinations

    Science.gov (United States)

    Airlangga, T. J.; Mangunatmadja, I.; Prihartono, J.; Zizlavsky, S.

    2017-08-01

    Congenital cytomegalovirus (congenital CMV) infection is a leading factor of nongenetic sensorineural hearing loss in children. Hearing loss caused by CMV infection does not have a pathognomonic configuration hence further research is needed. The development of knowledge on hearing loss caused by congenital CMV infection is progressing in many countries. Due to a lack of research in the context of Indonesia, this study assesses hearing impairment in children with congenital CMV infection in Indonesia, more specifically in the Cipto Mangunkusumo Hospital. Our objective was to profile hearing impairment in children 0-5 years of age with congenital CMV infection using Distortion Product Otoacoustic Emissions (DPOAE) and Brain Evoked Response Audiometry Stimulus Click (BERA Click) examinations. This cross-sectional study was conducted in the Cipto Mangunkusum Hospital from November, 2015 to May 2016 with 27 children 0-5 years of age with congenital CMV infection. Of individual ears studied, 58.0% exhibited sensorineural hearing loss. There was a significant relationship between developmental delay and incidence of sensorineural hearing loss. Subjects with a developmental delay were 6.57 times more likely (CI 95%; 1.88-22.87) to experience sensorineural hearing loss. Congenital CMV infection has an important role in causing sensorineural hearing loss in children.

  11. Diagnostic value of enzyme linked immuno-sorbent assay for cytomegalovirus disease.

    Directory of Open Access Journals (Sweden)

    Priya K

    2002-07-01

    Full Text Available BACKGROUND: Since interpretation of results of enzyme linked immuno-sorbent assay (ELISA for diagnosis of Cytomegalovirus (CMV infection in India is difficult, its diagnostic value required evaluation. AIMS: To evaluate the diagnostic value of ELISA against polymerase chain reaction (PCR in CMV disease. SETTINGS AND DESIGN: Results of ELISA test for CMV antibodies in CMV-DNA PCR positive and negative patients and normal healthy blood donors were analysed. METHODS AND MATERIAL: Anti-CMV antibodies were assayed by ELISA on the sera of 26 CMV PCR positive and 21 PCR negative patients and 35 normal healthy blood donors. STATISTICAL ANALYSIS: Chi square and Fischer exact test were used for statistical analysis. RESULTS: Anti-CMV antibodies (IgG or IgG and IgM were present in 20 (76.9% of 26 PCR positive and 13 (61.9% of 21 PCR negative patients. ELISA was negative in six (23.1% of 26 PCR positive patients. Of the 28 paediatric patients, ELISA was positive in 14 (73.7% of 19 PCR positive and three (33.3% of nine PCR negative patients showing a statistically significant difference (Chi square test, P value 0.038. Among the 19 patients having complications after organ transplant, ELISA showed anti-CMV antibodies in six (85.7% of seven PCR positive and 11 (91.7% of 12 PCR negative patients showing no significant difference. CMV-DNA was not detected in the buffy coat of 35 sero-positive blood donors. CONCLUSION: ELISA has no diagnostic value in the detection of CMV activation although it may help in the differential diagnosis of CMV infection in the paediatric age group.

  12. Seronegative invasive gastro-intestinal cytomegalovirus disease in renal allograft recipients a diagnostic dilemma! - Tissue PCR the saviour?

    Directory of Open Access Journals (Sweden)

    A Kaul

    2015-01-01

    Full Text Available Seronegative Invasive Gastro-intestinal cytomegalovirus disease in renal allograft recipients Background -CMV as oppurtunistic infection affecting the gastrointerstinal tract is the most common cause for tissue invasive CMV disease occuring in 10-30% of organ transplant recepients. Gastrointerstinal CMV disease can be diagnosed in presence of clinical suspecion along with histopathological findings (CMV inclusions and presence of mucosal lesion(s on endoscopic examination with collaborative evidences via molecular technique. Aims-Few cases of CMV infection affecting the gastrointerstinal tract show no evidences of dissemintion despite use of highly sensitive molecular techniques. We encountered 6 cases where in despite strong clinical suspecion of Gastrointerstinal CMV disease there were seronegative and endoscopic negative evidences for CMV, blind tissue biopsy yeilded positive results for CMV disease with excellent improvement with antiviral therapy. Conclusions-Blind biopsy specimen for tissue PCR could serve as saviour in an immunocompromised individiual who has a strong clinical symptomatology for GI-CMV disease in absence of viremia, normal endoscopy and histopathology, so that the early therapeutic interventions could help in excellent patient and graft survival.

  13. Human Cytomegalovirus and Autoimmune Disease

    Directory of Open Access Journals (Sweden)

    Anne Halenius

    2014-01-01

    Full Text Available Human cytomegalovirus (HCMV represents a prototypic pathogenic member of the β-subgroup of the herpesvirus family. A range of HCMV features like its lytic replication in multiple tissues, the lifelong persistence through periods of latency and intermitting reactivation, the extraordinary large proteome, and extensive manipulation of adaptive and innate immunity make HCMV a high profile candidate for involvement in autoimmune disorders. We surveyed the available literature for reports on HCMV association with onset or exacerbation of autoimmune disease. A causative linkage between HCMV and systemic lupus erythematosus (SLE, systemic sclerosis (SSc, diabetes mellitus type 1, and rheumatoid arthritis (RA is suggested by the literature. However, a clear association of HCMV seroprevalence and disease could not be established, leaving the question open whether HCMV could play a coresponsible role for onset of disease. For convincing conclusions population-based prospective studies must be performed in the future. Specific immunopathogenic mechanisms by which HCMV could contribute to the course of autoimmune disease have been suggested, for example, molecular mimicry by UL94 in SSc and UL83/pp65 in SLE patients, as well as aggravation of joint inflammation by induction and expansion of CD4+/CD28− T-cells in RA patients. Further studies are needed to validate these findings and to lay the grounds for targeted therapeutic intervention.

  14. Cytomegalovirus (CMV) seroprevalence in pregnant women, bone marrow donors and adolescents in Germany, 1996-2010.

    Science.gov (United States)

    Enders, Gisela; Daiminger, Anja; Lindemann, Lisa; Knotek, Frank; Bäder, Ursula; Exler, Simone; Enders, Martin

    2012-08-01

    In Germany, studies on the IgG seroprevalence in pregnancy and in women of childbearing age are rare. Therefore, we retrospectively evaluated the CMV IgG seropositive rate in 40,324 pregnant women as well as in 31,093 female and male bone marrow donors over 15 consecutive years (1996-2010). Furthermore, the result of a study conducted in 1999 investigating 1,305 healthy adolescents with known ethnicity was included. The overall CMV IgG seroprevalence in pregnant women (15-50 years) was 42.3%. Age-dependent analysis revealed a significantly higher seropositive rate (55.6%) in young women (15-25 years) than in those aged 26-40 years (37-42%) and in women older than 40 years (48.3%). Over the study period of 15 years, the rate of seroprevalence in pregnant women declined significantly (χ(2) test < 0.01) from 44.3% in the first interval period (1996-2000), to 42.8% (2001-2005) and to 40.9% (2006-2010). The most influencing factor on CMV seropositivity appeared to be the socioeconomic status (SES), which we characterized by type of health insurance: Seroprevalence in women with low, middle and upper SES was 91.8, 46.9 and 33.7%, respectively. Female bone marrow donors of childbearing age (15-45 years) showed a significantly higher seropositive rate of 36.5% than age-matched male donors (28.6%). In adolescents aged 13-16 years, no gender-specific differences were recognized. Concerning ethnicity, youngsters with German descent had a significantly lower seroprevalence (29.9%) than those with non-German descent (67.4%).

  15. Fatal Cytomegalovirus Disease after Combination Therapy with Corticosteroids and Rituximab for Granulomatosis with Polyangiitis

    Directory of Open Access Journals (Sweden)

    Talal Hilal

    2015-01-01

    Full Text Available The association of cytomegalovirus (CMV with autoimmune disease is poorly understood with suggested causality and reported viral reactivation coinciding with active inflammation. We report a case of a patient who presented with diffuse alveolar hemorrhage and acute renal failure from rapidly progressive glomerulonephritis ultimately diagnosed with granulomatosis with polyangiitis (GPA. She was acutely managed with plasmapheresis to reduce antibody-mediated end-organ damage, hemodialysis for worsening hyperkalemia and acidosis, and high-dose intravenous methylprednisolone. She was transitioned to oral prednisone and started on weekly rituximab with resultant remission induction over a three-week period at which point she developed reactivation of CMV causing severe fatal lung disease and viremia. The case highlights the multiple factors associated with CMV reactivation in cases of severe systemic inflammatory states and the need for further research to help establish practice guidelines regarding antimicrobial prophylaxis in patients with autoimmune diseases on prolonged courses of corticosteroids and biologic agents.

  16. Analysis of cellular and humoral immune responses against cytomegalovirus in patients with autoimmune Addison's disease.

    Science.gov (United States)

    Edvardsen, Kine; Hellesen, Alexander; Husebye, Eystein S; Bratland, Eirik

    2016-03-09

    Autoimmune Addison's disease (AAD) is caused by multiple genetic and environmental factors. Variants of genes encoding immunologically important proteins such as the HLA molecules are strongly associated with AAD, but any environmental risk factors have yet to be defined. We hypothesized that primary or reactivating infections with cytomegalovirus (CMV) could represent an environmental risk factor in AAD, and that CMV specific CD8(+) T cell responses may be dysregulated, possibly leading to a suboptimal control of CMV. In particular, the objective was to assess the HLA-B8 restricted CD8(+) T cell response to CMV since this HLA class I variant is a genetic risk factor for AAD. To examine the CD8(+) T cell response in detail, we analyzed the HLA-A2 and HLA-B8 restricted responses in AAD patients and healthy controls seropositive for CMV antibodies using HLA multimer technology, IFN-γ ELISpot and a CD107a based degranulation assay. No differences between patients and controls were found in functions or frequencies of CMV-specific T cells, regardless if the analyses were performed ex vivo or after in vitro stimulation and expansion. However, individual patients showed signs of reactivating CMV infection correlating with poor CD8(+) T cell responses to the virus, and a concomitant upregulation of interferon regulated genes in peripheral blood cells. Several recently diagnosed AAD patients also showed serological signs of ongoing primary CMV infection. CMV infection does not appear to be a major environmental risk factor in AAD, but may represent a precipitating factor in individual patients.

  17. Intravaginal cytomegalovirus (CMV challenge elicits maternal viremia and results in congenital transmission in a guinea pig model

    Directory of Open Access Journals (Sweden)

    Schleiss Mark R

    2011-03-01

    Full Text Available Abstract Background The objective of this study was to compare intravaginal (ivg and subcutaneous (sc administration of the guinea pig cytomegalovirus (GPCMV in pregnant and non-pregnant guinea pigs. These studies tested the hypotheses that ivg infection would elicit immune responses, produce maternal viremia, and lead to vertical transmission, with an efficiency similar to the traditionally employed sc route. Results Four groups of age- and size-matched guinea pigs were studied. Two groups were pregnant, and two groups were not pregnant. Animals received 5x105 plaque-forming units (PFU of a GPCMV reconstituted from an infectious bacterial artificial chromosome (BAC construct containing the full-length GPCMV genome. Seroconversion was compared by IgG ELISA, and viremia (DNAemia was monitored by PCR. In both pregnant and non-pregnant animals, sc inoculation resulted in significantly higher serum ELISA titers than ivg inoculation at 8 and 12 weeks post-infection. Patterns of viremia (DNAemia were similar in animals inoculated by either sc or ivg route. However, in pregnant guinea pigs, animals inoculated by both routes experienced an earlier onset of DNAemia than did non-pregnant animals. Neither the percentage of dead pups nor the percentage of GPCMV positive placentas differed by inoculation route. Conclusions In the guinea pig model of congenital CMV infection, the ivg route is as efficient at causing congenital infection as the conventional but non-physiologic sc route. This finding could facilitate future experimental evaluation of vaccines and antiviral interventions in this highly relevant animal model.

  18. "Aspergillosis following Cytomegalovirus disease in a kidney transplant patient "

    Directory of Open Access Journals (Sweden)

    "Ameri Sh

    2003-06-01

    Full Text Available A 32-year-old end stage renal disease (ESRD woman was scheduled for transplantation. Also, she has had fever of unknown origin (FUO, rise of ESR and PPD>22 mm. Therefore treatment with isoniazid and rifampin was started three months prior to transplantation. She developed allograft dysfunction on week after transplantation. She received a few course pulse therapy (methyl prednisolone, antilymphocyte globulin (ALG, hemodialysis and because of low blood level of cyclosporine, isoniazid and rifampin were stopped. She was seen because of unilateral decreased vision, fever, cough and in physical examination, chorioretinitis and bilateral infiltration in both lungs were seen three weeks later. Severe cytomegalovirus (CMV antigenemia was detected and she responded rapidly to gancyclovir. One month later, she complained of fever and productive cough again. In chest X-ray (CXR, cavitary lesions were shown and with transthoracic biopsy, invasive aspergillosis was detected. In spite of amphotericin B therapy, she developed CNs involvement. Unfortunately she expired six months post transplantation. This is an interesting case of aspergillosis following CMV infection most likely because of an excess of immunosuppression.

  19. Colonoscopy in the diagnosis of intestinal graft versus host disease and cytomegalovirus enteritis following allogeneic haematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    HE Jin-de; LIU Yu-lan; WANG Zhi-feng; LIU Dai-hong; CHEN Huan; CHEN Yu-hong

    2008-01-01

    Background Gastrointestinal graft versus host disease (GI-GVHD) and cytomegalovirus (CMV) enteritis are important complications following allogeneic haematopoietic stem cell transplantation (alIo-HSCT). We explored the role of colonoscopy in the diagnosis of GI-GVHD and CMV enteritis following alIo-HSCT to identify the endoscopic manifestations of GI-GVHD and CMV enteritis was made.Methods A retrospective analysis of the colonoscopic manifestations of GI-GVHD, CMV enteritis and GI-GVHD with concurrent CMV enteritis (GconC) and their related clinical issues.Results Forty-seven patients underwent 50 colonoscopies with diagnoses of 32 GI-GVHD, 7 CMV enteritis and 11 GconC. Both GI-GVHD and CMV enteritis had colonic mucosal lesions with various manifestations under colonoscopy. Tortoise shell like changes of the mucosa (12 of 32) and deep ulcers (2 of 7) were specific endoscopic manifestations for GI-GVHD and CMV enteritis, respectively, while mucosal oedema, erythema, congestion, erosion and shallow ulcers could not be used to differentiate GI-GVHD from CMV enteritis. GconC patients were prone to have oozing bleeding of the end ileal mucosa and typhlodicliditis. Of the biopsed specimens for GI-GVHD, CMV enteritis and GconC, 64%, 70% and 44% were taken from the rectum and sigmoid colon respectively.Conclusions Following alIo-HSCT, tortoise shell like changes and deep ulcers of the colonic mucosa are characteristic changes for Gl-GVHD and CMV enteritis, respectively, while the other lesions are not. Most of the GI-GVHDs and CMV enteritis cases can be diagnosed by left colon examination and tissue biopsy, but total colon examination to the terminal ileum is preferred.

  20. Are female daycare workers at greater risk of cytomegalovirus infection? A secondary data analysis of CMV seroprevalence between 2010 and 2013 in Hamburg, Germany

    Directory of Open Access Journals (Sweden)

    Stranzinger, Johanna

    2016-04-01

    Full Text Available Background: Close contact with asymptomatic children younger than three years is a risk factor for a primary cytomegalovirus (CMV infection. In pregnant women, such primary infection increases the risk of CMV-induced feto- or embryopathy. Daycare providers have therefore implemented working restrictions for pregnant daycare workers (DCWs in accordance with legislation and guidelines for maternity protection. However, little is known about the infection risk for DCWs. We therefore compared the prevalence of CMV antibodies of pregnant DCWs to that of female blood donors (BDs.Method: In a secondary data analysis, the prevalence of anti-CMV IgG among pregnant DCWs (N=509 in daycare centers (DCCs was compared to the prevalence of female first-time BDs (N=14,358 from the greater region of Hamburg, Germany. Data collection took place between 2010 and 2013. The influence of other risk factors such as age, pregnancies and place of residence was evaluated using logistic regression models. Results: The prevalence of CMV antibodies in pregnant DCWs was higher than in female BDs (54.6 vs 41.5%; OR 1.6; 95%CI 1.3–1.9. The subgroup of BDs who had given birth to at least one child and who lived in the city of Hamburg (N=2,591 had a prevalence of CMV antibodies similar to the prevalence in pregnant DCWs (53.9 vs 54.6%; OR 0.9; 95%CI 0.8–1.2. Age, pregnancy history and living in the center of Hamburg were risk factors for CMV infections.Conclusion: The comparison of pregnant DCWs to the best-matching subgroup of female first-time BDs with past pregnancies and living in the city of Hamburg does not indicate an elevated risk of CMV infection among DCWs. However, as two secondary data sets from convenience samples were used, a more detailed investigation of the risk factors other than place of residence, age and maternity was not possible. Therefore, the CMV infection risk in DCWs should be further studied by taking into consideration the potential preventive

  1. Cytomegalovirus Colitis and Subsequent New Diagnosis of Inflammatory Bowel Disease in an Immunocompetent Host: A Case Study and Literature Review

    Science.gov (United States)

    Khan, Tipu V.; Toms, Carla

    2016-01-01

    Patient: Male, 40 Final Diagnosis: CMV colitis Symptoms: Abdominal pain • diarrhea • jaundice Medication: — Clinical Procedure: Flexible sigmoidoscopy • colonoscopy Specialty: Family Medicine Objective: Rare co-existance of disease or pathology Background: Infection with gastrointestinal cytomegalovirus in an immunocompetent host is a rather rare occurrence in the literature. There are a few reports of gastrointestinal infection in the immunocompetent who are then subsequently given a new diagnosis of inflammatory bowel disease. It is speculated that the initial cytomegalovirus colitis infection triggers the onset of inflammatory bowel disease. Case Report: Herein we report a case of cytomegalovirus colitis and new diagnosis of inflammatory bowel disease identified in a 40-year-old immunocompetent adult man who presented with gastrointestinal symptoms and disseminated cytomegalovirus infection requiring anti-viral therapy, which successfully treated the episode of cytomegalovirus infection. He then went on to have persistent symptomatic inflammatory bowel disease confirmed by pathology. Conclusions: In this paper we will review the literature and explore the rare case of cytomegalovirus colitis in the immunocompetent host and discuss the pathology, physiology, diagnosis, and treatment of cytomegalovirus colitis. PMID:27460032

  2. Decreased proportion of cytomegalovirus specific CD8 T-cells but no signs of general immunosenescence in Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Gabriel Westman

    Full Text Available Cytomegalovirus (CMV has been suggested as a contributing force behind the impaired immune responsiveness in the elderly, with decreased numbers of naïve T-cells and an increased proportion of effector T-cells. Immunological impairment is also implicated as a part of the pathogenesis in Alzheimer's disease (AD. The aim of this study was to investigate whether AD patients present with a different CMV-specific CD8 immune profile compared to non-demented controls. Blood samples from 50 AD patients and 50 age-matched controls were analysed for HLA-type, CMV serostatus and systemic inflammatory biomarkers. Using multi-colour flow cytometry, lymphocytes from peripheral blood mononuclear cells were analysed for CMV-specific CD8 immunity with MHC-I tetramers A01, A02, A24, B07, B08 and B35 and further classified using CD27, CD28, CD45RA and CCR7 antibodies. Among CMV seropositive subjects, patients with AD had significantly lower proportions of CMV-specific CD8 T-cells compared to controls, 1.16 % vs. 4.13 % (p=0.0057. Regardless of dementia status, CMV seropositive subjects presented with a lower proportion of naïve CD8 cells and a higher proportion of effector CD8 cells compared to seronegative subjects. Interestingly, patients with AD showed a decreased proportion of CMV-specific CD8 cells but no difference in general CD8 differentiation.

  3. Clinical study on cytomegalovirus infection after hematopoietic stem cell transplantation in 26patients with primary immunodeficiency diseases

    Institute of Scientific and Technical Information of China (English)

    阙蜜

    2014-01-01

    Objective To explore the risk factors,and control measures of cytomegalovirus(CMV)infection after hematopoietic stem cell transplantation(HSCT)in children with primary immunodeficiency diseases(PID).Methods We retrospectively analyzed the results of 26 patients with PID-Wiskott-Aldrich syndrome(WAS,n=20),severe combined immunodeficiency(SCID,n=1),Xlinked chronic granulomatous disease(XCGD,n=2)and X-linked hyper-immunoglobulin M(Ig M)syndrome

  4. Evaluation of a standardised real-time PCR based DNA-detection method (Realstar®) in whole blood for the diagnosis of primary human cytomegalovirus (CMV) infections in immunocompetent patients.

    Science.gov (United States)

    Berth, M; Benoy, I; Christensen, N

    2016-02-01

    Cytomegalovirus (CMV) DNA detection in blood could, as a supplementary test to serology, improve the accuracy and speed of diagnosis of an acute CMV infection. In this study we evaluated the performance of a commercially available and standardised CMV PCR assay in whole blood for the diagnosis of a primary infection in immunocompetent adults. Moreover, the kinetics of viral DNA was evaluated in order to provide a time frame in which viral DNA could be detected during an acute primary infection. Whole blood samples were collected from 66 patients with an acute CMV infection, 65 patients with an acute Epstein-Barr virus infection, 27 patients with various other acute infections (parvovirus B19, HIV, Toxoplasma gondii), 20 patients with past CMV infections (>1 year) and 20 apparently healthy persons. For CMV DNA detection and quantification a commercially available real-time PCR was applied (RealStar®, altona Diagnostics). The clinical sensitivity of CMV PCR in whole blood for the diagnosis of a recent primary CMV infection was 93.9 % and the diagnostic specificity 99.2 %. In the majority of the patients CMV DNA was not detectable anymore approximately within 4 weeks after the first blood sample was taken. From these data we concluded that, together with a suggestive serological profile, a positive CMV PCR result in whole blood can be regarded as a diagnostic confirmation of a recent CMV infection on a single blood sample in an immunocompetent patient. However, a negative CMV PCR result does not exclude a recent CMV infection.

  5. Multifunctional cytomegalovirus (CMV)-specific CD8(+) T cells are not restricted by telomere-related senescence in young or old adults.

    Science.gov (United States)

    Riddell, Natalie E; Griffiths, Stephen J; Rivino, Laura; King, David C B; Teo, Guo H; Henson, Sian M; Cantisan, Sara; Solana, Rafael; Kemeny, David M; MacAry, Paul A; Larbi, Anis; Akbar, Arne N

    2015-04-01

    Antigen-specific multifunctional T cells that secrete interferon-γ, interleukin-2 and tumour necrosis factor-α simultaneously after activation are important for the control of many infections. It is unclear if these CD8(+) T cells are at an early or late stage of differentiation and whether telomere erosion restricts their replicative capacity. We developed a multi-parameter flow cytometric method for investigating the relationship between differentiation (CD45RA and CD27 surface phenotype), function (cytokine production) and replicative capacity (telomere length) in individual cytomegalovirus (CMV) antigen-specific CD8(+) T cells. This involves surface and intracellular cell staining coupled to fluorescence in situ hybridization to detect telomeres (flow-FISH). The end-stage/senescent CD8(+)  CD45RA(+)  CD27(-) T-cell subset increases significantly during ageing and this is exaggerated in CMV immune-responsive subjects. However, these end-stage cells do not have the shortest telomeres, implicating additional non-telomere-related mechanisms in inducing their senescence. The telomere lengths in total and CMV (NLV)-specific CD8(+) T cells in all four subsets defined by CD45RA and CD27 expression were significantly shorter in old compared with young individuals in both a Caucasian and an Asian cohort. Following stimulation by anti-CD3 or NLV peptide, similar proportions of triple-cytokine-producing cells are found in CD8(+) T cells at all stages of differentiation in both age groups. Furthermore, these multi-functional cells had intermediate telomere lengths compared with cells producing only one or two cytokines after activation. Therefore, global and CMV (NLV)-specific CD8(+) T cells that secrete interferon-γ, interleukin-2 and tumour necrosis factor-α are at an intermediate stage of differentiation and are not restricted by excessive telomere erosion.

  6. [Cycloferon therapy of cytomegalovirus infection in monkeys].

    Science.gov (United States)

    Mezentseva, M V; Agrba, V Z; Karal-ogly, D D; Agumava, A A

    2012-01-01

    Cytomegalovirus (CMV) infection is a wide-spread disease throw humans and monkeys, which and associated with various diseases. The development of this infection in human organism is much like that in rhesus macaque, which makes CMV-infected monkeys adequate model for studying and elaborating prophylactic and therapeutic measures against this disease in humans. This article presents data on the efficiency of cycloferon action on animals with the M. mulatta CMV infection. Cycloferon stimulated an increase in the IFN-alpha production and promoted the period of remission in CMV-infected animals.

  7. Cytomegalovirus : a culprit or protector in multiple sclerosis?

    NARCIS (Netherlands)

    Vanheusden, Marjan; Stinissen, Piet; 't Hart, Bert A.; Hellings, Niels

    2015-01-01

    Multiple sclerosis (MS) is a chronic disabling autoimmune disease of the central nervous system (CNS). Cytomegalovirus (CMV), a beta herpes virus, may have a detrimental or beneficial role in MS pathology. Accumulating evidence indicates that CMV contributes to MS disease via interplay of different

  8. Cytomegalovirus : a culprit or protector in multiple sclerosis?

    NARCIS (Netherlands)

    Vanheusden, Marjan; Stinissen, Piet; 't Hart, Bert A.; Hellings, Niels

    Multiple sclerosis (MS) is a chronic disabling autoimmune disease of the central nervous system (CNS). Cytomegalovirus (CMV), a beta herpes virus, may have a detrimental or beneficial role in MS pathology. Accumulating evidence indicates that CMV contributes to MS disease via interplay of different

  9. Anti-cytomegalovirus antibodies and other atherosclerosis risk factors in patients with cardiovascular diseases

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To determine anti-cytomegalovirus (CMV) antibodies along with anti-Chlamydia pneumoniae (CP)antibodies in comparison with inflammatory markers and other risk factors of atherosclerosis in patients with selected cardiovascular diseases(CVD).Methods A total of 228 patients with coronary heart disease (CHD) and/or hypertension (HT), and those who underwent reconstructive vascular surgery (RVS) on carotids or abdominal aorta were tested for the presence of anti-CMV IgG and IgM antibodies as well as for anti-CP IgA antibodies, C-reactive protein (CRP),and interleukin-6 (IL-6). Other risk factors for atherosclerosis, namely age, gender,smoking, hypercholesterolemia, and diabetes mellitus were also analyzed. Results Anti-CMV IgG antibodies were found in 204 patients sera (89.5%),compared with 46 positive of 68 sera in the controls (67.6%), whereas anti-CMV IgM antibodies were detected in 4 of 54 sera of patients tested (7.4%), but not in the controls. The highest proportion of positive sera with not only anti-CMV IgG antibodies (95.6.7%),but also anti-CP IgA antibodies (78.3%), IL-6 (84.8%) and CRP (97.8%), was observed in patients with RVS. The results obtained corresponded to age, hypercholesterolemia, and diabetes. Conclusions The presence of anti-CMV antibodies together with antibodies to CP and markers of inflammation (CRP and IL-6) in our study was associated with CVD, primarily in elderly patients who underwent RVS.

  10. Cytomegalovirus colitis in a patient with Behcet's disease receiving tumor necrosis factor alpha inhibitory treatment

    Institute of Scientific and Technical Information of China (English)

    Ismail Sari; Merih Birlik; Can Gonen; Server Akar; Duygu Gurel; Fatos Onen; Nurullah Akkoc

    2008-01-01

    Anti-tumor necrosis factor alpha (TNF-α) inhibitors are effective in the treatment of various inflammatory rheumatic conditions. Increased risks of serious infections are the major issues concerning the long-term safety of these agents. We present a case of a young male Behcet's patient whose disease was complicated by cytomegalovirus (CMV) colitis. Colitis started 10 d after the third Infliximab dose and responded to the cessation of TNF blocking treatment and administration of ganciclovir. Tumor necrosis factor alpha and interferon gamma act at several levels in combating viral infections.CMV infections should be kept in mind and included in the differential diagnosis of severe gastrointestinal symptoms in patients receiving anti-TNF agents.

  11. Failure in generating hemopoietic stem cells is the primary cause of death from cytomegalovirus disease in the immunocompromised host

    Energy Technology Data Exchange (ETDEWEB)

    Mutter, W.; Reddehase, M.J.; Busch, F.W.; Buehring, H.J.K.; Koszinowski, U.H.

    1988-05-01

    We have shown in a murine model system for cytomegalovirus (CMV) disease in the immunocompromised host that CMV infection interferes with the earliest detectable step in hemopoiesis, the generation of the stem cell CFU-S-I, and thereby prevents the autoreconstitution of bone marrow after sublethal irradiation. The antihemopoietic effect could not be ascribed to a direct infection of stem cells. The failure in hemopoiesis was prevented by adoptive transfer of antiviral CD8+ T lymphocytes and could be overcome by syngeneic bone marrow transplantation. CD8+ T lymphocytes and bone marrow cells both mediated survival, although only CD8+ T lymphocytes were able to limit virus multiplication in host tissues. We concluded that not the cytopathic effect of virus replication in host tissues, but the failure in hemopoiesis, is the primary cause of death in murine CMV disease.

  12. Cytomegalovirus iritis.

    Science.gov (United States)

    Cheng, L; Rao, N A; Keefe, K S; Avila, C P; Macdonald, J C; Freeman, W R

    1998-11-01

    We describe a case of focal cytomegalovirus iritis in a patient with acquired immunodeficiency syndrome (AIDS) who had CMV retinitis. The autopsy showed histologic evidence of focal iritis in the left eye. This iritis was characterized by infiltration of acute inflammatory cells mixed with cytomegalic cells, which was confirmed by CMV-specific immunohistochemical staining. The case suggested that cytomegalovirus could be a direct causative agent of infectious iritis in AIDS patients.

  13. Cytomegalovirus disease in a renal transplant recipient: the importance of pre-transplant screening of the donor and recipient

    Directory of Open Access Journals (Sweden)

    Ahmed H Mitwalli

    2013-01-01

    Full Text Available A 16-year-old female patient who was born with a single kidney developed chronic kidney disease during her early childhood due to reflux nephropathy and recurrent urinary tract infection. She progressed to end-stage renal disease (ESRD and was commenced on renal replacement therapy in the form of peritoneal dialysis in May 2011. Subsequently, she underwent living unrelated donor kidney transplantation in China. She was hospitalized soon after returning to Saudi Arabia for management of high-grade fever, shortness of breath, and deterioration of renal function, which was found to be due to cytomegalovirus (CMV disease, proved by kidney biopsy and presence of high level of anti-CMV immunoglobulins. Allograft biopsy showed mature viral particles sized between 120 and 149 nm in the nuclei of the glomerular endothelial cells. The patient was treated with valgancyclovir and specific CMV immunoglobulin, as well as by reducing and even stopping the dose of tacrolimus and mycophenolate. Despite all these measures, her condition continued to deteriorate and she finally died. Our study emphasizes that unrelated renal transplantation, especially if unplanned and improperly prepared, is a very risky procedure that might transfer dangerous diseases and increase the morbidity and mortality of the patients. We strongly stress the need for mandatory and proper screening for CMV carrier status among donors as well as recipients prior to transplantation. Also, a recommendation is made to reject CMV-positive donors.

  14. Association of Cytomegalovirus End-Organ Disease with Stroke in People Living with HIV/AIDS: A Nationwide Population-Based Cohort Study.

    Directory of Open Access Journals (Sweden)

    Yung-Feng Yen

    Full Text Available Cytomegalovirus (CMV infection might increase the risk of cardiovascular event. However, data on the link between incident stroke and co-infections of CMV and human immunodeficiency virus (HIV are limited and inconsistent. This nationwide population-based cohort study analyzed the association of CMV end-organ disease and stroke among people living with HIV/AIDS (PLWHA.From January 1, 1998, this study identified adult HIV individuals with and without CMV end-organ disease in the Taiwan National Health Insurance Research Database. All patients were observed for incident stroke and were followed until December 31, 2012. Time-dependent analysis was used to evaluate associations of CMV end-organ disease with stroke.Of the 22,581 PLWHA identified (439 with CMV end-organ disease and 22,142 without CMV end-organ disease, 228 (1.01% had all-cause stroke during a mean follow-up period of 4.85 years, including 169 (0.75% with ischemic stroke and 59 (0.26% with hemorrhagic stroke. After adjusting for age, sex, comorbidities, opportunistic infections after HIV diagnosis, and antiretroviral treatment, CMV end-organ disease was found to be an independent risk factor for incident all-cause stroke (adjusted hazard ratio [AHR], 3.07; 95% confidence interval [CI], 1.70 to 5.55. When stroke type was considered, CMV end-organ disease was significantly positively associated with the risk of ischemic stroke (AHR, 3.14; 95% CI, 1.49 to 6.62 but not hemorrhagic stroke (AHR, 2.52; 95% CI, 0.64 to 9.91.This study suggested that CMV end-organ disease was an independent predictor of ischemic stroke among PLWHA.

  15. Removal of cytomegalovirus DNA from donor blood by filtration.

    Science.gov (United States)

    Smith, K L; Cobain, T; Dunstan, R A

    1993-04-01

    Blood from five donors, previously shown to be positive for cytomegalovirus (CMV) DNA following polymerase chain reaction (PCR) amplification, was filtered through commercially available leucocyte filters. Analysis of pre- and post-filtration samples by PCR with ethidium bromide staining has shown that filtration was successful in removing CMV DNA from all samples. This is evidence that leucocyte filtration of red cell concentrates may greatly decrease the risk of CMV disease following transfusion to susceptible patients.

  16. Spotting the owl: surreptitious cytomegalovirus disease in a renal transplant recipient.

    Science.gov (United States)

    Tarkan, Joshua L; Woo, Sook-Bin; Pavlakis, Martha; Johnson, Scott R; Chirieac, Lucian R; Chimienti, Sonia N; Mandelbrot, Didier A

    2008-01-01

    Cytomegalovirus (CMV) is a known cause of ulcerative oral lesions among HIV-infected patients, but such ulcers have not been previously reported in recipients of solid organ transplants. We describe a case of a renal transplant recipient who developed severe CMV-associated oral lesions despite prophylaxis with valganciclovir, and in the absence of detectable CMV viremia. The diagnosis was made only after multiple biopsies of the lesions. The patient recovered upon reducing immunosuppression. Potential pitfalls in making a prompt diagnosis are reviewed. The differential diagnosis of a large oral ulceration in a transplant recipient is broad, but should include CMV infection.

  17. Incidence, risk factors, and outcome of cytomegalovirus viremia and gastroenteritis in patients with gastrointestinal graft-versus-host disease.

    Science.gov (United States)

    Bhutani, Divaya; Dyson, Gregory; Manasa, Richard; Deol, Abhinav; Ratanatharathorn, Voravit; Ayash, Lois; Abidi, Muneer; Lum, Lawrence G; Al-Kadhimi, Zaid; Uberti, Joseph P

    2015-01-01

    Gastrointestinal (GI) graft-versus-host disease (GVHD) is one of the most common causes of morbidity and mortality after allogeneic stem cell transplantation. In addition, cytomegalovirus (CMV) infection of the gastrointestinal tract can complicate the post-transplantation course of these patients and it can be difficult to differentiate the 2 diagnoses given that they can present with similar symptoms. We retrospectively analyzed 252 patients who were diagnosed with GI GVHD to evaluate the incidence, risk factors, and outcomes of CMV viremia and CMV gastroenteritis in these patients. The median age at the time of transplantation was 51 years, 35% were related donor transplantations, and 65% were unrelated donor transplantations. A total of 114 (45%) patients developed CMV viremia at a median of 34 days (range, 14 to 236 days) after transplantation. Only recipient CMV IgG serostatus was significantly associated with development of CMV viremia (P gastroenteritis; 2 patients had evidence of CMV gastroenteritis and GVHD on the first biopsy and 29 on the second biopsy. Median time to development of CMV gastroenteritis was 52 days (range, 19 to 236 days) after transplantation. Using death as a competing risk, the cumulative incidence of CMV gastroenteritis at 1 year was 16.4%. The incidence of CMV gastroenteritis in relation to the donor/recipient serostatus was as follows: D+/R+, 22%; D-/R+, 31%; D+/R-, 12%; and D-/R-, 0. Median follow-up time for the 252 patients was 35.4 (95% CI 23.8 to 44.8) months. The estimated overall survival rate at 1 and 2 years was .45 (95% confidence interval [CI], .39 to .52) and .39 (95% CI, .33 to .46), respectively. Of the examined variables, those related to the overall survival were maximal clinical GVHD grade (P gastroenteritis (P = .008). Development of CMV viremia was not associated with increased mortality. In conclusion, CMV gastroenteritis is common complication in patients with GI GVHD and can adversely affect the prognosis.

  18. Proposed clinical case definition for cytomegalovirus-immune recovery retinitis.

    Science.gov (United States)

    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.

  19. Cytomegalovirus Immunoglobulin After Thoracic Transplantation

    Science.gov (United States)

    Grossi, Paolo; Mohacsi, Paul; Szabolcs, Zoltán; Potena, Luciano

    2016-01-01

    Abstract Cytomegalovirus (CMV) is a highly complex pathogen which, despite modern prophylactic regimens, continues to affect a high proportion of thoracic organ transplant recipients. The symptomatic manifestations of CMV infection are compounded by adverse indirect effects induced by the multiple immunomodulatory actions of CMV. These include a higher risk of acute rejection, cardiac allograft vasculopathy after heart transplantation, and potentially bronchiolitis obliterans syndrome in lung transplant recipients, with a greater propensity for opportunistic secondary infections. Prophylaxis for CMV using antiviral agents (typically oral valganciclovir or intravenous ganciclovir) is now almost universal, at least in high-risk transplants (D+/R−). Even with extended prophylactic regimens, however, challenges remain. The CMV events can still occur despite antiviral prophylaxis, including late-onset infection or recurrent disease, and patients with ganciclovir-resistant CMV infection or who are intolerant to antiviral therapy require alternative strategies. The CMV immunoglobulin (CMVIG) and antiviral agents have complementary modes of action. High-titer CMVIG preparations provide passive CMV-specific immunity but also exert complex immunomodulatory properties which augment the antiviral effect of antiviral agents and offer the potential to suppress the indirect effects of CMV infection. This supplement discusses the available data concerning the immunological and clinical effects of CMVIG after heart or lung transplantation. PMID:26900989

  20. Diagnóstico rápido de citomegalovirus (CMV en pacientes inmunocomprometidos mediante anticuerpos monoclonales que reconocen proteinas precoces virales Rapid diagnosis of cytomegalovirus infection in immunocompromised patients by using monoclonal antibodies against early viral antigens

    Directory of Open Access Journals (Sweden)

    Maritza Alvarez

    1989-06-01

    Full Text Available Se aplicó la técnica de detección de antigenos precoces fluorescentes (DAPF usando el anticuerpo monoclonal E-13 McAb, mediante el cual se lograron detectar 15 casos positivos a CMV de 75 muestras de orina o sangre ("buffy coat" tomadas de 52 pacientes inmunocomprometidos ingresados en el Instituto de Nefrología de ciudad Habana. Aplicando las técnicas clásicas de aislamiento en fibroblastos humanos diploides (MRC-5, se lograron aislar 12 cepas de CMV de casos previamente positivos por DAPF; lográndose además un aislamiento en una muestra reportada negativa por fluorescencia. Se observó una coincidencia de un 80% entre ambas técnicas. Se detectó la presencia de anticuerpos IgG contra CMV en todos los casos estudiados, utilizando para ello la técnica ELISA.A technique was applied to detect early fluorescent antigens (DEFA of cytomegalovirus (CMV using the E13 monoclonal antibodies in 52 immunocompromised patients hospitalized in the Nephrology Institute of Havana. Of the 75 urine or blood (buffy coat samples taken, 15 were found positive to CMV. Using classical diploide human fibroblast isolation technique, 12 CMV strains were isloation of previously detected positive samples by DEFA. In addition, CMV was isolated from one sample reported to be negative by DEFA. A coincidence of 80% was found between both techniques. With the ELISA test, all the sample studied have IgG antibodies to CMV.

  1. Cytomegalovirus Hepatitis During Pregnancy

    Directory of Open Access Journals (Sweden)

    Ying Chan

    1995-01-01

    Full Text Available Background: Although cytomegalovirus (CMV is an uncommon cause of viral hepatitis during pregnancy, a definitive diagnosis is important because of the potential for congenital CMV. In the case reported here, a diagnosis of hepatitis caused by CMV was made after the more common viral pathogens had been ruled out.

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

    Science.gov (United States)

    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

  3. Review of cytomegalovirus coinfection in HIV-infected individuals in Africa.

    Science.gov (United States)

    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.

  4. Preemptive therapy prevents cytomegalovirus end-organ disease in treatment-naive patients with advanced HIV-1 infection in the HAART era.

    Directory of Open Access Journals (Sweden)

    Daisuke Mizushima

    Full Text Available 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 were 126 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.

  5. Congenital and perinatal cytomegalovirus infection

    Directory of Open Access Journals (Sweden)

    Chun Soo Kim

    2010-01-01

    Full Text Available Cytomegalovirus (CMV is currently the most common agent of congenital infection and the leading infectious cause of brain damage and hearing loss in children. Symptomatic congenital CMV infections usually result from maternal primary infection during early pregnancy. One half of symptomatic infants have cytomegalic inclusion disease (CID, which is characterized by involvement of multiple organs, in particular, the reticuloendothelial and central nervous system (CNS. Moreover, such involvement may or may not include ocular and auditory damage. Approximately 90% of infants with congenital infection are asymptomatic at birth. Preterm infants with perinatal CMV infection can have symptomatic diseases such as pneumonia, hepatitis, and thrombocytopenia. Microcephaly and abnormal neuroradiologic imaging are associated with a poor prognosis. Hearing loss may occur in both symptomatic and asymptomatic infants with congenital infection and may progress through childhood. Congenital infection is defined by the isolation of CMV from infants within the first 3 weeks of life. Ganciclovir therapy can be considered for infants with symptomatic congenital CMV infection involving the CNS. Pregnant women of seronegative state should be counseled on the importance of good hand washing and other control measures to prevent CMV infection. Heat treatment of infected breast milk at 72?#608;for 5 seconds can eliminate CMV completely.

  6. Cytomegalovirus infections following umbilical cord blood transplantation using reduced intensity conditioning regimens for adult patients.

    Science.gov (United States)

    Matsumura, Tomoko; Narimatsu, Hiroto; Kami, Masahiro; Yuji, Koichiro; Kusumi, Eiji; Hori, Akiko; Murashige, Naoko; Tanaka, Yuji; Masuoka, Kazuhiro; Wake, Atsushi; Miyakoshi, Shigesaburo; Kanda, Yoshinobu; Taniguchi, Shuichi

    2007-05-01

    Cytomegalovirus (CMV) infection is a major complication after allogeneic hematopoietic stem cell transplantation (Allo-HSCT); however, we have little information on the clinical features of CMV reactivation after cord blood transplantation using reduced-intensity regimens (RI-CBT) for adults. We reviewed medical records of 140 patients who underwent RI-CBT at Toranomon Hospital between January 2002 and March 2005. All the patients were monitored for CMV-antigenemia weekly, and, if turned positive, received preemptive foscarnet or ganciclovir. Seventy-seven patients developed positive antigenemia at a median onset of day 35 (range, 4-92) after transplant. Median of the maximal number of CMV pp65-positive cells per 50,000 cells was 22 (range, 1-1806). CMV disease developed in 22 patients on a median of day 35 (range, 15-106); 21 had enterocolitis and 1 had adrenalitis. CMV antigenemia had not been detected in 2 patients, when CMV disease was diagnosed. CMV disease was successfully treated using ganciclovir or foscarnet in 14 patients. The other 8 patients died without improvement of CMV disease. In multivariate analysis, grade II-IV acute graft-versus-host disease was a risk factor of CMV disease (relative risk 3.48, 95% confidential interval 1.47-8.23). CMV reactivation and disease develop early after RI-CBT. CMV enterocolitis may be a common complication after RI-CBT.

  7. Cytomegalovirus infection after liver transplantation: Current concepts and challenges

    Institute of Scientific and Technical Information of China (English)

    Raymund Rabe Razonable

    2008-01-01

    Cytomegalovirus(CMV)is a common viral pathogen that influences the outcome of liver transplantation.In addition to the direct effects of CMV syndrome and tissue-invasive diseases,CMV is 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.Risk factors for CMV disease are often interrelated,and include CMV D+/R-serostatus,acute rejection,female gender,age,use of high-dose mycophenolate mofetil and prednisone,and the overall state of immunity.In addition to the role of CHV-specific CD4+ and CD8+ T lymphocytes,there are data to suggest that functionality of the innate immune system contributes to CMV disease pathogenesis.In one study,liver transplant recipients with a specific polymorphism in innate immune molecules known as Toll-like receptors were more likely to develop higher Ievels of CMV replication and clinical disease.Because of the direct and indirect adverse effects of CMV disease,its prevention,whether through antiviral prophylaxis or preemptive therapy,is an essential component in improving the outcome of liver transplantation.In the majority of transplant centers,antiviral prophylaxis is the preferred strategy over preemptive therapy for the prevention of CMV disease in CMV-seronegative recipients of liver allografts from CMV-seropositive donors(D+/R-).However,the major drawback of antiviral prophylaxis is the occurrence of delayed-onset primary CMV disease.In several prospective and retrospective studies,the incidence of delayed-onset primary CMV disease ranged from 16% to 47% of CMV D+/R-liver transplant recipients.Current data suggests that delayed-onset CMV disease is associated with increased mortality after liver transplantation.Therefore,optimized strategies for prevention and novel drugs with unique modes of action are needed.Currently,a randomized controlled clinical trial is being

  8. CMV and immunosenescence: from basics to clinics

    NARCIS (Netherlands)

    Solana, R.; Tarazona, R.; Aiello, A.E.; Akbar, A.N.; Appay, V.; Beswick, M.; Bosch, J.A.; Campos, C.; Cantisán, S.; Cicin-Sain, L.; Derhovanessian, E.; Ferrando-Martínez, S.; Frasca, D.; Fulöp, T.; Govind, S.; Gruben-Loebenstein, B.; Hill, A.; Hurme, M.; Kern, F.; Larbi, A.; López-Botet, M.; Maier, A.B.; McElhaney, J.E.; Moss, P.; Naumova, E.; Nikolich-Zugich, J.; Pera, A.; Rector, J.L.; Riddell, N.; Sanchez-Correa, B.; Sansoni, P.; Sauce, D.; van Lier, R.; Wang, G.C.; Wills, M.R.; Zieliński, M.; Pawelec, G.

    2013-01-01

    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

  9. Canadian society of transplantation consensus workshop on cytomegalovirus management in solid organ transplantation final report.

    Science.gov (United States)

    Preiksaitis, Jutta K; Brennan, Daniel C; Fishman, Jay; Allen, Upton

    2005-02-01

    The Canadian Society of Transplantation sponsored a Cytomegalovirus (CMV) Consensus Working Group that met on March 19, 2003. The objectives of this group were to determine the current burden of CMV-associated disease in the setting of solid organ transplantation in Canada, make recommendations regarding optimal strategies for the diagnosis, treatment and prevention of CMV infection and disease, highlight gaps in knowledge and outline priorities for research and other initiatives that might further reduce the burden of CMV-associated effects in this setting. This report summarizes the recommendations of the working group including ratings of the strength of evidence supporting the recommendations.

  10. The advent of Cytomegalovirus infection in HIV infected patients: A review

    Directory of Open Access Journals (Sweden)

    Sundar Isaac Kirubakaran

    2004-03-01

    Full Text Available Cytomegalovirus is considered as one among the long list of latent infections in humans that although normally controlled by the cellular immune response, gets activated after HIV infection takes its role on infecting the T4 lymphocytes. Clinical disease due to Cytomegalovirus has been recognized in up to 40% of patients with advanced HIV disease. The clinical syndromes most commonly associated include chorioretinitis, esophagitis, colitis, pneumonitis, adrenalitis and neurological disorders. Cytomegalovirus infections are usually diagnosed clinically and by serological tests for CMV immunoglobulin. Chemotherapy using systemic agents, including ganciclovir, intravenous foscarnet and intravenous cidofovir is effective. New agents, as for example an anti-sense agent against cytomegalovirus, appear promising.

  11. Late-onset cytomegalovirus infection complicated by Guillain-Barre syndrome in a kidney transplant recipient: case report and review of the literature.

    Science.gov (United States)

    Shaban, E; Gohh, R; Knoll, B M

    2016-04-01

    Cytomegalovirus (CMV) infection remains a common infection after solid-organ transplantation. In the general population CMV disease is associated with Guillain-Barre syndrome (GBS), an autoimmune disease leading to an acute peripheral neuropathy, in 1 of 1000 cases. Interestingly, GBS is a rarely observed complication in solid-organ transplant recipients, possibly related to maintenance immunosuppression. We describe a case of CMV infection complicated by GBS in a kidney transplant recipient and review the literature.

  12. Microgravity Analogues of Herpes Virus Pathogenicity: Human Cytomegalovirus (hCMV) and Varicella Zoster (VZV) Infectivity in Human Tissue Like Assemblies (TLAs)

    Science.gov (United States)

    Goodwin, T. J.; McCarthy, M.; Albrecht, T.; Cohrs, R.

    2009-01-01

    The old adage we are our own worst enemies may perhaps be the most profound statement ever made when applied to man s desire for extraterrestrial exploration and habitation of Space. Consider the immune system protects the integrity of the entire human physiology and is comprised of two basic elements the adaptive or circulating and the innate immune system. Failure of the components of the adaptive system leads to venerability of the innate system from opportunistic microbes; viral, bacteria, and fungal, which surround us, are transported on our skin, and commonly inhabit the human physiology as normal and imunosuppressed parasites. The fine balance which is maintained for the preponderance of our normal lives, save immune disorders and disease, is deregulated in microgravity. Thus analogue systems to study these potential Risks are essential for our progress in conquering Space exploration and habitation. In this study we employed two known physiological target tissues in which the reactivation of hCMV and VZV occurs, human neural and lung systems created for the study and interaction of these herpes viruses independently and simultaneously on the innate immune system. Normal human neural and lung tissue analogues called tissue like assemblies (TLAs) were infected with low MOIs of approximately 2 x 10(exp -5) pfu hCMV or VZV and established active but prolonged low grade infections which spanned .7-1.5 months in length. These infections were characterized by the ability to continuously produce each of the viruses without expiration of the host cultures. Verification and quantification of viral replication was confirmed via RT_PCR, IHC, and confocal spectral analyses of the respective essential viral genomes. All host TLAs maintained the ability to actively proliferate throughout the entire duration of the experiments as is analogous to normal in vivo physiological conditions. These data represent a significant advance in the ability to study the triggering

  13. Microgravity Analogues of Herpes Virus Pathogenicity: Human Cytomegalovirus (hCMV) and Varicella Zoster (VZV) Infectivity in Human Tissue Like Assemblies (TLAs)

    Science.gov (United States)

    Goodwin, T. J.; McCarthy, M.; Albrecht, T.; Cohrs, R.

    2009-01-01

    The old adage we are our own worst enemies may perhaps be the most profound statement ever made when applied to man s desire for extraterrestrial exploration and habitation of Space. Consider the immune system protects the integrity of the entire human physiology and is comprised of two basic elements the adaptive or circulating and the innate immune system. Failure of the components of the adaptive system leads to venerability of the innate system from opportunistic microbes; viral, bacteria, and fungal, which surround us, are transported on our skin, and commonly inhabit the human physiology as normal and imunosuppressed parasites. The fine balance which is maintained for the preponderance of our normal lives, save immune disorders and disease, is deregulated in microgravity. Thus analogue systems to study these potential Risks are essential for our progress in conquering Space exploration and habitation. In this study we employed two known physiological target tissues in which the reactivation of hCMV and VZV occurs, human neural and lung systems created for the study and interaction of these herpes viruses independently and simultaneously on the innate immune system. Normal human neural and lung tissue analogues called tissue like assemblies (TLAs) were infected with low MOIs of approximately 2 x 10(exp -5) pfu hCMV or VZV and established active but prolonged low grade infections which spanned .7-1.5 months in length. These infections were characterized by the ability to continuously produce each of the viruses without expiration of the host cultures. Verification and quantification of viral replication was confirmed via RT_PCR, IHC, and confocal spectral analyses of the respective essential viral genomes. All host TLAs maintained the ability to actively proliferate throughout the entire duration of the experiments as is analogous to normal in vivo physiological conditions. These data represent a significant advance in the ability to study the triggering

  14. Refractory ulcerative colitis complicated by cytomegalovirus infection successfully treated with valganciclovir

    Directory of Open Access Journals (Sweden)

    Tiziana Larussa

    2012-11-01

    Full Text Available Cytomegalovirus (CMV infection is widespread in the general population. In patients with severe and/or steroid-refractory ulcerative colitis (UC, local reactivation of CMV can be detected in actively inflamed colonic tissue in approximately 30% of cases. However, the role of CMV in patients with UC is not clearly understood. There is evidence to show a possible role in exacerbating a colitis flare, whereas other studies describe CMV as an innocent bystander. We report the case of a patient with severe UC complicated by CMV infection who did not respond to conventional therapy. A complete diagnostic panel for CMV diagnosis, including tissue polymerase chain reaction and immunohistochemistry, was carried out. Three-week therapy with oral valganciclovir resulted in dramatic clinical and endoscopic improvement. Timing of diagnosis and treatment of CMV infection complicating UC is crucial in order to recognize the organ-disease and plan appropriate treatment.

  15. Cytomegalovirus oesophagitis in a patient with non-hodgkin′s lymphoma

    Directory of Open Access Journals (Sweden)

    Hingmire S

    2008-01-01

    Full Text Available Cytomegalovirus (CMV infection is frequent in immunocompromised patients, especially in AIDS, organ transplantation and rarely in Hodgkin′s disease and Non-Hodgkin′s lymphoma (NHL. We present a case of NHL with CMV oesophagitis, which has rarely been documented in literature. Apart from fungal and herpes simplex infections, as the common differential diagnosis for oesophagitis in patients of lymphoma, CMV should be considered an important etiologic agent. Early diagnosis and prompt treatment of CMV oesophagitis with gancyclovir can avert significant morbidity and avoid unacceptable treatment delays.

  16. Case of cytomegalovirus-associated direct anti-globulin test-negative autoimmune hemolytic anemia.

    Science.gov (United States)

    Kaneko, Saeko; Sato, Masanori; Sasaki, Goro; Eguchi, Hiroyuki; Oishi, Tsutomu; Kamesaki, Toyomi; Kawaguchi, Hiroyuki

    2013-12-01

    A 1-year-old boy developed autoimmune hemolytic anemia after a negative direct anti-globulin test. The concentration of erythrocyte membrane-associated immunoglobulin G, determined using an immunoradiometric assay, correlated with disease activity. He was positive for cytomegalovirus (CMV) both serologically and by quantitative real-time polymerase chain reaction, indicating that his autoimmune hemolytic anemia was directly caused by CMV infection. Since anti-CMV immunoglobulin G was not absorbed by the patient's erythrocytes, cross-reaction between erythrocyte antigens and CMV was not likely a causative factor for hemolysis.

  17. Cytomegalovirus in pregnancy and the neonate

    Science.gov (United States)

    Emery, Vincent C.; Lazzarotto, Tiziana

    2017-01-01

    Congenital cytomegalovirus (CMV) remains a leading cause of disability in children. Understanding the pathogenesis of infection from the mother via the placenta to the neonate is crucial if we are to produce new interventions and provide supportive mechanisms to improve the outcome of congenitally infected children. In recent years, some major goals have been achieved, including the diagnosis of primary maternal CMV infection in pregnant women by using the anti-CMV IgG avidity test and the diagnosis and prognosis of foetal CMV infection by using polymerase chain reaction real-time tests to detect and quantify the virus in amniotic fluid. This review summarises recent advances in our understanding and highlights where challenges remain, especially in vaccine development and anti-viral therapy of the pregnant woman and the neonate. Currently, no therapeutic options during pregnancy are available except those undergoing clinical trials, whereas valganciclovir treatment is recommended for congenitally infected neonates with moderately to severely symptomatic disease. PMID:28299191

  18. Preface of the Special Issue: “Recent CMV Research”

    Directory of Open Access Journals (Sweden)

    Kayla Dufrene

    2014-01-01

    Full Text Available This Viruses Special Issue on Recent Cytomegalovirus (CMV Research is dedicated to the patients who have suffered CMV infection and to their parents, families and caregivers. We are including as a Preface to this issue the insights of a young college student, Kayla Dufrene, who suffered congenital CMV infection and contacted me and Dr. Roberta DeBiasi, to interview us to learn more about CMV. As I was just returning to the DC area from the 4th Congenital CMV Conference in San Francisco, I was particularly receptive to her request. When we met Kayla, we were both impressed with her personal strength and ability to cope with her disabilities and needed medical treatments. Despite it all, Kayla has an exceptionally positive outlook on life, feeling even lucky. She has not only coped, but has transcended her difficulties. I am proud to say that she was on the Dean’s List (Figure 1 at Gallaudet University. Ultimately, her hope lies in our fields’ efforts to develop a vaccine to prevent CMV disease in other children.

  19. Report from the second cytomegalovirus and immunosenescence workshop

    Directory of Open Access Journals (Sweden)

    Wills Mark

    2011-10-01

    Full Text Available Abstract The Second International Workshop on CMV & Immunosenescence was held in Cambridge, UK, 2-4th December, 2010. The presentations covered four separate sessions: cytomegalovirus and T cell phenotypes; T cell memory frequency, inflation and immunosenescence; cytomegalovirus in aging, mortality and disease states; and the immunobiology of cytomegalovirus-specific T cells and effects of the virus on vaccination. This commentary summarizes the major findings of these presentations and references subsequently published work from the presenter laboratory where appropriate and draws together major themes that were subsequently discussed along with new areas of interest that were highlighted by this discussion.

  20. Report from the second cytomegalovirus and immunosenescence workshop.

    Science.gov (United States)

    Wills, Mark; Akbar, Arne; Beswick, Mark; Bosch, Jos A; Caruso, Calogero; Colonna-Romano, Giuseppina; Dutta, Ambarish; Franceschi, Claudio; Fulop, Tamas; Gkrania-Klotsas, Effrossyni; Goronzy, Joerg; Griffiths, Stephen J; Henson, Sian; Herndler-Brandstetter, Dietmar; Hill, Ann; Kern, Florian; Klenerman, Paul; Macallan, Derek; Macualay, Richard; Maier, Andrea B; Mason, Gavin; Melzer, David; Morgan, Matthew; Moss, Paul; Nikolich-Zugich, Janko; Pachnio, Annette; Riddell, Natalie; Roberts, Ryan; Sansoni, Paolo; Sauce, Delphine; Sinclair, John; Solana, Rafael; Strindhall, Jan; Trzonkowski, Piotr; van Lier, Rene; Vescovini, Rosanna; Wang, George; Westendorp, Rudi; Pawelec, Graham

    2011-10-28

    The Second International Workshop on CMV & Immunosenescence was held in Cambridge, UK, 2-4th December, 2010. The presentations covered four separate sessions: cytomegalovirus and T cell phenotypes; T cell memory frequency, inflation and immunosenescence; cytomegalovirus in aging, mortality and disease states; and the immunobiology of cytomegalovirus-specific T cells and effects of the virus on vaccination. This commentary summarizes the major findings of these presentations and references subsequently published work from the presenter laboratory where appropriate and draws together major themes that were subsequently discussed along with new areas of interest that were highlighted by this discussion.

  1. Comparison between valganciclovir and aciclovir/valaciclovir for CMV prophylaxis in pediatric renal transplantation

    Directory of Open Access Journals (Sweden)

    M Fila

    2015-01-01

    Full Text Available Prophylaxis has dramatically decreased the occurrence of cytomegalovirus (CMV infection after renal transplantation. Optimal regimens of treatment remain controversial, especially in pediatric recipients. The aim of this study was to evaluate the effectiveness of valganciclovir (VGC versus aciclovir/valaciclovir (ACV in a pediatric renal transplant population. Data from 101 renal transplantations were retrospectively analyzed. Except those with R-/Dstatus, all patients received prophylaxis either with ACV, n = 39 or VGC, n = 38. Incidences of positive CMV antigenemia and disease, as well as the delay in relation to the prophylaxis, were collected during at least 12 months after the end of treatment. Positive CMV antigenemia was reported in 34 patients (ACV: 16, VGC: 16, no prophylaxis: 2. CMV disease occurred in 15 patients (ACV: 5; VGC: 8 (ns. For the majority of patients under VGC, positive CMV antigenemia occurred within the year following the withdrawal of prophylaxis (VGC: 14; ACV: 5, P <0.05, whereas it occurred during prophylaxis in 11 patients under ACV versus two under VGC (P <0.05. The over-all incidence of positive CMV antigenemia was similar between ACV and VGC prophylaxis. However, VGC was more efficient to prevent early CMV infection while patients treated with ACV had less CMV infection or disease after the end of the prophylaxis.

  2. CMV and Immunosenescence: from basics to clinics

    Directory of Open Access Journals (Sweden)

    Solana Rafael

    2012-10-01

    Full Text Available Abstract 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.

  3. 造血干细胞移植后患者血浆巨细胞病毒DNA拷贝数与巨细胞病毒病的关系%Relationship between copies of cytomegalovirus in plasma and cytomegalovirus disease after allogenetic hematopoeitic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    陈育红; 赵婷; 黄晓军; 赵晓涛; 赵晓甦; 刘开彦; 许兰平; 刘代红; 陈欢; 张晓辉; 韩伟; 王昱

    2009-01-01

    目的 评价实时定量聚合酶链式反应(RQ-PCR)法监测造血干细胞移植后患者血浆巨细胞病毒(CMV)DNA水平的临床意义.方法 对2005年1月至2007年1月之间进行异基因造血干细胞移植的318例患者,自移植应采用RQ-PCR每周监测血浆CMV-DNA水平,6×102拷贝/ml视为CMV-PCR阳性.结果 共136例患者(42.8%)检测出1025例次血浆CMV-DNA阳性,首次阳性出现的中位时间为42 d,最高拷贝数及初始拷贝数中位值分别为1.5×104拷贝/ml和4.5×103拷贝/ml.318例患者中共发生CMV肺炎及肠炎23例,累积发病率为7.2%.14例患者在发生CMV病之前出现CMV血症,4例在出现临床表现后方检测出病毒阳性,另有5例CMV血症阴性的患者诊断为CMV疾病.发生CMV病的患者其CMV-DNA最高拷贝数高于未发生组患者(4.3×104拷贝/ml比1.3×104拷贝/ml,P=0.009),但初始拷贝数差异无统计学意义(3.7×103拷贝/ml比4.7×103拷贝/ml,P=0.63).CMV-DNA最高拷贝数随着发生CMV感染的次数增加而增高,在发生CMV感染1~4次的患者中,中位数值分别为82.6×102、261.3×102、440.8×102和10 659.0×102拷贝/ml(P<0.01),且CMV肺炎及CMV肠炎发病率也从2.7%(5/182)明显上升至50%(2/4)(P=0.001).结论 采用RQ-PCR法监测造血干细胞移植后患者血浆CMV-DNA水平对CMV病的发生有一定的预测意义,高CMV-DNA拷贝数及多次感染者预示着CMV病发生概率升高.%Objective To evaluate the clinical significance of using real-time quantitative polymerase chain reaction (RQ-PCR) in monitoring cytomegalovirus infection in allogenic hemapoietic stem-cell transplant (allo-HSCT) recipients. Methods A total of 318 patients who received allo-HSCT in the past 2 years were analyzed retrospectively. RQ-PCR was performed to monitor CMV viremia twice a week after transplantation. Results CMV-DNA was detected in the plasma of 136 patients. The median time for the occurrence of CMV-DNA was 42 days after HSCT. The highest CMV-DNA load was

  4. Comparative analysis of presence of Cytomegalovirus (CMV and Epsteinbarr virus -1 (EBV-1 in cases of chronic periodontitis and aggressive periodontitis with controls

    Directory of Open Access Journals (Sweden)

    Rupali Sharma

    2012-01-01

    Conclusion: Our studyshowed that the prevalence of EBV1 was higher in chronic and aggressive periodontitis subjects compared to controls and the prevalence of CMV was higher in aggressive periodontitis patients. The virus positive sites showed higher pocket depth compared to virus negative sites.

  5. CMV infection attenuates the disease course in a murine model of multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Istvan Pirko

    Full Text Available Recent evidence in multiple sclerosis (MS suggests that active CMV infection may result in more benign clinical disease. The goal of this pilot study was to determine whether underlying murine CMV (MCMV infection affects the course of the Theiler's murine encephalitis virus (TMEV induced murine model of MS. A group of eight TMEV-infected mice were co-infected with MCMV at 2 weeks prior to TMEV infection while a second group of TMEV-infected mice received MCMV two weeks post TMEV. We also used 2 control groups, where at the above time points MCMV was replaced with PBS. Outcome measures included (1 monthly monitoring of disability via rotarod for 8 months; (2 in vivo MRI for brain atrophy studies and (3 FACS analysis of brain infiltrating lymphocytes at 8 months post TMEV infection. Co-infection with MCMV influenced the disease course in mice infected prior to TMEV infection. In this group, rotarod detectable motor performance was significantly improved starting 3 months post-infection and beyond (p≤0.024. In addition, their brain atrophy was close to 30% reduced at 8 months, but this was only present as a trend due to low power (p = 0.19. A significant reduction in the proportion of brain infiltrating CD3+ cells was detected in this group (p = 0.026, while the proportion of CD45+ Mac1+ cells significantly increased (p = 0.003. There was also a strong trend for a reduced proportion of CD4+ cells (p = 0.17 while CD8 and B220+ cell proportion did not change. These findings support an immunomodulatory effect of MCMV infection in this MS model. Future studies in this co-infection model will provide insight into mechanisms which modulate the development of demyelination and may be utilized for the development of novel therapeutic strategies.

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

    Directory of Open Access Journals (Sweden)

    Pegah Karimian

    2016-01-01

    Full Text Available 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.

  7. Comparison between valganciclovir and aciclovir/valaciclovir for CMV prophylaxis in pediatric renal transplantation.

    Science.gov (United States)

    Fila, M; Dechartes, A; Maisin, A; Dossier, C; Zhao, W; Deschênes, G; Baudouin, V

    2015-01-01

    Prophylaxis has dramatically decreased the occurrence of cytomegalovirus (CMV) infection after renal transplantation. Optimal regimens of treatment remain controversial, especially in pediatric recipients. The aim of this study was to evaluate the effectiveness of valganciclovir (VGC) versus aciclovir/valaciclovir (ACV) in a pediatric renal transplant population. Data from 101 renal transplantations were retrospectively analyzed. Except those with R-/Dstatus, all patients received prophylaxis either with ACV, n = 39 or VGC, n = 38. Incidences of positive CMV antigenemia and disease, as well as the delay in relation to the prophylaxis, were collected during at least 12 months after the end of treatment. Positive CMV antigenemia was reported in 34 patients (ACV: 16, VGC: 16, no prophylaxis: 2). CMV disease occurred in 15 patients (ACV: 5; VGC: 8) (ns). For the majority of patients under VGC, positive CMV antigenemia occurred within the year following the withdrawal of prophylaxis (VGC: 14; ACV: 5, P ACV versus two under VGC (P ACV and VGC prophylaxis. However, VGC was more efficient to prevent early CMV infection while patients treated with ACV had less CMV infection or disease after the end of the prophylaxis.

  8. [Open clinical trial with oral acyclovir for the prophylaxis of disease by Cytomegalovirus in low risk liver transplant recipients].

    Science.gov (United States)

    Moreno, J; Montero, J L; Gavilán, F; Costán, G; Herrero, C; Cárdenas, M; Sánchez-Guijo, P; Torre-Cisneros, J

    1999-10-01

    Checking the first 70 low risk liver transplantation performed in our hospital, who did not receive prophylaxis for Cytomegalovirus, we found that the incidence of Cytomegalovirus-infection and Cytomegalovirus-disease were 47% and 16% respectively. For this reason we started a prospective, open clinical study, to address the safety of acyclovir prophylaxis in low-risk liver transplant patients. Seventy patients did not receive acyclovir. Fifty patients received oral acyclovir during 3 months (800-3,200 mg/day). The occurrence of Cytomegalovirus infection was not modified (40%) but Cytomegalovirus disease decreased dramatically (4%, p Varicela-zoster symptomatic disease in this group of patients.

  9. Evaluation of glycoprotein B genotypes and load of CMV infecting blood leukocytes on prognosis of AIDS patients

    Directory of Open Access Journals (Sweden)

    Aldo Albuquerque Cunha

    2011-04-01

    Full Text Available BACKGROUND: Cytomegalovirus (CMV remains an important pathogen to immunocompromised patients even in the era of HAART. The present study aimed at evaluating the influence of CMV viral load and its gB genotypes on AIDS patients' outcome. METHODS: Blood samples of 101 AIDS patients were collected and tested for HIV load, CD4 - cell count and opportunistic pathogens, including CMV. Semi-nested PCRs were run to detect CMV genome and in the positive samples, gB genotyping and CMV load were established using enzymatic restriction and real time PCR, respectively. All patients were clinically followed for four years. RESULTS: In thirty patients (31% CMV was detected and all fatal cases (n = 5 occurred in this group of patients (p = 0.007, but only two patients had CMV disease (1.9%. However, viral load was not statistically associated with any analyzed parameter. The most frequently observed CMV genotype was gB2 (45.16% followed by gB3 (35.48%. gB2 genotype was more frequently found in patients with CD4-cell counts under 200 cells/mm³ (p = 0.0017, and almost all fatal cases (80% had gB2 genotype. CONCLUSIONS: Our study suggests that CMV and its polymorphisms in biologically relevant genes, such as the gB encoding ORF, may still influence the prognosis and outcome of AIDS patients. The gB2 genotype was associated to patient's bad outcome.

  10. Cytomegalovirus-induced transient protein-losing hypertrophic gastropathy in an immunocompetent adult.

    Science.gov (United States)

    Suter, W R; Neuweiler, J; Borovicka, J; Binek, J; Fantin, A C; Meyenberger, C

    2000-01-01

    Transient protein-losing hypertrophic gastropathy with similarity to Ménétrier's disease is described. Acute infection with cytomegalovirus (CMV) could be shown to play a causative role. Immunodeficiency was ruled out. The 34-year-old patient had complete resolution of the disease without antiviral treatment. To our knowledge the present report is the first case of CMV-associated protein-losing hypertrophic gastropathy in an immunocompetent adult. To date, a similar disorder has only been described in children. CMV infection should be considered in patients with acute and symptomatic protein loss of gastrointestinal origin. Copyright 2000 S. Karger AG, Basel

  11. Cutaneous Ulcer as Leading Symptom of Systemic Cytomegalovirus Infection

    Directory of Open Access Journals (Sweden)

    Richard F. Guo

    2015-01-01

    Full Text Available Cytomegalovirus (CMV infection rarely manifests with skin ulcerations. We describe a case report of a 64-year-old woman with chronic immunosuppression for treatment of mixed connective tissue disease, presenting with new onset leg ulcerations after a recent change in immunosuppressive regimen. She subsequently developed fulminant hepatitis, encephalopathy, and pancytopenia and was found to have severe systemic CMV viremia. Skin ulcer biopsy was positive by immunohistochemical staining for CMV infected endothelial cells. Both systemic disease and skin ulcer rapidly improved after stopping immunosuppression and administering intravenous ganciclovir. New onset skin ulcers in an immunosuppressed individual, especially with recent changes in immunosuppressive regimen, should raise the suspicion of reactivation of CMV.

  12. Synthetic DNA approach to cytomegalovirus vaccine/immune therapy.

    Science.gov (United States)

    Wu, Stephan J; Villarreal, Daniel O; Shedlock, Devon J; Weiner, David B

    2015-01-01

    There is no licensed vaccine or cure for human cytomegalovirus (CMV), a ubiquitous β-herpes virus that infects 60-95 % of adults worldwide. Infection is a major cause of congenital abnormalities in newborns, contributes to development of childhood cerebral palsy and medulloblastoma, can result in severe disease in immunocompromised patients, and is a major impediment during successful organ transplantation. While CMV has been increasingly associated with numerous inflammatory diseases and cancers, only recently has it been correlated with increased risk of heart disease in adults, the number-one killer in the USA. These data, among others, suggest that subclinical CMV infection, or microinfection, in healthy individuals may play more of a causative role than an epiphenomenon in development of CMV-associated pathologies. Due to the myriad of diseases and complications associated with CMV, an efficacious vaccine would be highly valuable in reducing human morbidity and mortality as well as saving billions of dollars in annual health-care costs and disability adjusted life years (DALY) in the developing world. Therefore, the development of a safe efficacious CMV vaccine or immune therapy is paramount to the public health. This review aims to provide a brief overview on aspects of CMV infection and disease and focuses on current vaccine strategies. The use of new synthetic DNA vaccines might offer one such approach to this difficult problem.

  13. Cytomegalovirus-associated colitis causing diarrhea in an immunocompetent patient

    Institute of Scientific and Technical Information of China (English)

    Dan Carter; David Olchovsky; Russell Pokroy; David Ezra

    2006-01-01

    Cytomegalovirus (CMV) colitis rarely occurs in immunocompetent patients. We report a case of disabling and life threatening diarrhea in an immunocompetent elderly woman due to CMV colitis. The diagnosis of CMV was based on histological examination of tissues biopsied at colonoscopy, positive CMV antigen and high CMV-IgM titer in peripheral blood samples and a good response to systemic gancyclovir treatment.We conclude that CMV should be considered in the differential diagnosis of colitis in elderly immunocompetent patients.

  14. Transfusion in CMV seronegative T-depleted allogeneic stem cell transplant recipients with CMV-unselected blood components results in zero CMV transmissions in the era of universal leukocyte reduction: a U.K. dual centre experience.

    Science.gov (United States)

    Hall, S; Danby, R; Osman, H; Peniket, A; Rocha, V; Craddock, C; Murphy, M; Chaganti, S

    2015-12-01

    To establish rates of cytomegalovirus (CMV) transmission with use of CMV-unselected (CMV-U), leukocyte-reduced blood components transfused to CMV-seronegative patient/CMV-seronegative donor (CMV neg/neg) allogeneic stem cell transplantation (SCT) recipients including those receiving T-depleted grafts. CMV infection remains a major cause of morbidity following SCT. CMV-seronegative SCT recipients are particularly at risk of transfusion transmitted CMV (TT-CMV) and until recently they have received blood components from CMV-seronegative donors with significant resource implications. Although leukocyte reduction of blood components is reported to minimise risk of TT-CMV, its efficacy in high-risk situations, such as in T-depleted transplant recipients, is unknown. We retrospectively analysed the incidence of TT-CMV in CMV neg/neg allogeneic SCT recipients transfused with CMV-U, leukocyte-reduced blood components in two transplantation centres in the UK. Patients were monitored for CMV infection by weekly CMV polymerase chain reaction testing. Leukocyte reduction of blood components was in accordance with current UK standards. Among 76 patients, including 59 receiving in vivo T-depletion, no episodes of CMV infection were detected. Patients were transfused with 1442 CMV-unselected, leukocyte-reduced components, equating to 1862 donor exposures. Our findings confirm the safety of leukocyte reduction as a strategy in preventing TT-CMV in high-risk allogeneic SCT recipients. © 2015 British Blood Transfusion Society.

  15. CYTOMEGALOVIRUS INTERSTITIAL PNEUMONITIS FOLLOWING ALLOGENEIC PERIPHERAL BLOOD STEM CELL TRANSPLANTATION

    Institute of Scientific and Technical Information of China (English)

    XU Xiao-hua; HUANG Lian-sheng; ZHANG Xiao-hong; ZHU Kang-er; XU Yang; WU Dong; ZHAO Xiao-ying

    2005-01-01

    Objective: To explore the risk factors and prophylaxis and treatment of cytomegalovirus interstitial pneumonitis(CMV-IP) after allogeneic peripheral blood stem cell transplantation (allo-PBSCT). Methods: 43 patients who received allo-PBSCT were allocated to either a Gancyclovir(GCV)-prophylaxis group (n=19) or a non-GCV prophylaxis group (n=24).A comparison was made of the incidence of CMV-IP in patients given or not given prophylactic gancyclovir. Results: 9patients in non-GCV prophylaxis group developed late CMV-IP (P<0.05). Graft-versus-host-disease (GVHD) may be associated with a high risk of CMV-IP. 5 cases of CMV-IP were successfully treated with GCV, but 3 cases died of CMV-IP.The most common adverse event of GCV was neutropenia, but was reversible. Conclusion: CMV infection was a major cause of interstitial pneumonitis after allo-PBSCT, which correlated strongly with the severity of GVHD. Gancyclovir was shown to be effective in both prophylaxis and treatment of CMV-IP.

  16. Acute cervicitis and vulvovaginitis may be associated with Cytomegalovirus

    OpenAIRE

    Abou, Magali; Dällenbach, Patrick

    2013-01-01

    Cytomegalovirus (CMV) infection in immunocompetent hosts is generally asymptomatic or may present as a mononucleosic syndrome. Its association with acute cervicitis and vulvovaginitis has rarely been reported.

  17. Effects of oral valganciclovir prophylaxis for cytomegalovirus infection in heart transplant patients

    Directory of Open Access Journals (Sweden)

    Doesch AO

    2012-10-01

    Full Text Available Andreas O Doesch,1 Janika Repp,1 Nina Hofmann,1 Christian Erbel,1 Lutz Frankenstein,1 Christian A Gleissner,1 Constanze Schmidt,1 Arjang Ruhparwar,2 Christian Zugck,1 Paul Schnitzler,3 Philipp Ehlermann,1 Thomas J Dengler,4 Hugo A Katus11Department of Cardiology, 2Department of Cardiac Surgery, 3Department of Infectious Disease, Virology, University of Heidelberg, Heidelberg, 4Department of Cardiology, SLK Kliniken Heilbronn, Bad Friedrichshall, GermanyBackground: Cytomegalovirus (CMV infection is a serious complication following heart transplantation. This study (June 2003-January 2010 retrospectively assessed the effects of oral valganciclovir prophylaxis in adult heart transplant recipients during the first year after transplantation.Methods: In patients with normal renal function, 900 mg of oral valganciclovir was administered twice daily for 14 days after heart transplant followed by 900 mg per day for following 6 months. In the event of renal insufficiency, valganciclovir was adjusted according to the manufacturer's recommendations. Antigenemia testing for pp65 antigen and simultaneous polymerase chain reaction (PCR were used to document exposure to CMV. From 2003 to 2010, 146 patients (74.0% men of mean age 50.7 ± 10.3 years at the time of heart transplant were included.Results: A total of 16 patients (11.0% of total, 75.0% male had a positive pp65 and PCR result (ie, CMV infection during the year following heart transplant; three of these patients had discontinued valganciclovir prophylaxis within the first 6 months following transplant because of leukopenia, including one patient developed CMV colitis. Two further patients developed CMV pneumonia during prophylactic valganciclovir therapy. Eight patients had positive pp65 and PCR tests in the 6–12 months after heart transplant following cessation of routine prophylaxis. One of these patients developed CMV pneumonia and another developed CMV colitis and CMV pneumonia. Thirty-seven of

  18. Platelets, acting in part via P-selectin, mediate cytomegalovirus-induced microvascular dysfunction.

    Science.gov (United States)

    Khoretonenko, Mikhail V; Brunson, Jerry L; Senchenkov, Evgeny; Leskov, Igor L; Marks, Christian R; Stokes, Karen Y

    2014-12-15

    Cytomegalovirus (CMV) infects a majority of the population worldwide. It has been implicated in cardiovascular disease, induces microvascular dysfunction, and synergizes with hypercholesterolemia to promote leukocyte and platelet recruitment in venules. Although platelets and platelet-associated P-selectin contribute to cardiovascular disease inflammation, their role in CMV-induced vascular responses is unknown. We assessed the role of platelets in CMV-induced microvascular dysfunction by depleting platelets and developing bone marrow chimeric mice deficient in platelet P-selectin. Wild-type and chimeric mice received mock or murine (m)CMV intraperitoneally. Five weeks later, some mice were switched to a high-cholesterol diet (HC) to investigate the synergism between mCMV and HC. Arteriolar vasodilation and recruitment of leukocytes and donor platelets in venules were measured at 11wk. mCMV with or without HC caused significant endothelial dysfunction in arterioles. Platelet depletion restored normal vasodilation in mCMV-HC but not mCMV-ND mice, whereas protection was seen in both groups for platelet P-selectin chimeras. Only mCMV + HC elevated leukocyte and platelet recruitment in venules. Leukocyte adhesion was reduced to mock levels by acute platelet depletion but was only partially decreased in platelet P-selectin chimeras. Platelets from mCMV-HC mice and, to a lesser extent, mCMV-ND but not mock-HC mice showed significant adhesion in mCMV-HC recipients. Our findings implicate a role for platelets, acting through P-selectin, in CMV-induced arteriolar dysfunction and suggest that the addition of HC leads to a platelet-dependent, inflammatory infiltrate that is only partly platelet P-selectin dependent. CMV appeared to have a stronger activating influence than HC on platelets and may represent an additional therapeutic target in vulnerable patients.

  19. Trends in hospitalizations for diagnosed congenital cytomegalovirus in infants and children in Australia

    Directory of Open Access Journals (Sweden)

    MacIntyre C Raina

    2009-01-01

    Full Text Available Abstract Background Cytomegalovirus (CMV is responsible for a wide range of diseases in neonates, and has been recognized as a major cause of congenital defects in developed countries for many years. More children suffer serious disabilities caused by congenital CMV than by several better-known childhood maladies. Insight into the epidemiology of congenital CMV disease is needed for the assessment of preventive strategies. Methods Using data from the National Hospital Morbidity Database (NHMD complied by the Australian Institute of Health and Welfare (AIHW, we examined the rates of hospital admissions for children diagnosed with congenital cytomegalovirus (CMV by year, sex, age group and length of stay. Results Over an 8-year period (1993–2001, there were 1314 admissions for the congenital form of CMV disease. Of these admissions, 25% were principally hospitalized because of congenital CMV. The average annual rate of admissions in children aged 0–4, 5–9 and 10–14 years was 9.40, 2.40 and 0.85 per 100,000 Australian population respectively. Conclusion Compared with many other congenital illnesses, which are now vaccine preventable, the burden of congenital CMV is comparatively high. A vaccination program would be justifiable should a vaccine become available.

  20. Construction of aptamer-based surface plasma resonance biosensor microarray for the rapid detection of toxoplasma godii and cytomegalovirus IgG antibodies%快速检测TOX、CMV IgG抗体的适配子型SPR传感器微阵列的初步构建

    Institute of Scientific and Technical Information of China (English)

    刘星; 秦莲花; 罗阳; 苗杰; 王丰; 黄庆; 黄君富; 胡忠义; 府伟灵

    2012-01-01

    Objective To construct the aptamer-based surface plasma resonance ( SPR) microarray for rapid assay of toxoplasma gondii (TOX) and cytomegalovirus (CMV) IgG antibodies. Methods Aptamers of the TOX gondii and CMV IgG antibodies were screened with the SELEX technique and integrated into the real-time online analyzing system on the SPR biosensor. Hybridization of TOX and CMV IgG antibodies in solution was detected according to the probe molecules fixed on the surface of biosensor. The stability and linear detection range of this assay were further investigated. Results The novel rapid method could assay the TOX and CMV IgG antibodies with a good stability and a linear assay range of 20 to 300 μmol/L. Conclusion The stability of the rapid assay we established is good. Combined SPR biosensor and aptamer techniques have a broad prospect in clinical assay of TOX and CMV IgG antibody level.%目的 初步构建弓形虫(toxoplas ma gondii,TOX)、巨细胞病毒(cytomegalovirus,CMV)IgG抗体的适配子型SPR传感器微阵列的快速检测方法.方法 采用SELEX技术筛选TOX、CMV IgG的适配子,并将其整合于SPR生物传感器实时在线分析系统,通过在传感器表面固定探针分子,对溶液中的TOX、CMV IgG进行杂交检测,并进一步研究该检测方法的稳定性与线性检范围.结果 该新型快速检测方法能够实现对TOX、CMV IgG的实时检测,检测系统稳定性良好,八通道间检测时互不影响,线性检测范围为20~300 μmol/L.结论 该实验建立的快速检测方法,具有稳定性好等优点,SPR传感器技术结合适配子技术在临床诊断工作中有着广阔的应用前景.

  1. Trip to immunity: resistant cytomegalovirus infection in a lung transplant recipient

    Directory of Open Access Journals (Sweden)

    Nikolaus Kneidinger

    2014-11-01

    Full Text Available We report the case of a young female lung transplant recipient with difficult-to-treat cytomegalovirus (CMV disease. While treatment with intravenous (IV ganciclovir failed due to antiviral drug resistance, a trial with foscarnet resulted in severe side effects. In addition, the patient received IV CMV-specific immune globulins as adjunctive therapy and leflunomide as experimental therapy. In this context, CMV-specific immune monitoring was performed and was successfully implemented in management decisions. The patient was screened for acquisition of an adaptive immune response, and antiviral prophylaxis and therapy was tailored according to results. This report highlights the impact of CMV-specific immune monitoring on individualized therapy for appropriate prophylaxis and management of CMV infection and diseases.

  2. RATIONALE FOR A SPECIFIC THERAPY OF CYTOMEGALOVIRUS INFECTION IN CHILDREN WITH BRONCHIAL ASTHMA

    Directory of Open Access Journals (Sweden)

    E. N. Suprun

    2013-01-01

    Full Text Available Abstract. We propose a protocol of treatment in cases of bronchial asthma with cytomegalovirus (CMV persistence. This basic therapy is administered depending on the disease severity, according to the National Programme 2009. The treatment includes administration of human immunoglobulin, with dosage according on CMV antibodies titers. The study has revealed that such regimen of antibody administration based on the content of anti-CMV antibodies in bronchial asthma treatment stops active CMV replication in bronchial mucous membrane, alleviates clinical course of the disease, diminishes changes of immune system typical to children suffering from bronchial asthma and CMV reactivation, thus allowing to reduce the volume of basic therapy, along with maintaining control of asthma control.

  3. Anti-cytomegalovirus activity of the anthraquinone atanyl blue PRL.

    Science.gov (United States)

    Alam, Zohaib; Al-Mahdi, Zainab; Zhu, Yali; McKee, Zachary; Parris, Deborah S; Parikh, Hardik I; Kellogg, Glen E; Kuchta, Alison; McVoy, Michael A

    2015-02-01

    Human cytomegalovirus (CMV) causes significant disease in immunocompromised patients and serious birth defects if acquired in utero. Available CMV antivirals target the viral DNA polymerase, have significant toxicities, and suffer from resistance. New drugs targeting different pathways would be beneficial. The anthraquinone emodin is proposed to inhibit herpes simplex virus by blocking the viral nuclease. Emodin and related anthraquinones are also reported to inhibit CMV. In the present study, emodin reduced CMV infectious yield with an EC50 of 4.9μM but was cytotoxic at concentrations only twofold higher. Related anthraquinones acid blue 40 and alizarin violet R inhibited CMV at only high concentrations (238-265μM) that were also cytotoxic. However, atanyl blue PRL inhibited infectious yield of CMV with an EC50 of 6.3μM, significantly below its 50% cytotoxic concentration of 216μM. Atanyl blue PRL reduced CMV infectivity and inhibited spread. When added up to 1h after infection, it dramatically reduced CMV immediate early protein expression and blocked viral DNA synthesis. However, it had no antiviral activity when added 24h after infection. Interestingly, atanyl blue PRL inhibited nuclease activities of purified CMV UL98 protein with IC50 of 4.5 and 9.3μM. These results indicate that atanyl blue PRL targets very early post-entry events in CMV replication and suggest it may act through inhibition of UL98, making it a novel CMV inhibitor. This compound may provide valuable insights into molecular events that occur at the earliest times post-infection and serve as a lead structure for antiviral development.

  4. CMV reactivation after allogeneic HCT and relapse risk: evidence for early protection in acute myeloid leukemia.

    Science.gov (United States)

    Green, Margaret L; Leisenring, Wendy M; Xie, Hu; Walter, Roland B; Mielcarek, Marco; Sandmaier, Brenda M; Riddell, Stanley R; Boeckh, Michael

    2013-08-15

    The association between cytomegalovirus (CMV) reactivation and relapse was evaluated in a large cohort of patients with acute myeloid leukemia (AML) (n = 761), acute lymphoblastic leukemia (ALL) (n = 322), chronic myeloid leukemia (CML) (n = 646), lymphoma (n = 254), and myelodysplastic syndrome (MDS) (n = 371) who underwent allogeneic hematopoietic cell transplantation (HCT) between 1995 and 2005. In multivariable models, CMV pp65 antigenemia was associated with a decreased risk of relapse by day 100 among patients with AML (hazard ratio [HR] = 0.56; 95% confidence interval [CI], 0.3-0.9) but not in patients with ALL, lymphoma, CML, or MDS. The effect appeared to be independent of CMV viral load, acute graft-versus-host disease, or ganciclovir-associated neutropenia. At 1 year after HCT, early CMV reactivation was associated with reduced risk of relapse in all patients, but this did not reach significance for any disease subgroup. Furthermore, CMV reactivation was associated with increased nonrelapse mortality (HR = 1.31; 95% CI, 1.1-1.6) and no difference in overall mortality (HR = 1.05; 95% CI, 0.9-1.3). This report demonstrates a modest reduction in early relapse risk after HCT associated with CMV reactivation in a large cohort of patients without a benefit in overall survival.

  5. CMV IN HEMATOPOIETIC STEM CELL TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    Rafael de la Camara

    2016-06-01

    Full Text Available Due to its negative impact in 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. But 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.

  6. Congenital cytomegalovirus infection: new prospects for prevention and therapy.

    Science.gov (United States)

    Swanson, Elizabeth C; Schleiss, Mark R

    2013-04-01

    Cytomegalovirus is the commonest congenital viral infection in the developed world, with an overall prevalence of approximately 0.6%. Approximately 10% of congenitally infected infants have signs and symptoms of disease at birth, and these symptomatic infants have a substantial risk of subsequent neurologic sequelae. These include sensorineural hearing loss, mental retardation, microcephaly, development delay, seizure disorders, and cerebral palsy. Antiviral therapy for children with symptomatic congenital cytomegalovirus infection is effective at reducing the risk of long-term disabilities and should be offered to families with affected newborns. An effective preconceptual vaccine against CMV could protect against long-term neurologic sequelae and other disabilities.

  7. Cytomegalovirus enteritis in immunocompetent subjects: a case report and review of the literature.

    Science.gov (United States)

    Karigane, Daiki; Takaya, Saho; Seki, Yuki; Mastumoto, Yuka; Onose, Akira; Kosakai, Arifumi; Sugaya, Norio; Mori, Takehiko

    2014-05-01

    Cytomegalovirus (CMV) enteritis (or colitis) is generally diagnosed in immunocompromised patients in association with human immunodeficiency virus infection as well as in recipients of solid organ or hematopoietic stem cell transplant. CMV enteritis has been reported only sporadically in immunocompetent individuals. We encountered a 76-year-old woman who developed CMV enteritis without any previously identified immunocompromised states. An extensive literature review of 33 cases of CMV enteritis or colitis diagnosed in immunocompetent individuals, including the present case, revealed that the median age of the patients was 68, the accompanying symptoms were diarrhea (76%), abdominal pain (52%), and hematochezia or melena (27%), and that the outcome was generally favorable, including resolution without any treatment in 24% of the patients. CMV enteritis should be recognized more widely as a disease entity not only in immunocompromised patients but also in immunocompetent individuals, especially in elderly populations.

  8. Primary Cytomegalovirus Infection in Seronegative Kidney Transplant Patients Is Associated with Protracted Cold Ischemic Time of Seropositive Donor Organs

    Science.gov (United States)

    Hoffmann, Dieter; Matevossian, Edouard; Lutz, Jens; Heemann, Uwe; Hösel, Volker; Busch, Dirk H.; Renders, Lutz; Neuenhahn, Michael

    2017-01-01

    Human Cytomegalovirus (CMV) can lead to primary infection or reactivation in CMV-seronegative or -seropositive kidney transplant recipients, respectively. Complications comprise severe end-organ diseases and acute or chronic transplant rejection. Risk for CMV manifestation is stratified according to the CMV-IgG-serostatus, with donor+/recipient- (D+/R-) patients carrying the highest risk for CMV-replication. However, risk factors predisposing for primary infection in CMV-seronegative recipients are still not fully elucidated. Therefore, we monitored D+/R- high-risk patients undergoing kidney transplantation in combination with antiviral prophylaxis for the incidence of CMV-viremia for a median follow-up time of 784 days (156–1155 days). In this period, we analyzed the functional CMV-specific T cell response by intracellular cytokine staining and CMV-serology by ELISA. Only four of eight D+/R- patients developed clinically relevant CMV-viremia followed by seroconversion. Viremia triggered expansion of functional CMV-specific T cells correlating with protection against secondary CMV-reactivations. In contrast, all other patients remained permanently aviremic and showed no immunological correlate of infection after discontinuation of antiviral prophylaxis for up to three years. Comparing cold ischemic times (CIT) of viremic (median = 1020 min; 720–1080 min) and aviremic patients (median = 335 min; 120–660 min) revealed significantly (p = 0.0286) protracted CIT in patients with primary CMV-infection. Taken together, primary CMV-infection affects only a subgroup of D+/R- patients correlating with length of CIT. Therefore, patients with extended CIT should be thoroughly monitored for CMV-replication well beyond discontinuation of antiviral prophylaxis. In contrast, patients with short CIT remained permanently uninfected and might benefit from shorter prophylactic treatment. PMID:28129395

  9. A comparison of CMV detection in gastrointestinal mucosal biopsies using immunohistochemistry and PCR performed on formalin-fixed, paraffin-embedded tissue.

    Science.gov (United States)

    Mills, Anne M; Guo, Frances P; Copland, Andrew P; Pai, Reetesh K; Pinsky, Benjamin A

    2013-07-01

    Cytomegalovirus (CMV) can precipitate and exacerbate gastrointestinal (GI) mucosal injury. The gold standard for CMV detection in formalin-fixed, paraffin-embedded (FFPE) tissue is immunohistochemistry (IHC). Although CMV polymerase chain reaction (PCR) on fresh tissue may be a valuable adjunct to IHC, its utility is unknown for FFPE tissues. We therefore evaluated quantitative, real-time CMV PCR in a total of 102 FFPE GI biopsy specimens from 74 patients with a history of hematopoietic stem cell or solid organ transplant, inflammatory bowel disease, human immunodeficiency virus infection, or unspecified colitis. CMV DNA was detected by PCR in 90.9% (30/33) of IHC-positive, 14.5% (8/55) of IHC-negative, and 20.0% (1/5) of IHC-equivocal FFPE tissues. Quantitation of CMV DNA copies normalized to β-globin demonstrated a wide range of values (median 0.276; range, 0.0004 to 144.50). Importantly, 93.3% (14/15) of patients with IHC-positive, active colitis showed no evidence of CMV in matched concurrent, histologically normal biopsies tested by PCR. These results suggest that CMV PCR on FFPE GI biopsies complements IHC and has the potential to identify additional patients who may benefit from anti-CMV therapy.

  10. Cytomegalovirus and burns: current perceptions, awareness, diagnosis, and management strategies in the United States and Germany.

    Science.gov (United States)

    Tenenhaus, Mayer; Rennekampff, Hans Oliver; Pfau, Matthias; Hamprecht, Klaus

    2006-01-01

    Trauma and immunosuppressed patients are at risk for cytomegalovirus (CMV) disease. Attributing pathogenicity in burn patients remains difficult and controversial because data are sparse. In this work, we surveyed U.S. and German burn centers and evaluated them for awareness, perceptions, diagnosis, and treatment of CMV in patients with burn injury. A total of 58% German (G) and 21% U.S. centers responded. CMV infection incidence was 1:280 G and 1:870 U.S. A total of 41% G and 78% U.S. burn centers considered CMV to be of minor importance and 41% G and 13% U.S. centers considered CMV to be of significant importance. A total of 70% G and 97% U.S. centers performed no admission screening. When testing, 70% G and 19% U.S. centers used serology; 52% G and 25% U.S. centers used body fluid viral isolation; and 43% G and 6% U.S. centers used leukocyte CMV-DNA analysis. A total of 72% G and 48% U.S. centers distinguished infection from disease. Human CMV disease was diagnosed by CMV-DNA (82% G, 19% U.S.), direct virus isolation (43% G, 13% U.S.), or RNA detection (26% G, 0% U.S.). A total of 43% G and 19% U.S. would treat the established disease. Establishing consistent guidelines for screening, diagnosis, and treatment seems prudent in caring for the immunocompromised burn patient.

  11. Improving Cytomegalovirus-Specific T Cell Reconstitution after Haploidentical Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Xiao-Hua Luo

    2014-01-01

    Full Text Available Cytomegalovirus (CMV infection and delayed immune reconstitution (IR remain serious obstacles for successful haploidentical stem cell transplantation (haplo-SCT. CMV-specific IR varied according to whether patients received manipulated/unmanipulated grafts or myeloablative/reduced intensity conditioning. CMV infection commonly occurs following impaired IR of T cell and its subsets. Here, we discuss the factors that influence IR based on currently available evidence. Adoptive transfer of donor T cells to improve CMV-specific IR is discussed. One should choose grafts from CMV-positive donors for transplant into CMV-positive recipients (D+/R+ because this will result in better IR than would grafts from CMV-negative donors (D−/R+. Stem cell source and donor age are other important factors. Posttransplant complications, including graft-versus-host disease and CMV infection, as well as their associated treatments, should also be considered. The effects of varying degrees of HLA disparity and conditioning regimens are more controversial. As many of these factors and strategies are considered in the setting of haplo-SCT, it is anticipated that haplo-SCT will continue to advance, further expanding our understanding of IR and CMV infection.

  12. Improving Cytomegalovirus-Specific T Cell Reconstitution after Haploidentical Stem Cell Transplantation

    Science.gov (United States)

    Chang, Ying-Jun; Huang, Xiao-Jun

    2014-01-01

    Cytomegalovirus (CMV) infection and delayed immune reconstitution (IR) remain serious obstacles for successful haploidentical stem cell transplantation (haplo-SCT). CMV-specific IR varied according to whether patients received manipulated/unmanipulated grafts or myeloablative/reduced intensity conditioning. CMV infection commonly occurs following impaired IR of T cell and its subsets. Here, we discuss the factors that influence IR based on currently available evidence. Adoptive transfer of donor T cells to improve CMV-specific IR is discussed. One should choose grafts from CMV-positive donors for transplant into CMV-positive recipients (D+/R+) because this will result in better IR than would grafts from CMV-negative donors (D−/R+). Stem cell source and donor age are other important factors. Posttransplant complications, including graft-versus-host disease and CMV infection, as well as their associated treatments, should also be considered. The effects of varying degrees of HLA disparity and conditioning regimens are more controversial. As many of these factors and strategies are considered in the setting of haplo-SCT, it is anticipated that haplo-SCT will continue to advance, further expanding our understanding of IR and CMV infection. PMID:24864269

  13. Cytomegalovirus: its potential role in the development of cutaneous T-cell lymphoma.

    Science.gov (United States)

    Ballanger, F; Bressollette, C; Volteau, C; Planche, L; Dreno, B

    2009-06-01

    To investigate the potential role of CMV in cutaneous T-cell lymphoma (CTCL), we studied cytomegalovirus (CMV) seroprevalence in parapsoriasis (PP), mycosis fungoides (MF) and Sézary syndrome (SS) compared with healthy control patients. In cases where CMV seropositivity was observed, CMV PCR analyses were performed on skin biopsies. CMV seroprevalence was 37.1% in the control group, 50.68% in the PP + MF + SS group (P = 0.08), 56.2% in the MF + SS group (P = 0.07), 40% in the PP group (P = 0.9), 66.67% in the MF group (P = 0.009), 42.86% in the SS group (P = 0.9). CMV PCR in initial skin biopsies were all negative. However, PCR CMV was positive in two SS skin biopsies realized at an advanced stage. Our results show that latent CMV infection may play a role in the susceptibility of MF in predisposed subjects by inducing T-cell proliferation and resistance to apoptosis. Concerning SS, an immunosuppressive state may be responsible for CMV reactivation that in turn may interfere with evolution of the disease.

  14. Specific endoscopic features of ulcerative colitis complicated by cytomegalovirus infection

    Institute of Scientific and Technical Information of China (English)

    Hideyuki; Suzuki; Jun; Kato; Motoaki; Kuriyama; Sakiko; Hiraoka; Kenji; Kuwaki; Kazuhide; Yamamoto

    2010-01-01

    AIM:To identify specific colonoscopic findings in patients with ulcerative colitis (UC) complicated by cyto-megalovirus (CMV) infection.METHODS: Among UC patients who were hospitalized due to exacerbation of symptoms, colonoscopic findings were compared between 15 CMV-positive patients and 58 CMV-negative patients. CMV infection was determined by blood test for CMV antigenemia. Five aspects of mucosal changes were analyzed (loss of vascular pattern, erythema, mucosal edema, easy bleeding, and mucinous exuda...

  15. Seropositivity of cytomegalovirus in patients with recurrent pregnancy loss

    OpenAIRE

    Roya Sherkat; Mohsen Meidani; Hossein Zarabian; Abbas Rezaei; Ali Gholamrezaei

    2014-01-01

    Background: Some evidence has shown a relationship between human cytomegalovirus (CMV) infection and pregnancy loss. However, whether recurrent or latent CMV infection or altered immune response to CMV is related to recurrent pregnancy loss (RPL) is unclear. We evaluated CMV infection and avidity of antibodies to CMV in women with RPL. Materials and Methods: This case-control study was conducted on 43 women with RPL referred to a clinical immunology out-patient clinic in Isfahan (Iran), and 4...

  16. Cytomegalovirus ileocolitis in a rheumatoid arthritis patient: case report and literature review

    Directory of Open Access Journals (Sweden)

    M. S. Dag

    2015-06-01

    Full Text Available Rheumatoid arthritis (RA is an autoimmune, systemic, chronic, inflammatory disease generally treated with various immunosuppressive drugs. Cytomegalovirus (CMV is an opportunistic, viral infection that is commonly seen in immunosuppressed patients. A sixty-four-year old female diagnosed with RA and treated with immunosuppressive agents was admitted to our rheumatology outpatient service with complaints of diarrhea and abdominal pain, which had lasted longer than four weeks. The patient’s colonoscopy revealed inflamed and ulcerated areas in the colon and in the terminal ileum. A biopsy showed intra-nuclear inclusion particles consistent with CMV. We started an oral valganciclovir therapy in this serum-CMV-polymerase chain reactionpositive patient. The concomitant use of immunosuppressive agents and anti-viral drugs eased the patient’s complaints, and the endoscopic picture improved. Consequently, cytomegalovirus ileocolitis in immunosuppressed patients admitted with severe diarrhea must be considered in the differential diagnosis.

  17. Low Interferon Relative-Response to Cytomegalovirus Is Associated with Low Likelihood of Intrauterine Transmission of the Virus.

    Directory of Open Access Journals (Sweden)

    Yifat Eldar-Yedidia

    Full Text Available Congenital Cytomegalovirus (CMV is a very common intrauterine infection which can cause severe mental and hearing impairments. Notably, only 40% of primarily infected women transmit CMV to the fetus. CMV-specific T-cell response has a role in CMV disease but individual immune heterogeneity precludes reliable correlation between measurable T-cells response and intrauterine transmission.To establish a correlation between maternal T-cells response and fetal CMV transmission using an individual normalized immune response.We analyzed IFN-γ secretion upon whole blood stimulation from primary CMV-infected pregnant women, with either CMV-peptides or PHA-mitogen.We established a new normalization method of individual IFN-γ response to CMV by defining the ratio between specific-CMV response and non-specific mitogen response (defined as IFN-γ relative response, RR, aiming to overcome high person-to-person immune variability. We found a unique subpopulation of women with low IFN-γ RR strongly correlated with absence of transmission. IFN-γ RR lower than 1.8% (threshold determined by ROC analysis reduces the pre-test probability of transmission from 40% to 8%, revealing an unexpected link between low IFN-γ RR and non-transmission.In pregnant women with primary CMV infection, low IFN-γ RR is associated with low risk of transmission.

  18. Human Cytomegalovirus Secretome Contains Factors That Induce Angiogenesis and Wound Healing

    Energy Technology Data Exchange (ETDEWEB)

    Dumortier, Jerome; Streblow, Daniel N.; Moses, Ashlee V.; Jacobs, Jon M.; Kreklywich, Craig N.; Camp, David G.; Smith, Richard D.; Orloff, Susan L.; Nelson, Jay

    2008-07-01

    Human cytomegalovirus (HCMV) is implicated in the acceleration of a number of vascular diseases including transplant vascular sclerosis (TVS), the lesion associated with chronic rejection (CR) of solid organ transplants. Although the virus persists in the allograft throughout the course of disease, few cells are directly infected by CMV. This observation is in contrast to the global effects that CMV has on the acceleration of TVS/CR, suggesting that CMV infection indirectly promotes the vascular disease process. Recent transcriptome analysis of CMV-infected heart allografts indicates that the virus induces cytokines and growth factors associated with angiogenesis (AG) and wound healing (WH), suggesting that CMV may accelerate TVS/CR through the induction and secretion of AG/WH factors from infected cells. We analyzed virus-free supernatants from HCMV-infected cells (HCMV secretomes) for growth factors, by mass spectrometry and immunoassays, and found that the HCMV secretome contains over 1,000 cellular proteins, many of which are involved in AG/WH. Importantly, functional assays demonstrated that CMV but not herpes simplex virus secretomes not only induce AG/WH but also promote neovessel stabilization and endothelial cell survival for 2 weeks. These findings suggest that CMV acceleration of TVS occurs through virus-induced growth factors and cytokines in the CMV secretome.

  19. Thomas Huckle Weller MD: Nobel Laureate and research pioneer in poliomyelitis, varicella-zoster virus, cytomegalovirus, rubella, and other infectious diseases.

    Science.gov (United States)

    Ligon, B Lee

    2002-01-01

    In 1954, the Nobel Prize for Medicine was awarded to Drs John Enders, Thomas Weller, and Frederick Robbins for their watershed discovery that growth of poliomyelitis virus occurred in cultures of cells of extraneural origin, first reported in 1949. Their demonstration in 1949 that the Lansing type II strain of poliomyelitis could be grown in cultures of human embryonic tissue set into motion a race to develop a vaccine for the disease that had crippled countless thousands of individuals. The discovery and subsequent recognition were only the beginning of a prolific career for Thomas Huckle Weller, who made numerous contributions to the field of virology, including isolating the varicella-zoster virus (VZV) from cases of chickenpox and zoster, providing suggestive evidence that the same virus is responsible for both diseases; isolating the human cytomegalovirus (CMV) for the first time in tissue culture and suggesting the descriptive name now used for it; establishing Coxsackie viruses as the cause of epidemic pleurodynia: and first isolating rubella virus, the cause of German measles. This article presents a brief biography of Dr Thomas Huckle Weller, one of the field's most important figures, with primary focuses on his work on poliomyelitis, varicella-zoster virus, rubella virus, and cytomegalovirus.

  20. Cytomegalovirus Retinitis in an Immunocompetent Pregnant Woman

    African Journals Online (AJOL)

    Cytomegalovirus (CMV) is a beta-herpes virus. It belongs ... common virus that results in opportunistic infections ... ganciclovir therapy, and 2 weeks later blurred vision .... Barr Virus Viral Capsid Antigen Antibody, IgM: Immunoglobulin M, IgG: ...

  1. Clinical features of late cytomegalovirus infection after hematopoietic stem cell transplantation.

    Science.gov (United States)

    Asano-Mori, Yuki; Kanda, Yoshinobu; Oshima, Kumi; Kako, Shinichi; Shinohara, Akihito; Nakasone, Hideki; Sato, Hiroyuki; Watanabe, Takuro; Hosoya, Noriko; Izutsu, Koji; Asai, Takashi; Hangaishi, Akira; Motokura, Toru; Chiba, Shigeru; Kurokawa, Mineo

    2008-04-01

    Late cytomegalovirus (CMV) disease beyond day 100 after hematopoietic stem cell transplantation (HSCT) has become an increasing problem after the introduction of preemptive ganciclovir (GCV) administration. To clarify the risk factors and outcome for late CMV reactivation and disease, we retrospectively analyzed the records of 101 Japanese adult patients who underwent allogeneic HSCT between 1998 and 2005 at our hospital. Fifty-one developed late positive CMV antigenemia, with a cumulative incidence of 53%. Recipient CMV seropositivity, the use of alemtuzumab, chronic GVHD, and high-dose steroids were significantly associated with late positive antigenemia. Eight patients developed late CMV disease, with a cumulative incidence of 8%, including retinitis and gastrointestinal disease. None progressed to a fatal disease. The use of alemtuzumab was identified as an independent significant risk factor for late CMV disease, although it was not associated with increased non-relapse mortality. Among the 51 patients with late positive antigenemia, 28 had consistently less than three positive cells, 25 of whom showed negative conversion without antiviral agents. In conclusion, late CMV antigenemia appeared to develop frequently, especially in patients with profound immune suppression; however, a fatal outcome could be prevented by optimal preemptive therapy. Low-level antigenemia may not require antiviral treatments.

  2. Impact of Everolimus and Low-Dose Cyclosporin on Cytomegalovirus Replication and Disease in Pediatric Renal Transplantation.

    Science.gov (United States)

    Höcker, B; Zencke, S; Pape, L; Krupka, K; Köster, L; Fichtner, A; Dello Strologo, L; Guzzo, I; Topaloglu, R; Kranz, B; König, J; Bald, M; Webb, N J A; Noyan, A; Dursun, H; Marks, S; Ozcakar, Z B; Thiel, F; Billing, H; Pohl, M; Fehrenbach, H; Schnitzler, P; Bruckner, T; Ahlenstiel-Grunow, T; Tönshoff, B

    2016-03-01

    In order to investigate the hypothesis that the mammalian target of rapamycin inhibitor everolimus (EVR) shows anticytomegalovirus (CMV) activity in pediatric patients, we analyzed the impact of EVR-based immunosuppressive therapy on CMV replication and disease in a large cohort (n = 301) of pediatric kidney allograft recipients. The EVR cohort (n = 59), who also received low-dose cyclosporin, was compared with a control cohort (n = 242), who was administered standard-dose cyclosporin or tacrolimus and an antimetabolite, mostly mycophenolate mofetil (91.7%). Multivariate analysis revealed an 83% lower risk of CMV replication in the EVR cohort than in the control cohort (p = 0.005). In CMV high-risk (donor+/recipient-) patients (n = 88), the EVR-based regimen was associated with a significantly lower rate of CMV disease (0% vs. 14.3%, p = 0.046) than the standard regimen. In patients who had received chemoprophylaxis with (val-)ganciclovir (n = 63), the CMV-free survival rates at 1 year and 3 years posttransplant (100%) were significantly (p = 0.015) higher in the EVR cohort (n = 15) than in the control cohort (n = 48; 1 year, 75.0%; 3 years, 63.3%). Our data suggest that in pediatric patients at high risk of CMV, an EVR-based immunosuppressive regimen is associated with a lower risk of CMV disease than a standard-dose calcineurin inhibitor-based regimen. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  3. The clinical impact of cytomegalovirus infection following allogeneic hematopoietic cell transplantation: Why the quest for meaningful prophylaxis still matters.

    Science.gov (United States)

    Chan, Shawna T; Logan, Aaron C

    2017-02-02

    Latent infection with human cytomegalovirus (CMV) is common. Functional immunity effectively contains such latent infections; however, CMV reactivation may cause significant complications in patients undergoing allogeneic hematopoietic cell transplantation (alloHCT). In spite of the universal implementation of post-transplant screening for CMV viremia and the institution of pre-emptive antiviral management, CMV disease still occurs in a small portion of patients. Moreover, interactions between CMV and the immune system have significant implications for the incidence of graft-versus-host disease, the recurrence of malignancy, and non-relapse mortality following alloHCT, even in the era of pre-emptive antiviral management. CMV serostatus thus remains an important consideration for patients undergoing alloHCT. We review the clinical impact of CMV in the setting of alloHCT, interactions between CMV serostatus, viral reactivation, and transplant outcomes, as well as current and evolving strategies for prevention and treatment of CMV-related complications that may have significant impact for alloHCT recipients.

  4. Everolimus-treated renal transplant recipients have a more robust CMV-specific CD8+ T-cell response compared with cyclosporine- or mycophenolate-treated patients.

    Science.gov (United States)

    Havenith, Simone H C; Yong, Si La; van Donselaar-van der Pant, Karlijn A M I; van Lier, René A W; ten Berge, Ineke J M; Bemelman, Fréderike J

    2013-01-15

    In renal transplant recipients, mammalian target of rapamycin (mTOR) inhibitors have been reported to protect against cytomegalovirus (CMV) disease. Here, we questioned whether mTOR inhibitors specifically influence human CMV-induced T-cell responses. We studied renal transplant recipients treated with prednisolone, cyclosporine A (CsA), and mycophenolate sodium (MPS) for the first 6 months after transplantation followed by double therapy consisting of prednisolone/everolimus, which is an mTOR inhibitor (P/EVL; n=10), prednisolone/CsA (P/CsA; n=7), or prednisolone/MPS (P/MPS; n=9). All patients were CMV-IgG positive before transplantation. CMV reactivation was detectable in the first 6 months after transplantation and not thereafter. None of the patients included in this study suffered from CMV disease. Both CD27CD8 and CD27CD28CD4 effector-type T-cell counts, known to be associated with CMV infection, were measured before transplantation and at 6 and 24 months after transplantation. Additionally, we determined both number and function of CMV-specific CD8 T cells at these time points. The number of total CD8 T cells, CD27CD8 T cells, and CD28CD4 T cells increased significantly after switch to therapy with P/EVL but not after switch to P/CsA or P/MPS. Specifically, CMV-specific CD8 T-cell counts significantly increased after switch to therapy with P/EVL. Furthermore, the mTOR inhibitor sirolimus strongly inhibited alloresponses in vitro, whereas it did not affect CMV-specific responses. We observed a significant increase in (CMV-specific) effector-type CD8 and CD4 T-cell counts in everolimus-treated patients. These findings may at least in part explain the reported low incidence of CMV-related pathology in everolimus-treated patients.

  5. Controlling Cytomegalovirus: Helping the Immune System Take the Lead

    Directory of Open Access Journals (Sweden)

    Patrick J. Hanley

    2014-05-01

    Full Text Available Cytomegalovirus, of the Herpesviridae family, has evolved alongside humans for thousands of years with an intricate balance of latency, immune evasion, and transmission. While upwards of 70% of humans have evidence of CMV infection, the majority of healthy people show little to no clinical symptoms of primary infection and CMV disease is rarely observed during persistent infection in immunocompetent hosts. Despite the fact that the majority of infected individuals are asymptomatic, immunologically, CMV hijacks the immune system by infecting and remaining latent in antigen-presenting cells that occasionally reactivate subclinically and present antigen to T cells, eventually causing the inflation of CMV-specific T cells until they can compromise up to 10% of the entire T cell repertoire. Because of this impact on the immune system, as well as its importance in fields such as stem cell and organ transplant, the relationship between CMV and the immune response has been studied in depth. Here we provide a review of many of these studies and insights into how CMV-specific T cells are currently being used therapeutically.

  6. Maternal and neonatal anti-cytomegalovirus IgG level and risk of postnatal cytomegalovirus transmission in preterm infants

    NARCIS (Netherlands)

    Nijman, Joppe; van Loon, Anton M.; Krediet, Tannette G.; Verboon-Maciolek, Malgorzata A.

    2013-01-01

    Immunological mechanisms influencing the risk of mother-to-child cytomegalovirus (CMV) transmission in preterm infants have not been studied sufficiently. In this study, the correlation between maternal and neonatal serum anti-CMV IgG levels and risk of postnatal CMV transmission in preterm infants

  7. Cytomegalovirus and Toxoplasma gondii seroprevalence in a Brazilian liver transplant waiting

    Directory of Open Access Journals (Sweden)

    R. A. M. B. Almeida

    2007-01-01

    Full Text Available Cytomegalovirus (CMV disease is a major cause of morbidity and mortality in solid organ transplantation. Disseminated toxoplasmosis after liver transplantation is a rare but fatal event. Serologic screening of the donor and the recipient is essential to prophylactic management, early diagnosis and therapeutic strategies to minimize the consequences of these infections. The aim of the present study was to determine the seroprevalence of CMV and Toxoplasma gondii (TG in a Brazilian liver transplant waiting list (LTWL. Serological data were collected from 44 candidates on the LTWL between May 2003 and November 2004. Serological investigation of antibodies IgM and IgG against CMV (anti-CMV and TG (anti-T. gondii was performed using fluorometry commercial kits. IgG anti-CMV was positive in 37 patients (94.9% out of 39 available results. There were not IgM anti-CMV positive results. Out of 36 analyzed patients, 22 (61.1% presented positive IgG anti-T. gondii and none had positive IgM anti-T. gondii. The high CMV seroprevalence among our LTWL reinforces the need for appropriate protocols to avoid related complications, like reactivation and superinfection by CMV. Environmental and drug prophylactic strategies against primary infection and reactivation, as well as early diagnosis and treatment of toxoplasmosis complications, are essential for the good outcome of transplant patients.

  8. Hepatitis C viremia is associated with cytomegalovirus IgG antibody levels in HIV-infected women.

    Directory of Open Access Journals (Sweden)

    Mark H Kuniholm

    Full Text Available BACKGROUND: Individuals with HIV infection exhibit high cytomegalovirus (CMV IgG levels, but there are few data regarding the association of hepatitis C virus (HCV with the immune response against CMV. METHODS: Associations of HCV with CMV seropositivity and CMV IgG levels were studied in 635 HIV-infected women, 187 of whom were HCV-seropositive, with adjustment in multivariable models for age, race/ethnicity, and HIV disease characteristics. Eighty one percent of the women reported receipt of highly active antiretroviral therapy (HAART prior to or at CMV testing. RESULTS: In adjusted models women with chronic HCV had higher CMV IgG levels than those without HCV RNA (β = 2.86, 95% CI:0.89 - 4.83; P = 0.004. The association of HCV RNA with CMV IgG differed by age (P(interaction = 0.0007, with a strong association observed among women in the low and middle age tertiles (≤ 45.3 years of age; β = 6.21, 95% CI:3.30 - 9.11, P<0.0001 but not among women in the high age tertile. CMV IgG levels were not associated with non-invasive measures of liver disease, APRI and FIB-4, or with HCV RNA level and adjustment for Epstein-Barr virus (EBV IgG levels did not affect the association between HCV and CMV. CONCLUSIONS: CMV IgG levels are higher in HCV/HIV co-infected women than in HIV mono-infected women. Further research on the association of HCV with CMV IgG is indicated because prior studies have found CMV IgG to be associated with morbidity and mortality in the general population and subclinical carotid artery disease in HIV-infected patients.

  9. Cytomegalovirus ileitis in an immunocompetent patient Ileítis por citomegalovirus en paciente inmunocompetente

    Directory of Open Access Journals (Sweden)

    María Auxiliadora Tejedor-Cerdeña

    2011-03-01

    Full Text Available Cytomegalovirus (CMV is a virus that belongs to the family of Herpesviridae. Infection can cause a serious disease in immunocompromised patients, but it can also affect immunocompetent patients, creating generally self limiting symptoms. However, in some cases it can be fatal. We present a case of CMV ileitis with serious clinical symptoms that led to an operation in an immunocompetent patient.El citomegalovirus (CMV es un virus perteneciente a la familia de los Herperviridae. La infección puede causar una enfermedad grave en inmunodeprimidos, sin embargo también puede afectar a inmunocompetentes, y da lugar a cuadros clínicos generalmente autolimitados, aunque se han descrito casos graves que pueden llevar a la muerte. Presentamos un caso de ileítis por CMV con manifestaciones clínicas graves que motivaron intervención quirúrgica urgente en un paciente inmunocompetente.

  10. History of the molecular biology of cytomegaloviruses.

    Science.gov (United States)

    Stinski, Mark F

    2014-01-01

    The history of the molecular biology of cytomegaloviruses from the purification of the virus and the viral DNA to the cloning and expression of the viral genes is reviewed. A key genetic element of cytomegalovirus (the CMV promoter) contributed to our understanding of eukaryotic cell molecular biology and to the development of lifesaving therapeutic proteins. The study of the molecular biology of cytomegaloviruses also contributed to the development of antivirals to control the viral infection.

  11. Women's attitudes toward practicing cytomegalovirus prevention behaviors

    Directory of Open Access Journals (Sweden)

    Rosemary Thackeray

    2016-12-01

    Full Text Available Congenital cytomegalovirus (CMV infection causes severe disabilities and developmental delays. Women's awareness of CMV is low. Only about half of healthcare providers report counseling women about behaviors to reduce CMV risk and public health education is limited. Routine CMV counseling is not recommend. Providers may lack time to counsel women; other conditions may take priority for counseling; there may be a perception that women are reluctant to follow advice. This cross-sectional descriptive study examined women's attitudes toward CMV prevention behaviors. Data were collected from an online panel of 840 U.S. women 18–40 years of age, who had a child <5 years of age, and were pregnant or planning a pregnancy in the next 12 months. Questions assessed CMV awareness, frequency of past behaviors that transmit CMV, and attitudes toward eight CMV prevention behaviors. Only 15.5% of women were somewhat or very familiar with CMV. Very few women (6.1% reported hearing from their provider about CMV. Women held positive attitudes toward the CMV prevention behaviors and perceived them as feasible. Least positive attitudes were toward not kissing a child on the lips and not sharing foods. Predictors of positive attitudes were CMV awareness, past behavior, talking to a healthcare provider, and perceived risk reduction. Healthcare providers and public health practitioners should collaborate to increase CMV awareness. Encouraging behaviors to reduce saliva sharing may result in greater gains in reducing CMV infection.

  12. Reactivation of intestinal CMV in a renal transplant patient after 10 years from the transplant

    Directory of Open Access Journals (Sweden)

    Maria Landi

    2013-04-01

    Full Text Available Introduction.We analyzed the clinical case of a 51 years old man, kidney transplanted on December 2002. On April 2011, he had acute rectal bleeding, renal chronic rejection (creatinine 2.9 mg/dl, Hgb 8.7 g/dl, positive anti-CMV antibodies (IgG. A colonoscopy showed diverticulosis of the rectum associated with deepithelialisation. The patient was treated with maintenance immunosuppressive post-transplant therapy. On June 2011, the colonoscopy showed a stenosing lesion of the sigmoid colon, and blood sampling and intestinal biopsy were performed to search Cytomegalovirus (CMV DNA by PCR. Methods. The presence of CMV-DNA was sought by automatic extractor QIACUBE, using QIAamp DNA BLOOD Mini Kit (Qiagen for whole blood and QIAamp DNA Mini Kit (Qiagen for biopsy.The extracted DNA was then amplified by Real Time PCR using Q-CMV RealTime Complete Kit (Nanogen, on instrument Applied Biosystems 7300. Results. At disease onset the viral load in whole blood was 208000 Geq/ml, and biopsy was positive. Antiviral therapy with Ganciclovir led to the negativity of the viral load and remission of symptoms. Conclusions. The clinical case described presented a reactivation of CMV infection in the intestine after more than 10 years from kidney transplantation, while the highest incidence of CMV reactivation usually occurs during the first year. In our opinion, the reactivation can be traced to long-term immunosuppressive therapy (maintenance posttransplant therapy in combination with a state of inflammation of the intestinal mucosa. In fact, patients with IBD treated with steroid drugs, in particular the group of refractory to therapy and thus have a recovery of the inflammatory process, are exposed to reactivation of CMV with intestinal localization.

  13. Antibodies to early EBV, CMV, and HHV6 antigens in systemic lupus erythematosus patients

    DEFF Research Database (Denmark)

    Rasmussen, N S; Draborg, A H; Nielsen, C T

    2015-01-01

    OBJECTIVES: We investigated the antibody levels against early antigens of Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpesvirus 6 (HHV6) in systemic lupus erythematosus (SLE) patients and healthy controls, and further correlated these antibodies to haematology...

  14. Kinetics of host immune responses and cytomegalovirus resistance in a liver transplant patient.

    LENUS (Irish Health Repository)

    Schaffer, Kirsten

    2012-02-01

    Among solid organ transplant (SOT) recipients, donor-seropositive\\/recipient-seronegative (D+\\/R-) cytomegalovirus (CMV) status is associated with the highest risk of ganciclovir-resistant CMV disease, which has been reported for patients receiving oral ganciclovir but not valganciclovir prophylaxis. We report a case of CMV breakthrough infection in a D+\\/R- liver transplant patient while he was receiving oral valganciclovir. Forty samples collected over 6 months were analyzed for the CMV viral load, lymphocyte counts, cytokine levels, and lymphocyte differentiation status. Genotypic resistance testing of the viral UL97 gene was performed when the patient failed to respond. CMV viremia occurred on day 50 post-transplant, and 5 samples taken between days 50 and 85 showed the wild-type UL97 genotype. The appearance of deletion 594-595 was observed from day 114 post-transplant. Viral loads declined when foscarnet was commenced and remained below 10,000 copies\\/mL when the lymphocyte count was greater than 1000\\/microL (P = 0.02). T cell responses revealed significant expansion of CD8+ terminal effector memory cells. CD4+ cells were largely populations of naive and central memory cells. Circulating interleukin 10 (IL-10) levels correlated with the viral load (P < 0.0001). Seroconversion occurred on day 230. The CMV viral load in combination with lymphocyte counts and IL-10 may be a predictive marker for the risk of development of resistant CMV disease in D+\\/R- SOT patients.

  15. Cytomegalovirus pp65 limits dissemination but is dispensable for persistence

    OpenAIRE

    Malouli, Daniel; Hansen, Scott G.; Nakayasu, Ernesto S.; Marshall, Emily E.; Hughes, Colette M.; Ventura, Abigail B.; Gilbride, Roxanne M.; Lewis, Matthew S.; Xu, Guangwu; Kreklywich, Craig; Whizin, Nathan; Fischer, Miranda; Legasse, Alfred W.; Viswanathan, Kasinath; Siess, Don

    2014-01-01

    The most abundantly produced virion protein in human cytomegalovirus (HCMV) is the immunodominant phosphoprotein 65 (pp65), which is frequently included in CMV vaccines. Although it is nonessential for in vitro CMV growth, pp65 displays immunomodulatory functions that support a potential role in primary and/or persistent infection. To determine the contribution of pp65 to CMV infection and immunity, we generated a rhesus CMV lacking both pp65 orthologs (RhCMVΔpp65ab). While ...

  16. High-grade cytomegalovirus antigenemia after hematopoietic stem cell transplantation.

    Science.gov (United States)

    Asano-Mori, Y; Oshima, K; Sakata-Yanagimoto, M; Nakagawa, M; Kandabashi, K; Izutsu, K; Hangaishi, A; Motokura, T; Chiba, S; Kurokawa, M; Hirai, H; Kanda, Y

    2005-11-01

    Clinical impact of high-grade (HG) cytomegalovirus (CMV) antigenemia after hematopoietic stem cell transplantation has not been clarified. Therefore, in order to investigate the risk factors and outcome for HG-CMV antigenemia, we retrospectively analyzed the records of 154 Japanese adult patients who underwent allogeneic hematopoietic stem cell transplantation for the first time from 1995 to 2002 at the University of Tokyo Hospital. Among 107 patients who developed positive CMV antigenemia at any level, 74 received risk-adapted preemptive therapy with ganciclovir (GCV), and 17 of these developed HG-antigenemia defined as > or = 50 positive cells per two slides. The use of systemic corticosteroids at > or = 0.5 mg/kg/day at the initiation of GCV was identified as an independent significant risk factor for HG-antigenemia. Seven of the 17 HG-antigenemia patients developed CMV disease, with a cumulative incidence of 49.5%, which was significantly higher than that in the low-grade antigenemia patients (4%, P<0.001). However, overall survival was almost equivalent in the two groups. In conclusion, the development of HG-antigenemia appeared to depend on the profound immune suppression of the recipient. Although CMV disease frequently developed in HG-antigenemia patients, antiviral therapy could prevent a fatal outcome.

  17. Modulation of HLA Expression in Human Cytomegalovirus Immune Evasion

    Institute of Scientific and Technical Information of China (English)

    Aifen Lin; Huihui Xu; Weihua Yan

    2007-01-01

    Human cytomegalovirus (hCMV) has evolved multiple mechanisms to escape the host immune recognition and innate or adaptive immune responses. Among them, hCMV has developed strategies to modulate the expression and/or function of human leukocyte antigens (HLAs), including by encoding series of infection stage-dependent hCMV proteins to detain and destroy the expression of HLA molecules on the surface of infected cells. This disturbs the antigen presentation and processing, by encoding MHC class Ⅰ homologues or selective up-regulation of particular HLA class Ⅰ molecules binding to NK cell inhibitory receptors, and by encoding specific ligand antagonists to interfere with NK cell activating receptors. Here we discussed the molecular mechanisms utilized by the hCMV to alter the formation, transportation and expression of HLA antigens on the infected cell surface. The knowledge about hCMV modulating HLA expression could benefit us to further understand the pathogenesis of viral diseases and may eventually develop novel effective immunotherapies to counteract viral infections and viral associated diseases.

  18. Clinical Manifestations of Cytomegalovirus-Associated Posterior Uveitis and Panuveitis in Patients Without Human Immunodeficiency Virus Infection

    NARCIS (Netherlands)

    Pathanapitoon, Kessara; Tesavibul, Nattaporn; Choopong, Pitipol; Boonsopon, Sutasinee; Kongyai, Natedao; Ausayakhun, Somsanguan; Kunavisarut, Paradee; Rothova, Aniki

    2013-01-01

    Importance: Little attention has been paid to clinical features of cytomegalovirus (CMV) infections in individuals without human immunodeficiency virus (HIV). Objective: To describe the clinical manifestations and comorbidities of patients without HIV infection who have CMV-associated posterior uvei

  19. Infection of human endothelium in vitro by cytomegalovirus causes enhanced expression of purinergic receptors : A potential virus escape mechanism?

    NARCIS (Netherlands)

    Zandberg, Mariet; van Son, Willem J.; Harmsen, Martin C.; Bakker, Winston W.

    2007-01-01

    Background. Human cytomegalovirus (CMV) uses different strategies to escape from human host defense reactions. Previously we have observed that infection of endothelial cells with CMV in vitro leads to enhanced activity of endothelial ectonucleotidases. These ectoenzymes are responsible for hydrolys

  20. Infection of human endothelium in vitro by cytomegalovirus causes enhanced expression of purinergic receptors : A potential virus escape mechanism?

    NARCIS (Netherlands)

    Zandberg, Mariet; van Son, Willem J.; Harmsen, Martin C.; Bakker, Winston W.

    2007-01-01

    Background. Human cytomegalovirus (CMV) uses different strategies to escape from human host defense reactions. Previously we have observed that infection of endothelial cells with CMV in vitro leads to enhanced activity of endothelial ectonucleotidases. These ectoenzymes are responsible for

  1. Characterization of Cytomegalovirus Lung Infection in Non-HIV Infected Children

    Directory of Open Access Journals (Sweden)

    Sonia M. Restrepo-Gualteros

    2014-05-01

    Full Text Available Cytomegalovirus (CMV is a prevalent pathogen in the immunocompromised host and invasive pneumonia is a feared complication of the virus in this population. In this pediatric case series we characterized CMV lung infection in 15 non-HIV infected children (median age 3 years; IQR 0.2–4.9 years, using current molecular and imaging diagnostic modalities, in combination with respiratory signs and symptoms. The most prominent clinical and laboratory findings included cough (100%, hypoxemia (100%, diffuse adventitious breath sounds (100% and increased respiratory effort (93%. All patients had abnormal lung images characterized by ground glass opacity/consolidation in 80% of cases. CMV was detected in the lung either by CMV PCR in bronchoalveolar lavage (82% detection rate or histology/immunohistochemistry in lung biopsy (100% detection rate. CMV caused respiratory failure in 47% of children infected and the overall mortality rate was 13.3%. Conclusion: CMV pneumonia is a potential lethal disease in non-HIV infected children that requires a high-index of suspicion. Common clinical and radiological patterns such as hypoxemia, diffuse adventitious lung sounds and ground-glass pulmonary opacities may allow early identification of CMV lung infection in the pediatric population, which may lead to prompt initiation of antiviral therapy and better clinical outcomes.

  2. Characteristic endoscopic findings and risk factors for cytomegalovirus-associated colitis in patients with active ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Yutaka Hirayama; Takafumi Ando; Yoshiki Hirooka; Osamu Watanabe; Ryoji Miyahara; Masanao Nakamura; Takeshi Yamamura; Hidemi Goto

    2016-01-01

    AIM: To identify characteristic endoscopic findings and risk factors for cytomegalovirus(CMV)-associated colitis in patients with active ulcerative colitis(UC).METHODS: A total of 149 UC patients admitted to the Department of Gastroenterology, Nagoya University Hospital, from January 2004 to December 2013 with exacerbation of UC symptoms were enrolled in this retrospective study. All medical records, including colonoscopy results, were reviewed. CMV infection was determined by the presence of CMV antigen, CMV inclusion bodies in biopsy specimens, or positive specific immunohistochemical staining for CMV. Multivariate analysis was used to identify independent risk factors for CMV colitis.RESULTS: Multivariate analysis indicated independent associations with the extent of disease(pancolitis) anduse of > 400 mg corticosteroids for the previous 4 wk. In contrast, no association was seen with sex, age at UC diagnosis, immunomodulator use, or infliximab use. Punched-out ulceration was also significantly associated with CMV infection in patients with active UC(odds ratio = 12.672, 95%CI: 4.210-38.143).CONCLUSION: Identification of a total corticosteroid dose > 400 mg for 4 wk, extensive colitis and a specific endoscopic finding of punched-out ulcer might facilitate the more rapid diagnosis and timely initiation of antiviral therapy for CMV-associated colitis in patients with active UC.

  3. Cytomegalovirus in the Neonate: Immune Correlates of Infection and Protection

    Directory of Open Access Journals (Sweden)

    Mark R. Schleiss

    2013-01-01

    Full Text Available Fetal and neonatal infections caused by human cytomegalovirus (CMV are important causes of morbidity and occasional mortality. Development of a vaccine against congenital CMV infection is a major public health priority. Vaccine design is currently focused on strategies that aim to elicit neutralizing antibody and T-cell responses, toward the goal of preventing primary or recurrent infection in women of child-bearing age. However, there has been relatively little attention given to understanding the mechanisms of immune protection against acquisition of CMV infection in the fetus and newborn and how this information might be exploited for vaccine design. There has similarly been an insufficient study of what deficits in the immune response to CMV, both for mother and fetus, may increase susceptibility to congenital infection and disease. Protection of the fetus against vertical transmission can likely be achieved by protection of the placenta, which has its own unique immunological milieu, further complicating the analysis of the correlates of protective immunity. In this review, the current state of knowledge about immune effectors of protection against CMV in the maternal, placental, and fetal compartments is reviewed. A better understanding of immune responses that prevent and/or predispose to infection will help in the development of novel vaccine strategies.

  4. [Determination of cytomegalovirus IgG synthesis by the albumin correction in the aqueous humor of posner-schlossmann syndrome].

    Science.gov (United States)

    Wang, X L; Wang, Z J; Tang, L; Cao, W W; Sun, X H

    2017-02-11

    Objective: To evaluate the usefulness of albumin correction in determination of cytomegalovirus IgG in the aqueous humor of Posner-Schlossman syndrome (PSS) patients. Methods: Cases series studies. Forty-two patients (26 men and 16 women) who were diagnosed as PSS were enrolled from Oct. 2009 to Oct. 2015 at the Eye and ENT Hospital. During the same period, 20 patients with primary open-angle glaucoma (POAG) and 30 patients with bacterial endophthalmitis or retinal necrosis were enrolled as negative control group and inflammatory disease control group, respectively. Aqueous humor and serum samples were assayed to detect CMV IgG by enzyme-linked immunosorbent assay (ELISA), and albumin by scattering immunonephelometry. CMV DNA in aqueous humor was assayed by polymerase chain reaction (PCR). The ratio which was calculated as the (aqueous humor CMV IgG/serum CMV IgG)/(aqueous humor concentration of albumin/serum albumin concentration) over 0.6 was considered as intraocular antibody formation. Performance of differentiating control eyes from eyes with CMV-positive PSS was evaluated by the receiver operating characteristic curve. The ANOVA test, Mann-Whitney test and Chi-square test were performed to compare the differences among groups. Results: The detectable rate of CMV IgG antibody in the aqueous humor was 76.2%, 100.0% and 10.0% in PSS, inflammatory disease control and POAG groups, respectively. The levels of CMV IgG antibody in the PSS groups were significantly higher than that of POAG groups (Z=4.23, Phumor and serum albumin could effectively improve aqueous antibody specificity in PSS patients. Furthermore, CMV IgG antibody ratio combined with PCR could improve the sensitivity of CMV detection. All of which help clarify the CMV infection in PSS in CMV DNA negative eyes. (Chin J Ophthalmol, 2017, 53: 104-108).

  5. Cytomegalovirus and chronic allograft rejection in liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Liang-Hui Gao; Shu-Sen Zheng

    2004-01-01

    Cytomegalovirus (CMV) remains one of the most frequent viral infections and the most common cause of death after liver transplantation (LT). Chronic allograft liver rejection remains the major obstacle to long-term allograft survival and CMV infection is one of the suggested risk factors for chronic allograft rejection. The precise relationship between cytomegalovirus and chronic rejection remains uncertain.This review addresses the morbidity of cytomegalovirus infection and the risk factors associated with it, the relationship between cytomegalovirus and chronic allograft liver rejection and the potential mechanisms of it.

  6. Educating women about congenital cytomegalovirus: assessment of health education materials through a web-based survey.

    Science.gov (United States)

    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 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

  7. Direct and Indirect Effects of Cytomegalovirus-induced gamma-delta T Cells after Kidney Transplantation

    Directory of Open Access Journals (Sweden)

    Lionel eCouzi

    2015-01-01

    Full Text Available Despite effective anti-viral therapies, cytomegalovirus (CMV is still associated with direct (CMV disease and indirect effects (rejection and poor graft survival in kidney transplant recipients. Recently, an unconventional T cell population (collectively designated as Vδ2neg γδ T cells has been characterized during the anti-CMV immune response in all solid-organ and bone-marrow transplant recipients, neonates, and healthy people. These CMV-induced γδ T cells undergo a dramatic and stable expansion after CMV infection, in a conventional ‘adaptive’ manner. Similarly as CMV-specific CD8+ αβ T cells, they exhibit an effector/memory TEMRA phenotype and cytotoxic effector functions. Activation of Vd2neg gd T cells by CMV-infected cells involves the TCR and still ill-defined co-stimulatory molecules such LFA-1. A multiple of Vd2neg gd TCR ligands are apparently recognized on CMV-infected cells, the first one identified being the MHC-related molecule endothelial protein C receptor (EPCR. A singularity of CMV-induced Vd2neg gd T cells is to acquire CD16 expression and to exert an antibody-dependent cell-mediated inhibition on CMV replication, which is controlled by a specific cytokine microenvironment. Beyond the well-demonstrated direct anti-CMV effect of Vδ2neg γδ T cells, unexpected indirect effects of these cells have been also observed in the context of kidney transplantation. CMV-induced Vδ2neg γδ T cells have been involved in surveillance of malignancy subsequent to long term immunosuppression. Moreover, CMV-induced CD16+ γδ T cells are cell effectors of antibody-mediated rejection of kidney transplants, and represent a new physiopathological contribution to the well-known association between CMV infection and poor graft survival. All these basic and clinical studies paved the road to the development of a future γδ T cell-based immunotherapy. In the meantime, γδ T cell monitoring should prove a valuable immunological

  8. Association of vitamin D receptor FokI and ApaI polymorphisms with human cytomegalovirus disease in the first three months following kidney transplantation

    Institute of Scientific and Technical Information of China (English)

    ZHAO Yu-gang; SHI Bing-yi; XIAO Li; QIAN Ye-yong; FENG Kai; HE Xiu-yun; XU Xiao-guang

    2012-01-01

    Background Untreated human cytomegalovirus (CMV) disease (CMVD) is an identified risk factor for reduced rates of patient (and graft) survival,death or retransplantation in kidney transplant recipients due to increased immunological tolerance after transplant.Vitamin D receptor (VDR) gene polymorphisms have an obvious relationship with autoimmune diseases but the relationship between VDR gene polymorphisms and CMVD are not well understood.This study investigated the relationship between VDR Fokl and Apal gene polymorphisms and CMVD,and their value for predicting risk of CMVD.Methods Ninety-eight kidney transplantation recipients were randomly chosen for which peripheral blood samples and case histories for the first three months after kidney transplantation were obtained.Using polymerase chain reaction-restriction fragment length polymorphisms,30 recipients were found to be homozygous for the Fokl gene (FF),47 heterozygous (Ff),and 21 were homozygous (ff).Likewise,similar analyses determined that 12 recipients were homozygous for the Apa/ gene (AA),36 heterozygous (Aa),and 50 homozygous (aa).Factors affecting the prognosis of the kidney transplantation were compared for all genotypes by statistical analysis before operation.Infection by CMV for all recipients was detected by immunofluorescence assay to diagnose CMVD.Results No statistical significance was observed for the factors affecting the prognosis of the kidney transplantation between both genotypes; however,statistical differences in CMVD among the Fokl genotypes were identified.It was determined that the risk of CMVD was significantly increased for recipients of the ff genotype than for other genotypes.There was no statistical significance observed for CMVD among Apal genotypes.Conclusions The recessive f allelic gene of VDR can be regarded as a risk factor of CMVD while FF recipients have lower incidence of CMVD after kidney transplantation.Apal genotypes showed no relationship with predisposition to CMVD

  9. No Interactive Effects of Sex and Persistent Cytomegalovirus on Immune Phenotypes in Young Children: The Generation R Study.

    Science.gov (United States)

    Jansen, Michelle A E; van den Heuvel, Diana; Jaddoe, Vincent W V; Moll, Henriette A; van Zelm, Menno C

    2017-03-15

    Persistent infections with cytomegalovirus (CMV) differentially affect the host immune phenotype in middle-aged males and females. Because CMV already impacts on T-cell memory at a young age, we studied whether these effects were modified by sex in 1,079 children with an average age of 6 years. Sex and CMV independently impacted on multiple B-cell and T-cell subsets. However, there was no significant effect of their interaction. Importantly, the effects of sex and CMV were in part explained by age and infection with other herpesviruses. Thus, immune aging is likely to be more complex, with involvement of hormonal changes with age, socioeconomic status, birth characteristics, and pathogen exposure. © 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.

  10. Development and Evidence for Efficacy of CMV Glycoprotein B Vaccine with MF59 Adjuvant

    OpenAIRE

    Pass, Robert F.

    2009-01-01

    A vaccine comprised of recombinant cytomegalovirus (CMV) envelope glycoprotein B (gB) with MF59 adjuvant developed in the 1990s recently was recently found to have efficacy for prevention of CMV infection in a phase 2 clinical trial in young mothers. This review briefly considers the rationale for gB as a vaccine antigen, the history of this CMV gB vaccine and the data supporting vaccine efficacy.

  11. CMV-specific CD8 T Cell Differentiation and Localization: Implications for Adoptive Therapies

    Directory of Open Access Journals (Sweden)

    Corinne J Smith

    2016-09-01

    Full Text Available Human cytomegalovirus (HCMV is a ubiquitous virus that causes chronic infection, and thus is one of the most common infectious complications of immune suppression. Adoptive transfer of HCMV-specific T cells has emerged as an effective method to reduce the risk for HCMV infection and/or reactivation by restoring immunity in transplant recipients. However, the CMV-specific CD8+ T cell response is comprised of a heterogenous mixture of subsets with distinct functions and localization and it is not clear if current adoptive immunotherapy protocols can reconstitute the full spectrum of CD8+ T cell immunity. The aim of this review is to briefly summarize the role of these T cell subsets in CMV immunity and to describe how current adoptive immunotherapy practices might affect their reconstitution in patients. The bulk of the CMV-specific CD8+ T cell population is made up of terminally differentiated effector T cells with immediate effector function and a short life span. Self-renewing memory T cells within the CMV-specific population retain the capacity to expand and differentiate upon challenge and are important for the long-term persistence of the CD8+ T cell response. Finally mucosal organs, which are frequent sites of CMV reactivation, are primarily inhabited by tissue resident memory T cells, which do not recirculate. Future work on adoptive transfer strategies may need to focus on striking a balance between the formation of these subsets to ensure the development of long lasting and protective immune responses that can access the organs affected by CMV disease.

  12. Late onset hemorrhagic disease of newborn due to CMV hepatitis presenting as scalp hematoma

    OpenAIRE

    2013-01-01

    Vitamin K deficiency bleeding (VKDB) according to recent studies is the preferred term for hemorrhagic disease of the newborn (HDN). This is due to deficiency of clotting factors as a result of vitamin K deficiency. VKDB was first described over a hundred years ago but its relationship to vitamin K was not released until 40 years later. Vitamin K is required for the production of clotting factors II, VII, IX and X. It is involved in the normal clotting of blood, is present in some plants and ...

  13. Optimization of Naked DNA Delivery for Interferon Subtype Immunotherapy in Cytomegalovirus Infection

    Directory of Open Access Journals (Sweden)

    Bartlett Emmalene J.

    2003-01-01

    Full Text Available Type I interferon (IFN gene therapy modulates the immune response leading to inflammatory heart disease following cytomegalovirus (CMV infection in a murine model of post-viral myocarditis. Efficacy of different immunisation protocols for the IFN constructs was influenced by the dose of DNA, subtype choice, combination use, pre-medication, and timing of DNA administration. Optimal efficacy was found with bupivacaine treatment prior to DNA inoculation of 200mg IFN DNA 14 days prior to virus challenge. Maximal antiviral and antimyocarditic effects were achieved with this vaccination schedule. Furthermore, inoculation of synergistic IFN subtypes demonstrated enhanced efficacy when delivered either alone or with CMV gB DNA vaccination in the CMV model. Thus naked DNA delivery of IFN provides an avenue of immunotherapy for regulating herpesvirus-induced diseases.

  14. Prevalence of cytomegalovirus antibodies in blood donars at the ...

    African Journals Online (AJOL)

    Transmission of cytomegalovirus infection through blood transfusion is ... Objective: To determine the prevalence CMV IgG and IgM antibodies among blood ... deficiency syndrome (AIDS) due to human immunodeficiency virus infections (HIV) ...

  15. Cytomegalovirus as a cause of anterior uveitis in immunocompetent patients

    NARCIS (Netherlands)

    van Boxtel, Lonneke A. A.; van der Lelij, Allegonda; van der Meer, Johannes; Los, Leonoor I.

    2007-01-01

    Purpose: To describe 7 cases of unilateral, chronic and/or recurrent anterior uveitis caused by cytomegalovirus (CMV) in immunocompetent patients; to identify specific ophthalmologic characteristics; and to evaluate the clinical effect of valganciclovir treatment. Design: Retrospective observational

  16. Cytomegalovirus as a cause of anterior uveitis in immunocompetent patients

    NARCIS (Netherlands)

    van Boxtel, Lonneke A. A.; van der Lelij, Allegonda; van der Meer, Johannes; Los, Leonoor I.

    2007-01-01

    Purpose: To describe 7 cases of unilateral, chronic and/or recurrent anterior uveitis caused by cytomegalovirus (CMV) in immunocompetent patients; to identify specific ophthalmologic characteristics; and to evaluate the clinical effect of valganciclovir treatment. Design: Retrospective observational

  17. [Acyclovir may modulate clonal expansion of cd8+ lymphocytes induced by the Cytomegalovirus antigen].

    Science.gov (United States)

    Gavilán, F; Caballero, J; Cárdenas, M; Moreno, J; Martínez, L; Gallego, C; Sánchez-Guijo, P; Torre-Cisneros, J

    1999-10-01

    Although the potent antiviral effect of acyclovir on the Herpes-simplex (HSV) and Varicela-zoster (VZV) virus and the scarce effectiveness versus Cytomegalovirus (CMV) is known, some data suggest that it may have an immunodulator implicated in the control of these viral disease. The aim of this study was to characterize this possible effect of acyclovir versus the CMV antigen. We stimulated cultures of mononuclear cells obtained in 7 healthy patients who were seropositive for CMV and HSV with CMV antigen, HSV and with phitohemaglutinine (PHA). The proliferation index and culture cell phenotype were later determined in the absence and presence of acyclovir (2 micrograms/ml). In another group the proliferation index and cell phenotype following stimulation with the CMV antigen were studied prior to and after treating the same volunteers with acyclovir for one week (800 mg/6h). The CMV antigen and HSV induced T cell proliferation predominantly involving the CD8+ subpopulation leading to an inversion of the CD4/CD8 quotient. On addition of acyclovir to the cell culture a moderate reduction was produced in lymphoproliferative response versus the CMV antigen and HVS, characteristically modulating CD8+ cell proliferation, thereby leading to reestablishment of the CD4/CD8 quotient. However, the proliferation induced by PHA was not inhibited. These results were produced on oral administration of acyclovir. Acyclovir modulates the lymphoproliferative response induced by CMV antigen. Based on this observation, the authors hypothesize that this immunomodulation may be related to its preventive effect on CMV disease in transplanted patients.

  18. Incidence of cytomegalovirus infection among the general population and pregnant women in the United States

    Directory of Open Access Journals (Sweden)

    Dollard Sheila C

    2007-07-01

    Full Text Available Abstract Background Cytomegalovirus (CMV is a common opportunistic infection among HIV-infected individuals, a major source of serious complications among organ-transplant recipients, and a leading cause of hearing loss, vision loss, and mental retardation among congenitally infected children. Women infected for the first time during pregnancy are especially likely to transmit CMV to their fetuses. More children suffer serious disabilities caused by congenital CMV than by several better-known childhood maladies such as Down syndrome or fetal alcohol syndrome Methods Using CMV seroprevalence data from the nationally representative Third National Health and Nutrition Examination Survey, we estimated CMV incidence among the general United States population and among pregnant women. We employed catalytic models that used age-specific CMV seroprevalences as cumulative markers of past infections in order to derive estimates of three basic parameters: the force of infection, the basic reproductive rate, and the average age of infection. Our main focus was the force of infection, an instantaneous per capita rate of acquisition of infection that approximates the incidence of infection in the seronegative population. Results Among the United States population ages 12–49 the force of infection was 1.6 infections per 100 susceptible persons per year (95% confidence interval: 1.2, 2.4. The associated basic reproductive rate of 1.7 indicates that, on average, an infected person transmits CMV to nearly two susceptible people. The average age of CMV infection was 28.6 years. Force of infection was significantly higher among non-Hispanic Blacks (5.7 and Mexican Americans (5.1 than among non-Hispanic Whites (1.4. Force of infection was significantly higher in the low household income group (3.5 than in the middle (2.1 and upper (1.5 household income groups. Based on these CMV incidence estimates, approximately 27,000 new CMV infections occur among seronegative

  19. Impact of local endothelial challenge with cytomegalovirus or glycoprotein B on vasodilation in intact pressurized arteries from nonpregnant and pregnant mice.

    Science.gov (United States)

    Gombos, Randi B; Teefy, Jana; Lee, Albert; Hemmings, Denise G

    2012-10-01

    Cytomegalovirus (CMV) infections are associated with vascular diseases in the human population. We have previously shown vascular dysfunction in systemic and uterine arteries dissected from nonpregnant (NP) mouse CMV (mCMV)-infected mice that was further impaired during late pregnancy (LP). CMV attachment alone through glycoprotein B (GB) can generate signals that impact vascular tone regulation. However, the contribution of direct virus interactions with endothelium to the vascular dysfunction we previously observed after in vivo mCMV infection is not known. We used a pressure myograph system to infuse GB or whole intact mCMV inside arteries dissected from uninfected mice and assessed vasodilation to methacholine infused inside pressurized arteries rather than applied abluminally. These results were compared to those observed after methacholine infusion into untreated arteries dissected from mCMV-infected mice. In mesenteric arteries, vasodilation to infused methacholine did not differ among treatments in NP or LP groups in contrast to previously published studies. However, increased vasoconstrictor activity was unmasked after blocking thromboxane receptors or prostaglandin production. Vasodilation in uterine arteries from uninfected NP mice to infused methacholine was increased by both GB and whole intact mCMV pretreatment. Untreated uterine arteries from mCMV-infected NP mice showed even greater vasodilation. There was no effect of GB or whole intact mCMV pretreatment in uterine arteries from uninfected LP mice, whereas vasodilation to infused methacholine was reduced in untreated uterine arteries from mCMV-infected LP mice. CMV exerts direct effects on vascular function which should be considered during viral reactivation leading to viremia and during GB-based vaccine administration.

  20. Cytomegalovirus hepatitis and myopericarditis

    Institute of Scientific and Technical Information of China (English)

    Leire Zubiaurre; Eva Zapata; Luis Bujanda; María Castillo; Igor Oyarzabal; Maria A Gutiérrez-Stampa; Angel Cosme

    2007-01-01

    Cytomegalovirus (CMV) infection in inmunocompetent hosts generally is asymptomatic or may present as a mononucleosis syndrome but rarely can lead to severe organ complications. We report a case of simultaneous hepatic and pericardic CMV infection in a 36-year old immunocompetent man. He was admitted to coronary unit with fever, chest pain radiated to shoulders,changes on electrocardiogram with diffuse ST elevation and modest laboratory elevations in the MB fraction of creatine kinase (CK-MB) of 33.77 μg/L (0.1-6.73), serum cardiac troponin T of 0.904 ng/mL (0-0.4), creatine kinase of 454 U/L (20-195) and myoglobin of 480.4 μg/L (28-72). Routine laboratory test detected an elevation of aminotransferase level: alanine aminotransferase 1445 U/L, aspartate aminotransferase 601 U/L. We ruled out other causes of hepatitis with normal results except IgM CMV. The patient was diagnosed with myopericarditis and hepatitis caused by cytomegalovirus and started symptomatic treatment with salicylic acid. In few days the laboratory findings became normal and the patient was discharged.

  1. CMVpp65 Vaccine Enhances the Antitumor Efficacy of Adoptively Transferred CD19-Redirected CMV-Specific T Cells.

    Science.gov (United States)

    Wang, Xiuli; Wong, ChingLam W; Urak, Ryan; Mardiros, Armen; Budde, Lihua E; Chang, Wen-Chung; Thomas, Sandra H; Brown, Christine E; La Rosa, Corinna; Diamond, Don J; Jensen, Michael C; Nakamura, Ryotaro; Zaia, John A; Forman, Stephen J

    2015-07-01

    T cells engineered with chimeric antigen receptors (CAR) recognizing CD19 can induce complete remission of B-cell malignancies in clinical trials; however, in some disease settings, CAR therapy confers only modest clinical benefit due to attenuated persistence of CAR T cells. The purpose of this study was to enhance persistence and augment the antitumor activity of adoptively transferred CD19CAR T cells by restimulating CAR(+) T cells through an endogenous cytomegalovirus (CMV)-specific T-cell receptor. CMV-specific T cells from CMV seropositive healthy donors were selected after stimulation with pp65 protein and transduced with clinical-grade lentivirus expressing the CD19R:CD28:ζ/EGFRt CAR. The resultant bispecific T cells, targeting CMV and CD19, were expanded via CD19 CAR-mediated signals using CD19-expressing cells. The bispecific T cells proliferated vigorously after engagement with either endogenous CMVpp65 T-cell receptors or engineered CD19 CARs, exhibiting specific cytolytic activity and IFNγ secretion. Upon adoptive transfer into immunodeficient mice bearing human lymphomas, the bispecific T cells exhibited proliferative response and enhanced antitumor activity following CMVpp65 peptide vaccine administration. We have redirected CMV-specific T cells to recognize and lyse tumor cells via CD19CARs, while maintaining their ability to proliferate in response to CMV antigen stimulation. These results illustrate the clinical applications of CMV vaccine to augment the antitumor activity of adoptively transferred CD19CAR T cells in patients with B-cell malignancies. ©2015 American Association for Cancer Research.

  2. Perfil clínico da Enterocolite por Citomegalovírus (CMV na síndrome da imunodeficiência adquirida (Aids Clinical profile of Cytomegalovirus Colitis in AIDS

    Directory of Open Access Journals (Sweden)

    D.B. de Lima

    2000-03-01

    Full Text Available Múltiplos agentes estão envolvidos na etiopatogenia da diarréia em Aids. O exame de fezes e a colonoscopia são elementos decisivos para o diagnóstico específico. A enterocolite por CMV pode cursar com febre, emagrecimento, diarréia intermitente e hematoquesia. Outros agentes causadores de diarréia podem ter o mesmo espectro de apresentação. OBJETIVO: Definir o perfil clínico da enterocolite por CMV em pacientes com Aids, comparando os parâmetros clínicos, endoscópicos e de tempo de sobrevida entre dois grupos com diarréia crônica, grupo A com CMV e grupo B sem CMV. MÉTODOS: Foram acompanhados 48 pacientes com Aids e diarréia de duração maior que 30 dias, sendo 27 do grupo A e 21 do grupo B. Os parâmetros analisados foram idade, situação de risco, duração da diarréia, hematoquesia, intervalo de tempo entre diagnóstico da infecção por HIV e início de diarréia, achados endoscópicos e sobrevida. Foram realizados exames parasitológicos, culturas e colonoscopia com biópsias. Foi utilizado o teste "t-student" para amostras não pareadas e o teste Qui-Quadrado com correção de Yates para variáveis não paramétricas. Foram construídas curvas de sobrevida pelo método descrito por Kaplan-Meier e aplicado o teste de Mantel - Haenszel. Foi assumido como nível de significância estatística o valor de P menor que 0.05. RESULTADOS: O padrão endoscópico da infecção por CMV correspondeu a ulcerações associadas a hemorragia de submucosa 14 (51.8% P P > 0.001. Os outros parâmetros estudados não mostraram significância estatística. CONCLUSÕES: A presença de enterocolite por CMV em Aids é marcador de mau prognóstico e menor sobrevida. Existe um padrão endoscópico sugestivo da infecção por CMV.OBJECTIVE: To determine the clinical profile of CMV colitis in AIDS patients, comparing clinical, endoscopic parameters and survival time between 2 groups of AIDS patients having chronic diarrhea. Group A being CMV

  3. Cytomegalovirus Colitis with Common Variable Immunodeficiency and Crohn’s Disease

    Directory of Open Access Journals (Sweden)

    Betül Ünal

    2015-01-01

    Full Text Available Here we present an eleven-year-old male patient who had been diagnosed with common variable immunodeficiency (CVID three years ago due to recurrent sinopulmonary infections. Two years later he had been diagnosed with Crohn’s disease (CD due to diarrhea episodes which were unresponsive to the treatment. Depending on the active gastrointestinal bleeding and perforation he underwent total colectomy. Despite immunoglobulin and antiviral therapies, general condition of patient deteriorated and he died in the postoperative seventh day. Laboratory analysis was seronegative. CMV inclusion containing cells were detected in postmortem biopsies taken from liver, lungs, and lymph nodes.

  4. Prevention of maternal cytomegalovirus infection: current status and future prospects

    Directory of Open Access Journals (Sweden)

    Jessica L Nyholm

    2010-02-01

    Full Text Available Jessica L Nyholm1, Mark R Schleiss21Department of Obstetrics, Gynecology, and Women’s Health, and 2Department of Pediatrics, University of Minnesota School of Medicine, Minneapolis, MN, USAAbstract: Human cytomegalovirus (CMV infection is the most common cause of perinatal viral infection in the developed world, resulting in approximately 40,000 congenitally infected infants in the United States each year. Congenital CMV infection can produce varying degrees of neurodevelopmental disabilities. The significant impact of congenital CMV has led the Institute of Medicine to rank development of a CMV vaccine as a top priority. Vaccine development has been ongoing; however no licensed CMV vaccine is currently available. Treatment of pregnant women with CMV hyperimmune globulin has shown promising results, but has not been studied in randomized controlled trials. Education on methods to prevent CMV transmission, particularly among young women of child-bearing age, should continue until a CMV vaccine becomes available. The epidemiology, clinical manifestations, prevention strategies, and treatment of CMV infections are reviewed.Keywords: cytomegalovirus, CMV vaccines, congenital CMV, CMV infection, immunoglobulin

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

    DEFF Research Database (Denmark)

    da Cunha-Bang, Caspar; Sørensen, Søren S; Iversen, Martin

    2011-01-01

    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....

  6. Combination antiviral therapy for ganciclovir-resistant cytomegalovirus infection in solid-organ transplant recipients.

    Science.gov (United States)

    Mylonakis, Eleftherios; Kallas, Wendy M; Fishman, Jay A

    2002-05-15

    The resistance of cytomegalovirus (CMV) to ganciclovir is a factor in therapeutic failure and disease progression. The clinical significance of such resistance in solid-organ transplantation has not been completely established. Six patients who developed persistent infection due to ganciclovir-resistant CMV were treated with a combination of ganciclovir (50% of the therapeutic dose) and a daily dose of intravenous foscarnet that gradually increased to a maximum of 125 mg/kg. All patients responded clinically within 72-96 hours. Magnesium depletion occurred in all patients. No clinical or laboratory relapses have been observed in 6-30 months of follow-up. Gradually increasing doses of foscarnet combined with half-dose regimens of ganciclovir are safe and can be beneficial in organ transplant recipients with ganciclovir-resistant CMV infection. Larger studies are needed to identify the patients who are most likely to benefit from this regimen.

  7. Eosinophilic gastroenteritis with cytomegalovirus infection in an immunocompetent child

    Institute of Scientific and Technical Information of China (English)

    Junji Takeyama; Daiki Abukawa; Katsushi Miura

    2007-01-01

    A 3-year-old boy developed transient protein-losing gastroenteropathy associated with cytomegalovirus (CMV) infection. Both IgG and IgM antibodies to CMV were positive in a serologic blood test. Upper gastrointestinal endoscopy showed multiple erosions throughout the body of the stomach, without enlarged gastric folds. Histological examination of the biopsy specimens indicated eosinophilic gastroenteritis and CMV infection. The patient had complete resolution without specific therapy for CMV in four weeks. An allergic reaction as well as CMV infection played important roles in the pathogenesis of this case.

  8. Reduced dose of foscarnet as preemptive therapy for cytomegalovirus infection following reduced-intensity cord blood transplantation.

    Science.gov (United States)

    Narimatsu, H; Kami, M; Kato, D; Matsumura, T; Murashige, N; Kusumi, E; Yuji, K; Hori, A; Shibata, T; Masuoka, K; Wake, A; Miyakoshi, S; Morinaga, S; Taniguchi, S

    2007-03-01

    Although foscarnet is a promising alternative for the treatment of cytomegalovirus (CMV) infection, its toxicity can be significant in patients with advanced age. We retrospectively reviewed medical records of 123 patients (median age of 55; range, 17-79) who received reduced-intensity cord blood transplantation (RI-CBT). Patients preemptively received reduced-dose foscarnet 30 mg/kg twice daily when CMV antigenemia exceeded 10/50,000. Sixty-three patients developed CMV antigenemia on a median of day 34, and 29 received foscarnet preemptively. The median level of CMV antigenemia at the initiation of foscarnet was 30. Median duration of foscarnet administration was 24 days. Adverse effects included electrolyte abnormalities (n=19), renal impairment (n=13), and skin eruption requiring discontinuation of foscarnet (n=1). Preemptive therapy of foscarnet was completed in 18 patients. Seven patients died during foscarnet use without developing CMV disease. The remaining 3 developed CMV enterocolitis 5, 14, and 17 days after initiation of foscarnet. All of them were successfully treated with ganciclovir or foscarnet. Reduced dose of foscarnet is beneficial to control CMV reactivation following RI-CBT; however, it has considerable toxicities in RI-CBT recipients with advanced age. Further studies are warranted to minimize toxicities and identify optimal dosages.

  9. Successful use of oral ganciclovir for the treatment of intrauterine cytomegalovirus infection in a renal allograft recipient.

    Science.gov (United States)

    Puliyanda, D P; Silverman, N S; Lehman, D; Vo, A; Bunnapradist, S; Radha, R K; Toyoda, M; Jordan, S C

    2005-06-01

    Congenital cytomegalovirus (CMV) infection occurs in approximately 1% of newborns and is the leading infectious cause of congenital birth defects. Female renal allograft recipients who develop CMV infection during pregnancy are at risk for both graft dysfunction and fetal morbidity. DNA-based analysis of amniotic fluid (AF) from at-risk pregnancies has been suggested as an adjunct/substitute for traditional culture. We have shown that CMV-polymerase chain reaction of AF is a useful diagnostic test for congenital CMV infection. Using this test we diagnosed CMV infection in the fetus of a 30-year-old renal transplant recipient. As termination was not an option for the family, the patient was extensively counseled and treated with oral ganciclovir. This resulted in clearance of the virus from the AF and the delivery of a healthy newborn girl, free of CMV disease. This is the first reported case to our knowledge of successful use of maternal ganciclovir to treat intrauterine CMV infection in a pregnant renal transplant recipient.

  10. Childhood environments and cytomegalovirus serostatus and reactivation in adults

    NARCIS (Netherlands)

    Janicki-Deverts, D.; Cohen, S.; Doyle, W.J.; Marsland, A.L.; Bosch, J.

    2014-01-01

    Childhood adversity, defined in terms of material hardship or physical or emotional maltreatment has been associated with risk for infection with cytomegalovirus (CMV) among children and adolescents, and with CMV reactivation in children and adults. The present study examined whether different dimen

  11. Comparative evaluation of the cytomegalovirus DNA load in polymorphonuclear leukocytes and plasma of human immunodeficiency virus-infected subjects.

    Science.gov (United States)

    Boivin, G; Handfield, J; Toma, E; Murray, G; Lalonde, R; Bergeron, M G

    1998-02-01

    The cytomegalovirus (CMV) DNA load was determined in polymorphonuclear leukocytes (PMNL) and plasma samples from 106 human immunodeficiency virus-infected subjects at risk of developing CMV disease (group 1) and from 27 AIDS patients with documented CMV disease (group 2). For both groups, the number of CMV copies in PMNL was significantly higher than in plasma when results were derived from an equivalent blood volume (P < .001, PMNL vs. plasma). Additionally, group 2 (symptomatic) patients had a greater viral DNA load than group 1 (asymptomatic) subjects (P < .001 for both PMNL and plasma). The sensitivity, specificity, and positive and negative predictive values of qualitative polymerase chain reaction using PMNL (PCR-PMNL) for the presence of CMV disease were 100%, 58%, 38%, and 100%, respectively, compared with 70%, 93%, 74%, and 92% for qualitative PCR-plasma and 93%, 92%, 76%, and 98% for quantitative PCR-PMNL using a cutoff of 16,000 copies/mL. Thus, the best strategy for diagnosing CMV disease in these individuals relies on quantitative assessment of the viral DNA load in PMNL.

  12. Knowledge and Awareness of Congenital Cytomegalovirus Among Women

    Directory of Open Access Journals (Sweden)

    Jiyeon Jeon

    2006-01-01

    Full Text Available 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.

  13. Early-life environment influencing susceptibility to cytomegalovirus infection

    DEFF Research Database (Denmark)

    Mortensen, Laust Hvas; Maier, A B; Slagbom, P E

    2012-01-01

    Human cytomegalovirus (CMV) is a common herpesvirus establishing lifelong persisting infection, which has been implicated in immunosenescence and mortality in the elderly. Little is known about how and when susceptibility to CMV infection is determined. We measured CMV seroprevalence in two genet......--even under continuous within-partnership exposure--appears to be more strongly influenced by early-life environment than by genetic factors and adult environment....

  14. Cytomegalovirus reinfections stimulate CD8 T-memory inflation

    OpenAIRE

    Trgovcich, J; Kincaid, M; Thomas, A.; Griessl, M.; Zimmerman, P; Dwivedi, V; Bergdall, V; Klenerman, P.; Cook, CH

    2016-01-01

    Cytomegalovirus (CMV) has been shown to induce large populations of CD8 T-effector memory cells that unlike central memory persist in large quantities following infection, a phenomenon commonly termed “memory inflation”. Although murine models to date have shown very large and persistent CMV-specific T-cell expansions following infection, there is considerable variability in CMV-specific T-memory responses in humans. Historically such memory inflation in humans has been assumed a consequence ...

  15. Clinical assessment of anti-viral CD8+ T cell immune monitoring using QuantiFERON-CMV® assay to identify high risk allogeneic hematopoietic stem cell transplant patients with CMV infection complications.

    Directory of Open Access Journals (Sweden)

    Siok-Keen Tey

    Full Text Available The reconstitution of anti-viral cellular immunity following hematopoietic stem cell transplantation (HSCT is crucial in preventing cytomegalovirus (CMV-associated complications. Thus immunological monitoring has emerged as an important tool to better target pre-emptive anti-viral therapies. However, traditional laboratory-based assays are too cumbersome and complicated to implement in a clinical setting. Here we conducted a prospective study of a new whole blood assay (referred to as QuantiFERON-CMV® to determine the clinical utility of measuring CMV-specific CD8+ T-cell responses as a prognostic tool. Forty-one evaluable allogeneic HSCT recipients underwent weekly immunological monitoring from day 21 post-transplant and of these 21 (51.2% showed CMV reactivation and 29 (70.7% developed acute graft-versus-host disease (GvHD. Patients with acute GvHD (grade ≥ 2 within 6 weeks of transplant showed delayed reconstitution of CMV-specific T-cell immunity (p = 0.013 and a higher risk of CMV viremia (p = 0.026. The median time to stable CMV-specific immune reconstitution was 59 days and the incidence of CMV reactivation was lower in patients who developed this than those who did not (27% versus 65%; p = 0.031. Furthermore, a failure to reconstitute CMV-specific immunity soon after the onset of CMV viraemia was associated with higher peak viral loads (5685 copies/ml versus 875 copies/ml; p = 0.002. Hence, QuantiFERON-CMV® testing in the week following CMV viremia can be useful in identifying HSCT recipients at risk of complicated reactivation.

  16. Relation of high cytomegalovirus antibody titres to blood pressure and brachial artery flow-mediated dilation in young men: the Cardiovascular Risk in Young Finns Study.

    Science.gov (United States)

    Haarala, A; Kähönen, M; Lehtimäki, T; Aittoniemi, J; Jylhävä, J; Hutri-Kähönen, N; Taittonen, L; Laitinen, T; Juonala, M; Viikari, J; Raitakari, O T; Hurme, M

    2012-02-01

    Human cytomegalovirus (CMV) infection is associated with a higher risk of cardiovascular disease in immunocompromised organ transplant patients. It has been linked with the pathogenesis of elevated arterial blood pressure. However, controversy exists as to whether CMV infection is associated with endothelial function, and little is known about its role as a potential risk factor for early atherosclerosis development at a young age. We aimed to discover if CMV antibody titres are associated with early vascular changes (carotid intima-media thickness, carotid artery distensibility and brachial artery flow-mediated dilation), blood pressure elevation or other traditional cardiovascular risk factors. CMV antibody titres were measured in 1074 women and 857 men (aged 24-39 years) taking part in the Cardiovascular Risk in Young Finns study. CMV antibody titres were significantly higher in women compared to men. In men, high CMV antibody titres were associated directly with age (P blood pressure elevation, and associated inversely with flow-mediated dilation (P = 0·014). In women, CMV antibody titres did not associate with any of the analysed parameters. In a multivariate regression model, which included traditional atherosclerotic risk factors, CMV antibody titres were independent determinants for systolic (P = 0·029) and diastolic (P = 0·004) blood pressure elevation and flow-mediated dilation (P = 0·014) in men. High CMV antibody titres are associated independently with blood pressure and brachial artery flow-mediated dilation in young men. This association supports the hypothesis that common CMV infection and/or an immune response to CMV may lead to impaired vascular function at a young age. © 2012 The Authors. Clinical and Experimental Immunology © 2012 British Society for Immunology.

  17. Chronic lymphocytic leukemia patients have a preserved cytomegalovirus-specific antibody response despite progressive hypogammaglobulinemia.

    Directory of Open Access Journals (Sweden)

    Katrina Vanura

    Full Text Available Chronic lymphocytic leukemia (CLL is characterized by progressive hypogammaglobulinemia predisposing affected patients to a variety of infectious diseases but paradoxically not to cytomegalovirus (CMV disease. Moreover, we found reactivity of a panel of CLL recombinant antibodies (CLL-rAbs encoded by a germ-line allele with a single CMV protein, pUL32, despite differing antibody binding motifs. To put these findings into perspective, we studied prospectively relative frequency of viremia, kinetics of total and virus-specific IgG over time, and UL32 genetic variation in a cohort of therapy-naive patients (n=200. CMV-DNA was detected in 3% (6/200 of patients. The decay of total IgG was uniform (mean, 0.03; SD, 0.03 and correlated with that of IgG subclasses 1-4 in the paired samples available (n=64; p<0.001. Total CMV-specific IgG kinetics were more variable (mean, 0,02; SD, 0,06 and mean decay values differed significantly from those of total IgG (p=0.034. Boosts of CMV-specific antibody levels were observed in 49% (22/45 of CMV-seropositive patients. In contrast, VZV- and EBV-specific IgG levels decayed in parallel with total IgG levels (p=0.003 and p=0.001, respectively. VZV-specific IgG even became undetectable in 18% (9/50 of patients whereas CMV-specific ones remained detectable in all seropositive patients. The observed CMV-specific IgG kinetics were predicated upon the highly divergent kinetics of IgG specific for individual antigens - glycoprotein B-specific IgG were boosted in 51% and pUL32-specific IgG in 32% of patients. In conclusion, CLL patients have a preserved CMV-specific antibody response despite progressive decay of total IgG and IgG subclasses. CMV-specific IgG levels are frequently boosted in contrast to that of other herpesviruses indicative of a higher rate of CMV reactivation and antigen-presentation. In contrast to the reactivity of multiple different CLL-rAbs with pUL32, boosts of humoral immunity are triggered

  18. Acute cytomegalovirus infection complicated by venous thrombosis: a case report

    Directory of Open Access Journals (Sweden)

    Parola Philippe

    2005-08-01

    Full Text Available Abstract Background CMV-induced vasculopathy and thrombosis have been reported, but they are rare conditions usually encountered in immunocompromised patients. However more and more complications of CMV infections are recognized in immunocompetent patients. Case presentation We present a case report of a previously healthy adult with cytomegalovirus infection that was complicated by tibiopopliteal deep venous thrombosis and in whom Factor V Leiden heterozygous mutation was found. Conclusion This new case report emphasizes the involvement of cytomegalovirus in induction of vascular thrombosis in patients with predisposing risk factors for thrombosis. It is necessary to screen for CMV infection in patients with spontaneous thrombosis and an history of fever.

  19. Cytomegalovirus infection causes an increase of arterial blood pressure.

    Directory of Open Access Journals (Sweden)

    Jilin Cheng

    2009-05-01

    Full Text Available Cytomegalovirus (CMV infection is a common infection in adults (seropositive 60-99% globally, and is associated with cardiovascular diseases, in line with risk factors such as hypertension and atherosclerosis. Several viral infections are linked to hypertension, including human herpes virus 8 (HHV-8 and HIV-1. The mechanisms of how viral infection contributes to hypertension or increased blood pressure are not defined. In this report, the role of CMV infection as a cause of increased blood pressure and in forming aortic atherosclerotic plaques is examined. Using in vivo mouse model and in vitro molecular biology analyses, we find that CMV infection alone caused a significant increase in arterial blood pressure (ABp (p<0.01 approximately 0.05, measured by microtip catheter technique. This increase in blood pressure by mouse CMV (MCMV was independent of atherosclerotic plaque formation in the aorta, defined by histological analyses. MCMV DNA was detected in blood vessel samples of viral infected mice but not in the control mice by nested PCR assay. MCMV significantly increased expression of pro-inflammatory cytokines IL-6, TNF-alpha, and MCP-1 in mouse serum by enzyme-linked immunosorbent assay (ELISA. Using quantitative real time reverse transcriptase PCR (Q-RT-PCR and Western blot, we find that CMV stimulated expression of renin in mouse and human cells in an infectious dose-dependent manner. Co-staining and immunofluorescent microscopy analyses showed that MCMV infection stimulated renin expression at a single cell level. Further examination of angiotensin-II (Ang II in mouse serum and arterial tissues with ELISA showed an increased expression of Ang II by MCMV infection. Consistent with the findings of the mouse trial, human CMV (HCMV infection of blood vessel endothelial cells (EC induced renin expression in a non-lytic infection manner. Viral replication kinetics and plaque formation assay showed that an active, CMV persistent infection in

  20. Construction and Evaluation of Cytomegalovirus DNA Quantification System with Real-Time Detection Polymerase Chain Reaction

    OpenAIRE

    Hatayama, Yuki; Hashimoto, Yuki; Hara, Ayako; Motokura, Toru

    2016-01-01

    Background For patients with reactivation of human cytomegalovirus (CMV), a highly sensitive and accurate CMV quantification system is essential to monitor viral load. Methods We constructed a real-time detection PCR (RTD-PCR) system for CMV DNA and evaluated its linearity, lower detection limit, dynamic range and accuracy using two CMV standards. We used 219 clinical samples derived from 101 patients to compare the system with the pp65 antigen test. Results The 95% detection limit was determ...

  1. Construction of recombinant baculovirus Ac-CMV-hSox9 for gene therapy of intervertebral disc degeneration

    Institute of Scientific and Technical Information of China (English)

    LIU Xiao-yun; YANG Shu-hua; LIANG Chang-yong; SONG Jian-hua; LI Kang-hua; CHEN Xin-wen

    2007-01-01

    Objective: To construct the recombinant baculovirus Ac-cytomegalovirus (CMV)-hSox9 for gene therapy of intervertebral disc degeneration. Methods: Bac-to-Bac system was used for the construction of baculovirus Ac-CMV-hSox9. The cDNA of hSox9 was first cloned into a plasmid vector under the control of CMV promotor to generate the donor plasmid pFastBacDul-green fluorescene protein (GFP)-CMV (pFGC)-hSox9.The resultant plasmid was transformed into DH10Bac cells and then the transformation mixture was spread on Luria-Bertani (LB) agarose culture medium containing isopropyl-β-D-thiogalactoside (IPTG), X-gal, gentamicin, kanamycin and tetracycline.The white colonies were selected and cultured for amplification, and the hSox9Bacmid DNA was extracted. After verification, recombinant baculovirus Ac-CMV-hSox9 was obtained through transfecting Sf 21 cells.The expression of hSox9 gene in the intervertebral disc cells in rabbits was determined by Western blotting and immunohistochemical staining.Results: Polymerase chain reaction (PCR) confirmed the presence of hSox9 gene in the recombinant baculovirus and the Sf 21 cells transfected by the baculovirus showed the expression of fluorescence protein.Western blotting and immunohistochemical staining analysis indicated that exogenous hSox9 gene was expressed in the disc cells.Conclusions: The successful construction of the recombinant baculovirus Ac-CMV-hSox9 and the confirmation of the target gene expression provides a novel expression vector system for basic research and clinical treatment of intervertebral degenerative disc disease.

  2. Brincidofovir Use after Foscarnet Crystal Nephropathy in a Kidney Transplant Recipient with Multiresistant Cytomegalovirus Infection

    Directory of Open Access Journals (Sweden)

    Romain Vial

    2017-01-01

    Full Text Available Background. Cytomegalovirus (CMV antiviral drug resistance constitutes an increasing challenge in transplantation. Foscarnet is usually proposed when resistance for ganciclovir is suspected, but its use is limited by its nephrotoxicity. Case Presentation. We report a case of multiresistant CMV disease in a kidney transplant recipient. Foscarnet was prescribed after ganciclovir treatment failure in a patient with two mutations in the UL97 viral gene. Foscarnet induced biopsy-proven kidney crystal precipitation that resulted in severe acute transplant failure and nephrotic syndrome. Despite a large decrease in immunosuppression, CMV disease was not controlled and a salvage therapy with Brincidofovir (BCV, which is an oral lipid conjugate of cidofovir with limited nephrotoxicity, was attempted. Clinical and virological remission was observed after a 21-day course of BCV, despite mild and reversible liver toxicity. However, a new relapse could not be effectively cured by BCV due to a new mutation in the UL54 gene, which is known to confer resistance to cidofovir. A new course of foscarnet finally resulted in prolonged CMV remission. Herein, we present a review of foscarnet nephropathy cases in solid-organ transplanted patients. Conclusions. This unique case highlights the potential benefit of BCV use during resistant CMV infection, although mutations in the UL54 gene may limit its therapeutic efficacy. These findings need to be confirmed in clinical trials.

  3. Brincidofovir Use after Foscarnet Crystal Nephropathy in a Kidney Transplant Recipient with Multiresistant Cytomegalovirus Infection

    Science.gov (United States)

    Vial, Romain; Zandotti, Christine; Alain, Sophie; Decourt, Alexandre; Purgus, Raj; Bornet, Charleric; Daniel, Laurent; Moal, Valérie

    2017-01-01

    Background. Cytomegalovirus (CMV) antiviral drug resistance constitutes an increasing challenge in transplantation. Foscarnet is usually proposed when resistance for ganciclovir is suspected, but its use is limited by its nephrotoxicity. Case Presentation. We report a case of multiresistant CMV disease in a kidney transplant recipient. Foscarnet was prescribed after ganciclovir treatment failure in a patient with two mutations in the UL97 viral gene. Foscarnet induced biopsy-proven kidney crystal precipitation that resulted in severe acute transplant failure and nephrotic syndrome. Despite a large decrease in immunosuppression, CMV disease was not controlled and a salvage therapy with Brincidofovir (BCV), which is an oral lipid conjugate of cidofovir with limited nephrotoxicity, was attempted. Clinical and virological remission was observed after a 21-day course of BCV, despite mild and reversible liver toxicity. However, a new relapse could not be effectively cured by BCV due to a new mutation in the UL54 gene, which is known to confer resistance to cidofovir. A new course of foscarnet finally resulted in prolonged CMV remission. Herein, we present a review of foscarnet nephropathy cases in solid-organ transplanted patients. Conclusions. This unique case highlights the potential benefit of BCV use during resistant CMV infection, although mutations in the UL54 gene may limit its therapeutic efficacy. These findings need to be confirmed in clinical trials. PMID:28348914

  4. Small bowel perforation due to CMV enteritis infection in an HIV-positive patient

    Directory of Open Access Journals (Sweden)

    Michalopoulos Nick

    2013-02-01

    Full Text Available Abstract Background Cytomegalovirus infection of the gastrointestinal tract is common and is more often seen in patients with acquired immunodeficiency syndrome (AIDS. Although small bowel infection is less common than infection of other parts of the gastrointestinal system, it may lead to perforation, an acute complication, with dreadful results. Case presentation This article reports a case of Cytomegalovirus ileitis with multiple small bowel perforations in a young man with human immunodeficiency virus (HIV infection. The patient developed abdominal pain with diarrhea and fever, and eventually acute abdomen with pneumoperitoneum. The patient had poor prognosis and deceased despite the prompt surgical intervention and the antiviral therapy he received. At pathology a remarkable finding was the presence of viral inclusions in smooth muscle fibers. The destruction of muscle cells was the main cause of perforation. Conclusion Morbidity and mortality associated with perforation from CMV enteritis in AIDS patients are high and the life expectancy is short. Cytomegalovirus disease is multifocal; therefore, excision of one portion of the gastrointestinal tract may be followed by a complication elsewhere. Our case elucidate that muscle cell destruction by the virus is a significant cause leading to perforation.

  5. Mycotic aneurysm and subarachnoid hemorrhage following tubercular meningitis in an infant with congenital tuberculosis and cytomegalovirus disease.

    Science.gov (United States)

    Gupta, Kirti; Radotra, Bishan Dass; Suri, Deepti; Sharma, Kusum; Saxena, Akshay Kumar; Singhi, Pratibha

    2012-10-01

    We describe autopsy findings in a 5-month-old infant with disseminated tuberculosis and congenital cytomegalovirus disease. The infant manifested with tubercular meningitis complicating as ruptured mycotic right middle cerebral artery aneurysm. Infiltrative, proliferative, and necrotizing vascular pathologies have been described; however, the occurrence of these is dependent on the duration of illness. The vessel pathology appears to be a payback of its immersion in the local inflammatory cell-rich exudates. Strokes early in the course of the disease are believed to be a consequence of vasospasm, and those occurring later during the disease course are due to proliferative intimal disease. Intracranial mycotic aneurysm following tubercular meningitis developing at such a young age has not been reported in the literature. The lung lesions in a congenitally transmitted tuberculosis and cytomegalovirus disease have also been elaborated.

  6. Replacement of the human cytomegalovirus promoter with fish enhancer and core elements to control the expression of the G gene of viral haemorrhagic septicemia virus (VHSV).

    Science.gov (United States)

    Martinez-Lopez, A; Chinchilla, B; Encinas, P; Gomez-Casado, E; Estepa, A; Coll, J M

    2012-12-15

    This work explores some of the possibilities to replace human cytomegalovirus (CMV) core and/or enhancer promoter control elements to create new expression vectors for use with fish. The work is relevant to fish vaccination, since DNA vaccines use eukaryotic expression plasmids controlled by the human cytomegalovirus (CMV) promoter to be effective against novirhabdoviruses, such as viral haemorrhagic septicemia virus (VHSV), one of the most devastating fish viral European diseases. To reduce possible homologous recombination with fish genome, core and enhancer sequences from fish origin, such as trout interferon-inducible myxovirus protein (Mx), zebrafish retrovirus long terminal repeat (LTR) and carp β-actin (AE6), were combined with those of CMV to design alternative hybrid promoters. The substitution of CMV core and/or enhancer with the corresponding elements of Mx or the LTR core maintained a similar in vitro protein G expression level than that obtained by using the CMV promoter. Vectors using the dsRNA-inducible Mx enhancer followed either by the LTR or the AE6 cores showed the highest in vitro protein G expression levels. Furthermore, synthetic constructs using the Mx enhancer maintained their polyI:C induction capabilities despite the core used. Some of these hybrid promoters might contribute to the development of all-fish-vectors for DNA vaccines while others might be useful for more basic studies.

  7. Interstitial neumonia and cytomegalovirus: and immunopathological process Neumonía intersticial y citomegalovirus: un proceso inmunopatológico

    Directory of Open Access Journals (Sweden)

    Ana Isabel Toro

    1995-03-01

    Full Text Available

    Cytomegalovirus (CMV infection is a frequent cause of morbidity and mortality in immunocompromised individuals. including renal and bone marrow transplant recipients and patients with the acquired immunodeficiency syndrome (AIDS. CMV infection often affects the lung producing a fatal interstitial pneumonitis (IP. The pathogenesis of CMV IP is not well understood, but clinical observations in humans and laboratory studies with murine models, offer possibilities for explaining CMV-induced IP as an immunopathological disease.

    La infección activa por Citomegalovirus (CMV es causa frecuente de morbi-mortalidad en individuos inmunocomprometidos, particularmente entre receptores de trasplante renal y médula ósea y en personas afectadas por el virus de la inmunodeficiencia adquirida (HIV, en las cuales, a menudo, se presenta neumonía intersticial (NI fatal (1,2. La patogénesis de la NI causada por CMV no es clara aún, pero las observaciones clínicas en el hombre y los estudios con modelos murinos permiten pensar en ella como una alteración inmunopatológica. El análisis de tales conceptos es el objetivo de esta revisión.

  8. Clinical Outcome of Cytomegalovirus Infection on Low Birth Weight Infants

    Directory of Open Access Journals (Sweden)

    Ali Usman

    2014-09-01

    reactive only in 12% cases but after 3 weeks increased up to 32%. During neonatal up to infancy period, the prevalence of CMV infection in Bandung is high (12+32%:44% with long term sequelae which are serious and can be fatal. It is urgent and important to give information about this disease to new couples, every mother and healthcare providers in fetomaternal fields to prevent  CMV infection. Key words: CMV infection, long term sequelae, outcome   Abstract Cytomegalovirus (CMV adalah virus DNA dan termasuk dalam kelompok virus herpes. Virus ini hanya menyerang manusia dan infeksinya berlangsung lama. Penularan CMV pada janin/neonatus dapat melalui infeksi kongenital atau infeksi perinatal. Manifestasi Infeksi CMV pada janin terdiri dari dua bentuk yaitu manifestasi awal dan lanjut. Diagnosis infeksi CMV neonatal ditegakkan dengan tes serologis berdasarkan deteksi IgM CMV. Tujuan penelitian ini adalah menilai keluaran klinis infeksi CMV pada bayi berat lahir rendah dengan gejala sisa. Penelitian observasional telah dilakukan sejak Maret 2010 sampai dengan Desember 2011 di RS Advent dan RS Hermina Pasteur pada semua bayi berat lahir rendah (BBLR. Kriteria inklusi adalah semua BBLR yang lahir di kedua RS maupun merupakan pasien rujukan. Kriteria eksklusi adalah adanya kelainan kongenital mayor yang tidak berhubungan dengan infeksi CMV kongenital dan bayi yang meninggal dalam minggu pertama. Setiap bayi dilakukan pemeriksaan fisik dan laboratorium (hitung darah tepi, kadar glukosa dan kalsium, tes fungsi hati dilakukan pada bayi yang menderita hepatitis akut, pemeriksaan kadar IgG dan IgM CMV serial, USG kepala dan CT-scan/MRI kepala pada kasus hidrosefalus dan perdarahan intrakranial. Selama penelitian terdapat 50 kasus BBLR yang terdiri atas 41 bayi prematur, 30 bayi kecil masa kehamilan. Hepatitis akut ditemukan sebanyak 20% yang semuanya disertai peningkatan tes fungsi hati. Mikrosefali yang terjadi sampai usia 3 minggu sebanyak 8%. Dilatasi ventrikular lateralis

  9. Rapid detection of cytomegalovirus in bronchoalveolar lavage fluid and serum samples by polymerase chain reaction: correlation of virus isolation and clinical outcome for patients with human immunodeficiency virus infection

    DEFF Research Database (Denmark)

    Hansen, K K; Vestbo, Jørgen; Benfield, T;

    1997-01-01

    Bronchoalveolar lavage (BAL) fluids and serum samples from 153 patients with pulmonary symptoms who were infected with human immunodeficiency virus (HIV) and underwent BAL were examined for the presence of cytomegalovirus (CMV) by conventional culture and by polymerase chain reaction (PCR......) for detection of CMV DNA. PCR detected CMV more frequently than did cultures of BAL fluid (PCR of BAL fluid, 53%; PCR of serum, 40%; and culture, 30%). In a multivariate model, development of extrapulmonary CMV disease was predicted by the finding of CMV in BAL fluid by culture (relative risk [RR], 8.......0; confidence interval [CI], 3.8-16.8) or the finding of CMV DNA in serum (RR, 7.4; CI, 3.2-17.3) or BAL fluid (RR, 8.0; CI, 3.1-20.7) by PCR. Mortality was found to be similar for patients who did or did not have CMV detected by either culture or PCR. Detection of CMV DNA by PCR was a more rapid and sensitive...

  10. Rapid detection of cytomegalovirus in bronchoalveolar lavage fluid and serum samples by polymerase chain reaction: correlation of virus isolation and clinical outcome for patients with human immunodeficiency virus infection

    DEFF Research Database (Denmark)

    Hansen, K K; Vestbo, Jørgen; Benfield, T

    1997-01-01

    Bronchoalveolar lavage (BAL) fluids and serum samples from 153 patients with pulmonary symptoms who were infected with human immunodeficiency virus (HIV) and underwent BAL were examined for the presence of cytomegalovirus (CMV) by conventional culture and by polymerase chain reaction (PCR......) for detection of CMV DNA. PCR detected CMV more frequently than did cultures of BAL fluid (PCR of BAL fluid, 53%; PCR of serum, 40%; and culture, 30%). In a multivariate model, development of extrapulmonary CMV disease was predicted by the finding of CMV in BAL fluid by culture (relative risk [RR], 8.......0; confidence interval [CI], 3.8-16.8) or the finding of CMV DNA in serum (RR, 7.4; CI, 3.2-17.3) or BAL fluid (RR, 8.0; CI, 3.1-20.7) by PCR. Mortality was found to be similar for patients who did or did not have CMV detected by either culture or PCR. Detection of CMV DNA by PCR was a more rapid and sensitive...

  11. Evaluation of the AMPLICOR cytomegalovirus test with specimens from human immunodeficiency virus-infected subjects.

    Science.gov (United States)

    Boivin, G; Handfield, J; Toma, E; Murray, G; Lalonde, R; Tevere, V J; Sun, R; Bergeron, M G

    1998-09-01

    The AMPLICOR cytomegalovirus (CMV) test, a new qualitative assay for the detection of CMV DNA in plasma, was compared to conventional methods and quantitative PCR (Q-PCR) assays by using leukocytes and plasma from 179 blood samples from subjects with AIDS. For the diagnosis of CMV disease, cell-based assays such as a Q-PCR with polymorphonuclear leukocytes (Q-PCR-PMNL) and a pp65 antigenemia assay had the highest sensitivities but suffered from a lack of specificity. The best agreement between the results of the Q-PCR-PMNL assay and those of the AMPLICOR test was found when a threshold diagnostic value of 690 copies per 10(5) cells was selected for the Q-PCR-PMNL assay. In that context, the AMPLICOR CMV test had a sensitivity of 96.4% and a specificity of 95.3% when results were compared to results of the cell-based PCR assay. This threshold was close to the one described as associated with the best sensitivity and specificity for the diagnosis of CMV disease in a recently published study (4). Blood samples that tested positive by the Q-PCR-PMNL assay but negative by the AMPLICOR CMV test were associated with viral loads (mean, 785 copies, median, 96 copies per 10(5) leukocytes) lower than the viral loads of blood samples that tested positive by both assays (mean, 21,452 copies; median, 9,784 copies per 10(5) leukocytes) (P = 0.003). The AMPLICOR CMV test gave positive results at least 48 days before the development of symptomatic CMV disease in a longitudinal analysis of a limited subset of patients (n = 6) from whom sequential specimens were available for testing. In conclusion, the AMPLICOR CMV test is a very convenient assay combining rapidity, simplicity, and the possibility of batch testing. A positive result by this test seems particularly important since this implies, in most instances, the presence or the imminence of CMV disease, although a negative test result does not rule out disease.

  12. Molecular detection of cytomegalovirus, herpes simplex virus 2, human papillomavirus 16-18 in Turkish pregnants

    Directory of Open Access Journals (Sweden)

    Bedia Dinc

    2010-12-01

    Full Text Available OBJECTIVE: Human cytomegalovirus (CMV is the most common cause of viral intrauterine infections in the world. Herpes simplex virus type 2 (HSV-2 and human papillomavirus (HPV are the main agents of viral sexually transmitted diseases, which cause genital ulcers and genital warts, respectively. HPV infection has been linked to the majority of the anogenital malignancies. The aim of this study was to detect the existence of CMV, HSV-2 and HPV type 16-18 in Turkish pregnants by using sensitive molecular assays. METHODS: One hundred thirty-four women (18-41 years old; mean age ± SD: 27 ± 8 applied to outpatient clinic of Obstetrics and Gynecology, in between 18th - 22nd weeks of their pregnancy and a control group of 99 healthy women (15-39 years old; mean age ± SD: 24 ± 8 were included in the study. Cervical smear samples were used for DNA extraction. CMV, HSV-2 and HPV 16-18 detections were carried out by real time PCR and in house PCR method, respectively. RESULTS: Three patients (3/134; 2.2% were found to be positive for each HPV and HSV-2. Dual infection with HPV and HSV was found in just one patient. HPV 18 was detected in all positive samples. CMV was found to be positive in two patients (2/134; 1.4 %. CONCLUSION: HPV, HSV and CMV must be screened due to high prevalence of these viruses in pregnants by using sensitive molecular methods.

  13. Implementing neonatal screening for congenital cytomegalovirus: addressing the deafness of policy makers.

    Science.gov (United States)

    de Vries, Jutte J C; Vossen, Ann C T M; Kroes, Aloys C M; van der Zeijst, Bernard A M

    2011-01-01

    Congenital cytomegalovirus (CMV) infection is an important public health problem with approximately 7 in 1,000 newborns infected and consequently at risk for hearing impairment. Newborn hearing screening will fail to detect this hearing impairment in approximately half of the cases because late onset hearing loss is frequent. Hearing impairment has profound impact on cognitive and social development of children and their families, determining most of the disease burden of congenital CMV infection. The potential value of newborn screening for congenital CMV is increasingly discussed. To date, many experts acknowledge the benefit of antiviral treatment in the prevention of hearing deterioration in newborns with neurological symptoms, and the benefit of early identification of late-onset hearing impairment by means of extensive audiological follow up of infected infants. These opinions imply that the potential of newborn screening for CMV would lie in the identification of the large proportion of asymptomatic congenitally infected newborns at risk for developing late-onset hearing loss. Experience with postnatal antiviral treatment of symptomatic newborns is encouraging, but has not been studied in asymptomatic congenitally infected newborns. A large-scale study on the safety and effectiveness of combined screening and antiviral therapy for congenital CMV infection is the necessary next step to take and should not be delayed.

  14. Reversible silencing of cytomegalovirus genomes by type I interferon governs virus latency.

    Directory of Open Access Journals (Sweden)

    Franziska Dağ

    2014-02-01

    Full Text Available Herpesviruses establish a lifelong latent infection posing the risk for virus reactivation and disease. In cytomegalovirus infection, expression of the major immediate early (IE genes is a critical checkpoint, driving the lytic replication cycle upon primary infection or reactivation from latency. While it is known that type I interferon (IFN limits lytic CMV replication, its role in latency and reactivation has not been explored. In the model of mouse CMV infection, we show here that IFNβ blocks mouse CMV replication at the level of IE transcription in IFN-responding endothelial cells and fibroblasts. The IFN-mediated inhibition of IE genes was entirely reversible, arguing that the IFN-effect may be consistent with viral latency. Importantly, the response to IFNβ is stochastic, and MCMV IE transcription and replication were repressed only in IFN-responsive cells, while the IFN-unresponsive cells remained permissive for lytic MCMV infection. IFN blocked the viral lytic replication cycle by upregulating the nuclear domain 10 (ND10 components, PML, Sp100 and Daxx, and their knockdown by shRNA rescued viral replication in the presence of IFNβ. Finally, IFNβ prevented MCMV reactivation from endothelial cells derived from latently infected mice, validating our results in a biologically relevant setting. Therefore, our data do not only define for the first time the molecular mechanism of IFN-mediated control of CMV infection, but also indicate that the reversible inhibition of the virus lytic cycle by IFNβ is consistent with the establishment of CMV latency.

  15. Life-threatening intracranial bleeding in a newborn with congenital cytomegalovirus infection: late-onset neonatal hemorrhagic disease.

    Science.gov (United States)

    Dallar, Yildiz; Tiras, Ulku; Catakli, Tulin; Gulal, Gonul; Sayar, Yavuz; Selvar, Beray; Alioglu, Bulent

    2011-02-01

    The authors present a case of a 36-day-old infant with intracranial and intramuscular hemorrhage due to vitamin K deficiency bleeding, who received intramuscular vitamin K prophylaxis at birth. In this case, laboratory tests showed anemia, liver dysfunction with cholestasis, and coagulopathy, consistent with vitamin K deficiency abnormality. Serological analyses showed that cytomegalovirus immunoglobulin (Ig)M and IgG avidity were both positive. The infant was treated successfully with intravenous ganciclovir and blood products. This case suggests that it is imperative to meticulously investigate the etiology in neonates with late-onset hemorrhagic disease of the newborn. Cholestatic liver disease caused by congenital cytomegalovirus infection should be in mind in term infants who presented with late-onset hemorrhagic disease.

  16. Detection of donor-derived CMV-specific T cells in cerebrospinal fluid in a case of CMV meningoencephalitis after cord blood stem cell transplantation.

    Science.gov (United States)

    Ikegame, Kazuhiro; Kato, Ruri; Fujioka, Tatsuya; Okada, Masaya; Kaida, Katsuji; Ishii, Shinichi; Yoshihara, Satoshi; Inoue, Takayuki; Taniguchi, Kyoko; Tamaki, Hiroya; Soma, Toshihiro; Ogawa, Hiroyasu

    2013-02-01

    Cytomegalovirus (CMV) meningoencephalitis is a rather rare complication after allogeneic stem cell transplantation. We describe here the case of a 59-year-old man with acute myeloid leukemia who developed CMV meningoencephalitis after cord blood transplantation. The patient presented with a sudden onset of neurological symptoms, such as convulsion, on day 37. The analysis of cerebrospinal fluid (CSF) sample revealed an increase in the number of cells, which were of donor (cord blood) origin, consisting mainly of T cells. No bacteria were detected in the CSF sample. Real-time PCR analysis revealed that the CSF sample was positive for CMV, but was negative for HHV-6, adenovirus, or BK virus. The patient was diagnosed with CMV meningoencephalitis and received cidofovir. His neurological symptoms were gradually improved and completely disappeared by day 60. CMV-specific dextramer-positive CD8(+) T cells were detected in the peripheral blood and CSF samples, with the frequency being much higher in the CSF. To our knowledge, this is the first report on the appearance of CMV-specific T cells in CSF samples from a patient with CMV meningoencephalitis. Cord blood-derived CMV-specific T cells may develop early after transplantation, enter the intrathecal compartment, and likely contribute to the regulation of CMV-meningoencephalitis.

  17. Clinical evaluation of the Roche Elecsys CMV IgG Avidity assay.

    Science.gov (United States)

    Vauloup-Fellous, C; Lazzarotto, T; Revello, M G; Grangeot-Keros, L

    2014-08-01

    Congenital cytomegalovirus (CMV) infection has potentially severe consequences in newborns. The testing of pregnant women for CMV-specific antibodies may be useful for the identification of women at risk of transmitting the infection to the fetus. The determination of CMV IgG avidity helps to establish the timing of infection as IgG avidity matures during the course of infection. This study examines the performance of the Elecsys CMV IgG Avidity assay using preselected samples from patients at different phases of CMV infection. The Elecsys CMV IgG Avidity assay was tested at three sites using sequential samples from patients with recent primary CMV infection, as well as single samples from patients with recent primary or past CMV infection. The Elecsys assay discriminated well between early (low avidity) and late (high avidity) phases of infection in sequential serum samples. Overall, 98.8% of low-avidity samples corresponded to infection onset 90 days before sampling. The assay's sensitivity was 90-97%, with specificity ranging from 89 to 100%, depending on the consideration of gray-zone avidity values. Single samples from recent primary or past infection showed similar distributions of avidity results. The Elecsys CMV IgG Avidity assay results are in agreement with preselected samples from patients with primary or past CMV infection, showing that the test is an adequate predictor of the phase of infection.

  18. Cyclic cidofovir (cHPMPC prevents congenital cytomegalovirus infection in a guinea pig model

    Directory of Open Access Journals (Sweden)

    McGregor Alistair

    2006-03-01

    Full Text Available Abstract Background Congenital cytomegalovirus (CMV infection is a major public health problem. Antiviral therapies administered during pregnancy might prevent vertical CMV transmission and disease in newborns, but these agents have not been evaluated in clinical trials. The guinea pig model of congenital CMV infection was therefore used to test the hypothesis that antiviral therapy, using the agent agent cyclic cidofovir (cHPMPC, could prevent congenital CMV infection. Results Pregnant outbred Hartley guinea pigs were challenged in the early-third trimester with guinea pig CMV (GPCMV and treated with placebo, or the antiviral agent, cyclic cidofovir. To optimize detection of vertical infection, an enhanced green fluorescent protein (eGFP-tagged virus was employed. Compared to placebo, cyclic cidofovir-treated dams and pups had reduced mortality following GPCMV challenge. The magnitude of GPCMV-induced maternal and fetal mortality in this study was reduced from 5/25 animals in the placebo group to 0/21 animals in the treatment group (p = 0.05, Fisher's exact test. By viral culture assay, antiviral therapy was found to completely prevent GPCMV transmission to the fetus. In control pups, 5/19 (26% were culture-positive for GPCMV, compared to 0/16 of pups in the cyclic cidofovir treatment group (p Conclusion Antiviral therapy with cyclic cidofovir improves pregnancy outcomes in guinea pigs, and eliminates congenital CMV infection, following viral challenge in the third trimester. This study also demonstrated that an eGFP-tagged recombinant virus, with the reporter gene inserted into a dispensable region of the viral genome, retained virulence, including the potential for congenital transmission, facilitating tissue culture-based detection of congenital infection. These observations provide support for clinical trials of antivirals for reduction of congenital CMV infection.

  19. Cytomegalovirus Pneumonia in Patients with Rheumatic Diseases After Immunosuppressive Therapy: A Single Center Study in China

    Directory of Open Access Journals (Sweden)

    Yu Xue

    2016-01-01

    Results: One hundred and forty-two patients had positive CMV viral load tests. Of these 142 patients, 73 patients with CMV pneumonia were regarded as symptomatic, and the other 69 were asymptomatic. The symptomatic group received higher doses of prednisolone (PSL and more frequently immunosuppressants than the asymptomatic group (P 1.75 × 104 copies/ml. Lymphopenia (especially CD4+ T-cells, presence of symptoms, and other infections, especially fungal infection, are significant risk factors for poor outcome, and a higher PSL dosage combined with immunosuppressants may predict CMV pneumonia.

  20. Early cytomegalovirus reactivation remains associated with increased transplant-related mortality in the current era: a CIBMTR analysis.

    Science.gov (United States)

    Teira, Pierre; Battiwalla, Minoo; Ramanathan, Muthalagu; Barrett, A John; Ahn, Kwang Woo; Chen, Min; Green, Jaime S; Saad, Ayman; Antin, Joseph H; Savani, Bipin N; Lazarus, Hillard M; Seftel, Matthew; Saber, Wael; Marks, David; Aljurf, Mahmoud; Norkin, Maxim; Wingard, John R; Lindemans, Caroline A; Boeckh, Michael; Riches, Marcie L; Auletta, Jeffery J

    2016-05-19

    Single-center studies have reported an association between early (before day 100) cytomegalovirus (CMV) reactivation and decreased incidence of relapse for acute myeloid leukemia (AML) following allogeneic hematopoietic cell transplantation. To substantiate these preliminary findings, the Center for International Blood and Marrow Transplant Research (CIBMTR) Database was interrogated to analyze the impact of CMV reactivation on hematologic disease relapse in the current era. Data from 9469 patients transplanted with bone marrow or peripheral blood between 2003 and 2010 were analyzed according to 4 disease categories: AML (n = 5310); acute lymphoblastic leukemia (ALL, n = 1883); chronic myeloid leukemia (CML, n = 1079); and myelodysplastic syndrome (MDS, n = 1197). Median time to initial CMV reactivation was 41 days (range, 1-362 days). CMV reactivation had no preventive effect on hematologic disease relapse irrespective of diagnosis. Moreover, CMV reactivation was associated with higher nonrelapse mortality [relative risk [RR] among disease categories ranged from 1.61 to 1.95 and P values from .0002 to <.0001; 95% confidence interval [CI], 1.14-2.61). As a result, CMV reactivation was associated with lower overall survival for AML (RR = 1.27; 95% CI, 1.17-1.38; P <.0001), ALL (RR = 1.46; 95% CI, 1.25-1.71; P <.0001), CML (RR = 1.49; 95% CI, 1.19-1.88; P = .0005), and MDS (RR = 1.31; 95% CI, 1.09-1.57; P = .003). In conclusion, CMV reactivation continues to remain a risk factor for poor posttransplant outcomes and does not seem to confer protection against hematologic disease relapse.

  1. Review and guidelines on the prevention, diagnosis and treatment of post-natal cytomegalovirus infection

    National Research Council Canada - National Science Library

    Alarcón Allen, A; Baquero-Artigao, F

    2011-01-01

    Postnatal cytomegalovirus (CMV) infection in the newborn can occur from exposure to maternal cervical secretions during birth, ingestion of breast milk, transfusion of blood products or transmission by body fluids of infected people...

  2. The spectrum of cranial ultrasound and magnetic resonance imaging abnormalities in congenital cytomegalovirus infection

    NARCIS (Netherlands)

    Vries, L.S. de; Gunardi, H.; Barth, P.G.; Bok, L.A.; Verboon-Maciolek, M.; Groenendaal, F.

    2004-01-01

    Congenital cytomegalovirus (CMV) infection can lead to severe neurological sequelae and (progressive) sensorineural deafness. Neonatal imaging data is mainly based on cranial ultrasound (US) and computed tomography (CT). The additional value of magnetic resonance imaging (MRI) was assessed in

  3. Lymphotropic Herpesvirus infection and malignant lymphoma, immunological aspects of cytomegalovirus and Epstein- Barr virus infections

    NARCIS (Netherlands)

    Napel, Christianus Hubertus Henricus ten

    1979-01-01

    In de voorgaande hoofdstukken van dit proefschrift werd de oorspronkelijke chronologische volgorde van het onderzoek aangehouden. Maar in dit deel wordt hiervan afgeweken en zullen de resultaten worden samengevat en besproken volgens onderstaande indeling: 1. Cytomegalovirus( CMV)-specifieke immuunr

  4. Disseminated cytomegalovirus infection complicating active treatment of systemic lupus erythematosus: an emerging problem.

    Science.gov (United States)

    Berman, N; Belmont, H M

    2017-04-01

    Patients with systemic lupus erythematosus (SLE) often require immunosuppression to induce remission of active disease exacerbations. Over the past two decades, treatment modalities for this condition have emerged leading to improved morbidity from disease related outcomes. However, as a result, infection risks and patterns have changed, leading to higher rates of opportunistic infections among this population. We report four cases of cytomegalovirus (CMV) in patients with SLE who received immunosuppressive therapy, including pulse steroids, antimetabolites such as mycophenolate mofetil, and alkylating agents such as cyclophosphamide. We propose that given the rise in prevalence of CMV, there is a need for appropriate screening for this opportunistic pathogen and studies to determine the risks and benefits of prophylactic or preemptive treatment for this virus.

  5. Genetic Influence on the Peripheral Blood CD4+ T-cell Differentiation Status in CMV Infection

    DEFF Research Database (Denmark)

    Goldeck, David; Larsen, Lisbeth Aagaard; Christiansen, Lene

    2016-01-01

    A latent infection with cytomegalovirus (CMV), a ubiquitous beta herpesvirus, is associated with an accumulation of late-differentiated memory T-cells, often accompanied by a reciprocal reduced frequency of early-differentiated cells (commonly also referred to as "naïve"). However, this impact...... heritability analysis confirmed a substantial contribution of genetics to the differentiation status of T-cells in CMV infection. The humoral (IgG) response to different CMV antigens also seems to be genetically influenced, suggesting that a similar degree of immune control of the virus in MZ twins might...

  6. Detection of human CMV PP65 protein in glioma brain tumors with immunohistochemistry method

    Directory of Open Access Journals (Sweden)

    MR. Jabbari

    2015-08-01

    Full Text Available Background: Human cytomegalovirus (HCMV may play a role in the development of glioma disease that is one of the most common brain tumors. Objective: The aim of this study was to detect human CMV in patients with glioma in Imam Khomeini hospital, Tehran. Methods: This experimental study was conducted on paraffin-embedded tumor samples of 18 patients referred to Imam Khomeini hospital in 2012. Immunohistochemistry (IHC was performed with monoclonal antibody specific for HCMV PP65 protein and the samples were assessed using a light microscope. Findings: Of 18 patients, 13 (72.2% were positive for HCMV PP65 protein and four of them expired. Conclusion: With regards to the results, more comprehensive studies are recommended for detection of HCMV in patients with glioma using different diagnostic methods.

  7. [Giant gastric ulcer by cytomegalovirus in infection VIH/SIDA].

    Science.gov (United States)

    Pérez-Pereyra, Julia; Morales, Domingo; Díaz, Ramiro; Yoza, Max; Frisancho, Oscar

    2008-01-01

    Cytomegalovirus infection is an important cause of morbidity in immunosupressed patients with Human Immunodeficiency Virus (HIV). In this paper we present a 43 years old man with renal failure under hemodialysis, several blood transfusions because of anemia and three months of disease characterized by epigastric pain, specially at nights, ameliorated with antacid drugs. Other symptoms were early satisfy, vomits and weigh loss (18Kg). At clinical exam, the patient was pallid, presented adenopathies at cervical and inguinal regions and had a pain at epigastric region in profound touch palpation. The most important exams were HB: 10mg/dl, CMV: 83.5, leukocytes 7000, lymphocytes: 1715, erythrocyte sedimentation rate 49mm/h, the venon test (-), and Giardia lamblia trophozoites in stools. The studies demonstrated the patient was seropositive for HIV and the tests for IgG CMV and IgG Herpes virus resulted seropositives too. At endoscopy the esophagus mucosa was covered by a white plaque which suggests candida infection. In the stomach, over the body gastric, we found a big and deep ulcerated lesion (45 x 41mm), with defined rims and white fund. Biopsy from the edges of the gastric ulcer had the characteristic CMV intranuclear and intracytoplasmic inclusions; we confirmed the diagnosis by immunohystochemistry. The patient receives ganciclovir an then HAART and is getting well.

  8. Colonic perforation in a patient with systemic lupus erythematosus accompanied by cytomegalovirus infection: A case report

    OpenAIRE

    Yuichi Tachikawa; Hiroaki Nozawa; Junichiro Tanaka; Takeshi Nishikawa; Toshiaki Tanaka; Tomomichi Kiyomatsu; Keisuke Hata; Kazushige Kawai; Shinsuke Kazama; Hironori Yamaguchi; Soichiro Ishihara; Eiji Sunami; Joji Kitayama; Madoka Fujisawa; Katutoshi Takahashi

    2016-01-01

    Introduction: Cytomegalovirus (CMV) infection of the gastrointestinal tract is an uncommon illness, but can be observed in immunocompromised patients. Systemic lupus erythematosus (SLE) patients are generally at high risk of CMV infection. Here we report a subacute progressive case of colitis in SLE accompanied by cytomegalovirus infection. Presentation of case: The patient, a 79-year-old woman, was hospitalized complaining of fever, polyarthritis, and skin ulcer that had lasted seven days...

  9. Screening, prevention, and treatment of congenital cytomegalovirus.

    Science.gov (United States)

    Johnson, Julie; Anderson, Brenna

    2014-12-01

    Congenital cytomegalovirus (CMV) is a leading cause of permanent disability in children. The main source of maternal infection is from contact with young children. Primary maternal infection is diagnosed with demonstration of seroconversion or a positive CMV IgM in combination with a low-avidity CMV IgG. Fetal infection may be diagnosed with amniotic fluid polymerase chain reaction and culture. CMV-specific hyperimmune globulin has shown promise as a possible means to prevent congenital infection; large randomized trials are ongoing. To date, the only effective means of prevention is through reducing exposure to the virus. Rates of maternal infection may be reduced through education regarding sources of infection and improved hygiene.

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

    Directory of Open Access Journals (Sweden)

    Tun NiNi

    2011-08-01

    Full Text Available Abstract 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 3 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 3 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.

  11. The level of C.pneumoniae, Cytomegalovirus, and H.pylori antibody in a patient with coronary heart disease

    Directory of Open Access Journals (Sweden)

    Dasnan Ismail

    2002-12-01

    Full Text Available At herosclerosis is still the chief cause of morbidity and mortality in developed nations. Even though in developed nations the modification of risk factors is able to reduce the prevalence rate of atherosclerosis, such reduction is starting to slow down. Such condition has stimulated researchers to identify environmental exposure, including infection, that can influence the process of atherosclerosis. This cross sectional study was conducted from March to August 1998, on 122 patients that clinically demonstrate coronary heart disease and have underwent cardiac catheterization, 92 males and 30 females with an average age of 55 years. Patients undergo clinical and laboratory evaluation (blood glucose, cholesterol, triglyceride, and antibody for C.pneumoniae. Cytomegalovirus, and H.pylori. We found a significant difference in cholesterol, triglyceride, and HDL levels in those with coronary stenosis and those without. However, we did not find a significant difference in the levels of C.pneumoniae, Cytomegalovirus, and H.pylori antibodies. This study is unable to conclude the influence of these antibodies on atherosclerosis, since in the non-stenosis group, we cannot eliminate the possibility of atherosclerosis, since the average age of study subject is 55 years. Studies on the interaction between infection and traditional risk factors as well as gender and nutrition is needed to find a clear answer of the influence of infection in atherosclerosis. (Med J Indones 2002; 11: 211-4Keywords: Level of C.pneumoniae, Cytomegalovirus, H.pylori antibody, coronary heart disease.

  12. Trends in the treatment of cytomegalovirus infection in oncohematological patients

    Directory of Open Access Journals (Sweden)

    D. N. Balashov

    2013-01-01

    Full Text Available Cytomegalovirus (CMV-related complications remain an extremely serious and urgent problem in immunocompromised patients. Ganciclovir (GCV is efficient for the treatment of CMV-infection, but myelotoxicity limits the possibilities of their application. In addition, prolonged or intermittent courses of antiviral drugs predispose to the development of CMV drug-resistant strains. Valganciclovir is a safe and effective alternative to intravenous GCV. Despite the well-spread application of effective methods of early detection and pre-emptive treatment, the issue of the control of CMV-infection is not resolved. High intensive immunoablative therapy (alemtuzumab, ATG, еtс. and hematopoietic stem cell transplantation (HSCT from alternative donors greatly increase the risk of life-threatening visceral CMV-infections in patients. Thereby, studies of new therapeutic approaches (for example, transfusion of CMV-specific T-cells are actually in process.

  13. Trends in the treatment of cytomegalovirus infection in oncohematological patients

    Directory of Open Access Journals (Sweden)

    D. N. Balashov

    2014-07-01

    Full Text Available Cytomegalovirus (CMV-related complications remain an extremely serious and urgent problem in immunocompromised patients. Ganciclovir (GCV is efficient for the treatment of CMV-infection, but myelotoxicity limits the possibilities of their application. In addition, prolonged or intermittent courses of antiviral drugs predispose to the development of CMV drug-resistant strains. Valganciclovir is a safe and effective alternative to intravenous GCV. Despite the well-spread application of effective methods of early detection and pre-emptive treatment, the issue of the control of CMV-infection is not resolved. High intensive immunoablative therapy (alemtuzumab, ATG, еtс. and hematopoietic stem cell transplantation (HSCT from alternative donors greatly increase the risk of life-threatening visceral CMV-infections in patients. Thereby, studies of new therapeutic approaches (for example, transfusion of CMV-specific T-cells are actually in process.

  14. Neurologic cytomegalovirus complications in patients with AIDS: retrospective review of 13 cases and review of the literature

    Directory of Open Access Journals (Sweden)

    Camila Almeida Silva

    2010-12-01

    Full Text Available Neurological disorders caused by Cytomegalovirus (CMV in patients with Acquired Immunodeficiency Syndrome (AIDS are rarely reported in the Highly Active Antiretroviral Therapy (HAART period. The objective of this study was to describe the main clinical and laboratory features of patients with CMV-related neurological complications in HIV-infected patients admitted to a referral center in São Paulo, Brazil. CMV disease requires the identification of the virus in the cerebrospinal fluid (CSF using Polymerase Chain Reaction (PCR. Thirteen cases were identified between January, 2004 and December, 2008. The median age of patients was 38 years and nine (69% were men. At admission all patients were aware of their HIV status and only four (31% patients were on HAART. Patients who were not on antiretroviral therapy before admission received HAART while inpatients. CMV disease was the first AIDS-defining illness in eight (62% patients. The neurologic syndromes identified were diffuse encephalitis (n = 7; 62%, polyradiculopathy (n = 7; 54%, focal encephalitis (rhombencephalitis (n = 1; 8%, and ventriculo-encephalitis (n = 1; 8%. Seven (54% patients presented extra-neural CMV disease and four (31% had retinitis. The median of CD4+ T-cell count was 13 cells/µL (range: 1-124 cells/µL. Overall in-hospital mortality was 38%. Eight patients used ganciclovir or foscarnet (in-hospital mortality: 50% and five patients used ganciclovir and foscarnet (in-hospital mortality: 20%. None of the patients fulfilled the diagnosis criteria of immune reconstitution inflammatory syndrome. Four patients were lost to follow-up, and three patients presented immune recovery and discontinued secondary prophylaxis. Although infrequent, distinct neurological syndromes caused by CMV continue to cause high mortality among AIDS patients. Survival depends upon the use of effective antiviral therapy against CMV and the early introduction of HAART.

  15. Molecular and Culture-Based Bronchoalveolar Lavage Fluid Testing for the Diagnosis of Cytomegalovirus Pneumonitis.

    Science.gov (United States)

    Tan, Susanna K; Burgener, Elizabeth B; Waggoner, Jesse J; Gajurel, Kiran; Gonzalez, Sarah; Chen, Sharon F; Pinsky, Benjamin A

    2016-01-01

    Background.  Cytomegalovirus (CMV) is a major cause of morbidity and mortality in immunocompromised patients, with CMV pneumonitis among the most severe manifestations of infection. Although bronchoalveolar lavage (BAL) samples are frequently tested for CMV, the clinical utility of such testing remains uncertain. Methods.  Retrospective analysis of adult patients undergoing BAL testing via CMV polymerase chain reaction (PCR), shell vial culture, and conventional viral culture between August 2008 and May 2011 was performed. Cytomegalovirus diagnostic methods were compared with a comprehensive definition of CMV pneumonitis that takes into account signs and symptoms, underlying host immunodeficiency, radiographic findings, and laboratory results. Results.  Seven hundred five patients underwent 1077 bronchoscopy episodes with 1090 BAL specimens sent for CMV testing. Cytomegalovirus-positive patients were more likely to be hematopoietic cell transplant recipients (26% vs 8%, P definition, the sensitivity and specificity of PCR, shell vial culture, and conventional culture were 91.3% and 94.6%, 54.4% and 97.4%, and 28.3% and 96.5%, respectively. Compared with culture, PCR provided significantly higher sensitivity and negative predictive value (P ≤ .001), without significantly lower positive predictive value. Cytomegalovirus quantitation did not improve test performance, resulting in a receiver operating characteristic curve with an area under the curve of 0.53. Conclusions.  Cytomegalovirus PCR combined with a comprehensive clinical definition provides a pragmatic approach for the diagnosis of CMV pneumonitis.

  16. Acute confusional state: A manifestation of toxoplasma and CMV co-infection in HIV patient

    Directory of Open Access Journals (Sweden)

    Waqas Jehangir

    2014-01-01

    Full Text Available Context: When dealing with a patient with HIV that presents with an altered mental status, there are various infections and disease etiologies a physician has to rule out that may play a role in complicating the inherent complex nature of HIV. Toxoplasma gondii (T. gondii and cytomegalovirus (CMV affect a large part of the world′s population and lead to a varied and broad symptomatology depending upon the severity of HIV, the CD4 count and how early the infection is diagnosed. Case Report: We report an HIV+ patient in his early 50s and with a low CD4 count that presented with severe lethargy and confusion. Imaging studies that were performed after stabilizing the patient revealed a ring-enhancing lesion in the brain and after further testing, a diagnosis of reactivated T. gondii with co-infection with CMV was made. Patients infected with T.gondii that are already immune-compromised deteriorate rapidly and the disease diagnosis poses several challenges. Conclusion: Clinicians have to be extremely careful about making a prompt diagnosis and initiate treatment without delay before the infection takes a deadly toll on the patient. Since our patient was not on the required prophylactic medication to prevent infection with T. gondii, it was imperative to start treatment in a timely manner and to monitor the patient for any further decline in functioning.

  17. A single-dose cytomegalovirus-based vaccine encoding tetanus toxin fragment C induces sustained levels of protective tetanus toxin antibodies in mice.

    Science.gov (United States)

    Tierney, Rob; Nakai, Toru; Parkins, Christopher J; Caposio, Patrizia; Fairweather, Neil F; Sesardic, Dorothea; Jarvis, Michael A

    2012-04-26

    The current commercially available vaccine used to prevent tetanus disease following infection with the anaerobic bacterium Clostridium tetani is safe and effective. However, tetanus remains a major source of mortality in developing countries. In 2008, neonatal tetanus was estimated to have caused >59,000 deaths, accounting for 1% of worldwide infant mortality, primarily in poorer nations. The cost of multiple vaccine doses administered by injection necessary to achieve protective levels of anti-tetanus toxoid antibodies is the primary reason for low vaccine coverage. Herein, we show that a novel vaccine strategy using a cytomegalovirus (CMV)-based vaccine platform induces protective levels of anti-tetanus antibodies that are durable (lasting >13 months) in mice following only a single dose. This study demonstrates the ability of a 'single-dose' CMV-based vaccine strategy to induce durable protection, and supports the potential for a tetanus vaccine based on CMV to impact the incidence of tetanus in developing countries.

  18. THE STRATEGIES FOR PREVENTING AND TREATING INFECTION OF CYTOMEGALOVIRUS IN BONE MARROW TRANSPLANTATION

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Medović Raša

    2016-01-01

    Full Text Available Introduction. Infective mononucleosis is most commonly caused by Epstein-Barr virus (EBV, and in smaller percentage by cytomegalovirus (CMV. Objective. The aim of this paper was to determine the clinical and laboratory differences between EBV and CMV infectious mononucleosis in children. Methods. 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. Results. 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. Conclusion. 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.

  20. The time course of development and impact from viral resistance against ganciclovir in cytomegalovirus infection

    DEFF Research Database (Denmark)

    Cunha-Bang, C da; Kirkby, N; Sønderholm, M

    2013-01-01

    (Val)ganciclovir is used to treat cytomegalovirus (CMV) infection following solid organ (SOT) or hematopoietic stem cell (HSCT) transplantation. Treatment failures occur, but the contribution from 39 known ganciclovir-related mutations (GRMs) in the CMV-UL97 gene remains controversial. We propose...

  1. Investigation of the Role of the Cytomegalovirus as a Respiratory Pathogen in HIV-Infected Patients

    Directory of Open Access Journals (Sweden)

    Rafael E de la Hoz

    1996-01-01

    Full Text Available OBJECTIVE: To investigate the occurrence of cytomegalovirus (CMV pneumonitis in the setting of human immunodeficiency virus (HIV infection and whether the presence of CMV as copathogen is associated with increased clinical severity or short term mortality in patients with Pneumocystis carinii pneumonia.

  2. Maternal cytomegalovirus infection prevention: the role of Dutch primary care midwives.

    NARCIS (Netherlands)

    Pereboom, M.T.R.; Manniën, J.; Spelten, E.R.; Hutton, E.K.; Schellevis, F.G.

    2014-01-01

    Objective: to assess the knowledge of cytomegalovirus (CMV) infection among Dutch primary care midwives, and clinical approaches to informing women about CMV. Design: cross-sectional study, using self-administered questionnaires. Participants: 330 Dutch primary care midwives. Setting: primary midwif

  3. Ganciclovir and Foscarnet Therapy of Cytomegalovirus-Associated Meningoencephalitis in a Hemodialysis Patient With Liver Transplantation: Case Report.

    Science.gov (United States)

    Kang, G W; Hong, H L; Lee, I H; Ahn, K S; Kim, J D; Choi, D L

    2016-05-01

    Cytomegalovirus (CMV) infection in patients with liver transplantation (LT) remains a highly prevalent complication with a significant increase in morbidity and mortality. However, CMV-associated meningoencephalitis is rarely diagnosed, and treatment is very difficult. The aim of the present report is to review the experience of successful treatment with combined ganciclovir and foscarnet of CMV-associated meningoencephalitis refractory to ganciclovir alone in a hemodialysis (HD) patient after LT. A 54-year-old woman with end-stage renal disease on HD developed a seizure with loss of consciousness. She had received a liver transplant 4 months before. Blood CMV polymerase chain reaction was positive, and cerebrospinal fluid (CSF) analysis was compatible with viral meningitis. Brain magnetic resonance imaging (MRI) showed extensive dural thickening with enhancement and a round ring-like enhancement in the left centrum semiovale. She was diagnosed with CMV-associated meningoencephalitis. At that time, ganciclovir was started intravenously. After that, there were no improvements in mental state, CSF analysis, or brain MRI. Intravenous foscarnet at reduced dose was added to ganciclovir therapy. With combined ganciclovir and foscarnet, there was a slight improvement in her mental state and brain MRI.

  4. Strongyloides Hyperinfection Syndrome Combined with Cytomegalovirus Infection

    Science.gov (United States)

    Alsaeed, Mohammed; Ballool, Sulafa; Attia, Ashraf

    2016-01-01

    The mortality in Strongyloides hyperinfection syndrome (SHS) is alarmingly high. This is particularly common in bone marrow, renal, and other solid organ transplant (SOT) patients, where figures may reach up to 50–85%. Immunosuppressives, principally corticosteroids, are the primary triggering factor. In general, the clinical features of Strongyloides stercoralis hyperinfection are nonspecific; therefore, a high index of suspicion is required for early diagnosis and starting appropriate therapy. Although recurrent Gram-negative sepsis and meningitis have been previously reported, the combination of both cytomegalovirus (CMV) and strongyloidiasis had rarely been associated. We here describe a patient who survived SHS with recurrent Escherichia coli (E. coli) urosepsis and CMV infection. PMID:27703835

  5. Strongyloides Hyperinfection Syndrome Combined with Cytomegalovirus Infection

    Directory of Open Access Journals (Sweden)

    Fatehi Elnour Elzein

    2016-01-01

    Full Text Available The mortality in Strongyloides hyperinfection syndrome (SHS is alarmingly high. This is particularly common in bone marrow, renal, and other solid organ transplant (SOT patients, where figures may reach up to 50–85%. Immunosuppressives, principally corticosteroids, are the primary triggering factor. In general, the clinical features of Strongyloides stercoralis hyperinfection are nonspecific; therefore, a high index of suspicion is required for early diagnosis and starting appropriate therapy. Although recurrent Gram-negative sepsis and meningitis have been previously reported, the combination of both cytomegalovirus (CMV and strongyloidiasis had rarely been associated. We here describe a patient who survived SHS with recurrent Escherichia coli (E. coli urosepsis and CMV infection.

  6. CMV retinitis in China and SE Asia: the way forward

    Directory of Open Access Journals (Sweden)

    Heiden David

    2011-11-01

    Full Text Available Abstract AIDS-related CMV retinitis is a common clinical problem in patients with advanced HIV/AIDS in China and Southeast Asia. The disease is causing blindness, and current clinical management, commonly characterized by delayed diagnosis and inadequate treatment, results in poor clinical outcomes: 21% - 36% of eyes with CMV retinitis are already blind at the time the diagnosis is first established by an ophthalmologist. CMV retinitis also identifies a group of patients at extraordinary risk of mortality, and the direct or indirect contribution of extra-ocular CMV disease to AIDS-related morbidity and mortality is currently unmeasured and clinically often overlooked. The obvious way to improve clinical management of CMV retinitis is to screen all patients with CD4 counts

  7. Cytomegalovirus-associated esophageal ulcer in an immunocompetent infant: When should ganciclovir be administered?

    Directory of Open Access Journals (Sweden)

    Hyo-Jeong Jang

    2012-12-01

    Full Text Available Cytomegalovirus (CMV-associated esophageal ulcer is rare in immunocompetent infants. The presence of inclusion bodies and immunohistochemical staining for CMV in biopsy specimens obtained during esophagogastroduodenoscopy (EGD indicate that such ulcers occur because of CMV infection. A 7-week-old female infant who experienced frequent vomiting and feeding intolerance was diagnosed with a massive CMV-associated ulcer in the distal esophagus. The ulcer improved after conservative treatment using proton-pump inhibitors; however, ganciclovir was not administered. In a follow-up EGD biopsy specimen, no CMV inclusion bodies were present, and immunohistochemical staining results for this virus were negative. The presence of CMV inclusion bodies indicates active viral replication. If persistent inclusion bodies or positive immunohistochemical staining for CMV is observed in follow-up biopsy specimens, ganciclovir may be used to treat CMV-associated esophageal ulcers.

  8. Cytomegalovirus Reactivation in Adult Recipients of Autologous Stem Cell Transplantation: a Single Center Experience

    OpenAIRE

    Al-Rawi, Omar; Abdel-Rahman, Fawzi; Al-Najjar, Rula; Abu-Jazar, Husam; Salam, Mourad; Saad, Mustafa

    2015-01-01

    Introduction Cytomegalovirus (CMV) reactivation and infection are well-recognized complications after allogeneic stem cell transplantation (SCT). Only a few studies have addressed CMV reactivation after autologous SCT (ASCT). Methods We retrospectively reviewed medical records of 210 adult patients who underwent ASCT for lymphoma or multiple myeloma (MM) at a single center from January 1st, 2007 until December 31st, 2012. All patients were monitored weekly with CMV antigenemia test till day 4...

  9. Cytomegalovirus Infection following Kidney Transplantation: a Multicenter Study of 3065 Cases

    OpenAIRE

    2012-01-01

    Background: Cytomegalovirus (CMV) infection is a common complication following kidney transplantation. Objective: To assess the incidence and risk factors of CMV infection among renal transplant recipients. Methods: In a retrospective multicenter study, 3065 renal transplant recipients from 17 transplant centers of Iran were studied between April 2008 and January 2011. Kidney transplant patients were routinely monitored by sequential blood samples drawn for use in the CMV-pp65 antigenemia ass...

  10. Endoscopic diagnosis of cytomegalovirus gastritis after allogeneic hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    Yasuo; Kakugawa; Masahiro; Kami; Takahisa; Matsuda; Yutaka; Saito; Sung-Won; Kim; Takahiro; Fukuda; Shin-ichiro; Mori; Tadakazu; Shimoda; Ryuji; Tanosaki; Daizo; Saito

    2010-01-01

    AIM:To clarify the endoscopic and clinical findings of cytomegalovirus(CMV) gastritis after allogeneic hematopoietic stem cell transplantation(allo-SCT).METHODS:Between 1999 and 2005,523 patients underwent allo-SCT at our hospital,and 115 of these patients with gastrointestinal symptoms underwent esophagogastroduodenoscopy.RESULTS:CMV gastritis was diagnosed pathologically in seven patients(1.3%) with the other 108 patients serving as controls.Six of the seven patients developed positive CMV antigenemia,and...

  11. Transient Antiphospholipid Syndrome Associated with Primary Cytomegalovirus Infection: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Tsuyoshi Nakayama

    2014-01-01

    Full Text Available Viral infection is known to induce transient autoimmunity in humans. Acute cytomegalovirus (CMV infection is implicated in occasional thrombosis formation. We here, for the first time, report a 19-year-old female who had an acute CMV infection, leading to a deep venous thrombosis and a pulmonary embolism along with transient appearance of lupus anticoagulant. The pathological role of antiphospholipid antibodies in CMV-mediated thrombosis is discussed.

  12. Cytomegalovirus in pregnancy and the neonate [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Vincent C. Emery

    2017-02-01

    Full Text Available Congenital cytomegalovirus (CMV remains a leading cause of disability in children. Understanding the pathogenesis of infection from the mother via the placenta to the neonate is crucial if we are to produce new interventions and provide supportive mechanisms to improve the outcome of congenitally infected children. In recent years, some major goals have been achieved, including the diagnosis of primary maternal CMV infection in pregnant women by using the anti-CMV IgG avidity test and the diagnosis and prognosis of foetal CMV infection by using polymerase chain reaction real-time tests to detect and quantify the virus in amniotic fluid. This review summarises recent advances in our understanding and highlights where challenges remain, especially in vaccine development and anti-viral therapy of the pregnant woman and the neonate. Currently, no therapeutic options during pregnancy are available except those undergoing clinical trials, whereas valganciclovir treatment is recommended for congenitally infected neonates with moderately to severely symptomatic disease.

  13. Dynamics of Persistent Oral Cytomegalovirus Shedding During Primary Infection in Ugandan Infants.

    Science.gov (United States)

    Mayer, Bryan T; Matrajt, Laura; Casper, Corey; Krantz, Elizabeth M; Corey, Lawrence; Wald, Anna; Gantt, Soren; Schiffer, Joshua T

    2016-12-01

    Cytomegalovirus (CMV) infection occurs frequently in young children, who, when infected, are then a major source of transmission. Oral CMV shedding by 14 infants with primary infection was comprehensively characterized using quantitative polymerase chain reaction weekly for ≥9 months. Three phases of oral shedding were identified: expansion, transition, and clearance. Viral expansion occurred over a median of 7 weeks, with a median doubling time of 3 days. During the transition phase, expansion slowed over a median of 6 weeks before peak viral load was reached. Clearance was slow (22-day median half-life), and shedding did not resolve during observation for any infant. Mathematical modeling demonstrated that prolonged oral CMV expansion is explained by a low within-host reproduction number (median, 1.63) and a delayed immune response that only decreases the infected cell half-life by 44%. Thus, the prolonged oral CMV shedding observed during primary infection can be explained by slow viral expansion and inefficient immunologic control. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  14. Coexisting cytomegalovirus infection in immunocompetent patients with Clostridium difficile colitis.

    Science.gov (United States)

    Chan, Khee-Siang; Lee, Wen-Ying; Yu, Wen-Liang

    2016-12-01

    Cytomegalovirus (CMV) colitis usually occurs in immunocompromised patients with human immunodeficiency virus infection, organ transplantation, and malignancy receiving chemotherapy or ulcerative colitis receiving immunosuppressive agents. However, CMV colitis is increasingly recognized in immunocompetent hosts. Notably, CMV colitis coexisting with Clostridium difficile infection (CDI) in apparently healthy individuals has been published in recent years, which could result in high morbidity and mortality. CMV colitis is a rare but possible differential diagnosis in immunocompetent patients with abdominal pain, watery, or especially bloody diarrhea, which could be refractory to standard treatment for CDI. As a characteristic of CDI, however, pseudomembranous colitis may be only caused by CMV infection. Real-time CMV-polymerase chain reaction (PCR) for blood and stool samples may be a useful and noninvasive diagnostic strategy to identify CMV infection when treatment of CDI eventually fails to show significant benefits. Quantitative CMV-PCR in mucosal biopsies may increase the diagnostic yield of traditional histopathology. CMV colitis is potentially life-threatening if severe complications occur, such as sepsis secondary to colitis, massive colorectal bleeding, toxic megacolon, and colonic perforation, so that may necessitate pre-emptive antiviral treatment for those who are positive for CMV-PCR in blood and/or stool samples while pending histological diagnosis.

  15. Effect of combination antiretroviral therapy on cytomegalovirus retinitis

    Directory of Open Access Journals (Sweden)

    Banker Alay

    2002-01-01

    Full Text Available Purpose: To study the various changes in the course of cytomegalovirus (CMV retinitis following combination antiretroviral treatment. Methods: Combination antiretroviral treatment was given to 12 patients with active CMV retinitis following which all anti-CMV medications were discontinued once the CD4 cell counts were> 100/mm3 for 3 months. Results: The median CD4 cell count increased from 36.5/mm3 (range, 3-74/mm3 at baseline to 175.5/mm3 (range, 97-410/mm3 at 3 months. No patient had reactivation of CMV retinitis or developed extraocular CMV infection during median follow-up of 16.7 months. In one patient with peripheral active CMV retinitis, the retinitis resolved completely and remained so throughout the follow-up period without specific anti-CMV treatment. Five (41.7% patients had immune recovery vitritis. Conclusion: Patients receiving combination antiretroviral treatment following treatment for CMV retinitis have better control of CMV retinitis but immune recovery vitritis is a common sequelae. Reactivation of CMV retinitis is common in patients who discontinue combination antiretroviral treatment

  16. Congenital Cytomegalovirus Infection and Permanent Hearing Loss in Rural North Indian Children.

    Science.gov (United States)

    Dar, Lalit; Namdeo, Divya; Kumar, Pankaj; Thakar, Alok; Kant, Shashi; Rai, Sanjay; Singh, Pawan K; Kabra, Madhulika; Fowler, Karen B; Boppana, Suresh B

    2017-07-01

    Congenital cytomegalovirus infection (cCMV) is a leading nongenetic cause of permanent congenital or early-onset hearing loss (PCEHL). Although cCMV rates are high despite near-universal seroimmunity, the contribution of cCMV to PCEHL in the developing world is unclear. Neonates at a rural North Indian hospital were screened for cCMV by saliva polymerase chain reaction and hearing by distortion-product otoacoustic emission testing. Cytomegalovirus (CMV)-positive infants and those not passing newborn hearing screening (NHS) were evaluated by auditory brainstem response to confirm PCEHL. Infants with cCMV and those with PCEHL were tested for mutations within the GJB2 gene. Of the 1720 infants screened, 40 (2.3%) did not pass NHS and 20 (1.2%) were CMV positive. Auditory brainstem evoked response testing confirmed unilateral or bilateral PCEHL in 11 (0.64%) children who either did not pass NHS or CMV positive. PCEHL was 20-fold higher in neonates with cCMV (2/20, 10%) than those without (9/1700, 0.5%; P connexin 26 mutations. PCEHL incidence is high in India, with cCMV contributing significantly despite near-universal seroimmunity. Our findings also demonstrate the feasibility and the utility of simultaneous newborn screening for both cCMV and hearing loss in a resource-limited setting.

  17. Definitions of Cytomegalovirus Infection and Disease in Transplant Patients for Use in Clinical Trials

    DEFF Research Database (Denmark)

    Ljungman, Per; Boeckh, Michael; Hirsch, Hans H

    2017-01-01

    . Since then, there have been major developments in its diagnosis and management. Therefore, the CMV Drug Development Forum consisting of scientists, clinicians, regulators, and industry representatives has produced an updated version incorporating recent knowledge with the aim to support clinical......, and collaborative efforts between scientists, regulators, and industry can provide a platform for this work....

  18. Congenital CMV infection: prevalence in newborns and the impact on hearing deficit.

    Science.gov (United States)

    Engman, Mona-Lisa; Malm, Gunilla; Engstrom, Lotta; Petersson, Karin; Karltorp, Eva; Tear Fahnehjelm, Kristina; Uhlen, Inger; Guthenberg, Claes; Lewensohn-Fuchs, Ilona

    2008-01-01

    Congenital cytomegalovirus (CMV) infection is asymptomatic in 90% of infected newborns but approximately 10-20% of these infants are at risk of developing sequelae later, mostly hearing deficit. The aims of the study were to investigate the prevalence of congenital CMV infection in a Swedish population of newborns and investigate the relative risk of hearing deficit in newborns with congenital CMV infection. The dried blood spot (DBS) samples of 6060 newborns in southern Stockholm during 12 months (October 2003-June 2004; August 2004-October 2004) were analysed for CMV DNA by TaqMan based real-time PCR. Hearing deficit was assessed by otoacoustic emission (OAE) within a newborn screening programme. 12 infants out of 6060 or 0.2% (95% CI 0.1-0.3%) had congenital CMV infection. One boy among the 12 infected infants had unilateral hearing loss, indicating that the risk of hearing loss is greatly increased (about 20 times) in CMV infected infants. No child developed ocular complications such as chorioretinopathy during 3 y of follow-up. Congenital CMV has an impact on child health but can easily be overlooked due to lack of signs in the neonatal period. Surveillance for congenital CMV is important in addition to programmes for prevention and treatment.

  19. Early cytomegalovirus reactivation remains associated with increased transplant-related mortality in the current era : a CIBMTR analysis

    NARCIS (Netherlands)

    Teira, Pierre; Battiwalla, Minoo; Ramanathan, Muthalagu; Barrett, A John; Ahn, Kwang Woo; Chen, Min; Green, Jaime S; Saad, Ayman; Antin, Joseph H; Savani, Bipin N; Lazarus, Hillard M; Seftel, Matthew; Saber, Wael; Marks, David; Aljurf, Mahmoud; Norkin, Maxim; Wingard, John R; Lindemans, Caroline A; Boeckh, Michael; Riches, Marcie L; Auletta, Jeffery J

    2016-01-01

    Single-center studies have reported an association between early (before day 100) cytomegalovirus (CMV) reactivation and decreased incidence of relapse for acute myeloid leukemia (AML) following allogeneic hematopoietic cell transplantation. To substantiate these preliminary findings, the Center for

  20. Observational study to assess pregnant women’s knowledge and behaviour to prevent toxoplasmosis, listeriosis and cytomegalovirus.

    NARCIS (Netherlands)

    Pereboom, M.T.R.; Manniën, J.; Spelten, E.R.; Schellevis, F.G.; Hutton, E.K.

    2013-01-01

    Background: Toxoplasmosis, listeriosis and cytomegalovirus (CMV) can negatively affect pregnancy outcomes, but can be prevented by simple precautions of pregnant women. Literature suggests that pregnant women are not always adequately informed by their care provider about preventable infectious dise

  1. The association of killer cell immunoglobulin like receptor gene polylmorphism with cytomegalovirus infection after hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    吴小津

    2013-01-01

    Objective To explore the influence of the killer cell immunoglobulin like receptor(KIR)gene polymorphism on cytomegalovirus(CMV)infection and pathogenesis after hematopoietic stem cell transplantation(HSCT)

  2. Early cytomegalovirus reactivation remains associated with increased transplant-related mortality in the current era : a CIBMTR analysis

    NARCIS (Netherlands)

    Teira, Pierre; Battiwalla, Minoo; Ramanathan, Muthalagu; Barrett, A John; Ahn, Kwang Woo; Chen, Min; Green, Jaime S; Saad, Ayman; Antin, Joseph H; Savani, Bipin N; Lazarus, Hillard M; Seftel, Matthew; Saber, Wael; Marks, David; Aljurf, Mahmoud; Norkin, Maxim; Wingard, John R; Lindemans, Caroline A; Boeckh, Michael; Riches, Marcie L; Auletta, Jeffery J

    2016-01-01

    Single-center studies have reported an association between early (before day 100) cytomegalovirus (CMV) reactivation and decreased incidence of relapse for acute myeloid leukemia (AML) following allogeneic hematopoietic cell transplantation. To substantiate these preliminary findings, the Center for

  3. Observational study to assess pregnant women’s knowledge and behaviour to prevent toxoplasmosis, listeriosis and cytomegalovirus.

    NARCIS (Netherlands)

    Pereboom, M.T.R.; Manniën, J.; Spelten, E.R.; Schellevis, F.G.; Hutton, E.K.

    2013-01-01

    Background: Toxoplasmosis, listeriosis and cytomegalovirus (CMV) can negatively affect pregnancy outcomes, but can be prevented by simple precautions of pregnant women. Literature suggests that pregnant women are not always adequately informed by their care provider about preventable infectious

  4. SUPERIOR MESENTERIC VEIN THROMBOSIS AND CYTOMEGALOVIRUS: A DIAGNOSTIC DILEMMA. A CASE REPORT AND REVIEW OF THE LITERATURE.

    Directory of Open Access Journals (Sweden)

    Vincenzo Davide Palumbo

    2014-04-01

    Full Text Available Superior mesenteric vein thrombosis (SMVT is a rare condition, usually caused by infections, intra-abdominal inflammatory diseases, portal hypertension, hypercoagulable states, or contraceptive therapy. Due to its vague symptomatology, SMVT is often diagnosed only after an abdominal contrast-enhanced computed tomography (CT scan. In this article, we present a case of SMVT in a patient with a history of contraceptive drug use and a recent cytomegalovirus infection. A 36-year-old female was admitted to our department with the clinical symptoms of an acute appendicitis. The patient was a smoker and had been using hormonal contraceptives for over a year. Surgery was deemed the best course of action. Before the operation, blood tests showed a mild lymphocytosis and altered liver enzyme levels, while coagulation values were normal. A contrast-enhanced CT scan revealed a complete superior mesenteric vein thrombosis without signs of bowel ischemia. Anticoagulants were immediately administered. A thrombophilia panel did not highlight any noteworthy elements. Cytomegalovirus (CMV tests resulted positive. Since CMV is a rare, but potentially significant cause or precipitating factor for thrombosis in immunocompetent hosts, all patients with an unexplained fever and seemingly spontaneous thrombosis should be screened for CMV infection.

  5. Rapid genotyping of cytomegalovirus in dried blood spots by multiplex real-time PCR assays targeting the envelope glycoprotein gB and gH genes.

    Science.gov (United States)

    de Vries, Jutte J C; Wessels, Els; Korver, Anna M H; van der Eijk, Annemiek A; Rusman, Lisette G; Kroes, Aloys C M; Vossen, Ann C T M

    2012-02-01

    Genotyping of cytomegalovirus (CMV) is useful to examine potential differences in the pathogenicity of strains and to demonstrate coinfection with multiple strains involved in CMV disease in adults and congenitally infected newborns. Studies on genotyping of CMV in dried blood spots (DBS) are rare and have been hampered by the small amount of dried blood available. In this study, two multiplex real-time PCR assays for rapid gB and gH genotyping of CMV in DBS were developed. Validation of the assays with 39 CMV-positive plasma samples of transplant recipients and 21 urine specimens of congenitally infected newborns was successful in genotyping 100% of the samples, with gB1 and gB3 being the most prevalent genotypes. Multiple gB and gH genotypes were detected in 36% and 33% of the plasma samples, respectively. One urine sample from a newborn with symptomatic congenital CMV was positive for gB1 and gB2. DBS of congenitally infected newborns (n = 41) were tested using 9 μl of dried blood, and genotypes were detected in 81% (gB) and 73% (gH) of the samples, with gB3 being the most prevalent genotype. No clear association of specific genotypes with clinical outcome was observed. In conclusion, the CMV gB and gH PCR assays were found to be rapid, sensitive for detecting mixed infections, and suitable for direct usage on DBS. These assays are efficient tools for genotyping of CMV in DBS of congenitally infected newborns.

  6. Murine model for congenital CMV infection and hearing impairment

    Directory of Open Access Journals (Sweden)

    Tao Liu

    2011-02-01

    Full Text Available Abstract Background Congenital cytomegalovirus (CMV infection is the leading cause of sensorineural hearing loss (SNHL, and SNHL is the most frequent sequela of congenital CMV infection. But the pathogenic mechanism remains unknown, and there is no ideal CMV intrauterine infection animal model to study the mechanisms by which SNHL develops. Methods We established the congenital murine cytomegalovirus (MCMV infection model by directly injecting the virus into the placenta on day 12.5 of gestation. Then, we observed the development and the MCMV congenital infection rate of the fetuses on the day they were born. Furthermore, we detected the auditory functions, the conditions of the MCMV infection, and the histological change of the inner ears of 28-day-old and 70-day-old offspring. Results Both the fetal loss rate and the teratism rate of offspring whose placentas were inoculated with MCMV increased, and their body length, head circumference, and weight decreased. The hearing level of offspring both decreased at both 28- and 70-days post birth; the 70-day-old mice developed lower hearing levels than did the 28-day old mice. No significant inflammatory changes in the cochleae of the mice were observed. MCMV DNA signals were mainly detected in the spiral ganglion neurons and the endolymph area, but not in the perilymph area. The number of neurons decreased, and their ultrastructures changed. Moreover, with age, the number of neurons dramatically decreased, and the ultrastructural lesions of neurons became much more severe. Conclusions The results suggest that the direct injection of MCMV into the placenta may efficiently cause fetal infection and disturb the intrauterine development of the fetus, and placental inoculation itself has no obvious adverse effects on offspring. The reduction in the number of spiral ganglion neurons and the ultrastructural lesions of the neurons may be the major cause of congenital CMV infection-induced progressive SNHL.

  7. Mutual Interference between Cytomegalovirus and Reconstitution of Protective Immunity after Hematopoietic Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Matthias J. Reddehase

    2016-08-01

    Full Text Available Hematopoietic cell transplantation (HCT is a therapy option for aggressive forms of hematopoietic malignancies that are resistant to standard antitumoral therapies. Hematoablative treatment preceding HCT, however, opens a ‘window of opportunity’ for latent cytomegalovirus (CMV by releasing it from immune control with the consequence of reactivation of productive viral gene expression and recurrence of infectious virus. A ‘window of opportunity’ for the virus represents a ‘window of risk’ for the patient. In the interim between HCT and reconstitution of antiviral immunity, primarily mediated by CD8+ T cells, initially low amounts of reactivated virus can expand exponentially, disseminate to essentially all organs, and cause multiple organ CMV disease, with interstitial pneumonia (CMV-IP representing the most severe clinical manifestation. Here I will review predictions originally made in the mouse model of experimental HCT and murine CMV infection, some of which have already paved the way to translational preclinical research and promising clinical trials of a pre-emptive cytoimmunotherapy of human CMV disease. Specifically, the mouse model has been pivotal in providing ‘proof of concept’ for preventing CMV disease after HCT by adoptive transfer of preselected, virus epitope-specific effector and memory CD8+ T cells bridging the critical interim. CMV, however, is not a ‘passive antigen’ but is a pathogen that actively interferes with the reconstitution of protective immunity by infecting bone marrow stromal cells that otherwise form niches for hematopoiesis by providing the structural microenvironment and by producing hematopoietically active cytokines, the hemopoietins. Depending on the precise conditions of HCT, reduced homing of transplanted hematopoietic stem- and progenitor cells to infected bone marrow stroma and impaired colony growth and lineage differentiation can lead to ‘graft failure’. In consequence

  8. Cytomegalovirus immune evasion of myeloid lineage cells.

    Science.gov (United States)

    Brinkmann, Melanie M; Dağ, Franziska; Hengel, Hartmut; Messerle, Martin; Kalinke, Ulrich; Čičin-Šain, Luka

    2015-06-01

    Cytomegalovirus (CMV) evades the immune system in many different ways, allowing the virus to grow and its progeny to spread in the face of an adverse environment. Mounting evidence about the antiviral role of myeloid immune cells has prompted the research of CMV immune evasion mechanisms targeting these cells. Several cells of the myeloid lineage, such as monocytes, dendritic cells and macrophages, play a role in viral control, but are also permissive for CMV and are naturally infected by it. Therefore, CMV evasion of myeloid cells involves mechanisms that qualitatively differ from the evasion of non-CMV-permissive immune cells of the lymphoid lineage. The evasion of myeloid cells includes effects in cis, where the virus modulates the immune signaling pathways within the infected myeloid cell, and those in trans, where the virus affects somatic cells targeted by cytokines released from myeloid cells. This review presents an overview of CMV strategies to modulate and evade the antiviral activity of myeloid cells in cis and in trans.

  9. A cytomegalovirus-based vaccine provides long-lasting protection against lethal Ebola virus challenge after a single dose.

    Science.gov (United States)

    Tsuda, Yoshimi; Parkins, Christopher J; Caposio, Patrizia; Feldmann, Friederike; Botto, Sara; Ball, Susan; Messaoudi, Ilhem; Cicin-Sain, Luka; Feldmann, Heinz; Jarvis, Michael A

    2015-05-01

    Ebola virus (Zaire ebolavirus; EBOV) is a highly lethal hemorrhagic disease virus that most recently was responsible for two independent 2014 outbreaks in multiple countries in Western Africa, and the Democratic Republic of the Congo, respectively. Herein, we show that a cytomegalovirus (CMV)-based vaccine provides durable protective immunity from Ebola virus following a single vaccine dose. This study has implications for human vaccination against ebolaviruses, as well as for development of a 'disseminating' vaccine to target these viruses in wild African great apes.

  10. Does cytomegalovirus predict a poor prognosis in Pneumocystis carinii pneumonia treated with corticosteroids? A note for caution

    DEFF Research Database (Denmark)

    Jensen, A M; Lundgren, Jens Dilling; Benfield, T

    1995-01-01

    OBJECTIVE: To examine the importance of cytomegalovirus (CMV) in bronchoalveolar lavage (BAL) fluid of patients with HIV-associated Pneumocystis carinii pneumonia (PCP) treated with adjunctive corticosteroids (CS). DESIGN: Analysis of clinical data during a 5-year period. SETTING: Department...... of infectious diseases where clinical and paraclinical data on patients suspected of having PCP have been sampled prospectively. PATIENTS: 148 consecutive patients with a first episode of PCP in a 5-year period. MAIN OUTCOME MEASURE: Vital status 3 months after diagnosis of PCP. RESULTS: Patients with PCP...

  11. Immunomodulatory therapy of cytomegalovirus pneumonia after liver transplantation

    Institute of Scientific and Technical Information of China (English)

    WANG Gen-shu; CHEN Gui-hua; LU Min-qiang; YANG Yang; CAI Chang-jie; YI Hui-min; LI Hua; XU Chi; YI Shu-hong

    2006-01-01

    Background There has been increasing interest in the research into cytomegalovirus (CMV) pneumonia after liver transplantation (LT). This study was undertaken to investigate the immunomodulatory therapy of CMV pneumonia after LT.Methods Six patients with CMV pneumonia after LT from October 2003 to November 2005 were analyzed retrospectively. They were diagnosed according to clinical manifestations, chest X-ray findings and pathogenic changes and given comprehensive therapy including mainly immunomodulation therapy and anti-viral medication. At the early stage of CMV pneumonia, the dose of immunosuppressive agents was decreased or ceased, instead replaced by immunoenhancement therapy. During recovery period from CMV pneumonia, the dose of immunosuppressive agents was given again or enhanced, and immunoenhancement therapy was ceased.The liver function of the patients was monitored closely during the treatment.Results In this series, five patients were survived and one died. The liver function of the six patients remained normal during the treatment, and no episode of acute rejection took place.Conclusions Poor immunity is the pathogenic basis of CMV pneumonia after LT. At early stage of CMV pneumonia, the immunity of the patients should be enhanced, and during the recovery period from CMV pneumonia, immunosuppresants shoud be given again but immunoenhancement therapy ceased. Individualized immunomodulatory therapy is essential to the treatment of CMV pneumonia after LT.

  12. Foscarnet-Resistant Cytomegalovirus Esophagitis with Stricturing

    Directory of Open Access Journals (Sweden)

    Vinaya Gaduputi

    2013-01-01

    Full Text Available We report the case of a 52-year-old man with HIV-AIDS, non-complaint with highly active antiretroviral therapy, who presented with long-standing dysphagia. He was treated for three episodes of severe Candida esophagitis with fluconazole and later caspofungin due to poor response. In spite of the prolonged treatment courses the patient did not report an improvement in his symptoms. He was also concomitantly being treated for other opportunistic infections including cytomegalovirus (CMV retinitis with i.v. foscarnet for almost 2 months prior to the index presentation. Upper esophagogastroduodenoscopy revealed multiple superficial ulcers with stricturing. Bougie dilatation was attempted but failed. The biopsy specimens revealed multiple intracellular inclusion bodies pathognomonic of CMV infection. We aim to highlight the increasing resistance of CMV to conventional first-line antiviral agents such as foscarnet.

  13. Effects of Acute Cytomegalovirus Infection on Rat Islet Allograft Survival

    NARCIS (Netherlands)

    Smelt, M. J.; Faas, M. M.; Melgert, B. N.; de Vos, P.; de Haan, Bart; de Haan, Aalzen

    2011-01-01

    Transplantation of pancreatic islets is a promising therapy for the treatment of type 1 diabetes mellitus. However, long-term islet graft survival rates are still unsatisfactory low. In this study we investigated the role of cytomegalovirus (CMV) in islet allograft failure. STZ-diabetic rats receive

  14. Adjuvant and salvage therapy with leflunomide for recalcitrant cytomegalovirus infections in hematopoietic cell transplantation recipients: A case series.

    Science.gov (United States)

    El Chaer, Firas; Mori, Nobuyoshi; Shah, Dimpy; Oliver, Nora; Wang, Emily; Jan, Anna; Doan, Vi; Tverdek, Frank; Tayar, Jean; Ariza-Heredia, Ella; Chemaly, Roy F

    2016-11-01

    Cytomegalovirus (CMV) reactivation is a clinically significant complication in hematopoietic stem cell transplant (HCT) recipients. Alternative therapy for multidrug-resistant CMV is limited and often fails. Leflunomide has been used to treat resistant CMV infections, however, data on efficacy, safety, and guidance for therapeutic drug level monitoring are lacking. In this report, we describe 3 HCT recipients with multi-drug resistant CMV infections who received leflunomide as adjuvant and salvage therapy. The therapeutic effect of leflunomide as an anti-CMV agent based on virologic responses and therapeutic drug monitoring were evaluated.

  15. Impact of cytomegalovirus and grafts versus host disease on the dynamics of CD57+CD28-CD8+ T cells after bone marrow transplant

    Directory of Open Access Journals (Sweden)

    Ana Verena Almeida Mendes

    2008-01-01

    Full Text Available OBJECTIVES: The present study aimed to evaluate the dynamics of CD28 and CD57 expression in CD8+ T lymphocytes during cytomegalovirus viremia in bone marrow transplant recipients. METHODS: In a prospective study, blood samples were obtained once weekly once from 33 healthy volunteers and weekly from 33 patients. To evaluate the expression of CD57 and CD28 on CD8+ T lymphocytes, flow cytometry analysis was performed on blood samples for four months after bone marrow transplant, together with cytomegalovirus antigenemia assays. RESULTS: Compared to cytomegalovirus-seronegative healthy subjects, seropositive healthy subjects demonstrated a higher percentage of CD57+ and a lower percentage of CD28+ cells (p<0.05. A linear regression model demonstrated a continuous decrease in CD28+ expression and a continuous increase in CD57+ expression after bone marrow transplant. The occurrence of cytomegalovirus antigenemia was associated with a steep drop in the percentage of CD28+ cells (5.94%, p<0.01 and an increase in CD57+ lymphocytes (5.60%, p<0.01. This cytomegalovirus-dependent effect was for the most part concentrated in the allogeneic bone marrow transplant patients. The development of acute graft versus host disease, which occurred at an earlier time than antigenemia (day 26 vs. day 56 post- bone marrow transplant, also had an impact on the CD57+ subset, triggering an increase of 4.9% in CD57+ lymphocytes (p<0.05. CONCLUSION: We found continuous relative changes in the CD28+ and CD57+ subsets during the first 120 days post- bone marrow transplant, as part of immune system reconstitution and maturation. A clear correlation was observed between the expansion of the CD57+CD28-CD8+ T lymphocyte subpopulation and the occurrence of graft versus host disease and cytomegalovirus viremia.

  16. Clinical manifestations of cytomegalovirus-associated posterior uveitis and panuveitis in patients without human immunodeficiency virus infection

    NARCIS (Netherlands)

    K. Pathanapitoon (Kessara); N. Tesavibul (Nattaporn); P. Choopong (Pitipol); S. Boonsopon (Sutasinee); N. Kongyai (Natedao); S. Ausayakhun (Somsanguan); P. Kunavisarut (Paradee); A. Rothova (Aniki)

    2013-01-01

    textabstractImportance: Little attention has been paid to clinical features of cytomegalovirus (CMV) infections in individuals without human immunodeficiency virus (HIV). Objective: To describe the clinical manifestations and comorbidities of patients without HIV infection who have CMV-associated po

  17. Latent cytomegalovirus infection enhances anti-tumour cytotoxicity through accumulation of NKG2C+ NK cells in healthy humans

    NARCIS (Netherlands)

    Bigley, A.B.; Rezvani, K.; Shah, N.; Sekine, T.; Balneger, N.; Pistillo, M.; Agha, N.; Kunz, H.; O'Connor, D.P.; Bollard, C.M.; Simpson, R.J.

    2016-01-01

    Cytomegalovirus (CMV) infection markedly expands NKG2C+/NKG2A- NK cells, which are potent killers of infected cells expressing human leucocyte antigen (HLA)-E. As HLA-E is also over-expressed in several haematological malignancies and CMV has been linked to a reduced risk of leukaemic relapse, we

  18. Targeted preemptive therapy according to perceived risk of CMV infection after kidney transplantation

    Directory of Open Access Journals (Sweden)

    Cahue Henrique Pinto

    Full Text Available ABSTRACT Background: The identification of the best strategy to manage cytomegalovirus infection is hampered by uncertainties regarding the risk/benefit ratios of universal prophylaxis versus preemptive therapy, the impact of indirect cytomegalovirus effects and the associated costs. This study investigated the efficacy and safety of targeted preemptive therapy according to perceived risk of cytomegalovirus infection after kidney transplantation. Methods: 144 adult kidney transplant recipients were enrolled in this 12-month study. None received cytomegalovirus pharmacological prophylaxis. Only high risk patients (positive donor/negative recipient (D+/R−, use of induction therapy with antithymocyte globulin, treatment of rejection received preemptive therapy based on the result of pp65 antigenemia test. Low-risk patients with symptoms related to cytomegalovirus were screened for pp65 antigenemia and treatment initiated if confirmed cytomegalovirus disease. Blinded cytomegalovirus DNAemia was collected weekly during the first three months. Results: The incidence of cytomegalovirus infection was 34% and cytomegalovirus disease was 17%. The incidence was 25% in D+/R−, 69% in those receiving induction with rabbit antithymocite globulin (r-ATG, 46% in those treated for acute rejection, and 28% in low risk patients. By week 3 DNAemia was observed in 30% of patients who were not treated for cytomegalovirus infection/disease, and values ≥2.169 UI/mL showed 61% sensitivity and 85% specificity to detect cytomegalovirus disease (AUC = 0.849 ± 0.042, p < 0.001. Using multivariate analysis, only anti-thymocyte globulin induction was associated with cytomegalovirus infection/disease whereas only expanded donor criteria and renal function at 30 days were associated with renal function 12 months after transplantation. Conclusion: Targeted preemptive therapy in patients with perceived higher risk for cytomegalovirus infection/disease was effective in

  19. Intractable Diarrhea from Cytomegalovirus Colitis in a Case with Hereditary Spherocytosis

    Directory of Open Access Journals (Sweden)

    Murat Ozkale

    2015-09-01

    Full Text Available Cytomegalovirus (CMV infection is a common viral infection worldwide, with a frequency as high as 90% in developing countries. Only 10% of primary CMV infection is symptomatic in immunocompetent patients, and it rarely causes specific complications. We report CMV colitis in an immunocompetent adolescent with hereditary spherocytosis and spontaneous rupture of the spleen, who was critically ill with septicemia and significant non-bloody diarrhoea that responded to specific CMV treatment. [Cukurova Med J 2015; 40(3.000: 609-613

  20. Does cytomegalovirus predict a poor prognosis in Pneumocystis carinii pneumonia treated with corticosteroids? A note for caution

    DEFF Research Database (Denmark)

    Jensen, A M; Lundgren, Jens Dilling; Benfield, T;

    1995-01-01

    OBJECTIVE: To examine the importance of cytomegalovirus (CMV) in bronchoalveolar lavage (BAL) fluid of patients with HIV-associated Pneumocystis carinii pneumonia (PCP) treated with adjunctive corticosteroids (CS). DESIGN: Analysis of clinical data during a 5-year period. SETTING: Department of i...... of adjunctive CS in severe PCP, the role of CMV as a pulmonary copathogen may have changed. Active CMV infection may be an important cause of failing treatment of severe PCP in those treated with adjunctive CS....

  1. Identification of Symptomatic Fetuses Infected with Cytomegalovirus Using Amniotic Fluid Peptide Biomarkers.

    Directory of Open Access Journals (Sweden)

    Cyrille Desveaux

    2016-01-01

    Full Text Available Cytomegalovirus (CMV is the most common cause of congenital infection, and is a major cause of sensorineural hearing loss and neurological disabilities. Evaluating the risk for a CMV infected fetus to develop severe clinical symptoms after birth is crucial to provide appropriate guidance to pregnant women who might have to consider termination of pregnancy or experimental prenatal medical therapies. However, establishing the prognosis before birth remains a challenge. This evaluation is currently based upon fetal imaging and fetal biological parameters, but the positive and negative predictive values of these parameters are not optimal, leaving room for the development of new prognostic factors. Here, we compared the amniotic fluid peptidome between asymptomatic fetuses who were born as asymptomatic neonates and symptomatic fetuses who were either terminated in view of severe cerebral lesions or born as severely symptomatic neonates. This comparison allowed us to identify a 34-peptide classifier in a discovery cohort of 13 symptomatic and 13 asymptomatic neonates. This classifier further yielded 89% sensitivity, 75% specificity and an area under the curve of 0.90 to segregate 9 severely symptomatic from 12 asymptomatic neonates in a validation cohort, showing an overall better performance than that of classical fetal laboratory parameters. Pathway analysis of the 34 peptides underlined the role of viral entry in fetuses with severe brain disease as well as the potential importance of both beta-2-microglobulin and adiponectin to protect the injured fetal brain infected with CMV. The results also suggested the mechanistic implication of the T calcium channel alpha-1G (CACNA1G protein in the development of seizures in severely CMV infected children. These results open a new field for potential therapeutic options. In conclusion, this study demonstrates that amniotic fluid peptidome analysis can effectively predict the severity of congenital CMV

  2. γδ T Cell-Mediated Immunity to Cytomegalovirus Infection

    Science.gov (United States)

    Khairallah, Camille; Déchanet-Merville, Julie; Capone, Myriam

    2017-01-01

    γδ T lymphocytes are unconventional immune cells, which have both innate- and adaptive-like features allowing them to respond to a wide spectrum of pathogens. For many years, we and others have reported on the role of these cells in the immune response to human cytomegalovirus in transplant patients, pregnant women, neonates, immunodeficient children, and healthy people. Indeed, and as described for CD8+ T cells, CMV infection leaves a specific imprint on the γδ T cell compartment: (i) driving a long-lasting expansion of oligoclonal γδ T cells in the blood of seropositive individuals, (ii) inducing their differentiation into effector/memory cells expressing a TEMRA phenotype, and (iii) enhancing their antiviral effector functions (i.e., cytotoxicity and IFNγ production). Recently, two studies using murine CMV (MCMV) have corroborated and extended these observations. In particular, they have illustrated the ability of adoptively transferred MCMV-induced γδ T cells to protect immune-deficient mice against virus-induced death. In vivo, expansion of γδ T cells is associated with the clearance of CMV infection as well as with reduced cancer occurrence or leukemia relapse risk in kidney transplant patients and allogeneic stem cell recipients, respectively. Taken together, all these studies show that γδ T cells are important immune effectors against CMV and cancer, which are life-threatening diseases affecting transplant recipients. The ability of CMV-induced γδ T cells to act independently of other immune cells opens the door to the development of novel cellular immunotherapies that could be particularly beneficial for immunocompromised transplant recipients.

  3. [Twenty-three cases of cytomegalovirus infection in acquired immunodeficiency syndrome].

    Science.gov (United States)

    Tao, Mei-Mei; Ye, Jun-Jie; Kuang, Ji-Qiu

    2008-10-01

    To investigate the clinical features, therapeutic approaches, outcomes and alterations of peripheral lymphocytes subsets in cytomegalovirus (CMV) infections in patients with AIDS. Ninety-six cases of AIDS were treated in Peking Union Medical College Hospital and 23 of them had CMV infection. We analyzed the clinical features, peripheral lymphocytes subsets, outcomes, CMV pp65 antigen and/or specific anti-CMV IgM. In the 23 CMV patients, nonspecific symptoms including fever, cough, chest distress and diarrhea occurred in 18, 11, 9 and 8 patients, respectively. Thirteen patients had retinitis identified by ophthalmofundoscopy, 7 of them had blurred vision or floating as primary symptoms. Pneumocystis pneumonia, tuberculosis infection and other infection appeared in 18 patients. Fifteen (65.2%) of the patients had positive serum tests. The positive rates for CMV pp65 and specific anti-CMV-IgM were 43.5% and 30.4%, respectively. CD(4)(+)T cell count in CMV patients was remarkably decreased than that in non-CMV patients [14(4, 39) cells/microl vs (48(12, 128) cells/microl, P = 0.005] and the proportion of CD(8)(+)CD(38)(+)T cells in CMV patients was higher than that in non-CMV patients, whereas the difference of CD(8)(+)T cell was not statistically different between the 2 groups. CMV infection often occurs in advanced AIDS patients. In HIV/AIDS patients with CD(4)(+)T cell count AIDS should be considered.

  4. CLINICAL AND IMMUNOLOGICAL FEATURES OF KIDNEY TRANSPLANT RECIPIENTS WITH CYTOMEGALOVIRUS INFECTION MANIFESTATION IN THE EARLY POSTOPERATIVE PERIOD

    Directory of Open Access Journals (Sweden)

    L. V. Limareva

    2013-01-01

    Full Text Available Aim. To optimize the management of postoperative renal allograft recipients through the introduction of methods for predicting risk of manifestation of cytomegalovirus infection on the basis of a comprehensive assessment of the clinical and immunological status. Materials and methods. We retrospectively analyzed the medical records of 303 patients with end-stage renal disease, among them – were the recipients of renal allograft – 136, among whom 29 within 2 months after the operation had clinical signs of CMV infection. Assessable "CMV syndrome", laboratory evidence of CMV infection, the incidence of antigens (genes of HLA A, B and DRB *1, calculated goodness of fit χ2 and relative risk RR, changes MCP-1 in urine. Results. In renal allograft recipients with clinical and laboratory evidence of CMV infection in the early postoperative period, significantly more (χ2 > 3,8 met antigen B35. A positive association with CMV infection was detected also for DRB1 * 08, B21, B22, B41, A24 (9, B51 (5, DRB1*14 and DRB1*15. Protective effects possessed antigens / alleles of genes A26 (10, B14, B38 (16 B61 (40 and DRB1*16. MCP-1 levels in this group of recipients were raised to 2174,7 ± 296,3 pg/ml with a strong negative correlation with the levels of urea and creatinine in serum (r = 0,9, p < 0.001. Conclusion. Immunological markers of risk manifestation of CMV infection in recipients of kidneys in the early postoperative period are: the carriage of В35 и В55,56(22, В49(21, В41, DRB1*08 и DRB1*15, an increase of levels of MCP-1 in urine without increasing the levels of urea and creatinine in the serum. 

  5. Immune control in the absence of immunodominant epitopes: implications for immunotherapy of cytomegalovirus infection with antiviral CD8 T cells.

    Science.gov (United States)

    Ebert, Stefan; Lemmermann, Niels A W; Thomas, Doris; Renzaho, Angélique; Reddehase, Matthias J; Holtappels, Rafaela

    2012-11-01

    Adoptive transfer of virus-specific donor-derived CD8 T cells is a therapeutic option to prevent cytomegalovirus (CMV) disease in recipients of hematopoietic cell transplantation. Due to their high coding capacity, human as well as animal CMVs have the potential to encode numerous CD8 T cell epitopes. Although the CD8 T cell response to CMVs is indeed broadly specific in that it involves epitopes derived from almost every open reading frame when tested for cohorts of immune CMV carriers representing the polymorphic MHC/HLA distribution in the population, the response in any one individual is directed against relatively few epitopes selected by the private combination of MHC/HLA alleles. Of this individually selected set of epitopes, few epitopes are 'immunodominant' in terms of magnitude of the response directed against them, while others are 'subdominant' according to this definition. In the assumption that 'immunodominance' indicates 'relevance' in antiviral control, research interest was focused on the immunodominant epitopes (IDEs) and their potential use in immunotherapy and in vaccines. The murine model has provided 'proof of concept' for the efficacy of CD8 T cell therapy of CMV infection. By experimental modulation of the CD8 T cell 'immunome' of murine CMV constructing an IDE deletion mutant, we have used this established cytoimmunotherapy model (a) for evaluating the actual contribution of IDEs to the control of infection and (b) for answering the question whether antigenicity-determining codon polymorphisms in IDE-encoding genes of CMV strains impact on the efficacy of CD8 T cell immunotherapy in case the donor and the recipient harbor different CMV strains.

  6. Prevention of Primary Cytomegalovirus Infection in Pregnancy☆

    Science.gov (United States)

    Revello, Maria Grazia; Tibaldi, Cecilia; Masuelli, Giulia; Frisina, Valentina; Sacchi, Alessandra; Furione, Milena; Arossa, Alessia; Spinillo, Arsenio; Klersy, Catherine; Ceccarelli, Manuela; Gerna, Giuseppe; Todros, Tullia

    2015-01-01

    Background Cytomegalovirus (CMV) is the leading infectious agent causing congenital sensorineural hearing loss and psychomotor retardation. CMV vaccine is currently unavailable and treatment options in pregnancy are limited. Susceptible pregnant women caring for children are at high risk for primary infection. CMV educational and hygienic measures have the potential to prevent primary maternal infection. Methods A mixed interventional and observational controlled study was conducted to investigate the effectiveness of hygiene information among pregnant women at risk for primary CMV infection for personal/occupational reasons. In the intervention arm, CMV-seronegative women, identified at the time of maternal serum screening for fetal aneuploidy at 11–12 weeks of gestation, were given hygiene information and prospectively tested for CMV until delivery. The comparison arm consisted of women enrolled at delivery who were neither tested for nor informed about CMV during pregnancy, and who had a serum sample stored at the screening for fetal aneuploidy. By design, groups were homogeneous for age, parity, education, and exposure to at least one risk factor. The primary outcome was CMV seroconversion. Acceptance of hygiene recommendations was a secondary objective and was measured by a self-report. Findings Four out of 331 (1.2%) women seroconverted in the intervention group compared to 24/315 (7.6%) in the comparison group (delta = 6.4%; 95% CI 3.2–9.6; P < 0.001). There were 3 newborns with congenital infection in the intervention group and 8 in the comparison group (1 with cerebral ultrasound abnormalities at birth). Ninety-three percent of women felt hygiene recommendations were worth suggesting to all pregnant women at risk for infection. Interpretation This controlled study provides evidence that an intervention based on the identification and hygiene counseling of CMV-seronegative pregnant women significantly prevents maternal infection. While waiting for

  7. Natural killer cells regulate murine cytomegalovirus-induced sialadenitis and salivary gland disease.

    Science.gov (United States)

    Carroll, Virginia A; Lundgren, Alyssa; Wei, Hairong; Sainz, Susan; Tung, Kenneth S; Brown, Michael G

    2012-02-01

    The transmission of herpesviruses depends on viral shedding at mucosal surfaces. The salivary gland represents a major site of persistent viral replication for many viruses, including cytomegalovirus. We established a mouse model of salivary gland dysfunction after acute viral infection and investigated the cellular requirements for the loss of secretion. Murine cytomegalovirus (MCMV) infection severely impaired saliva secretion independently of salivary gland virus levels. Lymphocytes or circulating monocytes/macrophages were not required for secretory dysfunction. Dysfunction occurred before glandular inflammation, suggesting that a soluble mediator initiated the disruption of acinar cell function. Despite genetic differences in innate resistance to MCMV, NK cells protected the host against acinar atrophy and the loss of secretions under conditions of an exceedingly low virus inoculum. NK cells also modulated the type of glandular inflammation after infection, as they prevented an influx of Siglec-F(+) polymorphonuclear leukocytes (PMNs). Therefore, beyond their recognized role in controlling MCMV replication, NK cells preserve organ integrity and function and regulate the innate inflammatory response within the gland.

  8. Medical image of the week: CMV cytopathic effect

    Directory of Open Access Journals (Sweden)

    Sam A

    2014-12-01

    Full Text Available No abstract available. Article truncated at 150 words. Bronchoalveolar lavage (BAL was performed on a 45-year old man with a history of treated mycosis fungoides and Sézary syndrome, who presented with fever and pulmonary infiltrates. BAL Papanicolaou stain (Figure 1, 400x showed single cells (lymphocytes, arrows and alveolar macrophages, stars and a small cluster of 3 large cells, most likely infected type II pneumocytes, with a single prominent red stained nuclear inclusion surrounded by a clear halo. Nuclear chromatin was marginated on the nuclear membrane creating this “owl’s eye” appearance. In vitro, infected cells show cytomegalovirus (CMV virions within the nuclear inclusion (Figure 2, small black dots encircled, 8,800x The "owl's eye" appearance (Figure 1 is the “cytopathic effect” needed to definitively diagnose active CMV infection. While cells infected with adenovirus or herpesvirus may have nuclear inclusions, the cells typically are much smaller. CMV was cultured from the BAL, and no other pathogen was identified by cytology or ...

  9. Neonatal gastrointestinal involvement and congenital cytomegalovirus

    Directory of Open Access Journals (Sweden)

    Alessandro Porta

    2016-11-01

    Full Text Available Cytomegalovirus (CMV is the most common cause of congenital viral infection, affecting 0.2 to 2.3% of all live births in developed countries. Very low birth weight and extremely low birth weight newborns are at higher risk of symptomatic CMV infection, most commonly secondary and acquired through breast milk. Gastrointestinal involvement is rare in acquired CMV infections, but it could be an important manifestation of postnatal infection in preterm infants admitted to neonatal intensive care units. Early onset of CMV gastrointestinal signs/symptoms is very rare. In a review of the literature it is described in 5 newborns in the first 24 hours of life, and 6 considering the onset in the first week of life. This review describes also a case report of congenital CMV in an immunocompetent newborn with onset of gastrointestinal signs immediately after birth: a possible association between viral infection and enteric manifestations was considered in the differential diagnosis. A review of the literature of the different case reports found has done, with description and comparison of the different patients and clinical presentations.

  10. Lower CD28+ T cell proportions were associated with CMV-seropositivity in patients with Hashimoto’s thyroiditis

    Science.gov (United States)

    2013-01-01

    Background Alterations in the naive T cell subpopulations have been demonstrated in patients with T cell mediated autoimmune disorders, reminiscent of immunological changes found in the elderly during immunosenescence, including the switch from CD45RA + to CD45RO + T cells and decreased thymic function with increased compensatory proliferative mechanisms, partly associated with latent Cytomegalovirus (CMV) infection. The present study was aimed to investigate proportions of lymphocytes, their relation to CMV-seropositivity and the replicative history of CD45RA + expressing T cells in Hashimoto’s thyroiditis (HT, n = 18) and healthy controls (HC, n = 70). Methods Proportions of peripheral T cells were investigated by flow cytometry. The replicative history was assessed by T cell receptor excision circles (TRECs) and relative telomere length (RTL). Expression of CD62L was analyzed by immunohistochemistry in thyroid sections. The role of CMV was assessed by serology, ELISPOT assay and in situ hybridization. Results Our results demonstrated a significant increase of CD28-negative T cells, associated with CMV-seropositivity in HT patients. HT showed abundant CD45RO + T cells with peripheral loss of CD62L-expressing CD8 + CD45RA + T cells, the latter mainly depending on disease duration. CD62L was expressed in thyroid lymphocyte infiltrations. The diagnosis of HT and within the HT group CMV-seropositivity were the main determinants for the loss of CD28 expression. RTL was not different between HC and HT. HT showed significantly lower TRECs in CD4 + CD45RA + T cells compared to HC. Conclusions Patients with HT display a peripheral T cell phenotype reminiscent of findings in elderly persons or other autoimmune disorders. Whether these mechanisms are primary or secondary to the immunological alterations of autoimmune conditions should be investigated in longitudinal studies which may open research on new therapeutic regimes for

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

    Science.gov (United States)

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

    2017-09-15

    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.

  12. The association of metabolic syndrome and Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, and herpes simplex virus type 1: The Persian Gulf Healthy Heart Study

    Directory of Open Access Journals (Sweden)

    Pazoki Raha

    2006-12-01

    Full Text Available Abstract Background The metabolic syndrome together with insulin resistance and their consequences are basic factors in pathogenesis of atherosclerosis. Chronic infections with herpes simplex virus type 1 (HSV-1, cytomegalovirus (CMV, and Chlamydia pneumoniae are associated with the development of atherosclerosis and coronary heart disease. The infectious aspects of metabolic syndrome have not been investigated. Methods In a cross-sectional, population-based study, we used National Cholesterol Education Program (NCEP-Adult Treatment Panel (ATP-III criteria in 1791 subjects, aged 25 years and over, selected by cluster random sampling in three Iranian ports in the northern Persian Gulf. Sera were analyzed for IgG antibodies to Chlamydia pneumoniae, HSV-1, Helicobacter pylori (H. pylori and CMV using ELISA. Results In multiple logistic regression analysis, of the infectious agents, CMV [OR = 1.81 (1.05–3.10; p = 0.03], H. pylori [OR = 1.50 (1.12–2.00; p = 0.007] and Chlamydia pneumoniae [OR = 1.69 (1.27–2.25; p Conclusion The metabolic syndrome, which occurs very frequently in the general population, has a significant association with prior infection with Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus and herpes simplex virus type 1. Hypothesis about participation of infection in pathogenesis of metabolic syndrome should be investigated.

  13. Blood and alveolar lymphocyte subsets in pulmonary cytomegalovirus infection after lung transplantation

    Directory of Open Access Journals (Sweden)

    Grenet Dominique

    2001-09-01

    Full Text Available Abstract Background Cytomegalovirus (CMV pneumonitis has been shown to be associated with lymphocytic alveolitis after lung transplantation. In the present study, we investigated a series of bronchoalveolar (BAL and blood samples, collected in the absence of rejection or acute infectious episodes. in order -1: to evaluate intra-alveolar cell population changes concomitant with CMV replication and -2: to reappraise the value of cell population analysis in the management of patients after lung transplantation. Methods We used flow cytometry to investigate modifications of lymphocyte subpopulations related to pulmonary cytomegalovirus infections in blood and BAL samples from a series of 13 lung transplant recipients. After exclusion of samples obtained during pulmonary rejection, bronchiolitis obliterans or acute bacterial infection, 48 blood and BAL samples were retained for analysis: 17 were CMV positive by shell-vial assay and 31 were CMV negative in blood and BAL. Results Our results demonstrate that pulmonary CMV infection is associated with a significant increase in the total lymphocyte population in BAL samples, but with minor modifications of the various lymphocyte subpopulations and a significantly higher absolute number of B lymphocytes in blood samples. Conclusions Cytomegalovirus pulmonary infection is accompanied by only minor changes in BAL lymphocyte subpopulations. The study of BAL lymphocyte subpopulations therefore appears to be of limited clinical value in the diagnosis of pulmonary CMV infection. However, increased blood B-lymphocytes seems to be a clinical feature associated with CMV infection.

  14. Early kinetics of plasma cytomegalovirus DNA load in allogeneic stem cell transplant recipients in the era of highly sensitive real-time PCR assays: does it have any clinical value?

    Science.gov (United States)

    Giménez, Estela; Muñoz-Cobo, Beatriz; Solano, Carlos; Amat, Paula; Navarro, David

    2014-02-01

    We report that in a population of allogeneic stem cell transplant recipients, determination of the viral doubling time (dt) of the cytomegalovirus (CMV) DNA plasma load predicted the eventual need for inception of preemptive antiviral therapy, whereas the level of the initial plasma CMV DNA load did not. The data thus indicated that determination of the dt of CMV DNA may be useful in the therapeutic management of CMV infection in this clinical setting.

  15. 75 FR 13559 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Long Term...

    Science.gov (United States)

    2010-03-22

    ... Cytomegalovirus (CMV) Infection, Funding Opportunity Announcement (FOA) IP10-006, Initial Review In accordance... in response to ``Long Term Outcomes of Infants Identified with Congenital CMV Infection, FOA...

  16. Symptomatic Congenital Cytomegalovirus Infection in Children of Seropositive Women

    Directory of Open Access Journals (Sweden)

    Ines Mack

    2017-06-01

    Full Text Available Cytomegalovirus (CMV is the most frequent congenital virus infection worldwide. The risk of congenital CMV (cCMV transmission is highest in seronegative women who acquire primary CMV infection during pregnancy. A growing body of evidence indicates that secondary CMV infections in pregnant women with preconceptual immunity (either through reactivation of latent virus or re-infection with a new strain of CMV contribute to a much greater proportion of symptomatic cCMV than was previously thought. Here, we describe a case of symptomatic cCMV infection in the newborn of a woman with proven immunity prior to pregnancy. Diagnosis was confirmed by CMV PCR from amniotic fluid and fetal MR imaging. The newborn presented with typical cCMV symptoms including jaundice, hepatosplenomegaly, cholestasis, petechiae, small head circumference, and sensorineural hearing loss, the most common neurologic sequela. CMV was detected in infant blood and urine by PCR, and intravenous ganciclovir was initiated and continued orally for 6 weeks totally. Apart from persisting right-sided deafness, the child exhibited normal neurological development up through the last follow-up at 4.5 years. To date, the most effective strategy to prevent vertical CMV transmission is hygiene counseling for women of childbearing age, which, in our case, and in concordance with recent literature, applies to seronegative, as well as seropositive, women. Once an expecting mother shows seroconversion or signs of an active CMV infection, there are no established procedures to reduce the risk of transmission, or therapeutic options for the fetus with signs of infection. After birth, symptomatic infants can be treated with ganciclovir to inhibit viral replication and improve hearing ability and neurodevelopmental outcome. A comprehensive review of the literature, including our case study, reveals the most current and significant diagnostic and treatment options available. In conclusion, the triad

  17. Antiviral treatment in patients with cytomegalovirus positive ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Kadir; Ozturk

    2014-01-01

    Cytomegalovirus(CMV) is a common virus in patients with ulcerative colitis receiving immunosuppressive drugs. Many studies suggested that CMV infection is an exacerbating factor in patients with ulcerative colitis. The role of CMV in exacerbations of ulcerative colitis has been discussed. One of studies starting this discussion is an article entitled "CMV positive ulcerative colitis: A single center experience and literature review" by Kopylov et al. However, we think that there are some points that should be emphasized about the study. Especially, the small number of patients in the study has led to meaningless results. Large controlled prospective trials are needed to clarify the benefit of antiviral therapy for active ulcerative colitis patients.

  18. Acute cervicitis and vulvovaginitis may be associated with Cytomegalovirus.

    Science.gov (United States)

    Abou, Magali; Dällenbach, Patrick

    2013-04-19

    Cytomegalovirus (CMV) infection in immunocompetent hosts is generally asymptomatic or may present as a mononucleosic syndrome. Its association with acute cervicitis and vulvovaginitis has rarely been reported. A 24-year-old woman presented with pelvic pain, vulvodynia, abnormal vaginal discharge, burning with urination, fatigue, fever, vomiting and diarrhoea. The vulva and cervix were red with vesicular lesions on the cervix. Genital herpes simplex infection (HSV) was suspected and valacyclovir was given orally. However, serial viral cultures performed 7 weeks apart did not isolate HSV as suspected, but CMV was confirmed by immunofluorescence and early antigen research. Blood tests confirmed an acute CMV infection. Typical inclusions were found at histology. Symptoms resolved slowly with persistence of cervical lesions at 7 weeks from diagnosis. The frequency of CMV genital infection is probably underestimated. The infection is not always asymptomatic and might be confused with genital HSV infection. The clinical course is longer.

  19. Coinfection with EBV/CMV and other respiratory agents in children with suspected infectious mononucleosis

    Directory of Open Access Journals (Sweden)

    Wei Cong

    2010-09-01

    Full Text Available Abstract Background Numerous studies have shown that Epstein-Barr virus (EBV and cytomegalovirus (CMV can infect immunocompetent patients simultaneously with other agents. Nonetheless, multiple infections with other agents in EBV/CMV-infected children have received little attention. We conducted a retrospective study of children with suspected infectious mononucleosis. Peripheral blood samples were analyzed by indirect immunofluorescence to detect EBV, CMV and other respiratory agents including respiratory syncytial virus; adenovirus; influenza virus types A and B; parainfluenza virus types 1, 2 and 3; Chlamydia pneumoniae and Mycoplasma pneumoniae. A medical history was collected for each child. Results The occurrence of multipathogen infections was 68.9%, 81.3% and 63.6% in the children with primary EBV, CMV or EBV/CMV, respectively, which was significantly higher than that in the past-infected group or the uninfected group (p C. pneumoniae in children with primary infection was as high as 50%, significantly higher than in the other groups (p Conclusion Our study suggests that there is a high incidence of multipathogen infections in children admitted with EBV/CMV primary infection and that the distribution of these pathogens is not random.

  20. Construction of a cytomegalovirus-based amplicon: a vector with a unique transfer capacity.

    Science.gov (United States)

    Borst, Eva Maria; Messerle, Martin

    2003-07-01

    Cytomegalovirus (CMV) has a number of interesting properties that qualifies it as a vector for gene transfer. Especially appealing is the ability of the CMV genome to persist in hematopoietic progenitor cells and the packaging capacity of the viral capsid that accommodates a DNA genome of 230 kbp. In order to exploit the packaging capacity of the CMV capsid we investigated whether the principles of an amplicon vector can be applied to CMV. Amplicons are herpesviral vectors, which contain only the cis-active sequences required for replication and packaging of the vector genome. For construction of a CMV amplicon the sequences comprising the lytic origin of replication (orilyt) and the cleavage packaging recognition sites (pac) of human CMV were cloned onto a plasmid. A gene encoding the green fluorescent protein was used as a model transgene. The amplicon plasmid replicated in the presence of a CMV helper virus and was packaged into CMV particles, with replication and packaging being dependent on the presence of the orilyt and pac sequences. The packaged amplicon could be transferred to recipient cells and reisolated from the transduced cells. Analysis of the DNA isolated from CMV capsids revealed that the CMV amplicon was packaged as a concatemer with a size of approximately 210 kbp. The CMV amplicon vector has the potential to transfer therapeutic genes with a size of more than 200 kbp and thus provides a unique transfer capacity among viral vectors.

  1. Evolution of hearing in children with congenital cytomegalovirus infection

    Directory of Open Access Journals (Sweden)

    Ibáñez-Muñoz C, Calle-Cabanillas M.I, Pérez-Sáez J, Navazo-Eguía A.I, Clemente-García A, García-Vicario F, Sánchez-Hernández JM

    2013-10-01

    Full Text Available Introduction and Objectives: Congenital cytomegalovirus infection (CMV is the most common congenital viral infection and the most common cause of acquired congenital sensorineural hearing loss. Objective: To evaluate the characteristics and evolution of hearing in patients diagnosed with congenital cytomegalovirus (CMV infection. Methods and materials: In a retrospective study assessed the characteristics and evolution of hearing in children born in our hospital between 2000 and 2010 with symptomatic congenital cytomegalovirus infection. Depending on the age and neurological status, hearing assesment was performed by objective audiometry, audiometry through play or conventional audiometry. Results: During the period of 2000-2010 have been identified 5 cases of symptomatic congenital cytomegalovirus (0.025% of newborns, predominantly female (60%. In 40% of cases was the only symptom suspected microcephaly. In both instances the hearing was normal at birth, presenting one of the cases of late-onset profoundly deaf. One case (20% had major neurological involvement with petechiae, hepatosplenomegaly and profound sensorineural hearing loss. Two cases were very premature with other risk factors but no hearing impairment. All cases were treated with ganciclovir. Conclusion: It is necessary to identify patients with congenital CMV infection and hearing track during the first years of life due to the possibility of developing late-onset hearing loss.

  2. Optimal management of cytomegalovirus retinitis in patients with AIDS

    Directory of Open Access Journals (Sweden)

    Michael W Stewart

    2010-04-01

    Full Text Available Michael W StewartDepartment of Ophthalmology, Mayo School of Medicine, Jacksonville, FL, USAAbstract: Cytomegalovirus (CMV retinitis is the most common cause of vision loss in patients with acquired immunodeficiency syndrome (AIDS. CMV retinitis afflicted 25% to 42% of AIDS patients in the pre-highly active antiretroviral therapy (HAART era, with most vision loss due to macula-involving retinitis or retinal detachment. The introduction of HAART significantly decreased the incidence and severity of CMV retinitis. Optimal treatment of CMV retinitis requires a thorough evaluation of the patient’s immune status and an accurate classification of the retinal lesions. When retinitis is diagnosed, HAART therapy should be started or improved, and anti-CMV therapy with oral valganciclovir, intravenous ganciclovir, foscarnet, or cidofovir should be administered. Selected patients, especially those with zone 1 retinitis, may receive intravitreal drug injections or surgical implantation of a sustained-release ganciclovir reservoir. Effective anti-CMV therapy coupled with HAART significantly decreases the incidence of vision loss and improves patient survival. Immune recovery uveitis and retinal detachments are important causes of moderate to severe loss of vision. Compared with the early years of the AIDS epidemic, the treatment emphasis in the post-HAART era has changed from short-term control of retinitis to long-term preservation of vision. Developing countries face shortages of health care professionals and inadequate supplies of anti-CMV and anti-HIV medications. Intravitreal ganciclovir injections may be the most cost effective strategy to treat CMV retinitis in these areas.Keywords: cytomegalovirus, AIDS, retinitis, immune recovery uveitis, retinal detachment, treatment

  3. Allergenicity assessment of genetically modified cucumber mosaic virus (CMV) resistant tomato (Solanum lycopersicon).

    Science.gov (United States)

    Lin, Chih-Hui; Sheu, Fuu; Lin, Hsin-Tang; Pan, Tzu-Ming

    2010-02-24

    Cucumber mosaic virus (CMV) has been identified as the causal agent of several disease epidemics in most countries of the world. Insect-mediated virus diseases, such as those caused by CMV, caused remarkable loss of tomato (Solanum lycopersicon) production in Taiwan. With expression of the CMV coat protein gene (Cmvcp) in a local popular tomato cultivar L4783, transgenic tomato line R8 has showed consistent CMV resistance through T(0) to T(8). In this report, the allergenicity of the CMV coat protein (CMV cp) expressed in transgenic tomato R8 was assessed by investigation of the expression of the transgene source of protein, sequence similarity with known allergens, and resistance to pepsin hydrolysis. There is no known account for either the CMV or its coat protein being an allergen. The result of a bioinformatic search also showed no significant homology between CMV cp and any known allergen. The pepsin-susceptible property of recombinant CMV cp was revealed by a simulated gastric fluid (SGF) assay. Following the most recent FAO/WHO decision tree, all results have indicated that CMV cp was a protein with low possibility to be an allergen and the transgenic tomato R8 should be considered as safe as its host.

  4. Prevalence of specific IGM due to toxoplasma, rubella, CMV and c.trachomatis infections during pregnancy

    Directory of Open Access Journals (Sweden)

    Yasodhara P

    2001-01-01

    Full Text Available One hundred and seventy five apparently normal asymptomatic pregnant women were studied prospectively and 247 women with different complications of pregnancy were screened at the time of delivery for infections like Chlamydia trachomatis, Toxoplasma, Rubella and cytomegalovirus (CMV. One hundred and forty two women with normal outcome of pregnancy served as controls. Specific IgM due to these agents were determined in the sera using commercial diagnostic kits. Results of the study showed that chlamydial infection was the most prevalent (29.8% followed by Toxoplasmosis (13.1, Rubella (6.5% and CMV (5.8%. Adverse outcome was seen among those seropositive for Chlamydia, Toxoplasmosis and Rubella. CMV showed no association with adverse outcome of pregnancy. Since Chlamydia and Toxoplasmosis are amenable to treatment with antibiotics, screening for these infections and appropriate treatment would improve outcome of pregnancy.

  5. Maternal valacyclovir and infant cytomegalovirus acquisition: a randomized controlled trial among HIV-infected women.

    Directory of Open Access Journals (Sweden)

    Alison C Roxby

    Full Text Available BACKGROUND: Studies in HIV-1-infected infants and HIV-1-exposed, uninfected infants link early cytomegalovirus (CMV acquisition with growth delay and cognitive impairment. We investigated maternal valacyclovir to delay infant acquisition of CMV. METHODS: Pregnant women with HIV-1, HSV-2 and CD4 count >250 cells/µl were randomized at 34 weeks gestation to 500 mg twice-daily valacyclovir or placebo for 12 months. Maternal CMV DNA was measured in plasma at 34 weeks gestation, in cervical secretions at 34 and 38 weeks gestation, and in breast milk at 7 postpartum timepoints; infant CMV DNA was measured in dried blood spots at 8 timepoints including birth. RESULTS: Among 148 women, 141 infants were compared in intent-to-treat analyses. Maternal and infant characteristics were similar between study arms. Infant CMV acquisition did not differ between study arms, with 46/70 infants (66% in placebo arm and 47/71 infants (66% in the valacyclovir arm acquiring CMV; median time to CMV detection did not differ. CMV DNA was detected in 92% of 542 breast milk specimens with no difference in CMV level between study arms. Change in cervical shedding of CMV DNA between baseline and 38 weeks was 0.40-log greater in the placebo arm than the valacyclovir arm (p = 0.05. CONCLUSIONS: In this cohort of HIV-1-seropositive mothers, two-thirds of infants acquired CMV by one year. Maternal valacyclovir had no effect on timing of infant CMV acquisition or breast milk CMV viral loads, although it modestly reduced cervical CMV shedding. Maternal prophylaxis to reduce infant CMV acquisition warrants further evaluation in trials with antiviral agents. TRIALS REGISTRATION: ClinicalTrials.gov NCT00530777.

  6. Effectiveness of Valganciclovir 900mg Versus 450mg for Cytomegalovirus Prophylaxis in Renal Transplantation: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Xin, Wang; Hui, Yang; Xiaodong, Zhang; Xiangli, Cui; Shihui, Wang; Lihong, Liu

    2017-01-01

    Valganciclovir 900 mg/day is approved for cytomegalovirus (CMV) prophylaxis, but 450 mg/day is seems also effective. We systematically reviewed the efficacy and safety of low-dose versus high-dose valganciclovir prophylaxis in renal transplantation recipients. An electronic search was conducted up to November 29, 2016. The primary outcomes were incidences of CMV, CMV disease, mortality and opportunistic infection. The second outcomes were acute rejection, allograft loss, adverse drug reaction (ADR). 7 cohort studies, all with high quality involving (1431 patients) were included. There was no significant difference of the incidence of following CMV disease (1271 patients, odds ratio [OR] 0.74, 95% confidence interval [CI], 0.38-1.43, p=0.36), acute rejection (1343 patients, OR 0.77, 95%CI 0.53-1.14, p=0.19), allograft loss (1271 patients, OR 0.64, 95%CI 0.31-1.35, p=0.24), mortality (1271 patients, OR 0.55, 95%CI 0.20-1.47, p=0.23) and opportunistic infections (OI) (985 patients, OR 0.76, 95%CI 0.52-1.10, p=0.14) between the low-dose and the high-dose valganciclovir  prophylaxis. And no significant difference was observed for premature valganciclovir discontinuation (1010 patients, OR 0.81, 95%CI 0.52-1.25, p=0.33) and the incidence of leukopenia (1082 patients, OR 0.65, 95%CI 0.34-1.22, p=0.18) between the two regimens. 450 mg and 900 mg doses of valganciclovir are equipotent for CMV universal prophylaxis. CMV 450 mg prophylaxis should be used for renal transplant recipients. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

  7. Refractory ulcerative colitis accompanied with cytomegalovirus colitis and multiple liver abscesses:A case report

    Institute of Scientific and Technical Information of China (English)

    Takuya Inoue; Ken Toshina; Takashi Nishikawa; Norihiro Hamamoto; Ken Nakagawa; Ken-Ichi Katsu; Ichiro Hirata; Yutaro Egashira; Kumi Ishida; Ken Kawakami; Eijiro Morita; Naoko Murano; Shingo Yasumoto; Mitsuyuki Murano

    2005-01-01

    Various hepato-biliary complications are an increased incidence in patients with inflammatory bowel disease,and portal bacteremia is well documented in patients with ulcerative colitis (UC). However, few reports mention UC in association with liver abscesses. Recently, there are several reports describing cytomegalovirus (CMV) infection in association with disease exacerbation and steroid refractoriness in patients with UC. Here we present a case of refractory UC accompanied with multiple liver abscesses and CMV colitis. The patient, a 72-year-old male, with a five-year history of repeated admissions to our hospital for UC, presented with an exacerbation of his UC.Sigmoidoscopy performed on admission suggested that his UC was exacerbated, then he was given prednisolone and mesalazine orally, and betamethasone enemas.However, he had exacerbated symptoms. Repeat sigmoidoscopy revealed multiple longitudinal ulcers and pseudopolyps in the rectosigmoid colon. Although immunohistochemical staining of biopsy specimens and the serum testing for antigenemia were negative on admission and after the repeat sigmoidoscopy, they became histologically positive for CMV. Nonetheless, the patient developed spiking fevers, soon after ganciclovir was administered. Laboratory studies revealed an increased white cell count with left shift, and Enterococcus fecalis grew in blood cultures. An abdominal computed tomography (CT) scan was obtained and the diagnosis of liver abscesses associated with UC was made, based on CT results. The hepatic abscesses were successfully treated with intravenous meropenem for 6 wk, without further percutaneous drainage. To our knowledge, this is the first reported case of multiple liver abscesses that develop during UC exacerbation complicated by CMV colitis.

  8. 小肠移植术后巨细胞病毒感染二例的治疗体会%Cytomegalovirus infection after small bowel transplantation

    Institute of Scientific and Technical Information of China (English)

    李元新; 李宁; 李幼生; 倪小冬; 吴波; 王剑; 李民; 黎介寿

    2011-01-01

    目的 总结小肠移植术后巨细胞病毒(CMV)感染的治疗经验.方法 1994年至2009年间完成15例小肠移植,分为3个阶段:1994-1995年为第1阶段(3例),2003-2006年为第2阶段(7例),2007年以后为第3阶段(5例).第1阶段术后未进行CMV感染的预防;第2阶段通过肠镜、病理检查和血清学检查(CMV IgM、CMV pp65和CMV DNA)进行CMV感染的诊断,术后静脉注射更昔洛韦2~3周,口服阿昔洛韦3个月以预防CMV感染;第3阶段在第2阶段的基础上,应用实时定量PCR技术检测CMV DNA,并制定计划性监测方案,术后静脉注射更昔洛韦2~3周,口服更昔洛韦3个月预防CMV感染,采用CMV感染的抢先治疗方案.结果 15例患者中有2例(13.3 %)术后发生CMV感染.其中第2阶段1例术后45 d发生移植肠CMV肠炎,术后64 d并发CMV肺炎,应用更昔洛韦和胸腺肽,并停用他克莫司,最终转为重度排斥反应后死亡;第3阶段1例术后第3个月发生CMV感染,经CMV抢先治疗后治愈.结论 小肠移植术后应进行CMV的预防性治疗,严密监测CMV血清学指标,适时进行抢先治疗.对于CMV侵袭性疾病在进行有效治疗的同时应注意排斥反应的发生.%Objective Cytomegalovirus (CMV) has remained the most significant pathogen that threatens the outcome of small bowel transplantation (SBTx). This paper To outline preliminary experience of prophylaxis and treatment of cytomegalovirus (CMV) in 15 cases subject to small bowel transplantation (SBTx) and also review current progress of diagnosis and treatment of CMV.Methods Fifteen cases of SBTx were divided into 3 eras: era Ⅰ (1994-1995)-3 SBTx treated with cyclosporine-based immunosuppression; era Ⅱ (2003-2006)-7 SBTx treated with tacrolimus-based immunosuppression; and era Ⅲ (2007-present)-5 SBTx treated with Alemtuzumab induction therapy and maintenance tacrolimus monotherapy. No antiviral prophylaxis after SBTx was applied during era Ⅰ; in era Ⅱ, ileoscopic and pathological

  9. Human Leukocyte Antigen Alleles and Cytomegalovirus Infection After Renal Transplantation

    Directory of Open Access Journals (Sweden)

    Futohi

    2015-11-01

    Full Text Available Background Several studies have been conducted on the relationship between a number of human leukocyte antigen (HLA alleles and cytomegalovirus infection (CMV, in kidney transplant recipients, after transplantation. However, only a limited number of HLAs have been investigated, so far, and the results have been contradictory. Objectives This study aimed to investigate the relationship between 59 HLA alleles and the CMV infection, in transplant recipients, after kidney transplantation. Patients and Methods This retrospective cohort study was conducted on 200 patients, receiving a kidney transplant, in Baqiyatallah Hospital, in Tehran, during 2013. Throughout a one-year follow-up of kidney transplant recipients, in case of detecting the CMV antigen in patients’ blood, at any time, they were placed in the group of patients with CMV infection, whereas, if no CMV-specific antigen was developed, over a year, patients were placed in the group of patients without CMV infection, after transplantation. This study investigated the relationship between CMV infection in kidney transplant recipients and 59 HLA alleles, including 14 HLA-A, 28 HLA-B, and 17 HLA-DRB1 cases. Results Of all participants, 104 patients (52% were diagnosed with CMV infection. There was no significant difference between the two groups, with and without CMV infection, in terms of patient’s characteristics. The CMV infection, in patients receiving a transplanted organ from deceased donor, was significantly more prevalent than in those receiving kidney transplant from living donor (63% vs. 39%, respectively, P = 0.001. Recipients with HLA-B44 were more infected with CMV compared with patients without this allele (80% vs. 50%, respectively, P = 0.024; on the contrary, kidney recipients with HLA-DRB1-1 were less infected with CMV than patients without this allele (31% vs. 55%, respectively, P = 0.020. There was no significant relationship between CMV infection and other HLA alleles

  10. Preconceptual administration of an alphavirus replicon UL83 (pp65 homolog) vaccine induces humoral and cellular immunity and improves pregnancy outcome in the guinea pig model of congenital cytomegalovirus infection.

    Science.gov (United States)

    Schleiss, Mark R; Lacayo, Juan C; Belkaid, Yasmine; McGregor, Alistair; Stroup, Greg; Rayner, Jon; Alterson, Kimberly; Chulay, Jeffrey D; Smith, Jonathan F

    2007-03-15

    Development of a vaccine against congenital cytomegalovirus (CMV) infection is a major public health priority. We report the use of a propagation-defective, single-cycle, RNA replicon vector system, derived from an attenuated strain of the alphavirus Venezuelan equine encephalitis virus, to produce virus-like replicon particles (VRPs) expressing GP83, the guinea pig CMV (GPCMV) homolog of the human CMV pp65 phosphoprotein. Vaccination with VRP-GP83 induced antibodies and CD4(+) and CD8(+) T cell responses in GPCMV-seronegative female guinea pigs. Guinea pigs immunized with VRP-GP83 vaccine or with a VRP vaccine expressing influenza hemagglutinin (VRP-HA) were bred for pregnancy and subsequent GPCMV challenge during the early third trimester. Dams vaccinated with VRP-GP83 had improved pregnancy outcomes, compared with dams vaccinated with the VRP-HA control. For VRP-GP83-vaccinated dams, there were 28 live pups and 4 dead pups (13% mortality) among 10 evaluable litters, compared with 9 live pups and 12 dead pups (57% mortality) among 8 evaluable litters in the VRP-HA-vaccinated group (P<.001, Fisher's exact test). Improved pregnancy outcome was accompanied by reductions in maternal blood viral load, measured by real-time polymerase chain reaction. These results indicate that cell-mediated immune responses directed against a CMV matrix protein can protect against congenital CMV infection and disease.

  11. Seroprevalence of cytomegalovirus, toxoplasma and parvovirus in pregnancy.

    Science.gov (United States)

    Wong, A; Tan, K H; Tee, C S; Yeo, G S

    2000-04-01

    The aim of our study was to determine the seroprevalence of cytomegalovirus (CMV), toxoplasma and parvovirus infection in our local antenatal population, and to see the effects, if any, of age, race, parity and nationality on its seroprevalence. The sera of 120 consecutive antenatal women seen in KK Women's and Children's Hospital between the period of October 1997 and March 1998 were screened for cytomegalovirus (CMV) IgG, toxoplasma IgG and parvovirus B19 IgG and IgM. An antibody titer greater than 1:32 was regarded as positive. A total of 87.0% of patients were tested seropositive for CMV IgG, 17.2% seropositive for toxoplasma IgG and 30.0% seropositive for parvovirus IgG. There seemed to be a trend of increasing seropositivity with age in all three groups, however only parovirus B19 reached statistical significance. The incidence of all three infections were higher among the Malays, Indians and other races compared to the Chinese. CMV is endemic in our population and hence the most common infection. Toxoplasmosis and parvovirus is relatively low in our population but this implies that a large proportion of our antenatal women are still susceptible to these infections. Prevention of congenital CMV, toxoplasmosis and parvovirus infection is mainly by educating the antenatal population.

  12. Aquired Cytomegalovirus Infection of Extremely Low Birth Weight Infant

    Directory of Open Access Journals (Sweden)

    Serdar Alan

    2013-12-01

    Full Text Available Breast milk is a major source for acquired cytomegalovirus infection especially in premature infants and acquired CMV infection occurs in infants whose mothers were seropositive for CMV. Although most of mothers of premature infants are seropositive in Turkey, acquired life-threatening breast milk acquired CMV infection was reported occasionally. Treatment of preterm with symptomatic breast milk acquired CMV infection should be done according to the severity of clinical signs. In this report, a preterm case with a diagnosis of breast milk-acquired CMV meningitis and sepsis without multiorgan failure on the 111th day of life, who did not require antiviral therapy was presented and discussed in the context of the acquired CMV literature. In preterm babies, when there is sepsis with no apparent causes, unexplained thrombocytopenia, elevated liver transaminases and direct hyperbilirubinemia acquired CMV infection should be suspected. (Jo­ur­nal of Cur­rent Pe­di­at­rics 2013; 11: 138-41

  13. Childhood environments and cytomegalovirus serostatus and reactivation in adults.

    Science.gov (United States)

    Janicki-Deverts, Denise; Cohen, Sheldon; Doyle, William J; Marsland, Anna L; Bosch, Jos

    2014-08-01

    Childhood adversity, defined in terms of material hardship or physical or emotional maltreatment has been associated with risk for infection with cytomegalovirus (CMV) among children and adolescents, and with CMV reactivation in children and adults. The present study examined whether different dimensions of childhood experience-those pertaining to socioeconomic status (SES), physical environment, or family relationships-relate differentially to CMV serostatus and reactivation during adulthood. Participants were 140 healthy adults, aged 18-55years (41% female; 64% white). Childhood environments were assessed retrospectively and included family SES (parental housing tenure); childhood neighborhood environment (urban residence; physical conditions; safety; and social atmosphere); residential exposures (parental smoking and physical condition of home); and family relationships (parental divorce; warmth; harmony; dysfunction; parental bonding). Approximately 39% (n=53) of participants were CMV+. In individual analyses controlling for age, sex, race, body mass, current adult SES and smoking status, fewer years of parental home ownership, having a parent who smoked, and living in a poorly maintained or unsafe neighborhood each were associated with greater odds of infection with CMV. By comparison, in individual analyses limited to CMV+ participants, less family warmth, less harmony, greater dysfunction, and suboptimal parental bonding each were related to higher antibody levels, independent of the aforementioned covariates. Findings were not attributable to current adult perceptions of psychological stress or relative levels of emotional stability. These results suggest that different types of childhood adversity may be associated with differential effects on CMV infection and latency.

  14. Cross-Species Rhesus Cytomegalovirus Infection of Cynomolgus Macaques

    Science.gov (United States)

    Bimber, Benjamin N.; Reed, Jason S.; Uebelhoer, Luke S.; Bhusari, Amruta; Hammond, Katherine B.; Klug, Alex; Legasse, Alfred W.; Axthelm, Michael K.; Nelson, Jay A.; Streblow, Daniel N.; Picker, Louis J.; Früh, Klaus; Sacha, Jonah B.

    2016-01-01

    Cytomegaloviruses (CMV) are highly species-specific due to millennia of co-evolution and adaptation to their host, with no successful experimental cross-species infection in primates reported to date. Accordingly, full genome phylogenetic analysis of multiple new CMV field isolates derived from two closely related nonhuman primate species, Indian-origin rhesus macaques (RM) and Mauritian-origin cynomolgus macaques (MCM), revealed distinct and tight lineage clustering according to the species of origin, with MCM CMV isolates mirroring the limited genetic diversity of their primate host that underwent a population bottleneck 400 years ago. Despite the ability of Rhesus CMV (RhCMV) laboratory strain 68–1 to replicate efficiently in MCM fibroblasts and potently inhibit antigen presentation to MCM T cells in vitro, RhCMV 68–1 failed to productively infect MCM in vivo, even in the absence of host CD8+ T and NK cells. In contrast, RhCMV clone 68–1.2, genetically repaired to express the homologues of the HCMV anti-apoptosis gene UL36 and epithelial cell tropism genes UL128 and UL130 absent in 68–1, efficiently infected MCM as evidenced by the induction of transgene-specific T cells and virus shedding. Recombinant variants of RhCMV 68–1 and 68–1.2 revealed that expression of either UL36 or UL128 together with UL130 enabled productive MCM infection, indicating that multiple layers of cross-species restriction operate even between closely related hosts. Cumulatively, these results implicate cell tropism and evasion of apoptosis as critical determinants of CMV transmission across primate species barriers, and extend the macaque model of human CMV infection and immunology to MCM, a nonhuman primate species with uniquely simplified host immunogenetics. PMID:27829026

  15. Relationship between cytomegalovirus and colonization of the oropharynx by gram-negative bacilli following renal transplantation.

    OpenAIRE

    Mackowiak, P A; Goggans, M.; W. Torres; Dal Nogare, A.; Luby, J. P.; Helderman, H.

    1991-01-01

    Numerous investigators have reported an increased incidence of pneumonia caused by Gram-negative bacilli and other secondary pathogens in transplant recipients infected by cytomegalovirus (CMV). To determine if CMV infections are related to colonization of the upper respiratory tract by Gram-negative bacilli, we examined prospectively 22 renal transplant recipients with sequential bacteriological, virological and biochemical examinations performed just prior to and at various times after tran...

  16. The Role of Cytomegalovirus in the Development of ARC-AIDS

    Science.gov (United States)

    1991-08-30

    sera, taken in chronological order of receipt into the laboratory, from HLV -1- seropositive subjects, for the presence of antibodies to cellular...CI)4 +T-cell numbers in IIIV-1 infected subjects, but CMV infections appear to be important. The drug DHPG (gancyclovir) has been used in suppressing...CMV drugs that can be given orally. The data we have presented in this paper reinforce the recommendation of DiNubile [37] that in cytomegalovirus

  17. Cytomegalovirus implicated in a case of progressive outer retinal necrosis (PORN).

    Science.gov (United States)

    Sfeir, Maroun

    2015-08-01

    Progressive outer retinal necrosis, also known as PORN, has been described as a variant of necrotizing herpetic retinopathy, occurring particularly in patients with acquired immune deficiency syndrome (AIDS). Although the etiologic organism has been reported to be Varicella-zoster virus, cytomegalovirus (CMV) can be an etiologic agent. Our case illustrates the occurrence of two opportunistic infections: PORN associated with CMV and Mycobacterium avium intracellulare duodenitis in a patient with uncontrolled HIV infection.

  18. Development and preclinical evaluation of an alphavirus replicon particle vaccine for cytomegalovirus

    OpenAIRE

    Elizabeth A Reap; Morris, John; Dryga, Sergey A.; Maughan, Maureen; Talarico, Todd; Esch, Robert E.; Negri, Sarah; Burnett,Bruce; Graham, Andrew; Olmsted, Robert A.; Jeffrey D. Chulay

    2007-01-01

    We used a replication-incompetent, single-cycle, alphavirus replicon vector system to produce virus-like replicon particles (VRP) expressing the extracellular domain of human cytomegalovirus (CMV) glycoprotein B or a pp65/IE1 fusion protein. Efficient production methods were scaled to produce pilot lots and clinical lots of each alphavirus replicon vaccine component. The vaccine induced high-titered antibody responses in mice and rabbits, as measured by ELISA and CMV neutralization assays, an...

  19. Effects of cytomegalovirus infection in human neural precursor cells depend on their differentiation state

    OpenAIRE

    2015-01-01

    © 2015, Journal of NeuroVirology, Inc. Cytomegalovirus (CMV) is the most common cause of congenital infection in developed countries and a major cause of neurological disability in children. Although CMV can affect multiple organs, the most important sequelae of intrauterine infection are related to lesions of the central nervous system. However, little is known about the pathogenesis and the cellular events responsible for neuronal damage in infants with congenital infection. Some studies ha...

  20. Anti-CMV-IgG Positivity of Donors Is Beneficial for alloHSCT Recipients with Respect to the Better Short-Term Immunological Recovery and High Level of CD4+CD25high Lymphocytes

    Directory of Open Access Journals (Sweden)

    Emilia Jaskula

    2015-03-01

    Full Text Available Hematopoietic stem cell transplantation from anti-cytomegalovirus immunoglobulin G (anti-CMV-IgG positive donors facilitated immunological recovery post-transplant, which may indicate that chronic CMV infection has an effect on the immune system. This can be seen in the recipients after reconstitution with donor lymphocytes. We evaluated the composition of lymphocytes at hematologic recovery in 99 patients with hematologic malignancies post hematopoietic stem cell transplantation (HSCT. Anti-CMV-IgG seropositivity of the donor was associated with higher proportions of CD4+ (227.963 ± 304.858 × 106 vs. 102.050 ± 17.247 × 106 cells/L, p = 0.009 and CD4+CD25high (3.456 ± 0.436 × 106 vs. 1.589 ± 0.218 × 106 cells/L, p = 0.003 lymphocytes in the blood at hematologic recovery. The latter parameter exerted a diverse influence on the risk of acute graft-versus-host disease (GvHD if low (1.483 ± 0.360 × 106 vs. 3.778 ± 0.484 × 106 cells/L, p < 0.001 and de novo chronic GvHD (cGvHD if high (3.778 ± 0.780 × 106 vs. 2.042 ± 0.261 × 106 cells/L, p = 0.041. Higher values of CD4+ lymphocytes in patients who received transplants from anti-CMV-IgG-positive donors translated into a reduced demand for IgG support (23/63 vs. 19/33, p = 0.048, and these patients also exhibited reduced susceptibility to cytomegalovirus (CMV, Epstein–Barr virus (EBV and/or human herpes 6 virus (HHV6 infection/reactivation (12/50 vs. 21/47, p = 0.032. Finally, high levels (³0.4% of CD4+CD25high lymphocytes were significantly associated with better post-transplant survival (56% vs. 38%, four-year survival, p = 0.040. Donors who experience CMV infection/reactivation provide the recipients with lymphocytes, which readily reinforce the recovery of the transplanted patients’ immune system.

  1. Growth in agarose of human cells infected with cytomegalovirus.

    Science.gov (United States)

    Lang, D J; Montagnier, L; Latarjet, R

    1974-08-01

    After infection by human cytomegalovirus (CMV), human diploid fibroblasts could grow in agarose medium for several generations. Clones of infected cells grew for weeks, although in every case they ultimately underwent lysis owing to the cytopathic effect of the virus. Virus was inoculated at high dilution and after UV irradiation in an effort to derive cells infected with noninfectious defective particles still capable of inducing cell stimulation. Dilute or irradiated virus occasionally yielded large colonies of replicating cells, although permanent transformation was not observed. One clone derived from UV-CMV-infected cells was passaged four times before undergoing lysis. During these passages the cells exhibited alterations in morphology and orientation.

  2. Nodular inflammatory foci are sites of T cell priming and control of murine cytomegalovirus infection in the neonatal lung.

    Directory of Open Access Journals (Sweden)

    Felix R Stahl

    Full Text Available Neonates, including mice and humans, are highly susceptible to cytomegalovirus (CMV infection. However, many aspects of neonatal CMV infections such as viral cell tropism, spatio-temporal distribution of the pathogen as well as genesis of antiviral immunity are unknown. With the use of reporter mutants of the murine cytomegalovirus (MCMV we identified the lung as a primary target of mucosal infection in neonatal mice. Comparative analysis of neonatal and adult mice revealed a delayed control of virus replication in the neonatal lung mucosa explaining the pronounced systemic infection and disease in neonates. This phenomenon was supplemented by a delayed expansion of CD8(+ T cell clones recognizing the viral protein M45 in neonates. We detected viral infection at the single-cell level and observed myeloid cells forming "nodular inflammatory foci" (NIF in the neonatal lung. Co-localization of infected cells within NIFs was associated with their disruption and clearance of the infection. By 2-photon microscopy, we characterized how neonatal antigen-presenting cells (APC interacted with T cells and induced mature adaptive immune responses within such NIFs. We thus define NIFs of the neonatal lung as niches for prolonged MCMV replication and T cell priming but also as sites of infection control.

  3. Nodular inflammatory foci are sites of T cell priming and control of murine cytomegalovirus infection in the neonatal lung.

    Science.gov (United States)

    Stahl, Felix R; Heller, Katrin; Halle, Stephan; Keyser, Kirsten A; Busche, Andreas; Marquardt, Anja; Wagner, Karen; Boelter, Jasmin; Bischoff, Yvonne; Kremmer, Elisabeth; Arens, Ramon; Messerle, Martin; Förster, Reinhold

    2013-01-01

    Neonates, including mice and humans, are highly susceptible to cytomegalovirus (CMV) infection. However, many aspects of neonatal CMV infections such as viral cell tropism, spatio-temporal distribution of the pathogen as well as genesis of antiviral immunity are unknown. With the use of reporter mutants of the murine cytomegalovirus (MCMV) we identified the lung as a primary target of mucosal infection in neonatal mice. Comparative analysis of neonatal and adult mice revealed a delayed control of virus replication in the neonatal lung mucosa explaining the pronounced systemic infection and disease in neonates. This phenomenon was supplemented by a delayed expansion of CD8(+) T cell clones recognizing the viral protein M45 in neonates. We detected viral infection at the single-cell level and observed myeloid cells forming "nodular inflammatory foci" (NIF) in the neonatal lung. Co-localization of infected cells within NIFs was associated with their disruption and clearance of the infection. By 2-photon microscopy, we characterized how neonatal antigen-presenting cells (APC) interacted with T cells and induced mature adaptive immune responses within such NIFs. We thus define NIFs of the neonatal lung as niches for prolonged MCMV replication and T cell priming but also as sites of infection control.

  4. Cytomegalovirus survival and transferability and the effectiveness of common hand-washing agents against cytomegalovirus on live human hands.

    Science.gov (United States)

    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.

  5. Cytomegalovirus retinitis associated with acquired immunodeficiency syndrome

    Institute of Scientific and Technical Information of China (English)

    GENG Shuang; YE Jun-jie; ZHAO Jia-liang; LI Tai-sheng; HAN Yang

    2011-01-01

    Background 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.Methods 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).Results 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) ×106/L (range,(0-85) × 106/L). After intravitreal injections of ganciclovir, visual acuity was improved and fundus lesions regressed.Conclusions 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.

  6. Prognostic markers of symptomatic congenital cytomegalovirus infection.

    Science.gov (United States)

    Romanelli, Roberta Maia de Castro; Magny, Jean François; Jacquemard, François

    2008-02-01

    The objective of this research was to identify maternal and fetal characteristics as prognostic markers of congenital cytomegalovirus (CMV) infection. This is a descriptive study of 13 cases of congenital CMV infection referred to Institute de Puericulture et Perinatologie de Paris (IPP) from January 2005 to October 2006. Amniotic fluid puncture was performed to research CMV polimerase chain reaction (PCR). Cordocentesis and cord blood samples at delivery were also analyzed to determinate fetal platelets count, GGT, ASAT, ALAT, CMV-DNA and IgM antibody. Variables of symptomatic and asymptomatic infants were then compared. Data were analyzed by SPSS--15.0. Mean gestational age of amniocentesis was 24.6 weeks and there was no difference of mean viral load in amniotic fluid considering infant features. Mean gestational age of cordocentesis was 26.1 weeks. There were no statistical differences of fetal viral load, IgM, platelets, GGT, ASAT and ALAT analyzed at cordocentesis samples, but at delivery, mean values of IgM and ASAT of fetal blood were increased in symptomatic ones (p= 0.03 for both parameters). When considering groups with normal and abnormal parameters, ASAT of cordon samples was also increased in symptomatic infants (p= 0.02). Sensibility, specificity, positive and negative predictive value of fetal ultrasound anomalies to detect symptomatic infants were, respectively, 80%, 62.5%, 57.1% and 83.3%. Thus, identification of markers of CMV symptomatic infants should be aimed. Prenatal diagnosis, identification and follow up of congenital CMV infected infants are important to consider treatment for symptomatic infants, trying to avoid or reducing some possible sequels.

  7. Prognostic markers of symptomatic congenital cytomegalovirus infection

    Directory of Open Access Journals (Sweden)

    Roberta Maia de Castro Romanelli

    2008-02-01

    Full Text Available The objective of this research was to identify maternal and fetal characteristics as prognostic markers of congenital cytomegalovirus (CMV infection. This is a descriptive study of 13 cases of congenital CMV infection referred to Institute de Puericulture et Perinatologie de Paris (IPP from January 2005 to October 2006. Amniotic fluid puncture was performed to research CMV polimerase chain reaction (PCR. Cordocentesis and cord blood samples at delivery were also analyzed to determinate fetal platelets count, GGT, ASAT, ALAT, CMV-DNA and IgM antibody. Variables of symptomatic and asymptomatic infants were then compared. Data were analyzed by SPSS - 15.0. Mean gestational age of amniocentesis was 24.6 weeks and there was no difference of mean viral load in amniotic fluid considering infant features. Mean gestational age of cordocentesis was 26.1 weeks. There were no statistical differences of fetal viral load, IgM, platelets, GGT, ASAT and ALAT analyzed at cordocentesis samples, but at delivery, mean values of IgM and ASAT of fetal blood were increased in symptomatic ones (p= 0.03 for both parameters. When considering groups with normal and abnormal parameters, ASAT of cordon samples was also increased in symptomatic infants (p= 0.02. Sensibility, specificity, positive and negative predictive value of fetal ultrasound anomalies to detect symptomatic infants were, respectively, 80%, 62.5%, 57.1% and 83.3%. Thus, identification of markers of CMV symptomatic infants should be aimed. Prenatal diagnosis, identification and follow up of congenital CMV infected infants are important to consider treatment for symptomatic infants, trying to avoid or reducing some possible sequels.

  8. Activation of stress-activated MAP protein kinases up-regulates expression of transgenes driven by the cytomegalovirus immediate/early promoter.

    OpenAIRE

    Bruening, W; Giasson, B; Mushynski, W; Durham, H D

    1998-01-01

    The immediate/early promoter/enhancer of cytomegalovirus (CMV promoter) is one of the most commonly used promoters for expression of transgenes in eukaryotic cells. In practice, the CMV promoter is often thought of as a constitutively active unregulated promoter. However, we have observed that transcription from the CMV promoter can be up-regulated by a variety of environmental stresses. Many forms of cellular stress stimulate MAP kinase signalling pathways, resulting in activation of stress-...

  9. Epigenetic Control of Cytomegalovirus Latency and Reactivation

    Directory of Open Access Journals (Sweden)

    Mary Hummel

    2013-05-01

    Full Text Available Cytomegalovirus (CMV gene expression is repressed in latency due to heterochromatinization of viral genomes. In murine CMV (MCMV latently infected mice, viral genomes are bound to histones with heterochromatic modifications, to enzymes that mediate these modifications, and to adaptor proteins that may recruit co-repressor complexes. Kinetic analyses of repressor binding show that these repressors are recruited at the earliest time of infection, suggesting that latency may be the default state. Kidney transplantation leads to epigenetic reprogramming of latent viral chromatin and reactivation of immediate early gene expression. Inflammatory signaling pathways, which activate transcription factors that regulate the major immediate early promoter (MIEP, likely mediate the switch in viral chromatin.

  10. A comparative study of two histological techniques for the identification of cytomegalovirus infection in colorectal biopsies from patients with chronic inflammatory bowel disease Estudio comparativo entre dos técnicas histológicas para el diagnóstico de infección por citomegalovirus en biopsias colorrectales de pacientes con enfermedad inflamatoria intestinal crónica idiopática

    Directory of Open Access Journals (Sweden)

    M. L. de Castro

    2009-10-01

    Full Text Available Background: the role that cytomegalovirus (CMV plays in inflammatory bowel disease (IBD is controversial. The diagnosis of CMV infection in IBD depends on viral identification with hematoxylin-eosin (HE or immunohistochemistry (IHC. Our aim was to compare the sensitivity of HE and IHC for this diagnosis in IBD patients. Patients and methods: a case-control study. Our database was searched for IBD patients with HE- or IHC-based CMV-positivity from 1997 to 2007. Controls were selected among IBD inpatients matched for age and year of diagnosis with CMV. Their clinical characteristics were analyzed. HE and IHC were performed on biopsies from cases and controls at 6 months before and after inclusion in the study. In the statistical analysis, p values below 0.05 were considered significant. Results: ten IBD patients with CMV infection were identified. IBD-CMV patients were more steroid-resistant or steroid-dependent (p = 0.03, and underwent a higher number of colonic biopsies (p = 0.03. From 97 biopsies analyzed, 12 were HE-negative and IHC-positive, and 3 showed reversed results. The sensitivity of HE was 58.6%, 95% CI (38.9-78.3, and that of IHC was 89.7%, 95% CI (76.8-100. We did not find a good level of agreement between both techniques: kappa value 0.55, 95% CI (0.36-0.75. CMV positivity with IHC was associated with the use of more than one immunosuppressant drug, OR 13.5, 95% CI (1.2-152.2. Antiviral treatment was useful for CMV patients with steroid-dependent and steroid-refractory IBD. Conclusions: IHC shows a 30% higher sensitivity than HE for the diagnosis of CMV infection in IBD patients. There is no good level of agreement between both histological techniques.Introducción: el papel que el citomegalovirus (CMV juega en la enfermedad inflamatoria intestinal (EII es controvertido. El diagnóstico de infección por CMV en estos pacientes reside en su identificación en el tejido colónico mediante hematoxilina-eosina (HE o inmunohistoqu

  11. Direct ex vivo detection of HLA-DR3-restricted cytomegalovirus- and Mycobacterium tuberculosis-specific CD4+ T cells.

    Science.gov (United States)

    Bronke, Corine; Palmer, Nanette M; Westerlaken, Geertje H A; Toebes, Mireille; van Schijndel, Gijs M W; Purwaha, Veenu; van Meijgaarden, Krista E; Schumacher, Ton N M; van Baarle, Debbie; Tesselaar, Kiki; Geluk, Annemieke

    2005-09-01

    In order to detect epitope-specific CD4+ T cells in mycobacterial or viral infections in the context of human class II major histocompatibility complex protein human leukocyte antigen (HLA)-DR3, two HLA-DR3 tetrameric molecules were successfully produced. One contained an immunodominant HLA-DR3-restricted T-cell epitope derived from the 65-kDa heat-shock protein of Mycobacterium tuberculosis, peptide 1-13. For the other tetramer, we used an HLA-DR3-restricted T-cell epitope derived from cytomegalovirus (CMV) pp65 lower matrix protein, peptide 510-522, which induced high levels of interferon (IFN)-gamma-producing CD4+ T cells in three of four HLA-DR3-positive CMV-seropositive individuals up to 0.84% of CD4+ T cells by intracellular cytokine staining. In peripheral blood mononuclear cells from M. tuberculosis-exposed, Mycobacterium bovis bacille Calmette-Guérin (BCG)-vaccinated, or CMV-seropositive individuals, we were able to directly detect with both tetramers epitope-specific T cells up to 0.62% and 0.45% of the CD4+ T-cell population reactive to M. tuberculosis and CMV, respectively. After a 6-day culture with peptide p510-522, the frequency of CMV-specific tetramer-binding T cells was expanded up to 9.90% tetramer+ CFSElow (5,6-carboxyfluorescein diacetate succinimidyl ester) cells within the CD4+ T-cell population, further confirming the specificity of the tetrameric molecules. Thus, HLA-DR3/peptide tetrameric molecules can be used to investigate HLA-DR3-restricted antigen-specific CD4+ T cells in clinical disease or after vaccination.

  12. Fever and neutropenia due to cytomegalovirus infection in a breast cancer patient under chemotherapy: a case report

    Directory of Open Access Journals (Sweden)

    Ahmadinejad Z

    2010-06-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Fever in neutropenic patients is a medical emergency which may happen in patients undergoing chemotherapy. The definition of neutropenia varies from institution to institution but is usually defined as an absolute neutrophil count (ANC    < 500 cells/ml or < 1,000 cells/ml with a predicted nadir of < 500 cells/ml. Bacterial and fungal infections are the most important in neutropenic patients. Viral infections with agents such as herpes simplex virus and cytomegalovirus are common but less than other pathogens."n"nCase presentation: We report a patient with fever & neutropenia following cytomegalovirus infection during chemotherapy course for breast cancer."n"nConclusion: Although fever and neutropenia after cytomegalovirus infection is not very common but prompt diagnosis and treatment of this disease reduces the mortality and morbidity associated with cytomegalovirus. For this reason, screen testing for CMV infection in high risk patients including patients with cancer and preemptive therapy in patients with viremia, for prevention of CMV disease could be considered as a strategy for prevention of CMV infection.

  13. Cytomegalovirus retinitis after initiation of antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Zahra Ahmadinejad

    2013-10-01

    Full Text Available Patients with human immunodeficiency virus (HIV infection receiving antiretroviral therapy (ART, despite a reduced viral load and improved immune responses, may experience clinical deterioration. This so called "immune reconstitution inflammatory syndrome (IRIS" is caused by inflammatory response to both intact subclinical pathogens and residual antigens. Cytomegalovirus retinitis is common in HIV-infected patients on ART with a cluster differentiation 4 (CD4+ counts less than 50 cells/mm3. We reported a patient with blurred vision while receiving ART. She had an unmasking classic CMV retinitis after ART.

  14. Cytomegalovirus related fatal duodenal diverticular bleeding: Case report and literature review.

    Science.gov (United States)

    Makker, Jasbir; Bajantri, Bharat; Sakam, Sailaja; Chilimuri, Sridhar

    2016-08-21

    Involvement of gastrointestinal tract by cytomegalovirus (CMV) is common. CMV infections mainly run their course without any clinical signs in immunocompetent hosts. In contrast, CMV can cause severe infections with serious consequences in a immunocompromised state typically associated with organ transplants, highly immunosuppressive cancer chemotherapy, advanced HIV infection or treatment with corticosteroids. The incidence and severity of these manifestations of CMV is directly proportional with the degree of cellular immune dysfunction, i.e., CD8+ Cytotoxic T-cell response. Clinical manifestations of CMV can become apparent in different situations including reactivation of CMV from latency, primary infection in a seronegative host, or exposure of a seropositive host to a new strain of CMV. As the clinical signs of CMV in immunodeficient patients are usually sparse, physicians should be highly vigilant about CMV infection, a treatable condition that otherwise is associated with significant mortality. Here we report a rare case of severe gastrointestinal CMV infection with sustained immunodeficiency secondary to treatment with steroids manifesting as fatal duodenal diverticular bleeding.

  15. Cytomegalovirus related fatal duodenal diverticular bleeding: Case report and literature review

    Science.gov (United States)

    Makker, Jasbir; Bajantri, Bharat; Sakam, Sailaja; Chilimuri, Sridhar

    2016-01-01

    Involvement of gastrointestinal tract by cytomegalovirus (CMV) is common. CMV infections mainly run their course without any clinical signs in immunocompetent hosts. In contrast, CMV can cause severe infections with serious consequences in a immunocompromised state typically associated with organ transplants, highly immunosuppressive cancer chemotherapy, advanced HIV infection or treatment with corticosteroids. The incidence and severity of these manifestations of CMV is directly proportional with the degree of cellular immune dysfunction, i.e., CD8+ Cytotoxic T-cell response. Clinical manifestations of CMV can become apparent in different situations including reactivation of CMV from latency, primary infection in a seronegative host, or exposure of a seropositive host to a new strain of CMV. As the clinical signs of CMV in immunodeficient patients are usually sparse, physicians should be highly vigilant about CMV infection, a treatable condition that otherwise is associated with significant mortality. Here we report a rare case of severe gastrointestinal CMV infection with sustained immunodeficiency secondary to treatment with steroids manifesting as fatal duodenal diverticular bleeding. PMID:27610026

  16. Cytomegalovirus induces abnormal chondrogenesis and osteogenesis during embryonic mandibular development

    Directory of Open Access Journals (Sweden)

    Bringas Pablo

    2008-03-01

    Full Text Available Abstract Background Human clinical studies and mouse models clearly demonstrate that cytomegalovirus (CMV disrupts normal organ and tissue development. Although CMV is one of the most common causes of major birth defects in humans, little is presently known about the mechanism(s underlying CMV-induced congenital malformations. Our prior studies have demonstrated that CMV infection of first branchial arch derivatives (salivary glands and teeth induced severely abnormal phenotypes and that CMV has a particular tropism for neural crest-derived mesenchyme (NCM. Since early embryos are barely susceptible to CMV infection, and the extant evidence suggests that the differentiation program needs to be well underway for embryonic tissues to be susceptible to viral infection and viral-induced pathology, the aim of this study was to determine if first branchial arch NCM cells are susceptible to mCMV infection prior to differentiation of NCM derivatives. Results E11 mouse mandibular processes (MANs were infected with mouse CMV (mCMV for up to 16 days in vitro. mCMV infection of undifferentiated embryonic mouse MANs induced micrognathia consequent to decreased Meckel's cartilage chondrogenesis and mandibular osteogenesis. Specifically, mCMV infection resulted in aberrant stromal cellularity, a smaller, misshapen Meckel's cartilage, and mandibular bone and condylar dysmorphogenesis. Analysis of viral distribution indicates that mCMV primarily infects NCM cells and derivatives. Initial localization studies indicate that mCMV infection changed the cell-specific expression of FN, NF-κB2, RelA, RelB, and Shh and Smad7 proteins. Conclusion Our results indicate that mCMV dysregulation of key signaling pathways in primarily NCM cells and their derivatives severely disrupts mandibular morphogenesis and skeletogenesis. The pathogenesis appears to be centered around the canonical and noncanonical NF-κB pathways, and there is unusual juxtaposition of abnormal stromal

  17. Cytomegalovirus infection in transplant recipients

    Directory of Open Access Journals (Sweden)

    Luiz Sergio Azevedo

    2015-07-01

    Full Text Available Cytomegalovirus infection is a frequent complication after transplantation. This infection occurs due to transmission from the transplanted organ, due to reactivation of latent infection, or after a primary infection in seronegative patients and can be defined as follows: latent infection, active infection, viral syndrome or invasive disease. This condition occurs mainly between 30 and 90 days after transplantation. In hematopoietic stem cell transplantation in particular, infection usually occurs within the first 30 days after transplantation and in the presence of graft-versus-host disease. The major risk factors are when the recipient is cytomegalovirus seronegative and the donor is seropositive as well as when lymphocyte-depleting antibodies are used. There are two methods for the diagnosis of cytomegalovirus infection: the pp65 antigenemia assay and polymerase chain reaction. Serology has no value for the diagnosis of active disease, whereas histology of the affected tissue and bronchoalveolar lavage analysis are useful in the diagnosis of invasive disease. Cytomegalovirus disease can be prevented by prophylaxis (the administration of antiviral drugs to all or to a subgroup of patients who are at higher risk of viral replication or by preemptive therapy (the early diagnosis of viral replication before development of the disease and prescription of antiviral treatment to prevent the appearance of clinical disease. The drug used is intravenous or oral ganciclovir; oral valganciclovir; or, less frequently, valacyclovir. Prophylaxis should continue for 90 to 180 days. Treatment is always indicated in cytomegalovirus disease, and the gold-standard drug is intravenous ganciclovir. Treatment should be given for 2 to 3 weeks and should be continued for an additional 7 days after the first negative result for viremia.

  18. Analysis of HIV-1- and CMV-specific memory CD4 T-cell responses during primary and chronic infection.

    Science.gov (United States)

    Harari, Alexandre; Rizzardi, G Paolo; Ellefsen, Kim; Ciuffreda, Donatella; Champagne, Patrick; Bart, Pierre-Alexandre; Kaufmann, Daniel; Telenti, Amalio; Sahli, Roland; Tambussi, Giuseppe; Kaiser, Laurent; Lazzarin, Adriano; Perrin, Luc; Pantaleo, Giuseppe

    2002-08-15

    CD4 T-cell-specific memory antiviral responses to human immunodeficiency virus type 1 (HIV-1) and cytomegalovirus (CMV) were investigated in 16 patients with documented primary HIV-1 infection (4 of the 16 subjects also had primary CMV infection) and compared with those observed in patients with chronic HIV-1 and CMV coinfection. Virus-specific memory CD4 T cells were characterized on the basis of the expression of the chemokine receptor CCR7. HIV-1- and CMV-specific interferon-gamma-secreting CD4 T cells were detected in patients with primary and chronic HIV-1 and CMV coinfection and were mostly contained in the cell population lacking expression of CCR7. The magnitude of the primary CMV-specific CD4 T-cell response was significantly greater than that of chronic CMV infection, whereas there were no differences between primary and chronic HIV-1-specific CD4 T-cell responses. A substantial proportion of CD4(+)CCR7(-) T cells were infected with HIV-1. These results advance the characterization of antiviral memory CD4 T-cell response and the delineation of the potential mechanisms that likely prevent the generation of a robust CD4 T-cell immune response during primary infection.

  19. Human bone marrow as a source to generate CMV-specific CD4+ T cells with multifunctional capacity.

    Science.gov (United States)

    Na, Il-Kang; Letsch, Anne; Guerreiro, Manuel; Bauer, Sandra; Noack, Ines; Geginat, Jens; Reinke, Petra; Loesch, Michael; Kienapfel, Heino; Thiel, Eckhard; Volk, Hans Dieter; Scheibenbogen, Carmen

    2009-01-01

    The bone marrow (BM) is an important compartment for T cell memory. In cytomegalovirus (CMV)-seropositive individuals peripheral blood (PB) CMV-specific T cells constitute a large fraction of PB T cells but are mostly differentiated effector/effector memory T cells with limited survival and proliferative potential. In this study, we performed a comprehensive analysis of the CMV-specific T cell response in BM studying both CD4+ and CD8+ T cell responses against overlapping peptide pools of the CMV proteins pp65 and immediate early protein-1. CMV-specific T cell responses were characterized ex vivo and after in vitro expansion of paired PB/BM samples by multiparameter flow cytometry determining surface phenotype, cytokine profile, and cytotoxic capability. Comparable frequencies of CMV-specific T cells were found in un-manipulated PB and BM. Both total CD4+ and CD8+ T cells could be more rapidly expanded from BM. Expanded BM T cells contained significantly higher frequencies of CMV-specific CD4+ T cells than PB. Furthermore, higher frequencies of specific CD4+ T cells from BM were multifunctional, characterized by simultaneous production of interferon-gamma, tumor necrosis factor, and interleukin-2. Use of BM may thus facilitate more rapid generation of adoptive T cells with enhanced functionality.

  20. The value of CMV IgG avidity and immunoblot for timing the onset of primary CMV infection in pregnancy.

    Science.gov (United States)

    Enders, Gisela; Daiminger, Anja; Bäder, Ursula; Exler, Simone; Schimpf, Yvonne; Enders, Martin

    2013-02-01

    Primary CMV infections in pregnancy are usually asymptomatic and only detected by serology. Estimating the onset of infection is a major diagnostic goal, since primary infections around conception and in early gestation hold a higher risk for congenital disease than those in later pregnancy. To assess the ability of serological supplementary CMV assays to date the onset of primary infection. From our routine diagnosis we identified 61 pregnant women (n=188 serum samples) with precisely determined onset of CMV primary infection either by IgG seroconversion (n=24) or by significant IgG antibody rise (n=37). One hundred and forty-seven sera were investigated using the VIDAS(®) CMV IgG avidity EIA (BioMèrieux) and 83 sera using the recomBlot CMV IgG with avidity (Mikrogen). Both assays proofed to be reliable in terms of timing the onset of CMV primary infection. An avidity index (AI) in the VIDAS avidity EIA of <40% indicated primary infection within the last 20 weeks (positive predictive value 93.4%; 99/106), whereas an intermediate AI excluded primary infection within the last 12 weeks (negative predictive value 88.2%; 15/17). The recomBlot showed high reliability (PPV 96.9%; 31/33) for timing the onset of infection within the last 14 weeks. Avidity testing by blot however could not be interpreted in 11 of 47 sera (23.4%). For timing the onset of infection (before or in early pregnancy) CMV avidity testing is most helpful if carried out within the first trimester up to the beginning of second trimester. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. Retrospective analysis of cytomegalovirus infection in children of Wuhu City%芜湖市患儿巨细胞病毒感染回顾性分析

    Institute of Scientific and Technical Information of China (English)

    苏贵灵; 李光友; 王佐; 潘嘉严

    2014-01-01

    目的:了解芜湖市患儿巨细胞病毒感染状况。方法应用酶联免疫吸附试验对874例可疑巨细胞病毒感染患儿血清CMV-IgM抗体进行检测。结果874例患儿CMV-IgM检出率为4.46%。其中男童阳性26例(26/531),阳性率4.89%;女童阳性13例(13/343),阳性率3.79%;男童与女童CMV-IgM阳性率之间差异无统计学意义(χ2=0.37,P>0.05)。在不同年龄组中,以>6个月~1岁组阳性率最高,达10.19%。其中主要表现依次为肝功能异常、神经系统疾病、黄疸、肺炎。结论芜湖市患儿CMV感染率较高,应引起儿科医生的重视。%Objective To investigate the cytomegalovirus( CMV) infection in children of Wuhu City. Methods Serum samples from children n=874 were tested for CMV-IgM using commercial ELISA kits. Re-sults The CMV-IgM detective rate of serum samples from 874 children was 4. 46%. The positive rate of CMV-IgM was 4. 89%(26/531cases)and 3. 79%(13/343 cases)in boys and girls,respectively. There was no signifi-cant difference in the positive rate of CMV-IgM between boys and girls(χ2 =0. 37,P>0. 05). The positive rate peaked in children at age of >6 months~1 year(10. 19%). Clinical manifestations included liver dysfunction, neurological diseases,jaundice and pneumonia. Conclusion The positive rate of CMV-IgM in children in local district of Wuhu city is high,which should be given due attention.

  2. Rapid quantitative PCR assays for the simultaneous detection of herpes simplex virus, varicella zoster virus, cytomegalovirus, Epstein-Barr virus, and human herpesvirus 6 DNA in blood and other clinical specimens

    NARCIS (Netherlands)

    Engelmann, I.; Petzold, D. R.; Kosinska, A.; Hepkema, B. G.; Schulz, T. F.; Heim, A.

    Rapid diagnosis of human herpesvirus primary infections or reactivations is facilitated by quantitative PCRs. Quantitative PCR assays with a standard thermal cycling profile permitting simultaneous detection of herpes simplex virus (HSV), varicella zoster virus (VZV), cytomegalovirus (CMV),

  3. Congenital cytomegalovirus infection and Wiskott-Aldrich syndrome successfully treated with unrelated cord blood transplantation.

    Science.gov (United States)

    Almagor, Yotam; Revel-Vilk, Shoshana; Averbuch, Diana; Mechoulam, Hadas; Engelhard, Dan; Resnick, Igor B; Weintraub, Michael; Stepensky, Polina

    2011-10-01

    We report a successful umbilical cord blood transplantation (UCBT) in an 8-month male with Wiskott-Aldrich syndrome (WAS) and congenital cytomegalovirus (CMV) infection. The child presented at 3 months of age with symptomatic thrombocytopenia and CMV infection. Despite appropriate antiviral treatment no rise in the platelet count was observed. Genetic analysis confirmed the diagnosis of WAS. The clinical course was complicated by severe CMV retinitis with bilateral retinal hemorrhages and renal vasculitis. He underwent unrelated UCBT resulting in a rapid resolution of autoimmunity and thrombocytopenia. Copyright © 2011 Wiley-Liss, Inc.

  4. Comparison of Three Nucleic Acid Amplification Assays of Cerebrospinal Fluid for Diagnosis of Cytomegalovirus Encephalitis

    Science.gov (United States)

    Bestetti, Arabella; Pierotti, Chiara; Terreni, Mariarosa; Zappa, Alessandra; Vago, Luca; Lazzarin, Adriano; Cinque, Paola

    2001-01-01

    The diagnostic reliabilities of three cytomegalovirus (CMV) nucleic acid amplification assays of cerebrospinal fluid (CSF) were compared by using CSF samples from human immunodeficiency virus-infected patients with a postmortem histopathological diagnosis of CMV encephalitis (n = 15) or other central nervous system conditions (n = 16). By using a nested PCR assay, the quantitative COBAS AMPLICOR CMV MONITOR PCR, and the NucliSens CMV pp67 nucleic acid sequence-based amplification assay, sensitivities were 93.3, 86.6, and 93.3%, respectively, and specificities were 93.7, 93.7, and 87.5%, respectively. The COBAS AMPLICOR assay revealed significantly higher CMV DNA levels in patients with diffuse ventriculoencephalitis than in patients with focal periventricular lesions. PMID:11230445

  5. Epidemiology of cytomegalovirus infection in pregnant women living in the Greater Romagna Area, Italy

    Directory of Open Access Journals (Sweden)

    Patrizia Billi

    2015-12-01

    Full Text Available Background. Aim of this study was to assess the incidence of Cytomegalovirus (CMV infection in pregnant women living in Romagna area, in North East Italy to implement the best management of this infection. Materials and Methods. In 2012, 23,727 serological tests for CMV IgG and IgM antibodies were performed in the Microbiology Unit, the Hub Laboratory of the Greater Romagna Area: 6931 were pregnant women. Results and Conclusions. 179 subjects were positive for CMV IgM antibodies: 82 were not pregnant; 97 were IgM positive during pregnancy or in the course of a pre-conception evaluation. The detected incidence of the CMV infection in pregnancy (calculated at 1.40% actually validates the literature data. This study’s findings clearly underline the usefulness of testing the CMV specific immune response in the pre-conception period or as early as possible during pregnancy.

  6. Cytomegalovirus and Epstein-Barr virus in breast cancer.

    Science.gov (United States)

    Richardson, Ann K; Currie, Margaret J; Robinson, Bridget A; Morrin, Helen; Phung, Yen; Pearson, John F; Anderson, Trevor P; Potter, John D; Walker, Logan C

    2015-01-01

    Findings of polymerase chain reaction (PCR) studies of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) and breast cancer vary, making it difficult to determine whether either, both, or neither virus is causally associated with breast cancer. We investigated CMV and EBV in paired samples of breast cancer and normal breast tissue from 70 women using quantitative PCR. A serum sample from each woman was tested for CMV and EBV IgG. To place our results in context, we reviewed the existing literature and performed a meta-analysis of our results together with previous PCR studies of EBV, CMV, and breast cancer. Of the serology samples, 67 of 70 (96%) were EBV IgG positive and 49 of 70 (70%) were CMV IgG positive. QPCR detected EBV in 24 (34%) of the tumour and 9 (13%) of the paired normal specimens and CMV in 0 (0%) of the tumour and 2 (3%) of the paired normal specimens. Our findings, together with earlier results summarised in the meta-analysis, suggest several possibilities: variable findings may be due to limitations of molecular analyses; 'hit and run' oncogenesis may lead to inconsistent results; one or both viruses has a role at a later stage in breast cancer development; infection with multiple viruses increases breast cancer risk; or neither virus has a role. Future studies should focus on ways to investigate these possibilities, and should include comparisons of breast cancer tissue samples with appropriate normal tissue samples.

  7. Cytomegalovirus and Epstein-Barr virus in breast cancer.

    Directory of Open Access Journals (Sweden)

    Ann K Richardson

    Full Text Available Findings of polymerase chain reaction (PCR studies of cytomegalovirus (CMV and Epstein-Barr virus (EBV and breast cancer vary, making it difficult to determine whether either, both, or neither virus is causally associated with breast cancer. We investigated CMV and EBV in paired samples of breast cancer and normal breast tissue from 70 women using quantitative PCR. A serum sample from each woman was tested for CMV and EBV IgG. To place our results in context, we reviewed the existing literature and performed a meta-analysis of our results together with previous PCR studies of EBV, CMV, and breast cancer. Of the serology samples, 67 of 70 (96% were EBV IgG positive and 49 of 70 (70% were CMV IgG positive. QPCR detected EBV in 24 (34% of the tumour and 9 (13% of the paired normal specimens and CMV in 0 (0% of the tumour and 2 (3% of the paired normal specimens. Our findings, together with earlier results summarised in the meta-analysis, suggest several possibilities: variable findings may be due to limitations of molecular analyses; 'hit and run' oncogenesis may lead to inconsistent results; one or both viruses has a role at a later stage in breast cancer development; infection with multiple viruses increases breast cancer risk; or neither virus has a role. Future studies should focus on ways to investigate these possibilities, and should include comparisons of breast cancer tissue samples with appropriate normal tissue samples.

  8. Prevalence of CMV infection among staff in a metropolitan children’s hospital – occupational health screening findings

    Directory of Open Access Journals (Sweden)

    Stranzinger, Johanna

    2016-09-01

    Full Text Available 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.

  9. Impact of cytomegalovirus infection, year of transplantation, and donor age on outcomes after liver transplantation for hepatitis C.

    Science.gov (United States)

    Burak, Kelly W; Kremers, Walter K; Batts, Kenneth P; Wiesner, Russell H; Rosen, Charles B; Razonable, Raymund R; Paya, Carlos V; Charlton, Michael R

    2002-04-01

    Recurrence of hepatitis C virus (HCV) infection after liver transplantation (LT) is almost universal. However, variables that hasten the progression of allograft injury have not been fully defined. Cytomegalovirus (CMV) is a common infection post-LT, and its impact on the course of post-LT HCV infection remains unclear. We investigated the impact of CMV infection on patient and graft outcomes in 93 consecutive HCV-infected liver transplant recipients. Data were collected prospectively, with surveillance cultures for CMV and protocol liver biopsies. CMV infection (defined as isolation of CMV from blood and treatment with ganciclovir) occurred in 25 patients (26.9%). Graft failure (defined as cirrhosis, relisting for LT, re-LT, or death) was significantly more common in CMV-positive compared with CMV-negative patients (52% v 19.1%; P =.002). Fibrosis stage 2 or greater on the 4-month liver biopsy specimen was more common in CMV-infected patients (45% v 16.4%; P =.01). Patients who underwent LT in more recent years had an increased risk for graft failure. Donor and recipient age, CMV infection, and mycophenolate mofetil use were significantly associated with graft failure in a stepwise multivariate analysis. CMV infection occurs in approximately one quarter of HCV-infected liver transplant recipients and is an independent risk factor for graft failure in these patients. Whether CMV mediates this by inducing increased immunosuppression or directly enhancing HCV replication requires further study.

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

    Science.gov (United States)

    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

  11. How I treat resistant cytomegalovirus infection in hematopoietic cell transplantation recipients

    Science.gov (United States)

    El Chaer, Firas; Shah, Dimpy P.

    2016-01-01

    Cytomegalovirus (CMV) infection is a significant complication in hematopoietic cell transplantation (HCT) recipients. Four antiviral drugs are used for preventing or treating CMV: ganciclovir, valganciclovir, foscarnet, and cidofovir. With prolonged and repeated use of these drugs, CMV can become resistant to standard therapy, resulting in increased morbidity and mortality, especially in HCT recipients. Antiviral drug resistance should be suspected when CMV viremia (DNAemia or antigenemia) fails to improve or continue to increase after 2 weeks of appropriately dosed and delivered antiviral therapy. CMV resistance is diagnosed by detecting specific genetic mutations. UL97 mutations confer resistance to ganciclovir and valganciclovir, and a UL54 mutation confers multidrug resistance. Risk factors for resistance include prolonged or previous anti-CMV drug exposure or inadequate dosing, absorption, or bioavailability. Host risk factors include type of HCT and degree of immunosuppression. Depending on the genotyping results, multiple strategies can be adopted to treat resistant CMV infections, albeit no randomized clinical trials exist so far, after reducing immunosuppression (if possible): ganciclovir dose escalation, ganciclovir and foscarnet combination, and adjunct therapy such as CMV-specific cytotoxic T-lymphocyte infusions. Novel therapies such as maribavir, brincidofovir, and letermovir should be further studied for treatment of resistant CMV. PMID:27760756

  12. Congenital Cytomegalovirus: a "Now" Problem-No Really, Now.

    Science.gov (United States)

    Bernstein, David I

    2017-01-01

    Despite the clear need, progress toward a vaccine for congenital cytomegalovirus (CMV) has been slow. However, recent events have provided new interest, and several vaccine candidates are either in clinical trials or the trials are close to starting. In this issue of Clinical and Vaccine Immunology, Schleiss and colleagues show that a nonreplicating lymphocytic choriomeningitis virus (rLCMV)-vectored vaccine expressing CMV glycoprotein B (gB) and/or pp65 induces B and T cells and improves pup survival in a guinea pig model of congenital CMV infection (Clin Vaccine Immunol 24:e00300-16, 2017, https://doi.org/10.1128/CVI.00300-16). The combination vaccine appeared to be the most effective. Copyright © 2017 American Society for Microbiology.

  13. Magnetic resonance imaging of the brain in congenital cytomegalovirus infection

    Energy Technology Data Exchange (ETDEWEB)

    Boesch, C.; Issakainen, J.; Kewitz, G.; Kikinis, R.; Martin, E.; Boltshauser, E.

    1989-01-01

    The children (age 2 months to 8 years) with a congenital cytomegalovirus (CMV) infection were studied by magnetic resonance imaging (MRI) using a 2.35 Tesla magnet. CMV infection was confirmed by serological investigations and virus culture in the neonatal period. Nine children had severe mental retardation and cerebral palsy, 1 patient suffered from microcephaly, ataxia and deafness. The cranial MRI examination showed the following abnormalities (N): Dilated lateral ventricles (10) and subarachnoid space (8), oligo/pacgyria (8), delayed/pathological myelination (7), paraventricular cysts (6), intra-cerebral calcification (1). This lack of sensitivity for calcification is explainable by the basic principles of MRI. The paraventricular cystic lesions were adjacent ot the occipital horns of the lateral ventricles and separated only by a thin membrane. This finding might represent a 'new sign' for congenital CMV infection in MRI examinations, being characteristic but nevertheless nonspecific, like calcification in CT.

  14. Cytomegalovirus reactivation and mortality in patients with acute respiratory distress syndrome

    NARCIS (Netherlands)

    Ong, David S Y; Spitoni, Cristian; Klein Klouwenberg, Peter M C; Verduyn Lunel, Frans M; Frencken, Jos F; Schultz, Marcus J; van der Poll, Tom; Kesecioglu, Jozef; Bonten, Marc J M; Cremer, Olaf L

    2015-01-01

    PURPOSE: Cytomegalovirus (CMV) reactivation occurs frequently in patients with the acute respiratory distress syndrome (ARDS) and has been associated with increased mortality. However, it remains unknown whether this association represents an independent risk for poor outcome. We aimed to estimate t

  15. Neuro-imaging findings in infants with congenital cytomegalovirus infection : Relation to trimester of infection

    NARCIS (Netherlands)

    Oosterom, Natanja; Nijman, Joppe; Gunkel, Julia; Wolfs, Tom F W; Groenendaal, Floris; Verboon-Maciolek, Malgosia A.; De Vries, Linda S.

    2015-01-01

    Background: Congenital cytomegalovirus (cCMV) infection early in pregnancy may result in major disabilities. Cerebral abnormalities detected using cranial ultrasound (cUS) and magnetic resonance imaging (MRI) have been related to neurological sequelae. Objective: To evaluate the additional value of

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

    NARCIS (Netherlands)

    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.

  17. Susceptibility of Human Pancreatic beta Cells for Cytomegalovirus Infection and the Effects on Cellular Immunogenicity

    NARCIS (Netherlands)

    Smelt, M.J.; Faas, M.M.; de Haan, Bart; Draijer, C.; Hugenholtz, G.C.G.; de Haan, A.; Engelse, M.A.; de Koning, E.J.P.; de Vos, P.

    2012-01-01

    Objectives: Human cytomegalovirus (HCMV) infection has been suggested to be a causal factor in the development of type 1 diabetes, posttransplantation diabetes, and the failure of islet allografts. This effect of CMV has been interpreted as an indirect effect on the immune system rather than direct

  18. Possible contribution of cytomegalovirus infection to the high risk of (recurrent) venous thrombosis after renal transplantation

    NARCIS (Netherlands)

    Lijfering, Willem M.; de Vries, Aiko R. J.; Veeger, Nic J. G. M.; van Son, Willem J.; Bakker, Stephan J. L.; van der Meer, Jan

    2008-01-01

    Renal transplant recipients are at an increased risk of venous thrombosis, which has been regarded as a postoperative complication, although it may persist afterwards. As numerous case reports have shown that active cytomegalovirus (CMV) infection can be found at time of onset of venous thrombosis,

  19. Cytomegalovirus vaccines and methods of production (WO20009049138): the emerging recognition of the importance of virus neutralization at the epithelial/endothelial interface.

    Science.gov (United States)

    Schleiss, Mark R

    2010-04-01

    Human cytomegalovirus (CMV) is the most common cause of congenital viral infection in the developed world. Approximately 40,000 congenitally infected infants are born in the US each year. Congenital CMV infection is responsible for a wide range of neurodevelopmental disabilities and is the most common infectious cause of hearing loss in children. The significant public health impact of congenital CMV has led the Institute of Medicine to rank development of a CMV vaccine as a top priority. Vaccine development has been ongoing; however, there is no licensed CMV vaccine currently available. Before vaccines can be optimized, a better understanding of how CMV infects the host is required. Recently, it has been demonstrated that CMV enters epithelial and endothelial cells by different pathways than those used for entry into fibroblasts, and that a recently described complex of CMV proteins, the gH/gL/UL128/130/131 complex, is essential for this process to occur. This discovery has allowed identification of a novel, heretofore unexplored, potential CMV vaccine targets, and provides the basis for the patent, 'Cytomegalovirus Vaccines and Methods of Production - WO2009049138.' In this patent evaluation, the basis for this patent is reviewed. The potential application of this discovery for future CMV vaccine design is discussed.

  20. Reevaluation of the Coding Potential and Proteomic Analysis of the BAC Derived Rhesus Cytomegalovirus Strain 68-1

    Energy Technology Data Exchange (ETDEWEB)

    Malouli, Daniel; Nakayasu, Ernesto S.; Viswanathan, Kasinath; Camp, David G.; Chang, W. L.; Barry, Peter A.; Smith, Richard D.; Fruh, Klaus

    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 with 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.

  1. Case of cytomegalovirus colitis in an immunocompetent patient: a rare cause of abdominal pain and diarrhea in the elderly

    Directory of Open Access Journals (Sweden)

    Harano Y

    2015-03-01

    Full Text Available Yumi Harano, Lisa Kotajima, Hiroko Arioka Department of General Internal Medicine, St Luke's International Medical Center, Tokyo, Japan Abstract: Cytomegalovirus (CMV colitis usually occurs in immunocompromised patients after undergoing organ transplantation or chemotherapy. We report the case of a 60-year-old immunocompetent Japanese woman who presented with abdominal pain and bloody diarrhea. She was initially diagnosed as having ischemic colitis with pseudomembranous colitis on the basis of her symptoms, Clostridium difficile antigen positivity, and colonoscopic findings, which showed ulcer formation from the sigmoid colon to rectum. In spite of bowel rest and administration of metronidazole, her symptoms did not improve. On follow-up colonoscopy, ulcerations remained unchanged. Biopsy of the ulceration revealed CMV-infected cells leading to a diagnosis of CMV colitis. CMV colitis is a rare but possible differential diagnosis in immunocompetent patients. We recommend endoscopic biopsy in a case of refractory abdominal pain and bloody diarrhea. Keywords: cytomegalovirus, colitis, immunocompetent, enterocolitis

  2. Intrauterine transmission and clinical outcome of 248 pregnancies with primary cytomegalovirus infection in relation to gestational age.

    Science.gov (United States)

    Enders, Gisela; Daiminger, Anja; Bäder, Ursula; Exler, Simone; Enders, Martin

    2011-11-01

    The risk of intrauterine cytomegalovirus (CMV) infection and disease in the fetus or newborn largely depends on time of primary maternal infection during pregnancy. Prospective cohort study of pregnancy outcome in relation to gestational age at primary maternal CMV infection. In a total of 248 pregnancies with primary infection the onset of infection was determined by IgG seroconversion, IgG avidity and/or onset of clinical symptoms. Congenital infection was diagnosed by CMV detection in amniotic fluid, fetal tissue or urine of the neonate in the first 2 weeks of life. Clinical symptoms were retrieved from ultrasound and medical records. The intrauterine transmission rates following primary CMV infection in the pre- and periconceptional period were 16.7% (4/24) and 34.5% (10/29), respectively. For the first, second and third trimester of pregnancy transmission rates were 30.1% (25/83), 38.2% (29/76) and 72.2% (26/36), respectively. The rate of symptomatically infected fetuses or newborns at birth was 22.8% for any symptoms and 10.3% for severe manifestations. No symptoms were observed in infected newborns of mothers with primary infection in the preconceptional period and in the third trimester. The risk of intrauterine transmission following primary maternal infection in the third trimester is high, but the risk of neonatal disease is low. The highest risk of severe symptoms in the fetus and newborn exists around conception and in the first trimester of pregnancy. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Cytomegalovirus Infection and Pre-Eclampsia

    Directory of Open Access Journals (Sweden)

    Rădulescu Carmen

    2016-06-01

    Full Text Available Introduction: Pre-eclampsia is a pregnancy-specific disease characterized by hypertension after 20 weeks of gestation and proteinuria. It is a major cause of maternal and perinatal morbidity and mortality. The pathogenesis of pre-eclampsia is not completely understood. In our study we investigated if there is a potential link between cytomegalovirus infection and pre-eclampsia and if cytomegalovirus infection is the triggering factor of pre-eclampsia.

  4. Cytomegalovirus Infection and Pre-Eclampsia

    OpenAIRE

    Rădulescu Carmen; Huţanu Adina; Gabor Rozalia; Şincu Nina

    2016-01-01

    Introduction: Pre-eclampsia is a pregnancy-specific disease characterized by hypertension after 20 weeks of gestation and proteinuria. It is a major cause of maternal and perinatal morbidity and mortality. The pathogenesis of pre-eclampsia is not completely understood. In our study we investigated if there is a potential link between cytomegalovirus infection and pre-eclampsia and if cytomegalovirus infection is the triggering factor of pre-eclampsia.

  5. Murine cytomegalovirus protein pM92 is a conserved regulator of viral late gene expression.

    Science.gov (United States)

    Chapa, Travis J; Perng, Yi-Cheih; French, Anthony R; Yu, Dong

    2014-01-01

    In this study, we report that murine cytomegalovirus (MCMV) protein pM92 regulates viral late gene expression during virus infection. Previously, we have shown that MCMV protein pM79 and its human cytomegalovirus (HCMV) homologue pUL79 are required for late viral gene transcription. Identification of additional factors involved is critical to dissecting the mechanism of this regulation. We show here that pM92 accumulated abundantly at late times of infection in a DNA synthesis-dependent manner and localized to nuclear viral replication compartments. To investigate the role of pM92, we constructed a recombinant virus SMin92, in which pM92 expression was disrupted by an insertional/frameshift mutation. During infection, SMin92 accumulated representative viral immediate-early gene products, early gene products, and viral DNA sufficiently but had severe reduction in the accumulation of late gene products and was thus unable to produce infectious progeny. Coimmunoprecipitation and mass spectrometry analysis revealed an interaction between pM92 and pM79, as well as between their HCMV homologues pUL92 and pUL79. Importantly, we showed that the growth defect of pUL92-deficient HCMV could be rescued in trans by pM92. This study indicates that pM92 is an additional viral regulator of late gene expression, that these regulators (represented by pM92 and pM79) may need to complex with each other for their activity, and that pM92 and pUL92 share a conserved function in CMV infection. pM92 represents a potential new target for therapeutic intervention in CMV disease, and a gateway into studying a largely uncharted viral process that is critical to the viral life cycle.

  6. Massive alimentary tract bleeding due to cytomegalovirus infection in an elderly patient

    Directory of Open Access Journals (Sweden)

    Bora Koc

    2014-09-01

    Full Text Available In recent years, cytomegalovirus (CMV has been recognized as an important common pathogen in immunocompromized patients. This is due to the increasing number of immunosuppressive medications, intensive cancer chemotherapy use, recurrent transplantations, progressively aging population, and the higher number of human immunodeficiency virus infections. Cytomegalovirus infection especially interests the gastrointestinal tract, anywhere, from the mouth to the anus. Namely, the most commonly affected area is the colon, followed by duodenum, stomach, esophagus and small intestine. The most frequent manifestations of CMV colitis are: diarrhea, fever, gastrointestinal bleeding and abdominal pain. We report here the case of an 82-year-old woman, who was treated for non-Hodgkin lymphoma; she was admitted to the emergency department for abdominal pain and diffuse arthralgia, following massive upper- and lower- gastrointestinal bleeding, due to duodenal and colonic ulcers related to CMV infection.

  7. Cytomegalovirus infection in severe ulcerative colitis patients undergoing continuous intravenous cyclosporine treatment in Japan

    Institute of Scientific and Technical Information of China (English)

    Masaaki Minami; Michio Ohta; Teruko Ohkura; Takafumi Ando; Naoki Ohmiya; Yasumasa Niwa; Hidemi Goto

    2007-01-01

    AIM: To investigate active cytomegalovirus (CMV) infection following the cyclosporine A (CyA) treatment of steroid-refractory ulcerative colitis (UC).METHODS: Twenty-three patients with severe UC not responding to steroid therapy (male 14, and female 9)enrolled at Nagoya University Hospital from 1999 to 2005. They received continuous intravenous infusion of CyA (average 4 mg/kg per day) for 1 mo. Serum and colonic biopsy samples were collected before CyAtreatment and 4 d, 10 d, 20 d, and 30 d after treatment.Patients were evaluated for CMV by using serology (IgM antibody by ELISA), quantitative real-time PCR for CMV DNA, and histopathological assessment of hematoxylin and eosin (HE)-stained colonic biopsies. CMV infection was indicated by positive results in any test.RESULTS: No patients had active CMV infection before CyA treatment. Eighteen of 23 UC patients treated with CyA were infected with active CMV (IgM antibody in 16/23 patients, 69.6%; CMV DNA in 18/23 patients,78.2%; and inclusion bodies in 4/23 patients, 17.3%).There was no difference in the active CMV-infection rate between males and females. Active CMV infection was observed after approximately 8 d of CyA treatment,leading to an exacerbation of colitis. Fifteen of these 18 patients with active CMV infection (83.3%) required surgical treatment because of severe deteriorating colitis.Treatment with ganciclovir rendered surgery avoidable inthree patients.CONCLUSION: Our results suggest that active CMV infection in severe UC patients treated with CyA is associated with poor outcome. Further, ganciclovir is useful for treatment of CMV-associated UC after immunosuppressive therapy.

  8. Maternal immunoglobulin G avidity as a diagnostic tool to identify pregnant women at risk of congenital cytomegalovirus infection.

    Science.gov (United States)

    Kaneko, Masatoki; Ohhashi, Masanao; Minematsu, Toshio; Muraoka, Junsuke; Kusumoto, Kazumi; Sameshima, Hiroshi

    2017-03-01

    The immunoglobulin (Ig) G avidity index (AI) is useful to detect primary cytomegalovirus (CMV) infection. However, because IgG matures with time, this index is not useful to detect a primary infection, unless measured at an appropriate time. We aimed to clarify the difference between using IgG AI and IgM positivity according to the stage of pregnancy to identify congenital CMV infection risk. We collected the serum samples from 1115 pregnant women who underwent maternal screening for primary infection (n = 956) and were referred to our hospital because of CMV IgM positivity (n = 155) or had abnormal fetal ultrasonography findings (n = 4). The same sera samples were used to measure CMV IgM, IgG, and IgG AI. An IgG AI of <35% was defined as low. Neonatal urine collected within 5 days after birth was examined by polymerase chain reaction to confirm congenital infection. Fourteen mothers gave birth to infected neonates. The sensitivity, specificity, and negative predictive values of the low IgG AI group with IgM-positive samples to discriminate between women with congenital infection at ≤14 weeks of gestation were 83.3, 83.8, and 99.1, respectively, which were higher than those of other subjects. Uni- and multivariate analyses revealed that IgM positivity and low IgG AI were independent variables associated with congenital infection at any stage of pregnancy, except low IgG AI at ≥15 weeks of gestation. Low IgG AI with IgM positivity at ≤14 weeks of gestation was a good indicator of congenital infection, which should prove useful in obstetric practice. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  9. Cytomegalovirus Colitis with Common Variable Immunodeficiency and Crohn’s Disease

    OpenAIRE

    Betül Ünal; Cumhur İbrahim Başsorgun; Sinem Çil Gönülcü; Aslı Uçar; Fatih Çelik; Gülsüm Özlem Elpek

    2015-01-01

    Here we present an eleven-year-old male patient who had been diagnosed with common variable immunodeficiency (CVID) three years ago due to recurrent sinopulmonary infections. Two years later he had been diagnosed with Crohn’s disease (CD) due to diarrhea episodes which were unresponsive to the treatment. Depending on the active gastrointestinal bleeding and perforation he underwent total colectomy. Despite immunoglobulin and antiviral therapies, general condition of patient deteriorated and h...

  10. Infección por Citomegalovarius con compromiso hepático en adultos inmunocompetentes Cytomegalovirus infection with hepatic involvement in immunocompetent adults

    Directory of Open Access Journals (Sweden)

    Claudia Vujacich

    2006-06-01

    Full Text Available Evaluamos retrospectivamente a 73 adultos inmunocompetentes que consultaron entre marzo de 1999 y marzo de 2004 a un centro infectológico ambulatorio por fiebre y astenia, con elevación discreta de las transaminasas y serología compatible con infección reciente por citomegalovirus (CMV. Excluimos a pacientes con antecedentes de transfusiones, adicciones e inmunodeficiencias, así como aquellos con alteraciones hepáticas preexistentes o con serología compatible con infección aguda por hepatitis A, B, C (VHA, VHB, VHC o virus Epstein Barr (VEB. El diagnóstico de infección reciente por citomegalovirus se efectuó mediante la detección de IgM específica (ELISA de captura, seroconversión o aumento cuádruple del título de IgG específica, en presencia de un cuadro clínico compatible. Los síntomas más frecuentes fueron: fiebre (85% y astenia (83%, cefalea (25%, esplenomegalia (20%, adenomegalia (22%, faringitis (25%, mialgia (25% y hepatomegalia (19 %. Se encontró elevación discreta de transaminasas y linfomonocitosis en todos los pacientes (73/73. La elevación promedio de GPT fue de 6 veces y la de GOT fue de 3.5 veces su valor límite. Las características clínicas que diferencian la infección por CMV de la infección por VEB son la menor frecuencia de poliadenopatías y faringitis en la primera. El diagnóstico diferencial de la infección por CMV con compromiso hepático con las hepatitis A y B agudas se basa en la ausencia de ictericia, la menor elevación de las transaminasas, la linfomonocitosis intensa y la presencia de IgM específica que caracterizan a la infección por CMV. En conclusión, ante un paciente joven, previamente sano, con fiebre, astenia intensa, linfomonocitosis y elevación discreta de transaminasas, es importante investigar infección por citomegalovirus.We retrospectively evaluated 73 immunocompetent adult patients assisted at our Infectious Diseases Clinic between March 1999 and March 2004 who

  11. THE ANALYSIS OF HUMAN CYTOMEGALOVIRUS INFECTION DURING PREGNANCY IN QINBA MOUNTAINOUS AREA

    Institute of Scientific and Technical Information of China (English)

    李芬; 韩蓁; 于学文; 李琦; 李燕琴; 史小薇; 张富昌

    2003-01-01

    Objective To study the epidemiology of cytomegalovirus (CMV) infection in Qinba mountainous area Shaanxi Province China, where there was high prevalence of mental retardation(MR) in children. Methods 367 pregnant women in Qinba mountainous area were monitored with ELISA and PCR and presented with questionnaire. We detected the following: CMV-DNA in urine of 63 neonates born within two weeks whose mother infected CMV during pregnancy and CMV-DNA in breast milk post-delivery within two weeks of 61 women infected and 84 women non-infected. Results Infection rate of CMV in mental retardation prevalent area was 19.62%, the incidence of transmission in uterus was 33.33%, the incidence of excretion by breast milk was 39.34%, CMV infection during pregnancy relates to age, education, economic states, pregnant frequency and pathological delivery. It has no relation with gestational age. Conclusion The study points out that attention should also be paid to detecting CMV infection during pregnancy in mental retardation prevalence. Less education, worse financial condition, more frequent or pathological delivery should be regarded as high risk factors of CMV infection during pregnancy.

  12. Endoscopic diagnosis of cytomegalovirus gastritis after allogeneic hematopoietic stem cell transplantation

    Science.gov (United States)

    Kakugawa, Yasuo; Kami, Masahiro; Matsuda, Takahisa; Saito, Yutaka; Kim, Sung-Won; Fukuda, Takahiro; Mori, Shin-ichiro; Shimoda, Tadakazu; Tanosaki, Ryuji; Saito, Daizo

    2010-01-01

    AIM: To clarify the endoscopic and clinical findings of cytomegalovirus (CMV) gastritis after allogeneic hematopoietic stem cell transplantation (allo-SCT). METHODS: Between 1999 and 2005, 523 patients underwent allo-SCT at our hospital, and 115 of these patients with gastrointestinal symptoms underwent esophagogastroduodenoscopy. RESULTS: CMV gastritis was diagnosed pathologically in seven patients (1.3%) with the other 108 patients serving as controls. Six of the seven patients developed positive CMV antigenemia, and five complained of abdominal pain. Development of abdominal pain preceded CMV antigenemia in four of the five patients. Endoscopic examination showed oozing (n = 2), erosion (n = 6), and redness (n = 5) in the seven patients with CMV gastritis, while the control patients showed oozing (n = 3), erosion (n = 24), and redness (n = 100). Erosion and oozing were more frequently documented in patients with CMV gastritis compared with the controls, and the differences were statistically significant (P = 0.0012 and 0.029, respectively). CMV inclusion bodies were documented in 12 of 14 biopsy specimens obtained from erosive lesions, while they were identified in 4 of 15 biopsy specimens obtained from lesions other than erosions (P = 0.0025). CONCLUSION: This study suggests that erosion and oozing, as well as abdominal pain, are useful indicators in the diagnosis of CMV gastritis following allo-SCT. PMID:20556837

  13. Sero-prevalence of Human Cytomegalovirus among blood donors in Lahore, Pakistan

    Directory of Open Access Journals (Sweden)

    Chahat Batool Rizvi

    2015-08-01

    Full Text Available Background: Transfusion-transmitted cytomegalovirus (TT-CMV infection can cause severe illness and even death among immunocompromised patients; therefore, the spread of CMV through blood products should be prevented. To our knowledge, no study has been carried out in Pakistan to determine the seroprevalence of CMV in general population as well as among blood donors. The goal of this study was to determine CMV seropositivity among blood donors at the blood bank of INMOL Hospital, Lahore, Pakistan. Methods: A sero-epidemiological cross-sectional study was conducted. Sera from 91 blood donors were screened for CMV specific IgG antibodies by enzyme-linked immunosorbent assay (ELISA based kit. Results: The CMV-specific IgG antibodies were detected in 89 blood donors, which gave seroprevalence rate of 97.8%. The statistical analysis of results was done using pearson chi-square test and appeared non-significant with values 0.625 and 0.705 for different age groups and blood groups of donors. Conclusion: Because of high seroprevalence in this study area, an adequate supply of CMV seronegative blood is difficult to maintain. Therefore, we propose that the future strategies for the prevention of post-transfusion CMV infection in recipients should include the transfusion of leukoreduced blood products. Further a prospective study with much greater population can be done to identify major causative risk factors for such highest prevalence rate.

  14. 21 CFR 866.3175 - Cytomegalovirus serological reagents.

    Science.gov (United States)

    2010-04-01

    ... cytomegalic inclusion disease) and provides epidemiological information on these diseases. Cytomegalic inclusion disease is a generalized infection of infants and is caused by intrauterine or early postnatal... (abnormal smallness of the head), motor disability, and mental retardation. Cytomegalovirus infection...

  15. The Cell Biology of Cytomegalovirus: Implications for Transplantation.

    Science.gov (United States)

    Kaminski, H; Fishman, J A

    2016-08-01

    Interpretation of clinical data regarding the impact of cytomegalovirus (CMV) infection on allograft function is complicated by the diversity of viral strains and substantial variability of cellular receptors and viral gene expression in different tissues. Variation also exists in nonspecific (monocytes and dendritic cells) and specific (NK cells, antibodies) responses that augment T cell antiviral activities. Innate immune signaling pathways and expanded pools of memory NK cells and γδ T cells also serve to amplify host responses to infection. The clinical impact of specific memory T cell anti-CMV responses that cross-react with graft antigens and alloantigens is uncertain but appears to contribute to graft injury and to the abrogation of allograft tolerance. These responses are modified by diverse immunosuppressive regimens and by underlying host immune deficits. The impact of CMV infection on the transplant recipient reflects cellular changes and corresponding host responses, the convergence of which has been termed the "indirect effects" of CMV infection. Future studies will clarify interactions between CMV infection and allograft injury and will guide interventions that may enhance clinical outcomes in transplantation.

  16. Insertion and deletion mutagenesis of the human cytomegalovirus genome

    Energy Technology Data Exchange (ETDEWEB)

    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, with 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.

  17. Amino acid 1-209 is essential for PDX-1-mediated repression of human CMV IE promoter activity

    Institute of Scientific and Technical Information of China (English)

    Jing CHEN; Lei CHEN; Ge LI; Lu CHENG; Yin HUANG; Jia-xin ZHANG; Wei-wei FAN; Da-ru LU

    2006-01-01

    Aim: To explore the different roles of pancreatic duodenal homeobox factors-1 (PDX-1) domains in PDX-1 mediated repression of human cytomegalovirus immediately early (CMV IE) promoter. Methods: A series of truncated PDX-1 mutants were constructed. The binding of PDX-1 and CMV IE promoter was identified by electrophoretic mobility shift assay (EMSA). The dual-reporter assay was applied to examine the repression activities of PDX-1 mutants on CMV IE promoter. In addition, RNAi technology was used to specifically knock down the endogenous PDX-1 expression. Results: The reporter assay indicated that compared to the mock controls (pEGFP-N2), overexpression of PDX-1 resulted in a 41% decrease of CMV IE promoter activity in the 293 cells (P<0.05) and 43% decrease in HeLa cells (P<0.05), and the repression levels of various truncated mutants played on CMV IE promoter were different. Specific knock down of the endogenous PDX-1 expression significantly restored the activity of CMV IE promoter. EMS A demonstrated that domain 3 is necessary for nuclear localization and DNA binding activity of PDX-1. However, binding of PDX-1 alone to CMV IE promoter was not sufficient to inhibit its transcriptional activity, and other domains of PDX-1 presented were also required. Conclusion: Our data suggested that the DNA binding activity of PDX-1 domain 3 and the cooperative binding of PDX-1 domain 1/2 with other proteins were required for PDX-1 mediated repression of CMV IE promoter.

  18. A dominant role for the immunoproteasome in CD8+ T cell responses to murine cytomegalovirus.

    Directory of Open Access Journals (Sweden)

    Sarah Hutchinson

    Full Text Available Murine cytomegalovirus (MCMV is an important animal model of human cytomegalovirus (HCMV, a β-Herpesvirus that infects the majority of the world's population and causes disease in neonates and immunocompromised adults. CD8(+ T cells are a major part of the immune response to MCMV and HCMV. Processing of peptides for presentation to CD8(+ T cells may be critically dependent on the immunoproteasome, expression of which is affected by MCMV. However, the overall importance of the immunoproteasome in the generation of immunodominant peptides from MCMV is not known. We therefore examined the role of the immunoproteasome in stimulation of CD8(+ T cell responses to MCMV - both conventional memory responses and those undergoing long-term expansion or "inflation". We infected LMP7(-/- and C57BL/6 mice with MCMV or with newly-generated recombinant vaccinia viruses (rVVs encoding the immunodominant MCMV protein M45 in either full-length or epitope-only minigene form. We analysed CD8(+ T cell responses using intracellular cytokine stain (ICS and MHC Class I tetramer staining for a panel of MCMV-derived epitopes. We showed a critical role for immunoproteasome in MCMV affecting all epitopes studied. Interestingly we found that memory "inflating" epitopes demonstrate reduced immunoproteasome dependence compared to non-inflating epitopes. M45-specific responses induced by rVVs remain immunoproteasome-dependent. These results help to define a critical restriction point for CD8(+ T cell epitopes in natural cytomegalovirus (CMV infection and potentially in vaccine strategies against this and other viruses.

  19. Cutaneous cytomegalovirus infection in a child with hyper IgE and specific defects in antibody response to protein vaccines

    Directory of Open Access Journals (Sweden)

    Shahrzad Fallah

    2011-10-01

    Full Text Available Cytomegalovirus (CMV infection is a common opportunistic systemic infection in immunocompromised patients, but skin involvement is rare. Herein, we report a 10 year-old girl from consanguineous parents who was referred to our center because of disseminated maculopapular rash. She had history of upper and lower respiratory tract infections. In immunological studies, increased serum IgE level and decreased responses to tetanus and diphtheria were detected. Polymerase chain reaction (PCR examination of bronchoalveolar lavage and serum sample revealed the presence of CMV. Early diagnosis of cutaneous CMV and appropriate treatment are the key actions in management of patients with underlying immunodeficiencies to avoid further complications.

  20. An artesunate-containing antimalarial treatment regimen did not suppress cytomegalovirus viremia.

    Science.gov (United States)

    Gantt, Soren; Huang, Meei-Li; Magaret, Amalia; Bunts, Lisa; Selke, Stacy; Wald, Anna; Rosenthal, Philip J; Dorsey, Grant; Casper, Corey

    2013-09-01

    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. To evaluate the effect of artesunate on CMV infection, using blood samples collected from children who participated in malaria treatment trials. 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. 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 0.01-0.58, 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. 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. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Diagnosis and prevention of cytomegalovirus infection after organtransplantation

    NARCIS (Netherlands)

    H.J. Metselaar (Herold)

    1990-01-01

    textabstractAlthough the introduction of cyclosporin A (GsA) as the main immunosuppressive agent seems to have influenced the incidence and severity of CMV disease in a positive way, the reported incidence of clinical overt CMV infection is still 2 - 23 % and 1 - 3 % of the transplant recipients die

  2. Severe cytomegalovirus infections in immunocompetent patients at admission as dengue mimic:Successful treatment with intravenous ganciclovir

    Institute of Scientific and Technical Information of China (English)

    Suhasini Tirumala; Bijayini Behera; Shilpa Lingala; B.Vijay Kumar; Pradeep Kumar Mishra; Gurunath JM; HariCharan; Kartik; Naresh

    2012-01-01

    Cytomegalovirus (CMV) infection is associated with adverse clinical outcomes in immunosuppressed persons. The incidence and association of CMV reactivation with adverse clinical outcomes in critically ill persons lacking evidence of immunosuppression at ICU admission has received great attention in the practice of critical care medicine. Critically ill patients in ICU who had associated risk factors such as mechanical ventilation, severe sepsis, or blood transfusion are more prone to CMV activation, which in turn led to increased mortality and morbidity in terms of increased ICU stay, longer duration of mechanical ventilation, and higher rates of nosocomial infections. However, severe CMV as initial presentation mimicking dengue infection is rare. We recently came across seven cases with positive CMV serology at ICU admission, which we discuss in the light of current literature.

  3. Clinical application of real time-polymerase chain reaction in determining cytomegalovirus viral DNA load in renal transplant recipients

    Institute of Scientific and Technical Information of China (English)

    ZHANG Chuan-bao; LAI Hui-ying; XU Hong-tao; WANG Da-guang; XIAO Fei

    2012-01-01

    Background Cytomegalovirus (CMV) remains a significant clinical problem among immunosuppressed renal transplant patients.Quantitative PCR assays have become the most common methods in the determination of CMV infections in transplant patients.This study was to determine the relationship between CMV infection and the acute rejection of the transplanted kidney.Methods Plasma samples from 77 renal transplant patients that were pre-transplant negative for CMV infection were tested using real-time quantitative PCR and CMV gene-specific primers.The detected viral loads were retrospectively compared with the acute rejection rate and the chronic or mild rejection rates of the renal transplant.Results CMV-DNA was detected in 29 of 77 recipients,yielding a positive rate of detection of 37.7% for this procedure.Twelve of the 21 recipients (57.1%) who suffered acute rejection had positive CMV-DNA.Among the 56 recipients suffered from chronic or mild rejection,17 (30.4%) had positive CMV-DNA plasma.Moreover,of the 29 recipients who had detectable CMV-DNA after transplant,12 (41.4%) suffered from acute rejection; of the 48 recipients with undetectable CMV-DNA,only nine (18.8%) developed acute rejection.Post-transplant patients with acute rejection had a higher rate (57.1% vs.30.4%,P=0.03) of post-transplant CMV infection than those with chronic or mild rejection.Conclusion CMV infection is a risk factor of acute renal transplant rejection and CMV infection should be prevented and treated in renal transplant recipients.Chin Med J 2012; 125(19):3575-3577

  4. cmv treatment in south africa review

    African Journals Online (AJOL)

    THE SOUTHERN AFRICAN JOURNAL OF HIV MEDICINE APRIL 2010. Almost all humans ... was noted to increase with time.10 A cross-sectional study screening all ... VALGANCICLOVIR PRICE REDUCTION IN SA FOR. CMV TREATMENT ...

  5. CMV+ Serostatus Associates Negatively with CD4:CD8 Ratio Normalization in Controlled HIV-Infected Patients on cART

    Science.gov (United States)

    Poizot-Martin, Isabelle; Allavena, Clotilde; Duvivier, Claudine; Cano, Carla Eliana; Guillouet de Salvador, Francine; Rey, David; Dellamonica, Pierre; Cuzin, Lise; Cheret, Antoine; Hoen, Bruno

    2016-01-01

    Cytomegalovirus (CMV) infection is common among HIV-infected patients but its repercussion on the course of CD4+ and CD8+ T cells after cART initiation remains elusive. The French Dat'AIDS cohort enrolled 5,688 patients on first-line cART, from which we selected patients who achieved HIV suppression for at least 12 months without modification of cART, and for whom CMV serostatus was available. Five hundred and three patients fulfilled the selection criteria (74% male, median age 43 yrs, 15.5% CDC stage C), of whom 444 (88.3%) were seropositive for CMV (CMV+). Multivariate analyses using mixed-linear models adjusted for the time from HIV suppression, sex, age, transmission risk group, duration of HIV follow-up, the interaction between time from HIV suppression and CMV+ serology, and the nadir CD4 count revealed a negative correlation between CMV+ and CD4:CD8 ratio (coeff. = -0.16; p = 0.001). This correlation was also observed among patients displaying optimal CD4 recovery (≥500 cells/mm3 at M12; coeff. = -0.24; p = 0.002). Hence, CMV+ serostatus antagonizes normalization of the CD4:CD8 ratio, although further analyses of the impact of co-morbidities that associate with CMV serostatus, like HCV infection, are needed to elucidate this antagonism formally. However, this might reflect a premature T cell senescence, thus advocating for a close monitoring of T cells in CMV co-infected patients. In addition, our results raise the question of the benefit of treatment for asymptomatic CMV co-infection in HIV-infected patients. PMID:27824907

  6. Analysis of memory T lymphocyte activity following stimulation with overlapping HLA-A*2402, A*0101 and Cw*0402 restricted CMV pp65 peptides

    Directory of Open Access Journals (Sweden)

    Provenzano Maurizio

    2005-05-01

    Full Text Available Abstract The continuous efforts aimed at the identification of new immune epitopes across the MHC system has led to the discovery that more than one peptide may be restricted to the same HLA antigen and function as an immune determinant for that association. The aim of this study was to compare the ability of two overlapping peptides, the nonamer (9-mer cytomegalovirus (CMV pp65341–349 (QYDPVAALF and the decamer (10-mer CMV pp65341–350 (QYDPVAALFF, and the esadecamer (16-mer peptide containing both the 9-mer and 10-mer sequences, CMV pp65340–355 (RQYDPVAALFFFDIDL, to stimulate and maintain over time a T cell immune reactivation by HLA-A*2402, A*0101, and Cw*0402 cells from CMV-seropositive subjects. The 9-mer, 10-mer, and 16-mer peptides effectively stimulated CTLs from HLA-A*2402, HLA-A*0101, and HLA-Cw*0402 CMV seropositive donors. This data confirms that both the 9-mer and the 10-mer peptides are promiscuous and are not restricted to a single HLA antigen. CMV pp65341–349 and CMV pp65341–350 have the ability to produce CMV-specific CTLs in subjects with several different HLA types, presenting a practical advantage over other peptides that are restricted only to a single HLA antigen, and thus being optimal for CMV adoptive immune therapy. Moreover, since the 16-mer peptide encompasses both the 9-mer and 10-mer peptides, it may be better than either of these peptides for CMV adoptive immune therapy.

  7. DIAGNOSIS OF CONGENITAL CYTOMEGALOVIRUS INFECTION IN HIGH RISK NEONATES

    Directory of Open Access Journals (Sweden)

    Ehab abdelmoniem Albanna

    2013-07-01

    Full Text Available Objectives: This study aimed to compare polymerase chain reaction (PCR and IgM detection using enzyme linked immune-sorbent assay (ELISA in diagnosis of congenital cytomegalovirus (CMV infection.   Methods: This study was conducted from May 2009 to December 2010. Urine and blood samples were collected from 94 neonates with suspected congenital CMV infection. Serum and part of urine samples were stored at -20°C freezer, until the serologic and PCR tests were achieved. A 94 fresh urine samples were processed for cell culture. Nineteen (20.2% out of 94 urine samples were proven positive for CMV infection by viral culture. For comparing PCR and IgM ELISA we used tissue culture technique as a reference, the 19 positive samples on culture (CMV group and 20 negative samples (control group were included in the comparison. Some characteristics of CMV and control groups were compared including sex, age, birth weight, gestational age < 37 and small for gestational age. Clinical and laboratory abnormalities were also compared in both groups.   Results: This study showed that the sensitivity and specificity of PCR in relation to viral culture were 100% and 100% respectively, there was excellent agreement between both tests (Kappa coefficient was 1 and P=0.000. On the other hand, the sensitivity of IgM CMV ELISA in relation to viral culture was 63.2% and the specificity was 85%. There was good agreement between both tests (Kappa coefficient was 0.48 and P=0.002. By comparing CMV and control groups, there were high statistically significant differences between both groups as regard the birth weight, gestational age < 37 and small for gestational age items (P= 0.00, 0.03 and 0.01 respectively. There were statistically insignificant differences as regarding the clinical and laboratory abnormalities detected for neonates of both groups. In this study jaundice (63% and hepato-splenomegaly (42% were the most common clinical signs in both groups.   Conclusion

  8. Principal component analysis uncovers cytomegalovirus-associated NK cell activation in Ph(+) leukemia patients treated with dasatinib.

    Science.gov (United States)

    Ishiyama, K; Kitawaki, T; Sugimoto, N; Sozu, T; Anzai, N; Okada, M; Nohgawa, M; Hatanaka, K; Arima, N; Ishikawa, T; Tabata, S; Onaka, T; Oka, S; Nakabo, Y; Amakawa, R; Matsui, M; Moriguchi, T; Takaori-Kondo, A; Kadowaki, N

    2017-01-01

    Dasatinib treatment markedly increases the number of large granular lymphocytes (LGLs) in a proportion of Ph(+) leukemia patients, which associates with a better prognosis. The lymphocytosis is predominantly observed in cytomegalovirus (CMV)-seropositive patients, yet detectable CMV reactivation exists only in a small fraction of patients. Thus, etiology of the lymphocytosis still remains unclear. Here, we identified NK cells as the dominant LGLs expanding in dasatinib-treated patients, and applied principal component analysis (PCA) to an extensive panel of NK cell markers to explore underlying factors in NK cell activation. PCA displayed phenotypic divergence of NK cells that reflects CMV-associated differentiation and genetic differences, and the divergence was markedly augmented in CMV-seropositive dasatinib-treated patients. Notably, the CMV-associated highly differentiated status of NK cells was already observed at leukemia diagnosis, and was further enhanced after starting dasatinib in virtually all CMV-seropositive patients. Thus, the extensive characterization of NK cells by PCA strongly suggests that CMV is an essential factor in the NK cell activation, which progresses stepwise during leukemia and subsequent dasatinib treatment most likely by subclinical CMV reactivation. This study provides a rationale for the exploitation of CMV-associated NK cell activation for treatment of leukemias.

  9. Cytomegalovirus and herpes simplex virus effect on the prognosis of mechanically ventilated patients suspected to have ventilator-associated pneumonia.

    Science.gov (United States)

    Coisel, Yannael; Bousbia, Sabri; Forel, Jean-Marie; Hraiech, Sami; Lascola, Bernard; Roch, Antoine; Zandotti, Christine; Million, Matthieu; Jaber, Samir; Raoult, Didier; Papazian, Laurent

    2012-01-01

    Cytomegalovirus (CMV) and herpes simplex virus (HSV) are common viruses that can affect critically ill patients who are not immunocompromised. The aim of this study was to determine whether the identification of CMV and/or HSV in mechanically ventilated critically ill patients suspected of having pneumonia was associated with an increased mortality. Prospective epidemiological study. Medical intensive care unit of a tertiary medical center. Ninety-three patients with suspected pneumonia. Patients with suspected pneumonia had bronchoalveolar lavage and blood samples taken to confirm the diagnosis. Antigenemia was used to detect CMV in the blood. Bronchoalveolar lavage samples were submitted to testing using quantitative real-time Polymerase Chain Reaction. We identified 22 patients with a CMV infection, 26 patients with an HSV infection and 45 patients without CMV or HSV infection (control group). Mortality at day 60 was higher in patients with a CMV infection than in patients from the control group (55% vs. 20%, P<0.01). Mortality at day 60 was not significantly increased in the group with HSV infection. Duration of ICU stay and ICU mortality were significantly higher in patients with CMV infections when compared to patients from the control group, whereas ventilator free days were significantly lower in patients with CMV infections when compared to patients from the control group. In critically ill patients, a CMV infection is associated with an increased mortality. Further interventional studies are needed to evaluate whether treatment could improve the prognosis.

  10. Determination of CMV infection in CSF of children with meningoencephalitis: PCR method

    Directory of Open Access Journals (Sweden)

    Noorbakhsh S

    2009-01-01

    Full Text Available "nBackground: In recent years, many ill cases with cytomegalovirus reactivation in non-immuno compromised persons reported. Goal of study: to determine the CMV infection in cerebrospinal fluid of aseptic meningoencephalitis children hospitalized in Rasul & Mofid hospital (2005-2007. "nMethods: In a cross sectional study 132 cases selected with simple sampling. CMV-DNA in their Cerebro spinal fluids searched by qualitative PCR. "nResults: The age range of the study patients was 5 month- 13 years, median age= 2±3.7 years; 87(65.9% male and 45(34.1% was female. The presenting signs and symptoms were convulsion 77(69.4%; meningitis 25(18.8%, loss of consciousness 47(37%; neurologic defects 15.9%. DNA extrated in 11 cases. Mycoplasma- DNA in 2cases; DNA-CMV detected 2(1.5%. Positive DNA HSV found in 7(15.3% of patients. DNA- HSV type- 15.3% (7/132 cases. An infant 5 month age with developmental delay, microcephaly and recurrent convulsions. A 1 year girl with brain atrophy and progressive hydrocephaly with intracranial shunt "nConclusions: Differentiation between herpes meningoencephalitis and other encephalopathy based on clinical signs in children is too difficult. CMV (1.5% has lower rate than herpes simplex type-1 (5.7%. In addition to CMV and HSV1 all of herpes family viruses (varicella, herpes 6, 7, Epstein barr virus could have role in  children with meningoencephalitis. In recent years a sensitive, rapid, simple diagnostic  test "Single tube Multiplex PCR" in cerebro spinal fluid recommend. Rapid diagnosis and faster treatment is necessary for decreasing mortality and morbidity in all of herpes meningoencephalitis cases

  11. Postnatally acquired cytomegalovirus infection in preterm infants : a prospective study on risk factors and cranial ultrasound findings

    NARCIS (Netherlands)

    Nijman, Joppe; de Vries, Linda S.; Koopman-Esseboom, Corine; Uiterwaal, Cuno S. P. M.; van Loon, Anton M.; Verboon-Maciolek, Malgorzata A.

    2012-01-01

    Objective To study risk factors and cranial ultrasound (cUS) findings in a large cohort of preterm infants, admitted to a neonatal intensive care unit and diagnosed with postnatally acquired cytomegalovirus (CMV) infection. Study design This prospective, observational study was performed from April

  12. The dissemination of CMV in urine of different group from Guangxi and the relationship between CMV infection and renal disease%人巨细胞病毒在广西不同人群中的感染情况及其与肾脏疾病关系的初步研究

    Institute of Scientific and Technical Information of China (English)

    陈智平; 覃锦耀; 王健; 阳晶; 阳艳华; 蔡豪斌; 何雨; 李山; 王丽兰; 劳小霞; 李泰阶; 胡春卉; 邓燕

    2010-01-01

    目的 调查广西壮族自治区孕妇、患病新生儿、肾病患者、肾移植患者及正常体检者尿中人巨细胞病毒阳性率,了解人类巨细胞病毒在广西不同人群中的分布情况,初步探讨人巨细胞病毒感染与肾脏疾病的关系.方法 用荧光定量PCR检测研究对象晨尿中人巨细胞病毒DNA.结果 孕妇、患病新生儿、肾病者、肾移植患者及正常体检者尿中人巨细胞病毒DNA阳性率依次为8.18%、3.45%、18.54%、25.42%、0.56%,其在各类肾病患者中的感染率均在10%左右,尤其在狼疮肾炎患者中的感染率更是达到27.78%.结论 人巨细胞病毒在黄疸和早产新生儿中的感染率均较高,需要加强母婴人巨细胞病毒感染的防控工作.人巨细胞病毒很可能在肾病患者发病时对患者肾脏造成损害,并且加重肾病患者的病情,成为肾衰的一个诱因.%Objective To detect Human Cytomegalovirus (HCMV) DNA in urine samples from the following groups:pregnant women,sick newborns,hospitalized nephropathy patients,renal transplant recipients and normal population.Preliminarily study the relationship of HCMVinfection and renal disease.Methods To detect HCMV DNA in morning urine samples by Real-time fluorescence quantitative PCR (FQ-PCR).Results The positive rates of HCMV DNA in the urine of pregnant women,sick newborns,hospitalized nephropathy patients,renal transplant recipients and normal population are 8.1 8%,3.45%,18.54%,25.42%,0.56%.Conclusion The infection rates of HCMV in the urine of pregnant women and sick newborns are very high in Guangxi,it should take serious measures to prevent and control the situation.HCMV probably participate in the iniury of kidney,and worsen the disease.It should be one of the causes of renal disease.

  13. The use of saliva as a practical and feasible alternative to urine in large-scale screening for congenital cytomegalovirus infection increasesinclusion and detection rates

    Directory of Open Access Journals (Sweden)

    Emanuelle Santos de Carvalho Cardoso

    2015-04-01

    Full Text Available INTRODUCTION: Although urine is considered the gold-standard material for the detection of congenital cytomegalovirus (CMV infection, it can be difficult to obtain in newborns. The aim of this study was to compare the efficiency of detection of congenital CMV infection in saliva and urine samples. METHODS: One thousand newborns were included in the study. Congenital cytomegalovirus deoxyribonucleic acid (DNA was detected by polymerase chain reaction (PCR. RESULTS: Saliva samples were obtained from all the newborns, whereas urine collection was successful in only 333 cases. There was no statistically significant difference between the use of saliva alone or saliva and urine collected simultaneously for the detection of CMV infection. CONCLUSIONS: Saliva samples can be used in large-scale neonatal screening for CMV infection.

  14. A MULTICENTER, LONGITUDINAL, INTERVENTIONAL, DOUBLE BLIND RANDOMIZED CLINICAL TRIAL IN HEMATOPOIETIC CELL TRANSPLANT RECIPIENTS RESIDING IN REMOTE AREAS: LESSONS LEARNED FROM THE LATE CYTOMEGALOVIRUS PREVENTION TRIAL.

    Science.gov (United States)

    Kimball, Louise E; Stevens-Ayers, Terry; Green, Margaret L; Xie, Hu; Flowers, Mary E D; Jerome, Keith R; LeBlanc, Renee; Dahlgren, Christi; Nichols, W Garrett; Chemaly, Roy F; Papanicolaou, G; Boeckh, Michael

    2016-12-15

    The logistics of conducting double-blinded phase III clinical trials with participants residing in remote locations are complex. Here we describe the implementation of an interventional trial for the prevention of late cytomegalovirus (CMV) disease in hematopoietic cell transplantation (HCT) subjects in a long-term follow-up environment. A total of 184 subjects at risk for late CMV disease surviving 80 days following allogeneic HCT were randomized to receive six months of valganciclovir or placebo. Subjects were followed through day 270 post-transplant at their local physician's office within the United States. Anti-viral treatment interventions were based on CMV DNAemia as measured by polymerase chain reaction (PCR) (>1000 copies/mL) and granulocyte colony stimulating factor (G-CSF) was prescribed for neutropenia (absolute neutrophil count (ANC <1.0 × 10(9) cells/L). Blood samples for viral testing and safety monitoring were shipped to a central laboratory by overnight carrier. Real-time communication was established between the coordinating center and study sites, primary care physicians, and study participants to facilitate starting, stopping and dose adjustments of antiviral drugs and G-CSF. The time required to make these interventions was analyzed. Of the 4169 scheduled blood specimens, 3832 (92%) were received and analyzed; the majority (97%) arriving at the central site within 2 days. Among subjects with positive CMV DNAemia (N=46), over 50% received open label antiviral medication within one day. The median time to start G-CSF for neutropenia was <1 day after posting of laboratory results (range 0-6; N=38). Study drug dose adjustments for abnormal renal function were implemented 203 times; within one day for 48% of cases and within 2 days for 80% of cases. Complex randomized, double-blind, multicenter interventional trials with treatment decisions made at a central coordinating site can be conducted safely and effectively according to Good Clinical

  15. The history of vaccination against cytomegalovirus.

    Science.gov (United States)

    Plotkin, Stanley

    2015-06-01

    Cytomegalovirus vaccine development started in the 1970s with attenuated strains. In the 1980s, one of the strains was shown to be safe and effective in renal transplant patients. Then, attention switched to glycoprotein gB, which was shown to give moderate but transient protection against acquisition of the virus by women. The identification of the pp65 tegument protein as the principal target of cellular immune responses resulted in new approaches, particularly DNA, plasmids to protect hematogenous stem cell recipients. The subsequent discovery of the pentameric protein complex that generates most neutralizing antibodies led to efforts to incorporate that complex into vaccines. At this point, there are many candidate CMV vaccines, including live recombinants, replication-defective virus, DNA plasmids, soluble pentameric proteins, peptides, virus-like particles and vectored envelope proteins.

  16. Combined CMV- and HSV-1 brainstem encephalitis restricted to medulla oblongata.

    Science.gov (United States)

    Katchanov, J; Branding, G; Stocker, H

    2014-04-15

    We report a very rare case of a combined CMV- and HSV-1 isolated brainstem encephalitis restricted to medulla oblongata in a patient with advanced HIV disease. Neither limbic nor general ventricular involvement was detected on neuroimaging. The case highlights the importance of testing for HSV-1 and CMV in HIV-infected patients presenting with an isolated brainstem syndrome. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. [Universal cytomegalovirus infection screening in premature newborns less than 1500 g].

    Science.gov (United States)

    Botet, F; Figueras Aloy, J; Álvarez, E; de Alba, C; Dorronsolo, I; Echaniz Urcelay, I; Rite, S; Moreno, J; Fernández Lorenzo, J R; Herranz Carrillo, G; Salguero, E; Sánchez Luna, M

    2014-10-01

    Cytomegalovirus (CMV) infection is endemic, and children who attend day care are the most important source of infection. To establish recommendations based on the medical evidence on the vertical transmission of cytomegalovirus in preterm infants weighing less than 1500g at birth. Infection in pregnant women may be primary or secondary. Although there is fetal infection, 85% of newborn infants are asymptomatic. Symptoms of infection include low birth weight, hepatosplenomegaly, thrombocytopenia, microcephaly and neurological disorders. The prognosis of symptomatic children is very poor, with high mortality and neurological disorders. The virus can be reactivated during breast feeding, and early infection is possible through breast milk, probably with little impact in term infants, although the long-term neurological outcome worsens in preterm infants. The diagnostic method of choice is the identification of CMV in urine; the determination in the first two weeks of life suggests congenital infection; later it can be acquired at birth or through breast milk or contaminated blood transfusion. Determine viral DNA at 4-6 weeks of life by protease chain reaction. If it is positive, monitoring of samples from the first days of life and breast milk are mandatory. This should allow the newborn to be classified into three states: "Without CMV infection", "Congenital CMV infection", "Acquired CMV infection". Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  18. Analysis of risk factors associated to cytomegalovirus infection in dentistry students

    Directory of Open Access Journals (Sweden)

    Claudia De la Tejera-Hernández

    2015-06-01

    Full Text Available Objective: The purpose of the study was to analyze the association between cytomegalovirus (CMV infection in dental students with occupational risk factors and a genetic trait (NKG2C gene deletion. Study design: Case-control study. 176 students were included and divided in two groups according to CMV serological results: those with CMV infection (case group and those without prior infection (control group. Demographic, occupational, and the presence of NKG2C gene deletion were compared between both groups. Results: The presence of CMV IgG antibodies was detected in 104 (59.1% students (case group while 72 (40.9% students were CMV negative (control group. The frequency of patient contact, the use of protective barriers, and the number of reported accidents was compared between the study groups; no significant differences were noted. The appropriate use of infection-control measures was observed in the majority of students in both study groups. In the case group the frequency of NKG2C deletion was 9.7% compared to 5.6% in the control group (p=0.33. Conclusion: No association between the presence of CMV infection with occupational and genetic risk factors was found in this population. Dentists should be aware of the CMV prevalence and risks factors associated to this infection, particularly among child-bearing age dentist women.

  19. The association between cytomegalovirus infection, obesity, and metabolic syndrome in U.S. adult females.

    Science.gov (United States)

    Fleck-Derderian, Shannon; McClellan, William; Wojcicki, Janet M

    2017-03-01

    The purpose of this analysis was to determine whether cytomegalovirus (CMV) infection is associated with the prevalence of metabolic syndrome (MetS) and whether this relationship differs by BMI. Data from the 1999-2004 National Health and Nutrition Examination Survey (NHANES) were pooled (N = 2,532). Logistic regression was used for assessing the association between CMV and MetS, stratified by gender and BMI, categorized as normal weight, overweight, obesity, and extreme obesity, and adjusted for age, race/ethnicity, and poverty level. In unadjusted analyses, CMV infection was significantly associated with MetS in females (OR: 1.50; 95% CI: 1.1-2.1) but not males. After adjusting for confounders, the odds of MetS were higher in CMV+ normal-weight females (aOR: 65.31; 95% CI: 6.8-625.6) but lower in CMV+ females with extreme obesity (aOR: 0.25; 95% CI: 0.1-0.9). CMV infection was associated with higher high-density lipoprotein cholesterol (HDL-C) and lower triglycerides in females with extreme obesity but lower HDL-C in normal-weight females. CMV infection was found to be associated with unique MetS phenotypes that differ between BMI categories and gender. Seropositive normal-weight females had a higher prevalence of MetS and dyslipidemia, while infection in females with extreme obesity was associated with a more metabolically benign profile. © 2017 The Obesity Society.

  20. Congenital cytomegalovirus infection - a common cause of hearing loss of unknown aetiology.

    Science.gov (United States)

    Karltorp, Eva; Hellström, Sten; Lewensohn-Fuchs, Ilona; Carlsson-Hansén, Eva; Carlsson, Per-Inge; Engman, Mona-Lisa

    2012-08-01

    The aim of this study was to investigate the role of congenital cytomegalovirus (CMV) infection as a cause of various types of sensorineural hearing loss (SNHL) in a group of nonsyndromic children with otherwise unknown aetiology of hearing loss. Furthermore, the occurrence of combined congenital CMV infection and connexin 26 (Cx26) mutations was investigated. The dried blood spot (DBS) cards of 45 children with various degrees of hearing deficits and 46 children with severe/profound hearing loss were tested for CMV DNA with polymerase chain reaction (PCR) technique. The DBS cards of the 46 children with severe/profound hearing loss were also analysed for Cx26 mutations. Of the 45 children with various degrees of hearing loss, nine were positive for CMV DNA (20%). The nine children represented severe/profound, mild and unilateral hearing loss. From the 46 children with severe/profound hearing loss, nine of 46 (20%) were positive for CMV DNA. In addition, three of the CMV DNA-positive children were carriers of mutations of Cx26. Congenital CMV infection is a high risk factor in hearing impairment among children. © 2012 The Author(s)/Acta Paediatrica © 2012 Foundation Acta Paediatrica.

  1. Changes in cytomegalovirus seroprevalence in pregnant Japanese women-a 10-year single center study.

    Science.gov (United States)

    Taniguchi, Kosuke; Watanabe, Noriyoshi; Sato, Anna; Jwa, Seung Chik; Suzuki, Tomo; Yamanobe, Yuji; Sago, Haruhiko; Kozuka, Kazuto

    2014-03-01

    Human cytomegalovirus (CMV) causes congenital infections during pregnancy, and seroepidemiological data are important for estimating the risk of infection. However, only a few reports of CMV seroprevalence exist for pregnant Japanese women. The purpose of this study was to assess CMV seroprevalence in pregnant Japanese women. This cross-sectional study involved pregnant Japanese women who delivered from 2003 to 2012 at our hospital (n=15,616). Among these women, 14,099 (90.3%) underwent tests for the presence of CMV IgG. Those with an equivocal test result were excluded (n=195) from this analysis, leaving a study sample of 13,904 Japanese pregnant women. The prevalence of CMV IgG was also assessed by calendar year, age, and parity. The overall CMV IgG prevalence rate was 66.0%. CMV IgG prevalence significantly decreased over the course of 10 years from 2003 to 2012 (from 69.9% in 2003 to 65.2% in 2012) (p40 years were 1.66 (95%CI: 1.25-2.20), 1.20 (95%CI: 1.07-1.35), 1.16 (95%CI: 1.07-1.26), and 1.44 (95%CI: 1.28-1.62), respectively, compared to women aged 30-35 years. Adjusted odds ratios for CMV IgG positivity for a parity of 1, 2, and ≥3 were 1.14 (95%CI: 1.06-1.23), 1.52 (95%CI: 1.32-1.77), and 2.54 (95%CI: 2.69-3.84), respectively, compared to nulliparous women. We found that 34% of pregnant Japanese women were susceptible to CMV infection. Calendar year, maternal age, and parity were significantly associated with changes in CMV seroprevalence among this population. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Emergence and prevalence of cytomegalovirus UL97 mutations associated with ganciclovir resistance in AIDS patients.

    Science.gov (United States)

    Gilbert, C; Handfield, J; Toma, E; Lalonde, R; Bergeron, M G; Boivin, G

    1998-01-22

    To evaluate the prevalence of the most common cytomegalovirus (CMV) UL97 mutations associated with ganciclovir resistance directly in polymorphonuclear leukocytes (PMNL) of patients with AIDS and CMV retinitis. Also to correlate the presence (or absence) of these mutations with the systemic CMV viral load and the ophthalmologic outcome of these subjects. Monthly blood samples were obtained from 19 patients with AIDS and CMV retinitis who had been treated with systemic ganciclovir for > or = 2 months. Detection of CMV UL97 mutations was done using nested PCR amplification followed by restriction enzyme analysis. The viral load was assessed with a polymerase chain reaction-based assay and non-isotopic hybridization detection. CMV UL97 mutations were detected in PMNL of four of 13 (30.8%) patients who had been treated with ganciclovir for > or = 3 months but in none of six patients who had been treated for 10000 copies per 10(5) PMNL contrasting with the copy numbers in the 15 subjects without mutations (mean, 492.9 copies per 10(5) PMNL after a mean of 146.8 days of ganciclovir). The prevalence of the most common CMV UL97 mutations associated with ganciclovir resistance in PMNL of patients with AIDS treated for > or = 3 months (30.8%) appears to be higher than the rate of emergence of ganciclovir-resistant CMV isolates as previously reported using phenotypic assays (about 8%). Moreover, the detection of these mutations is associated with a considerable increase in the CMV DNA load in the blood as well as with progression of CMV retinitis during ganciclovir therapy.

  3. CMV latent infection improves CD8+ T response to SEB due to expansion of polyfunctional CD57+ cells in young individuals.

    Directory of Open Access Journals (Sweden)

    Alejandra Pera

    Full Text Available Cytomegalovirus (CMV latent infection has a deleterious effect on the efficacy of influenza vaccination in the elderly, suggesting that CMV restricts immunological diversity impairing the immune system functionality in old age. Polyfunctional T cells produce multiple cytokines and higher amounts than mono-functional T cells. High number of polyfunctional T cells correlates with better prognosis during infection. Thus, the efficiency of T cell response associates with quality (polyfunctionality rather than with quantity (percentage of T cells. We analyze the effect of CMV infection on CD8+ T cells polyfunctionality --degranulation (CD107a, IFN-gamma and TNF-alpha production--, from young CMV-seropositive and CMV-seronegative individuals and in middle age CMV-seropositive donors, in response to Staphylococcal Enterotoxin B (SEB. Our results show a higher percentage of polyfunctional CD8+ T cells in young CMV-seropositive individuals compared to CMV-seronegative. Also, we find an expansion of CD8+CD57+ T cells in CMV-seropositive individuals, which are more polyfunctional than CD8+CD57- cells. In middle age individuals there is a higher frequency of SEB-responding CD8+ T cells, mainly TNF-alpha or TNF-alpha/IFN-gamma producers, whereas the percentage of polyfunctional cells (IFN-gamma/TNF-alpha/CD107a is similar to the percentages found in young CMV-seropositive. Therefore, whereas it has been shown that CMV latent infection can be detrimental for immune response in old individuals, our results indicate that CMV-seropositivity is associated to higher levels of polyfunctional CD8+ T cells in young and middle age donors. This increase in polyfunctionality, which can provide an immunological advantage in the response to other pathogens, is due to a CD8+CD57+ T cell expansion in CMV-seropositive individuals and it is independent of age. Conversely, age could contribute to the inflammation found in old individuals by increasing the percentage of cells

  4. An atypical case of acute disseminated encephalomyelitis associated with cytomegalovirus infection.

    Science.gov (United States)

    De Fino, Chiara; Nociti, Viviana; Modoni, Anna; Bizzarro, Alessandra; Mirabella, Massimiliano

    2016-01-01

    We present the case of a young man admitted to our hospital for persistent headache associated with fever, retrorbitary pain and vomiting, who rapidly developed encephalopathy with drowsiness, paraplegia, hypoesthesia with a D6 sensory level and urinary retention. Brain and spinal cord MRI revealed findings compatible with acute disseminated encephalomyelitis (ADEM) and microbiological tests documented a cytomegalovirus (CMV) infection. CMV infection is extraordinarily associated with ADEM, but must be included in microbiological tests, because early diagnosis and treatment ameliorate the neurological outcome. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Partial functional complementation between human and mouse cytomegalovirus chemokine receptor homologues

    DEFF Research Database (Denmark)

    Farrell, Helen E; Abraham, Alexander M; Cardin, Rhonda D

    2011-01-01

    The human cytomegalovirus (CMV) proteins US28 and UL33 are homologous to chemokine receptors (CKRs). Knockout of the mouse CMV M33 protein (UL33 homologue) results in substantial attenuation of salivary gland infection/replication and reduced efficiency of reactivation from tissue explants. M33......-mediated G protein-coupled signaling is critical for the salivary gland phenotype. In this report, we demonstrate that US28 and (to a lesser degree) UL33 restore reactivation from tissue explants and partially restore replication in salivary glands (compared to a signaling-deficient M33 mutant...

  6. A Cmv2 QTL on chromosome X affects MCMV resistance in New Zealand male mice.

    Science.gov (United States)

    Rodriguez, Marisela R; Lundgren, Alyssa; Sabastian, Pearl; Li, Qian; Churchill, Gary; Brown, Michael G

    2009-07-01

    NK cell-mediated resistance to viruses is subject to genetic control in humans and mice. Here we used classical and quantitative genetic strategies to examine NK-mediated murine cytomegalovirus (MCMV) control in genealogically related New Zealand white (NZW) and black (NZB) mice. NZW mice display NK cell-dependent MCMV resistance while NZB NK cells fail to limit viral replication after infection. Unlike Ly49H(+) NK resistance in C57BL/6 mice, NZW NK-mediated MCMV control was Ly49H-independent. Instead, MCMV resistance in NZW (Cmv2) involves multiple genetic factors. To establish the genetic basis of Cmv2 resistance, we further characterized a major chromosome X-linked resistance locus (DXMit216) responsible for innate MCMV control in NZW x NZB crosses. We found that the DXMit216 locus affects early MCMV control in New Zealand F(2) crosses and demonstrate that the NZB-derived DXMit216 allele enhances viral resistance in F(2) males. The evolutionary conservation of the DXMit216 region in mice and humans suggests that a Cmv2-related mechanism may affect human antiviral responses.

  7. Exploitation of Interleukin-10 (IL-10) Signaling Pathways: Alternate Roles of Viral and Cellular IL-10 in Rhesus Cytomegalovirus Infection.

    Science.gov (United States)

    Eberhardt, Meghan K; Deshpande, Ashlesha; Fike, Joseph; Short, Rebecca; Schmidt, Kimberli A; Blozis, Shelley A; Walter, Mark R; Barry, Peter A

    2016-11-01

    There is accumulating evidence that the viral interleukin-10 (vIL-10) ortholog of both human and rhesus cytomegalovirus (HCMV and RhCMV, respectively) suppresses the functionality of cell types that are critical to contain virus dissemination and help shape long-term immunity during the earliest virus-host interactions. In particular, exposure of macrophages, peripheral blood mononuclear cells, monocyte-derived dendritic cells, and plasmacytoid dendritic cells to vIL-10 suppresses multiple effector functions including, notably, those that link innate and adaptive immune responses. Further, vaccination of RhCMV-uninfected rhesus macaques with nonfunctional forms of RhCMV vIL-10 greatly restricted parameters of RhCMV infection following RhCMV challenge of the vaccinees. Vaccinees exhibited significantly reduced shedding of RhCMV in saliva and urine following RhCMV challenge compared to shedding in unvaccinated controls. Based on the evidence that vIL-10 is critical during acute infection, the role of vIL-10 during persistent infection was analyzed in rhesus macaques infected long term with RhCMV to determine whether postinfection vaccination against vIL-10 could change the virus-host balance. RhCMV-seropositive macaques, which shed RhCMV in saliva, were vaccinated with nonfunctional RhCMV vIL-10, and shedding levels of RhCMV in saliva were evaluated. Following robust increases in vIL-10-binding and vIL-10-neutralizing antibodies, shedding levels of RhCMV modestly declined, consistent with the interpretation that vIL-10 may play a functional role during persistent infection. However, a more significant association was observed between the levels of cellular IL-10 secreted in peripheral blood mononuclear cells exposed to RhCMV antigens and shedding of RhCMV in saliva. This result implies that RhCMV persistence is associated with the induction of cellular IL-10 receptor-mediated signaling pathways. Human health is adversely impacted by viruses that establish lifelong

  8. Growth in Agarose of Human Cells Infected with Cytomegalovirus

    Science.gov (United States)

    Lang, David J.; Montagnier, Luc; Latarjet, Raymond

    1974-01-01

    After infection by human cytomegalovirus (CMV), human diploid fibroblasts could grow in agarose medium for several generations. Clones of infected cells grew for weeks, although in every case they ultimately underwent lysis owing to the cytopathic effect of the virus. Virus was inoculated at high dilution and after UV irradiation in an effort to derive cells infected with noninfectious defective particles still capable of inducing cell stimulation. Dilute or irradiated virus occasionally yielded large colonies of replicating cells, although permanent transformation was not observed. One clone derived from UV-CMV-infected cells was passaged four times before undergoing lysis. During these passages the cells exhibited alterations in morphology and orientation. Images PMID:4367907

  9. Congenital Cytomegalovirus Hepatitis in the XXI Century is not Uncommon!

    Directory of Open Access Journals (Sweden)

    N.P. Skorodumova

    2014-09-01

    Full Text Available The article presents features of early clinical and laboratory diagnosis of congenital cytomegalovirus (CMV hepatitis. The analysis of the causes of late diagnosis of chronic hepatitis is carried out. Some children have repeatedly appealed to the doctor and treated for gastroduodenitis, cholecystitis, biliary dyskinesia, ulcerative colitis. Chart review allowed to assume that the extrahepatic manifestations of chronic hepatitis and liver cirrhosis district pediatricians interpreted as allergy (recurrent urticaria, juvenile rheumatoid arthritis (arthritis, vegetovascular dystonia (ECG changes; endocrine violations (delayed menstruation, striae on the abdominal skin — as the feature of puberty; signs of hypo- or hyperthyroidism — as endemic pathology. A sequence of doctor’s actions in diagnosing congenital CMV infection, mainly affecting the liver, is provided.

  10. Development of fully automated determination of marker-specific immunoglobulin G (IgG) avidity based on the avidity competition assay format: application for Abbott Architect cytomegalovirus and Toxo IgG Avidity assays.

    Science.gov (United States)

    Curdt, Ingo; Praast, Gerald; Sickinger, Eva; Schultess, Jan; Herold, Iris; Braun, Hans Bertram; Bernhardt, Stephanie; Maine, Gregory T; Smith, Darwin D; Hsu, Stephen; Christ, Heike M; Pucci, Dominick; Hausmann, Michael; Herzogenrath, Jörg

    2009-03-01

    Determination of the avidity of immunoglobulin G (IgG) directed against a specific marker has become an established diagnostic tool for identifying or excluding acute infections with pathogens. A novel assay format termed AVIcomp (avidity competition based on mass action) circumventing the conventional chaotropic format has been developed for determination of the avidity of marker-specific IgG in patient specimens. Its applications for cytomegalovirus (CMV) and Toxoplasma gondii are presented. Specific high-avidity IgG from the patient specimen is selectively blocked using a soluble antigen in a sample pretreatment reagent, and the amount of remaining specific low-avidity IgG is determined relative to that in an untreated control. The comparison of the conventional chaotropic format, represented by the Radim CMV IgG Avidity assay, and the newly developed AVIcomp method, as exemplified by the Architect CMV IgG Avidity assay, on blood drawn within 4 months after seroconversion revealed a sensitivity of 100% (97.3% by an alternative calculation) for the AVIcomp format versus 87.5% (75.7% by an alternative calculation) for the chaotropic avidity assay. The specificity on 312 CMV IgG reactive and CMV IgM nonreactive specimens from pregnant women was 100% for the AVIcomp assay and 99.7% for the conventional avidity assay. The Architect Toxo IgG Avidity assay showed an agreement of 97.2% with the bioMérieux Vidas Toxo IgG Avidity Assay employing chaotropic reagents. These performance data suggest that the AVIcomp format shows superior sensitivity and equivalent specificity for the determination of IgG avidity to assays based on the chaotropic method and that the AVIcomp format may also be applicable to other disease states.

  11. Sclerosing cholangitis by cytomegalovirus in highly active antiretroviral therapy era

    Directory of Open Access Journals (Sweden)

    Carmen Hidalgo-Tenorio

    2013-10-01

    Full Text Available Sclerosing colangitis (SC due to cytomegalovirus (CMV is very rare. It has been described mainly in immunocompromised patients. Currently, in HIV infected patients it is exceptional. The most of cases belong to pre-highly active antiretroviral therapy (pre-HAART and those cases were in stage AIDS with less than 100 CD4/μl. The most frequently involved pathogen in pre-HAART period was Cryptosporidium parvum (30-57% and CMV (10-30%; in late HAART period this information are unaware. CMV has been implicated as a possible etiological agent in primary SC partly because of the ability to cause liver damage and its relationship with smooth muscle antibodies. The most effective treatment for SC was the combination of antiretroviral therapy and endoscopic retrograde cholangiopancreatography with sphincterotomy and stent placement. Following, we present the first case of late HAART period which describes a SC extrahepatic without papillary stenosis with CMV as the only cause and clinical presentation of HIV infection in a woman with 177 CD4/μl.

  12. A young patient with multisystem complications after cytomegalovirus infection

    Directory of Open Access Journals (Sweden)

    Swaroopa Pulivarthi

    2014-01-01

    Full Text Available We are describing a case of an 18-year-old male patient with cytomegalovirus (CMV associated guillain-barre syndrome (GBS who presented with an acute onset of generalized weakness and numbness in the extremities, dysphagia, and facial diplegia, followed by respiratory failure, which led to mechanical ventilation. He had positive immunoglobulin G and immunoglobulin M antibodies against CMV, and CMV polymerase chain reaction was positive with <2000 copies of deoxyribonucleic acid. Human immunodeficiency virus test was negative. He received a course of ganciclovir, intravenous immunoglobulin, and plasmapheresis. After improving from acute episode, patient was transferred to a rehabilitation facility for physical and occupational therapy. At the rehabilitation facility, he exhibited signs of acute abdomen with pain in the left upper quadrant secondary to peritonitis from dislodged gastrostomy tube and underwent exploratory laparotomy. During the hospital course he was found to have splenic infarct and colitis on the computed tomography of abdomen. This case showed an immunocompetent young patient with multisystem complications including guillain-barre syndrome (GBS, splenic infarct, hepatitis, and colitis due to CMV.

  13. [Mononucleosis caused by cytomegalovirus].

    Science.gov (United States)

    Lajo Plaza, A; del Castillo Martín, F; Martínez Zapico, R

    1990-01-01

    Sixteen cases of mononucleosis due to cytomegalovirus, are presented. The selection of patients was based on clinical criteria. Symptoms are compared with another series of patients affected with mononucleosis by Epstein-Barr virus. We have not found differences comparing the fever, cervical adenopathies and faringoamigdalitis. Differences were significant in hepatomegaly. We conclude that the clinical picture of cytomegalovirus mononucleosis is very similar to those of the Epstein-Barr mononucleosis.

  14. Effect of mammalian target of rapamycin inhibitors on cytomegalovirus infection in kidney transplant recipients receiving polyclonal antilymphocyte globulins: a propensity score-matching analysis.

    Science.gov (United States)

    Cervera, Carlos; Cofan, Frederic; Hernandez, Cristina; Soy, Dolors; Marcos, Maria Angeles; Sanclemente, Gemma; Bodro, Marta; Moreno, Asunción; Diekmann, Fritz; Campistol, Josep Maria; Oppenheimer, Frederic

    2016-11-01

    Mammalian target of rapamycin inhibitors (mTORi) prevents cytomegalovirus (CMV) infection in kidney transplant (KT) patients. From May 2010 to December 2013, all KT recipients were retrospectively analysed. Maintenance immunosuppression regimen was divided into mTORi or calcineurin inhibitors (CNI)-based regimen. Since June 2011, CMV-seropositive recipients (R+) treated with high-intensity immunosuppression and mTORi did not receive anti-CMV prophylaxis. We analysed 350 consecutive patients, of which 95 (27%) received mTORi and 255 (73%) CNI-based immunosuppression. A Cox-regression multivariate analysis showed that the use of mTORi-based immunosuppression during all follow-up reduced the risk of CMV infection (HR 0.36, 95% CI 0.15-0.89, P = 0.028) and confirmed in a propensity score-matched cohort (HR 0.4, 95% CI 0.1-0.9, P = 0.047). Early discontinuation of mTORi increased the risk of CMV infection (HR 3.2; 95% CI 1.7-6.0) in univariate analysis. The incidence of CMV infection was not higher among CMV R+ patients on mTORi and requiring high-intensity immunosuppression when CMV prophylaxis was not given. The use of mTORi protected for CMV infection in KT patients, allowing to avoid antiviral prophylaxis for R+ patients receiving high-intensity immunosuppression. The increased risk of CMV infection after early discontinuation of mTORi warrants further research. © 2016 Steunstichting ESOT.

  15. [Blood transfusion and viral diseases. Recent acquisitions concerning viral hepatitis viruses, cytomegaloviruses and Epstein-Barr virus].

    Science.gov (United States)

    Spanò, C

    1979-02-11

    In recent years, an increasingly clear picture has been formed of the virus-induced syndromes that may follow a blood transfusion or the use of blood derivatives. Up to about 10 years ago, post-infusion infection was predominantly due to serum hepatitis. Blumberg's discovery of HBsAg (formerly known as Australia antigen) has made it possible to check and prevent viral hepatitis, type B, and to recognise such distinct forms as the mononucleosis-like syndrome caused by cytomegalic virus, infectious mononucleosis caused by EB virus, and so-called non A/non B hepatitis. A brief account of recent advances with respect to the biological features of the viruses responsible for type A and type B hepatitis, CMV and EB virus, and their behaviour in man is followed by an examination of the transfusional aspects, the methods used in their study, and the difficulties involved. The soundness of existing methods and the need for their standardisation are discussed.

  16. Risk factors of CMV replication after allogeneic hematopoietic stem cell transplantation in children and adolescents

    Directory of Open Access Journals (Sweden)

    S. N. Shiriaev

    2014-09-01

    Full Text Available Risk factors of CMV replication in early period after allo-HSCT (D0‑D100 were – myeloablative conditioning – HR 3.74 (1.67–8.37, р = 0.001; unrelated donor – HR 2.18 (0.86–5.26, р = 0.10; HLA-matched donor – HR 0.24 (0.05–1.06, р = 0,06. In late posttransplant period (from D+100 significant risk factors of CMV-reactivation were (according to multivariate analysis myeloablative conditioning – HR 13.17 (3.00–57.86, р = 0.001; combination of pretransplant remission of leukemia and using cyclosporine and methotrexate – HR 0.13 (0.03–0.50, р = 0.003; combination of aGVHD and CMV reactivation in early posttransplant period – HR 2.71 (0.86–8.50, р = 0.088; using of bone marrow – HR 0.37 (0.12–1.19, р = 0.095. We revealed the significant association of aGVHD and CMV-reactivation –OR 2.91 (1.07–7.92, р=0.006, and increased rate of cGVHD in patients with CMV replication at third month after allo-HSCT OR – 2.29 (1.03–5.08, р = 0.066. We revealed a tend to decreasing relapse risk in patients who had CMV-replication – HR 0.07 (0.004–1.17, р = 0.06. Cumulative incidence of CMV-disease was 28 %. CMV-disease was lethal in 44 % patients.

  17. Risk factors of CMV replication after allogeneic hematopoietic stem cell transplantation in children and adolescents

    Directory of Open Access Journals (Sweden)

    S. N. Shiriaev

    2014-01-01

    Full Text Available Risk factors of CMV replication in early period after allo-HSCT (D0‑D100 were – myeloablative conditioning – HR 3.74 (1.67–8.37, р = 0.001; unrelated donor – HR 2.18 (0.86–5.26, р = 0.10; HLA-matched donor – HR 0.24 (0.05–1.06, р = 0,06. In late posttransplant period (from D+100 significant risk factors of CMV-reactivation were (according to multivariate analysis myeloablative conditioning – HR 13.17 (3.00–57.86, р = 0.001; combination of pretransplant remission of leukemia and using cyclosporine and methotrexate – HR 0.13 (0.03–0.50, р = 0.003; combination of aGVHD and CMV reactivation in early posttransplant period – HR 2.71 (0.86–8.50, р = 0.088; using of bone marrow – HR 0.37 (0.12–1.19, р = 0.095. We revealed the significant association of aGVHD and CMV-reactivation –OR 2.91 (1.07–7.92, р=0.006, and increased rate of cGVHD in patients with CMV replication at third month after allo-HSCT OR – 2.29 (1.03–5.08, р = 0.066. We revealed a tend to decreasing relapse risk in patients who had CMV-replication – HR 0.07 (0.004–1.17, р = 0.06. Cumulative incidence of CMV-disease was 28 %. CMV-disease was lethal in 44 % patients.

  18. Cellular Interferon Gamma and Granzyme B Responses to Cytomegalovirus-pp65 and Influenza N1 Are Positively Associated in Elderly.

    Science.gov (United States)

    Theeten, Heidi; Mathei, Catharina; Peeters, Kelly; Ogunjimi, Benson; Goossens, Herman; Ieven, Margareta; Van Damme, Pierre; Cools, Nathalie

    2016-04-01

    Morbidity and mortality in the elderly are associated with viral infections, including influenza and cytomegalovirus (CMV). With increasing age, cellular immunity gains importance in protection to influenza, but latent CMV is highly prevalent and associated with immune dysfunction. An insight into the association between immunity against influenza and CMV adds to the understanding of healthy aging. Here we first aimed to measure influenza-specific cellular immunity using granzyme B (GrzB) and interferon-gamma (IFN-γ)-ELISpot. Next, influenza-specific cellular immunity was associated with humoral and cellular CMV-specific immunity in healthy 65+ elderly. Vaccine trial participants gave additional blood samples 3 weeks after receiving a H1N1 containing vaccine. CMV serology was determined and peripheral blood mononuclear cells were stimulated with influenza N1 or CMV pp65-derived peptide pools for 7 days and rechallenged to assess antigen-specific GgrzB and IFN-γ responses using ELISpot assays. Results were compared using chi-square and correlation analysis. Eighty-three individuals (60% men, 65% CMV IgG+, age range 65-78y) participated. We found significant positive associations between IFN-γ and GrzB responses to both influenza and CMV, but also between a positive CMV serostatus and an influenza N1-specific activation marker response (p = 0.013). CMV pp65 responses were detected in CMV IgG+ individuals, but remarkably also in CMV IgG- individuals (27%). In this study, following influenza vaccination, elderly with cellular immunity against CMV were more likely to have cellular immunity against influenza vaccine N1 antigen. These findings stress the need to continue exploring the possible role of CMV in immunosenescence.

  19. The Influence of Cytomegalovirus on Expression of HLA-G and its Ligand KIR2DL4 by Human Peripheral Blood Leucocyte Subsets.

    Science.gov (United States)

    Albayati, Z; Alyami, A; Alomar, S; Middleton, D; Bonnett, L; Aleem, S; Flanagan, B F; Christmas, S E

    2017-08-17

    HLA-G is a non-classical class I HLA antigen, normally expressed in high levels only on extravillous cytotrophoblast. It has immunosuppressive properties in pregnancy and has also been found to be upregulated on leucocytes in viral infection. In this study, proportions of all leucocyte subsets expressing HLA-G were found to be low in healthy subjects positive or negative for cytomegalovirus (CMV). Significantly greater proportions of CD4+ CD69+ and CD56+ T cells expressed HLA-G compared to other T cells. However, following stimulation with CMV antigens or intact CMV, proportions of CD4+, CD8+, CD69+ and CD56+ T cells, and also B cells expressing HLA-G, were significantly increased in CMV+ subjects. Despite some subjects having alleles of HLA-G associated with high levels of expression, no relationship was found between HLA-G genotype and expression levels. Purified B cells from CMV+ subjects stimulated in mixed culture with CMV antigens showed significantly increased HLA-G mRNA expression by real-time polymerase chain reaction. Serum levels of soluble HLA-G were similar in CMV- and CMV+ subjects but levels in culture supernatants were significantly higher in cells from CMV+ than from CMV- subjects stimulated with CMV antigens. The HLA-G ligand KIR2DL4 was mainly expressed on NK cells and CD56+ T cells with no differences between CMV+ and CMV- subjects. Following stimulation with IL-2, an increase in the proportion of CD56+ T cells positive for KIR2DL4 was found, together with a significant decrease in CD56dimCD16+ NK cells. The results show that CMV influences HLA-G expression in healthy subjects and may contribute to viral immune evasion. © 2017 The Foundation for the Scandinavian Journal of Immunology.

  20. Cost-effectiveness of Universal and Targeted Newborn Screening for Congenital Cytomegalovirus Infection.

    Science.gov (United States)

    Gantt, Soren; Dionne, Francois; Kozak, Fred K; Goshen, Oran; Goldfarb, David M; Park, Albert H; Boppana, Suresh B; Fowler, Karen

    2016-12-01

    Congenital cytomegalovirus (cCMV) infection is a major cause of childhood deafness. Most cCMV infections are not diagnosed without newborn screening, resulting in missed opportunities for directed care. To estimate the cost-effectiveness of universal and targeted newborn cCMV screening programs compared with no cCMV screening. Models were constructed using rates and outcomes from prospective cohort studies of newborn cCMV screening in US postpartum care and early hearing programs. Costs of laboratory testing, treatment, and hearing loss were drawn from Medicaid data and published estimates. The benefits of cCMV screening were assumed to come from antiviral therapy for affected newborns to reduce hearing loss and from earlier identification of hearing loss with postnatal onset. Analyses were performed from July 2014 to March 2016. Models compared universal or targeted cCMV screening of newborns with a failed hearing screen, with standard care for cCMV infection. The incremental costs of identifying 1 cCMV infection, identifying 1 case of cCMV-related hearing loss, and preventing 1 cochlear implant; the incremental reduction in cases of severe to profound hearing loss; and the differences in costs per infant screened by universal or targeted strategies under different assumptions about the effectiveness of antiviral treatment. Among all infants born in the United States, identification of 1 case of cCMV infection by universal screening was estimated to cost $2000 to $10 000; by targeted screening, $566 to $2832. The cost of identifying 1 case of hearing loss due to cCMV was as little as $27 460 by universal screening or $975 by targeted screening. Assuming a modest benefit of antiviral treatment, screening programs were estimated to reduce severe to profound hearing loss by 4.2% to 13% and result in direct costs of $10.86 per newborn screened. However, savings of up to $37.97 per newborn screened were estimated when costs related to functionality were included

  1. Complexity of Host Micro-RNA Response to Cytomegalovirus Reactivation After Organ Transplantation.

    Science.gov (United States)

    Egli, A; Lisboa, L F; O'Shea, D; Asberg, A; Mueller, T; Emery, V; Kumar, D; Humar, A

    2016-02-01

    Human (Homo sapiens) micro-RNAs (hsa-miRNAs) regulate virus and host-gene translation, but the biological impact in patients with human cytomegalovirus (hCMV) infection is not well defined in a clinically relevant model. First, we compared hsa-miRNA expression profiles in peripheral blood mononuclear cells from 35 transplant recipients with and without CMV viremia by using a microarray chip covering 847 hsa-miRNAs. This approach demonstrated a set of 142 differentially expressed hsa-miRNAs. Next, we examined the effect of each of these miRNAs on viral growth by using human fibroblasts (human foreskin fibroblast-1) infected with the hCMV Towne strain, identifying a subset of proviral and antiviral hsa-miRNAs. miRNA-target prediction software indicated potential binding sites within the hCMV genome (e.g., hCMV-UL52 and -UL100 [UL = unique long]) and host-genes (e.g., interleukin-1 receptor, IRF1). Luciferase-expressing plasmid constructs and immunoblotting confirmed several predicted miRNA targets. Finally, we determined the expression of selected proviral and antiviral hsa-miRNAs in 242 transplant recipients with hCMV-viremia. We measured hsa-miRNAs before and after antiviral therapy and correlated hsa-miRNA expression levels to hCMV-replication dynamics. One of six antiviral hsa-miRNAs showed a significant increase during treatment, concurrent with viral decline. In contrast, six of eight proviral hsa-miRNAs showed a decrease during viral decline. Our results indicate that a complex and multitargeted hsa-miRNA response occurs during CMV replication in immunosuppressed patients. This study provides mechanistic insight and potential novel biomarkers for CMV replication. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  2. Annexin 2-mediated enhancement of cytomegalovirus infection opposes inhibition by annexin 1 or annexin 5.

    Science.gov (United States)

    Derry, Mélanie C; Sutherland, Michael R; Restall, Christina M; Waisman, David M; Pryzdial, Edward L G

    2007-01-01

    Biochemical studies have suggested that annexin 2 (A2) may participate in cytomegalovirus (CMV) infection. In the current work, effects of A2 monomer (p36) and heterotetramer (A2t; p36(2)p11(2)) were investigated. Demonstrating a role for endogenous A2, the four stages of infection that were followed were each inhibited by anti-p36 or anti-p11 at 37 degrees C. Immuno-inhibition was attenuated when the virus and cells were pre-incubated at 4 degrees C to coordinate virus entry initiated afterwards at 37 degrees C, reconciling controversy in the literature. As an explanation, CMV-induced phosphorylation of p36 was prevented by the 4 degrees C treatment. Supporting these immuno-inhibition data, purified A2t or p11 increased CMV infectious-progeny generation and CMV gene expression. A specific role for A2t was indicated by purified p36 having no effect. Unlike other steps, primary plaque formation was not enhanced by purified A2t or p11, possibly because of undetectable phosphorylation. As annexins 1 (A1) and 5 (A5) interact with A2, their effect on CMV was also tested. Both purified proteins inhibited CMV infection. In each experiment, the concentration of A1 required for half-maximal inhibition was five- to 10-fold lower than that of A5. Addition of A2 opposed A1- or A5-mediated inhibition of CMV, as did certain A2-specific antibodies that had no effect in the absence of added A1 or A5. Transfection of the p36-deficient cell line HepG2 increased CMV infection and was required for inhibition by the other annexins. These data suggest that CMV exploits A2t at physiological temperature to oppose the protection of cells conferred by A1 or A5.

  3. Cytomegalovirus IgM Seroprevalence among Women of Reproductive Age in the United States.

    Science.gov (United States)

    Wang, Chengbin; Dollard, Sheila C; Amin, Minal M; Bialek, Stephanie R

    2016-01-01

    Cytomegalovirus (CMV) IgM indicates recent active CMV infection. CMV IgM seroprevalence is a useful marker for prevalence of transmission. Using data from the National Health and Nutrition Examination Survey (NHANES) III 1988-1994, we present estimates of CMV IgM prevalence by race/ethnicity, provide a comparison of IgM seroprevalence among all women and among CMV IgG positive women, and explore factors possibly associated with IgM seroprevalence, including socioeconomic status and exposure to young children. There was no difference in IgM seroprevalence by race/ethnicity among all women (3.1%, 2.2%, and 1.6% for non-Hispanic white, non-Hispanic black and Mexican American, respectively; P = 0.11). CMV IgM seroprevalence decreased significantly with increasing age in non-Hispanic black women (Pwomen (P = 0.07), while no apparent trend with age was seen in non-Hispanic white women (P = 0.99). Among 4001 IgG+ women, 118 were IgM+, resulting in 4.9% IgM seroprevalence. In IgG+ women, IgM seroprevalence varied significantly by age (5.3%, 7.3%, and 3.7% for women of 12-19, 20-29, and 30-49 years; P = 0.04) and race/ethnicity (6.1%, 2.7%, and 2.0% for non-Hispanic white, non-Hispanic black, and Mexican American; P<0.001). The factors reported associated with IgG seroprevalence were not associated with IgM seroprevalence. The patterns of CMV IgM seroprevalence by age, race/ethnicity, and IgG serostatus may help understanding the epidemiology of congenital CMV infection as a consequence of vertical transmission and are useful for identifying target populations for intervention to reduce CMV transmission.

  4. Can we build it better? Using BAC genetics to engineer more effective cytomegalovirus vaccines

    OpenAIRE

    Mark R. Schleiss

    2010-01-01

    The magnitude and durability of immunity to human cytomegalovirus (HCMV) following natural infection is compromised by the presence of immune modulation genes that appear to promote evasion of host clearance mechanisms. Since immunity to HCMV offers limited protection, rational design of effective vaccines has been challenging. In this issue of the JCI, Slavuljica and colleagues employ techniques to genetically modify the highly related mouse CMV (MCMV), in the process generating a virus that...

  5. Structural basis for translational stalling by human cytomegalovirus and fungal arginine attenuator peptide

    OpenAIRE

    2010-01-01

    Specific regulatory nascent chains establish direct interactions with the ribosomal tunnel, leading to translational stalling. Despite a wealth of biochemical data, structural insight into the mechanism of translational stalling in eukaryotes is still lacking. Here we use cryo-electron microscopy to visualize eukaryotic ribosomes stalled during the translation of two diverse regulatory peptides: the fungal arginine attenuator peptide (AAP) and the human cytomegalovirus (hCMV) gp48 upstream op...

  6. Donor killer immunoglobulin-like receptor genes and reactivation of cytomegalovirus after HLA-matched hematopoietic stem-cell transplantation: HLA-C allotype is an essential cofactor

    Directory of Open Access Journals (Sweden)

    Carolyn E. Behrendt

    2013-02-01

    Full Text Available Natural Killer (NK cells whose killer immunoglobulin-like receptors (KIR recognize human leukocyte antigen (HLA ligand are licensed for activity. In contrast, non-licensed NK cells display KIRs for which ligand is absent from the self genotype and are usually hyporesponsive. Surprisingly, non-licensed cells are active in tumor control after hematopoietic stem-cell transplantation (HSCT and dominate NK response to murine cytomegalovirus (CMV infection. From those reports, we hypothesized that control of human CMV early after HSCT is influenced by donor KIR genes whose HLA ligand is absent-from-genotype of HLA-matched donor and recipient. To investigate, we studied CMV reactivation through Day 100 after grafts involving CMV-seropositive donor and/or recipient. A multivariate proportional rates model controlled for variability in surveillance and established covariates including acute graft-versus-host disease; statistical significance was adjusted for testing of multiple KIRs with identified HLA class I ligand (2DL1, 2DL2/3, 2DS1, 2DS2, full-length 2DS4, 3DL1/3DS1, 3DL2. Among HSCT recipients (n=286, CMV reactivation-free survival time varied with individual donor KIR genes evolutionarily-specific for HLA-C: when ligand was absent from the donor/recipient genotype, inhibitory KIRs 2DL2 (P<0.0001 and 2DL1 (P=0.015 each predicted inferior outcome, and activating KIRs 2DS2 (P<0.0001, 2DS1 (P=0.016, and 2DS4 (P=0.016 each predicted superior outcome. Otherwise, with ligand present-in-genotype, donor KIR genes had no effect. In conclusion, early after HLA-matched HSCT, individual inhibitory and activating KIR genes have qualitatively different effects on risk of CMV reactivation; unexpectedly, absence of HLA-C ligand from the donor/recipient genotype constitutes an essential cofactor in these associations. Being KIR and HLA-C specific, these findings are independent of licensing via alternate NK cell receptors (NKG2A, NKG2C that recognize HLA-E.

  7. The role of cytomegalovirus, Haemophilus influenzae and Epstein Barr virus in Guillain Barre syndrome.

    Directory of Open Access Journals (Sweden)

    Shahriar Nafissi

    2013-06-01

    Full Text Available Guillain Barre Syndrome (GBS is an inflammatory, usually demyelinating, polyneuropathy; clinically characterized by acute onset of symmetric progressive muscle weakness with loss of myotatic reflexes. Thirty five patients with GBS, defined clinically according to the criteria of Asbury and Cornblath, were recruited from three hospital affiliated to Tehran University of Medical Sciences.As a control group 35 age and sex matched patients with other neurological diseases admitted to the same hospital at the same time, were included in our study. Serum samples were collected before treatment from each patient (within 4 weeks after the disease onset and controls, and stored frozen at -80ºC until serologic assays were done. Serologic testing of pretreatment serum was performed in all patients. Positive titer of virus specific IgM antibody against cytomegalovirus (CMV was found in 6 cases and 2 controls. 34 patients and 31 controls had high titer of anti Haemophilus influenzae IgG and one patient had serologic evidence of a recent Epstein Barr virus (EBV infection. The mean titer of IgG antibody against Haemophilus influenzae in cases and controls was 5.21 and 2.97 respectively. Although serologic evidence of all these infections were more frequent in cases than in controls, only Haemophilus influenzae infection appeared to be significantly related to GBS (P=0.002. Eleven cases and 3 controls had high titers of IgG antibody against Haemophilus influenzae type B (titer >8. There is significant association between high titer of IgG antibody against Haemophilus influenzae and GBS (P=0.017. Our results provide further evidence that Haemophilus influenzae and probably CMV, can be associated with GBS.

  8. CMV and the art of memory maintenance.

    Science.gov (United States)

    Klenerman, Paul; Dunbar, P Rod

    2008-10-17

    The CD8(+) T cell responses to CMV gradually increase in magnitude over time-so-called memory "inflation." In this issue of Immunity, Snyder et al. (2008) examine the dynamics of memory inflation and demonstrate continuous turnover of inflating T cells, drawing on both memory cells and naive cells to replace them.

  9. Detection and quantification of EBV, HHV-6 and CMV DNA in the gastrointestinal tract of HIV-positive patients.

    Science.gov (United States)

    Falasca, F; Maida, P; Gaeta, A; Verzaro, S; Mezzaroma, I; Fantauzzi, A; Donato, G; Bonci, E; Castilletti, C; Antonelli, G; Turriziani, O

    2014-12-01

    Human herpes viruses (HHVs) have been frequently detected in the gastrointestinal (GI) tract and may contribute to the development of gastric cancer. In the present study, the detection rate and viral load of Epstein Barr virus (EBV), HHV-6 and Cytomegalovirus (CMV) were assessed in the GI tract of human immunodeficiency virus (HIV) positive patients and of uninfected patients. The analysis revealed a significantly higher detection rate of EBV and HHV-6 in HIV-infected individuals than in uninfected subjects (88.5 vs 63%; p = 0.03). Moreover, EBV DNA load was significantly higher in the stomach of HIV patients than in controls. These data suggest that the HIV infection status may increase the persistence of these viruses in the GI compartment. Intriguingly, CMV DNA was undetectable in all biopsy specimens analyzed.

  10. Risk of congenital cytomegalovirus infection among HIV-exposed uninfected infants is not decreased by maternal nelfinavir use during pregnancy.

    Science.gov (United States)

    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 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.

  11. Ruptura espontánea de bazo asociada a infección activa por citomegalovirus Spontaneous spleen rupture associated with active cytomegalovirus infection

    Directory of Open Access Journals (Sweden)

    P. J. Duarte

    2003-01-01

    Full Text Available Presentamos un paciente inmunocompetente de 24 años, sexo masculino, que padeció una ruptura espontánea de bazo (REB durante una infección activa (IA por citomegalovirus (CMV. El único antecedente clínico fue un cuadro gripal dos semanas antes de la REB. El diagnóstico de CMV fue confirmado por la presencia de anticuerpos IgM en suero y por PCR positiva para CMV en biopsia de pieza de esplenectomía. El paciente se recuperó completamente luego de la cirugía. La ruptura espontánea de bazo es un evento poco común en la IA por CMV y éste es el primer caso referido en nuestro país.We present a 24 year old immunocompetent male who developed a spontaneous rupture of the spleen (SRE during an acute cytomegalovirus (CMV infection. The only previous clinical feature was the presence of flu-like symptoms two weeks before the SRE. The diagnosis was confirmed by the presence of IgM antibodies to CMV in the serum and a positive CMV-PCR in the splenic biopsy after splenectomy. The patient recovered completely after surgery. Spontaneous splenic rupture is an uncommon event associated with primary cytomegalovirus infection, and this is the first case reported in our country.

  12. Ganciclovir-Resistant Cytomegalovirus Infection in Abdominal Solid Organ Transplant Recipients: Case Series and Review of the Literature.

    Science.gov (United States)

    Rolling, Katherine E; Jorgenson, Margaret R; Descourouez, Jillian L; Mandelbrot, Didier A; Redfield, Robert R; Smith, Jeannina A

    2017-07-12

    Ganciclovir-resistant cytomegalovirus (GR-CMV) is emerging as a significant infection in the abdominal transplant population. GR-CMV is difficult to manage, and treatment options are limited. We report a descriptive case series of 15 patients who had documented GR-CMV at our center and review the literature on treatment of GR-CMV. The first case in this series was detected in 2012; the majority of cases occurred after January 1, 2014, with approximately 50% occurring in 2015. UL97 and UL54 viral genome mutations were present in 100% and 40% of CMV-infected patients, respectively. GR-CMV infection occurred ≤ 1 year posttransplantation in 11 patients (73%). All patients experienced dose reduction of valganciclovir (the oral prodrug of ganciclovir) before the development of GR-CMV. Initial treatment for GR-CMV included a variety of regimens, all including reduction in maintenance immunosuppression. Of the 6 patients with detectable GR-CMV by polymerase chain reaction (PCR) who were discharged without GR-CMV treatment and had a length of stay (LOS) less than 14 days, 83% were subsequently readmitted for treatment of GR-CMV within 2 months (60% in < 20 days); none received leflunomide. Of six patients with a LOS ≥ 14 days, 80% had CMV PCR below quantification on hospital discharge, and only one patient was readmitted in less than 20 days; 83% received leflunomide. Following GR-CMV, there was a 50% rejection incidence, 27% graft loss, and 20% mortality. For patients with more than three admissions for GR-CMV treatment, 100% had a major complication: 60% rejection, 20% graft loss, and 40% mortality. Common clinical characteristics of patients with GR-CMV included high-risk serostatus, lymphocyte depletion, and history of valganciclovir dose reduction. Overall, outcomes were poor. It appears that hospital readmission rate was reduced when CMV was treated to negativity with an initial treatment regimen of reduced immunosuppression, foscarnet, intravenous immunoglobulins

  13. Cytomegalovirus pp65 limits dissemination but is dispensable for persistence

    Energy Technology Data Exchange (ETDEWEB)

    Malouli, Daniel; Hansen, Scott G.; Nakayasu, Ernesto S.; Marshall, Emily E.; Hughes, Colette M.; Ventura, Abigail B.; Gilbride, Roxanne M.; Lewis, Matthew S.; Xu, Guangwu; Kreklywich, Craig; Whizin, Nathan; Fischer, Miranda; Legasse, Alfred W.; Viswanathan, Kasinath; Siess, Don; Camp, David G.; Axthelm, Michael K.; Kahl, Christoph; DeFilippis, Victor R.; Smith, Richard D.; Streblow, Daniel N.; Picker, Louis J.; Früh, Klaus

    2014-04-01

    The tegument phosphoprotein pp65 (UL83) is the most abundant virion protein in human cytomegalovirus (HCMV). Since pp65 is immunodominant in persistently infected individuals, subunit vaccines against HCMV often include pp65 as T cell stimulatory component. Although HCMV pp65 is non-essential for viral growth in vitro it is thought to have an important role in primary and persistent infection since pp65 displays multiple immunomodulatory functions. To determine whether pp65 is required for infection and to evaluate its role in natural and vaccination-induced immunity we generated a rhesus CMV lacking both homologues, pp65a (Rh111) and pp65b (Rh112). Lack of pp65 resulted in a slight growth defect in vitro and an increase of defective particle formation. However, most pp65-deleted virions in the supernatant were phenotypically normal and proteomics analysis revealed that the ratios of the remaining viral proteins were largely unchanged. RhCMV Δpp65ab was able to persistently infect CMV-negative rhesus macaques (RM) and to super-infect RM previously infected with CMV. To determine whether T cells against pp65 are essential for protection against CMV, we challenged Δpp65ab-infected animals with RhCMV ΔUS2-11, a viral recombinant that lacks inhibitors of MHC-I antigen presentation and is thus unable to overcome CMV-specific T cell immunity. Despite a complete lack of pp65-specific T cells, Δpp65ab protected against ΔUS2-11 challenge suggesting that pp65-specific T cells are not essential for T cell immunity against CMV. Using the same approach we further demonstrate that pp65b-specific T cells, induced by heterologous prime/boost vaccination, are not sufficient to protect against ΔUS2-11 challenge. Our data provides a new approach to test the efficacy of subunit vaccine candidates and suggest that pp65 vaccines are insufficient to induce a T cell response that recapitulates the protective effect of natural infection.

  14. Case of cytomegalovirus colitis in an immunocompetent patient: a rare cause of abdominal pain and diarrhea in the elderly.

    Science.gov (United States)

    Harano, Yumi; Kotajima, Lisa; Arioka, Hiroko

    2015-01-01

    Cytomegalovirus (CMV) colitis usually occurs in immunocompromised patients after undergoing organ transplantation or chemotherapy. We report the case of a 60-year-old immunocompetent Japanese woman who presented with abdominal pain and bloody diarrhea. She was initially diagnosed as having ischemic colitis with pseudomembranous colitis on the basis of her symptoms, Clostridium difficile antigen positivity, and colonoscopic findings, which showed ulcer formation from the sigmoid colon to rectum. In spite of bowel rest and administration of metronidazole, her symptoms did not improve. On follow-up colonoscopy, ulcerations remained unchanged. Biopsy of the ulceration revealed CMV-infected cells leading to a diagnosis of CMV colitis. CMV colitis is a rare but possible differential diagnosis in immunocompetent patients. We recommend endoscopic biopsy in a case of refractory abdominal pain and bloody diarrhea.

  15. Pathological spectrum of cytomegalovirus infection of renal allograft recipients-an autopsy study from north India.

    Science.gov (United States)

    Joshi, Kusum; Nada, Ritambhra; Radotra, Bishan Das; Jha, Vivekanand; Sakhuja, Vinay

    2004-07-01

    This is a retrospective study of autopsy material to highlight the histo-morphological changes in cytomegalovirus (CMV) infection amongst renal allograft recipients. Nineteen out of 80 patients (23.75%) autopsied during a seventeen-year period (1985-2001) had CMV infection. Pulmonary infection was present in 14 out of 19 cases of which four had isolated lung involvement. Likewise, there were two cases each of isolated oesophageal and renal involvement; one case with isolated colonic involvement. The other 10 cases had multi-organ involvement and the organs involved were kidneys (4), esophagus (6), stomach (1), colon (5), adrenals (3), pancreas (3), liver (1) and spleen (1). Pulmonary infection with CMV was associated with acute pneumonitis in 3 cases and lymphocytic interstitial pneumonitis in 9 instances. Four out of 6 cases had acute tubulo-interstitial nephritis induced by CMV and only two cases had no significant inflammatory response. Glomerular involvement in the form of CMV inclusions in the glomeruli was present in only one case. Gastrointestinal CMV infection (15) presented as acute necrotizing ulceration because of predominant endothelial involvement. Post transplant survival period varied from one month to three years, with majority (14) of the patients having survived for less than one year.

  16. Clinical Application of Variation in Replication Kinetics During Episodes of Post-transplant Cytomegalovirus Infections

    DEFF Research Database (Denmark)

    Lodding, I P; Sengeløv, Henrik; da Cunha-Bang, C

    2015-01-01

    of the first CMV infection in the first year post-transplant could be calculated for 193 recipients of haematopoietic stem cell or solid organ transplantation. Factors determining the proportion of recipients with a high diagnostic CMV viral load (≥ 18,200 IU/mL) were explored using mathematical simulation......BACKGROUND: Cytomegalovirus (CMV) infection in transplant recipients is reported to replicate with a doubling time of 1.2-2 days, and weekly screening is recommended for early diagnosis. We re-evaluated these features in our cohort of transplant recipients. METHODS: The CMV doubling time....... FINDINGS: The overall median doubling time was 4.3 days (IQR 2.5-7.8) and was not influenced by prior CMV immunity, or type of transplantation (p > 0.4). Assuming a fixed doubling time of 1.3 days and screening intervals of 7 or 10 days, 11.1% and 33.3% were projected to have a high CMV viral load...

  17. Host genetics and susceptibility to congenital and childhood cytomegalovirus infection: a systematic review

    Science.gov (United States)

    Gelemanović, Andrea; Dobberpuhl, Katie; Krakar, Goran; Patarčić, Inga; Kolčić, Ivana; Polašek, Ozren

    2016-01-01

    Aim To summarize available evidence on the role of host genetics in the susceptibility to congenital and childhood cytomegalovirus (CMV) infections by conducting a systematic review of published studies. Methods We searched online databases (PubMed, Web of Science, Scopus and HuGe Navigator) for relevant studies with well-defined inclusion and exclusion criteria and assessed the risk of bias using novel Confounding-Selection-Information bias score (CSI). Results 5105 studies were initially identified, but only 5 met all the inclusion criteria and were analyzed in detail. Polymorphisms of the toll-like receptors (TLRs) and mannose-binding lectin (MBL) genes were shown to have an impact on the CMV infection in infants. Polymorphisms of the TLR2 (rs3804100, rs1898830), TLR4 (rs4986791), and TLR9 (rs352140) were shown to have a role in congenital CMV infection. Low MBL levels were associated with CMV infection in Chinese individuals, a finding that was not replicated in Caucasians. The overall credibility of evidence was weak. Conclusions Based on currently available very limited amount of evidence, it is uncertain whether congenital and childhood CMV infections are under host genetic control. Additional primary studies are needed with more specific research hypotheses that will enable gradual understanding of specific mechanisms of the CMV pathogenesis. More genetic studies in the future will facilitate better understanding of host susceptibility and likely enable novel preventative and curative measures. PMID:27586547

  18. Thrombosis associated with cytomegalovirus infection in patients with ANCA-positive vasculitis.

    Science.gov (United States)

    Wolf, G; Porth, J; Stahl, R A

    2001-11-01

    Three cases of venous thrombosis with pulmonary embolism in two patients associated with underlying antineutrophil cytoplasmic autoantibody (ANCA)-positive vasculitis and reactivated cytomegalovirus (CMV) infection are described. In vitro studies previously have shown that infection of endothelium with CMV increases the release of procoagulant factors and stimulates the expression of adhesion molecules. Because the endothelial cell plays a pivotal role in maintaining the equilibrium between procoagulant and anticoagulant states, injury by ANCA-positive vasculitis and additional infection with CMV may ignite a local thrombosis easily. Although venous thrombosis is uncommon in CMV infection (eg, in the immunosuppressed state after organ transplantation), the combination of vasculitis and reactivated CMV infection may have contributed to injury of the vessel wall with subsequent development of thrombosis. A better awareness of this association could improve morbidity and may lead to prevention of potentially life-threatening pulmonary embolism. Patients with ANCA-positive vasculitis and CMV infection may profit from prophylactic anticoagulant therapy with heparin or low-molecular-weight heparin.

  19. Sequence and Timing of Intracranial Changes in Cytomegalovirus in Pregnancy: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Cynthia O’Sullivan

    2017-01-01

    Full Text Available Cytomegalovirus (CMV is the most common cause of intrauterine infection, occurring in up to 2% of all live births. Most women are asymptomatic or experience nonspecific symptoms, which can lead to long-term sequelae in newborns including neurological impairment, hearing loss, and mental retardation. A 41-year-old woman (G6 P2, with a medical history of epilepsy, presented for her routine anomaly scan at 20 + 4/40. A single finding of echogenic bowel was noted on ultrasound which prompted a full investigation. A repeat ultrasound only five days later demonstrated progressive changes, which included bilateral ventriculomegaly with oedema of the posterior ventricular wall, periventricular hyperechogenicity, and enlargement of the cisterna magna. CMV DNA was detected at amniocentesis. Ultrasound findings are not diagnostic for CMV with only 11–15% of at-risk fetuses being identified. Unfortunately, these findings may be the only indication of an abnormality. There is a well-documented lack of awareness surrounding CMV and screening is not routinely offered. Given the risk to the pregnancy of CMV and to subsequent pregnancies, simple education at the start of a pregnancy could significantly reduce the incidence of maternal CMV.

  20. Chorioretinal scars and visual deprivation are common in children with cochlear implants after congenital cytomegalovirus infection.

    Science.gov (United States)

    Teär Fahnehjelm, Kristina; Olsson, Monica; Fahnehjelm, Cecilia; Lewensohn-Fuchs, Ilona; Karltorp, Eva

    2015-07-01

    The aim of this study was to compare visual function and ocular characteristics in children with cochlear implants, due to severe hearing impairment caused by the congenital cytomegalovirus (CMV) infection, with control children fitted with cochlear implants due to connexin 26 mutations (Cx26), a genetic cause of hearing impairment. We carried out ophthalmological assessments, including visual acuity, ocular alignment, Ocular Motor Score, biomicroscopy and fundus photography, on 26 children with congenital CMV (median age 8.3 years, range 1.4-16.7) and 13 Cx26 controls (median age 5.6 years, range 1.7-12.5). We found unilateral chorioretinal macular scars that reduced best-corrected visual acuity ≤0.3 in five (19%) of the children with congenital CMV, but in none of the children with Cx26 (p = 0.15). Ocular motility problems were more common among children with congenital CMV, but the difference was not significant (p = 0.20). The vestibulo-ocular reflex was more frequently pathological in children with congenital CMV (p = 0.011). Ocular complications with central chorioretinal scars and ocular motility disturbances were common in children treated with cochlear implants due to severe hearing impairment caused by the congenital CMV infection. Ophthalmological assessments are advisable in such children for early identification, intervention and follow-up. ©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  1. RELATIONSHIP BETWEEN CYTOMEGALOVIRUS INFECTION AND THE PRODUCTION OF AN TICARDIOLIPIN ANTIBODY IN RENAL TRANSPLANT RECIPIENTS

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To investigate the relationship bet wee n cytomegalovirus (CMV) infection and the production of anticardiolipin antibody (ACA) in renal transplant recipients.Methods Polymerase c hain reaction (PCR) was used qualitat ively for detection of CMV-DNA in 146 renal transplant recipients.Meanwhile,enz yme-linked immunosorbent assay (ELISA) was used for detection of ACA-IgG in bl ood serum samples from these recipients and 32 healthy individuals. Results The ACA positive rate was 17.1% among the 146 ren al transplant recipients,and that of the control group was 6.3%.There was no sig nificant difference.However,the ACA positive rate of the renal transplant recipi ents infected with CMV was 31.2%.It was clearly higher than that of those with n o infection of CMV and that of the control group (P<0.005). Con clusion The production of ACA was closely related to CMV infection.It m ight be one of the factors of chronic angiopathy of the transpl anted kidney due to CMV infection.

  2. Human cytomegalovirus and mucoepidermoid carcinoma of salivary glands: cell-specific localization of active viral and oncogenic signaling proteins is confirmatory of a causal relationship.

    Science.gov (United States)

    Melnick, Michael; Sedghizadeh, Parish P; Allen, Carl M; Jaskoll, Tina

    2012-02-01

    Human cytomegalovirus (hCMV) infection is common. Although still controversial, there is growing evidence that active hCMV infection is associated with a variety of malignancies, including brain, breast, lung, colon, and prostate. Given that hCMV is frequently resident in salivary gland (SG) ductal epithelium, we hypothesized that hCMV would be important to the pathogenesis of SG mucoepidermoid carcinoma (MEC). This was initially supported by our finding that purified CMV induces malignant transformation in SG cells in an in vitro mouse model, and utilizes a pathogenic pathway previously reported for human MEC. Here we present the histologic and molecular characterizations of 39 human SG MECs selected randomly from a repository of cases spanning 2004-2011. Serial sections were obtained from formalin-fixed, paraffin embedded, tissue blocks from previous incisional or excisional biopsies. Immunohistochemical assays were performed for active hCMV proteins (IE1 and pp65) and the activated COX/AREG/EGFR/ERK signaling pathway. All four prospective causal criteria for viruses and cancer are fully satisfied: (1) protein markers for active hCMV are present in 97% of MECs; (2) markers of active hCMV are absent in non-neoplastic SG tissues; (3) hCMV-specific proteins (IE1, pp65) are in specific cell types and expression is positively correlated with severity; (4) hCMV correlates and colocalizes with an upregulation and activation of an established oncogenic signaling pathway (COX/AREG/EGFR/ERK). Thus, the evidential support reported here and previously in a mouse model is strongly confirmatory of a causal relationship between hCMV and SG mucoepidermoid carcinoma. To our knowledge, this is the first demonstration of hCMV's role in human oncogenesis that fully responds to all of Koch's Postulates as revised for viruses and cancer. In the absence of any contrary evidence, hCMV can reasonably be designated an "oncovirus."

  3. Insertion of core CpG island element into human CMV promoter for enhancing recombinant protein expression stability in CHO cells.

    Science.gov (United States)

    Mariati; Yeo, Jessna H M; Koh, Esther Y C; Ho, Steven C L; Yang, Yuansheng

    2014-01-01

    The human cytomegalovirus promoter (hCMV) is susceptible to gene silencing in CHO cells, most likely due to epigenetic events, such as DNA methylation and histone modifications. The core CpG island element (IE) from the hamster adenine phosphoribosyltransferase gene has been shown to prevent DNA methylation. A set of modified hCMV promoters was developed by inserting one or two copies of IE in either forward or reverse orientations either upstream of the hCMV enhancer, between the enhancer and core promoter (CP), or downstream of the CP. The modified hCMV with one copy of IE inserted between the enhancer and core promoter in reverse orientation (MR1) was most effective at enhancing expression stability without compromising expression level when compared with the wild-type (WT) hCMV. A third of 18 EGFP expressing clones generated using MR1 retained 70% of their starting expression level after 8 weeks of culture in the absence of selection pressure, while none of 18 WT hCMV generated clones had expression above 50%. MR1 also improved antibody expression stability of methotrexate (MTX) amplified CHO cell lines. Stably transfected pools generated using MR1 maintained 62% of their original monoclonal antibody titer after 8 weeks of culture in the absence of MTX, compared to only 37% for WT hCMV pools. Low levels of CpG methylation within both WT hCMV and MR1 were observed in all the analyzed cell lines and the methylation levels did not correlate to the expression stability, suggesting IE enhances expression stability by other mechanisms other than preventing methylation. © 2014 American Institute of Chemical Engineers.

  4. Enumeration of NKG2C+ natural killer cells early following allogeneic stem cell transplant recipients does not allow prediction of the occurrence of cytomegalovirus DNAemia.

    Science.gov (United States)

    Giménez, Estela; Solano, Carlos; Amat, Paula; de la Cámara, Rafael; Nieto, José; López, Javier; Garcia-Noblejas, Ana; Navarro, David

    2015-09-01

    The role of Natural killer (NK) cells in the control of cytomegalovirus (CMV) infection in allogeneic stem cell transplant recipients has not been precisely characterized. The current study is aimed at investigating the potential role of NK cells expressing the activating receptor NKG2C in affording protection against the development of CMV DNAemia in patients exhibiting detectable CMV-specific CD8(+) T-cell responses early following transplantation. A total of 61 nonconsecutive patients were included in the study. Peripheral levels of CD56(bright) CD16(-/low) and CD56(dim) CD16(+) NKG2C(+) NK cells and CMV pp65/IE-1-specific IFN-γ-producing CD8(+) T-cells were enumerated by flow cytometry at days +30 and +60 after transplant. Neither the absolute number of NKG2C(+) NK cells, nor that of CD56(bright) CD16(-/low) and CD56(dim) CD16(+) NKG2C(+) NK-cell subsets at day 30 differed significantly between patients with or without subsequent CMV DNAemia. No significant correlation was found between levels of both NKG2C(+) NK-cell populations and the peak CMV DNA load within subsequent episodes of CMV DNAemia. The data indicate that enumeration of NKG2C(+) NK cells early after transplant is unlikely to be helpful in identifying those patients at highest risk of developing CMV DNAemia. Moreover, the data do not support a direct implication of NKG2C(+) NK cells in preventing the development of CMV DNAemia.

  5. Cytomegalovirus-based vaccine expressing Ebola virus glycoprotein protects nonhuman primates from Ebola virus infection.

    Science.gov (United States)

    Marzi, Andrea; Murphy, Aisling A; Feldmann, Friederike; Parkins, Christopher J; Haddock, Elaine; Hanley, Patrick W; Emery, Matthew J; Engelmann, Flora; Messaoudi, Ilhem; Feldmann, Heinz; Jarvis, Michael A

    2016-02-15

    Ebolaviruses pose significant public health problems due to their high lethality, unpredictable emergence, and localization to the poorest areas of the world. In addition to implementation of standard public health control procedures, a number of experimental human vaccines are being explored as a further means for outbreak control. Recombinant cytomegalovirus (CMV)-based vectors are a novel vaccine platform that have been shown to induce substantial levels of durable, but primarily T-cell-biased responses against the encoded heterologous target antigen. Herein, we demonstrate the ability of rhesus CMV (RhCMV) expressing Ebola virus (EBOV) glycoprotein (GP) to provide protective immunity to rhesus macaques against lethal EBOV challenge. Surprisingly, vaccination was associated with high levels of GP-specific antibodies, but with no detectable GP-directed cellular immunity.

  6. Asymptomatic superior mesenteric vein thrombosis as unusual complication of acute cytomegalovirus infection: a case report

    Directory of Open Access Journals (Sweden)

    Michele Bertoni

    2015-10-01

    Full Text Available We describe a 39-year-old male who presented with a fever of unknown origin, the diagnostic work-up of which disclosed an acute cytomegalovirus (CMV infection complicated by a partial superior mesenteric vein (SMV thrombosis. Further investigations revealed the presence of factor V Leiden mutation. Oral anticoagulant treatment with warfarin led to a complete recanalization of SMV two months after. A literature review on the association between CMV infection and portal system (PS thrombosis in immunocompetent patients was performed. We found that, in agreement with our case, in a minority of case reports patients did not complain of abdominal pain, but presented with a mononucleosis-like syndrome with malaise and prolonged fever and displayed a variable elevation of aminotransferase levels. Interestingly, most of them exhibited a limited extension of portal thrombosis. On the whole, these data suggest that PS thrombosis during acute CMV infection may be an underestimated complication.

  7. Development and preclinical evaluation of an alphavirus replicon particle vaccine for cytomegalovirus.

    Science.gov (United States)

    Reap, Elizabeth A; Morris, John; Dryga, Sergey A; Maughan, Maureen; Talarico, Todd; Esch, Robert E; Negri, Sarah; Burnett, Bruce; Graham, Andrew; Olmsted, Robert A; Chulay, Jeffrey D

    2007-10-16

    We used a replication-incompetent, single-cycle, alphavirus replicon vector system to produce virus-like replicon particles (VRP) expressing the extracellular domain of human cytomegalovirus (CMV) glycoprotein B or a pp65/IE1 fusion protein. Efficient production methods were scaled to produce pilot lots and clinical lots of each alphavirus replicon vaccine component. The vaccine induced high-titered antibody responses in mice and rabbits, as measured by ELISA and CMV neutralization assays, and robust T-cell responses in mice, as measured by IFN-gamma ELISPOT assay. A toxicity study in rabbits showed no adverse effects in any toxicology parameter. These studies support clinical testing of this novel CMV alphavirus replicon vaccine in humans.

  8. Cytomegalovirus Reactivation after Allogeneic Hematopoietic Stem Cell Transplantation is Associated with a Reduced Risk of Relapse in Patients with Acute Myeloid Leukemia Who Survived to Day 100 after Transplantation: The Japan Society for Hematopoietic Cell Transplantation Transplantation-related Complication Working Group.

    Science.gov (United States)

    Takenaka, Katsuto; Nishida, Tetsuya; Asano-Mori, Yuki; Oshima, Kumi; Ohashi, Kazuteru; Mori, Takehiko; Kanamori, Heiwa; Miyamura, Koichi; Kato, Chiaki; Kobayashi, Naoki; Uchida, Naoyuki; Nakamae, Hirohisa; Ichinohe, Tatsuo; Morishima, Yasuo; Suzuki, Ritsuro; Yamaguchi, Takuhiro; Fukuda, Takahiro

    2015-11-01

    Cytomegalovirus (CMV) infection is a major infectious complication after allogeneic hematopoietic cell transplantation (allo-HSCT). Recently, it was reported that CMV reactivation is associated with a decreased risk of relapse in patients with acute myeloid leukemia (AML). The aim of this study was to evaluate the impact of early CMV reactivation on the incidence of disease relapse after allo-HSCT in a large cohort of patients. The Japan Society for Hematopoietic Cell Transplantation's Transplantation-Related Complication Working Group retrospectively surveyed the database of the Transplant Registry Unified Management Program at the Japan Society for Hematopoietic Cell Transplantation. Patients with AML (n = 1836), acute lymphoblastic leukemia (ALL, n = 911), chronic myeloid leukemia (CML, n = 223), and myelodysplastic syndrome (MDS, n = 569) who underwent their first allo-HSCT from HLA-matched related or unrelated donors between 2000 and 2009 and who survived without disease relapse until day 100 after transplantation were analyzed. Patients who received umbilical cord blood transplantation were not included. Patients underwent surveillance by pp65 antigenemia from the time of engraftment, and the beginning of preemptive therapy was defined as CMV reactivation. Cox proportional hazards models were used to evaluate the risk factors of relapse, nonrelapse, and overall mortality. CMV reactivation and acute/chronic graft-versus-host disease (GVHD) were evaluated as time-dependent covariates. CMV reactivation was associated with a decreased incidence of relapse in patients with AML (20.3% versus 26.4%, P = .027), but not in patients with ALL, CML, or MDS. Among 1836 patients with AML, CMV reactivation occurred in 795 patients (43.3%) at a median of 42 days, and 436 patients (23.7%) relapsed at a median of 221 days after allo-HSCT. Acute GVHD grades II to IV developed in 630 patients (34.3%). By multivariate analysis considering competing risk factors, 3

  9. Partial corrosion casting to assess cochlear vasculature in mouse models of presbycusis and CMV infection.

    Science.gov (United States)

    Carraro, Mattia; Park, Albert H; Harrison, Robert V

    2016-02-01

    Some forms of sensorineural hearing loss involve damage or degenerative changes to the stria vascularis and/or other vascular structures in the cochlea. In animal models, many methods for anatomical assessment of cochlear vasculature exist, each with advantages and limitations. One methodology, corrosion casting, has proved useful in some species, however in the mouse model this technique is difficult to achieve because digestion of non vascular tissue results in collapse of the delicate cast specimen. We have developed a partial corrosion cast method that allows visualization of vasculature along much of the cochlear length but maintains some structural integrity of the specimen. We provide a detailed step-by-step description of this novel technique. We give some illustrative examples of the use of the method in mouse models of presbycusis and cytomegalovirus (CMV) infection.

  10. Human cytomegalovirus gH stability and trafficking are regulated by ER-associated degradation and transmembrane architecture.

    Science.gov (United States)

    Gardner, Thomas J; Hernandez, Rosmel E; Noriega, Vanessa M; Tortorella, Domenico

    2016-03-30

    The prototypic betaherpesvirus human cytomegalovirus (CMV) establishes life-long persistence within its human host. While benign in healthy individuals, CMV poses a significant threat to the immune compromised, including transplant recipients and neonates. The CMV glycoprotein complex gH/gL/gO mediates infection of fibroblasts, and together with the gH/gL/UL128/130/131 a pentameric complex permits infection of epithelial, endothethial, and myeloid cells. Given the central role of the gH/gL complex during infection, we were interested in studying cellular trafficking of the gH/gL complex through generation of human cells that stably express gH and gL. When expressed alone, CMV gH and gL were degraded through the ER-associated degradation (ERAD) pathway. However, co-expression of these proteins stabilized the polypeptides and enhanced their cell-surface expression. To further define regulatory factors involved in gH/gL trafficking, a CMV gH chimera in which the gH transmembrane and cytoplasmic tail were replaced with that of human CD4 protein permitted cell surface gH expression in absence of gL. We thus demonstrate the ability of distinct cellular processes to regulate the trafficking of viral glycoproteins. Collectively, the data provide insight into the processing and trafficking requirements of CMV envelope protein complexes and provide an example of the co-opting of cellular processes by CMV.

  11. Cytomegalovirus-Driven Adaptive-Like Natural Killer Cell Expansions Are Unaffected by Concurrent Chronic Hepatitis Virus Infections

    Directory of Open Access Journals (Sweden)

    David F. G. Malone

    2017-05-01

    Full Text Available Adaptive-like expansions of natural killer (NK cell subsets are known to occur in response to human cytomegalovirus (CMV infection. These expansions are typically made up of NKG2C+ NK cells with particular killer-cell immunoglobulin-like receptor (KIR expression patterns. Such NK cell expansion patterns are also seen in patients with viral hepatitis infection. Yet, it is not known if the viral hepatitis infection promotes the appearance of such expansions or if effects are solely attributed to underlying CMV infection. In sizeable cohorts of CMV seropositive hepatitis B virus (HBV, hepatitis C virus (HCV, and hepatitis delta virus (HDV infected patients, we analyzed NK cells for expression of NKG2A, NKG2C, CD57, and inhibitory KIRs to assess the appearance of NK cell expansions characteristic of what has been seen in CMV seropositive healthy individuals. Adaptive-like NK cell expansions observed in viral hepatitis patients were strongly associated with CMV seropositivity. The number of subjects with these expansions did not differ between CMV seropositive viral hepatitis patients and corresponding healthy controls. Hence, we conclude that adaptive-like NK cell expansions observed in HBV, HCV, and/or HDV infected individuals are not caused by the chronic hepatitis infections per se, but rather are a consequence of underlying CMV infection.

  12. Cytomegalovirus-induced embryopathology: mouse submandibular salivary gland epithelial-mesenchymal ontogeny as a model

    Directory of Open Access Journals (Sweden)

    Huang Jing

    2006-09-01

    Full Text Available Abstract Background Human studies suggest, and mouse models clearly demonstrate, that cytomegalovirus (CMV is dysmorphic to early organ and tissue development. CMV has a particular tropism for embryonic salivary gland and other head mesenchyme. CMV has evolved to co-opt cell signaling networks so to optimize replication and survival, to the detriment of infected tissues. It has been postulated that mesenchymal infection is the critical step in disrupting organogenesis. If so, organogenesis dependent on epithelial-mesenchymal interactions would be particularly vulnerable. In this study, we chose to model the vulnerability by investigating the cell and molecular pathogenesis of CMV infected mouse embryonic submandibular salivary glands (SMGs. Results We infected E15 SMG explants with mouse CMV (mCMV. Active infection for up to 12 days in vitro results in a remarkable cell and molecular pathology characterized by atypical ductal epithelial hyperplasia, apparent epitheliomesenchymal transformation, oncocytic-like stromal metaplasia, β-catenin nuclear localization, and upregulation of Nfkb2, Relb, Il6, Stat3, and Cox2. Rescue with an antiviral nucleoside analogue indicates that mCMV replication is necessary to initiate and maintain SMG dysmorphogenesis. Conclusion mCMV infection of embryonic mouse explants results in dysplasia, metaplasia, and, possibly, anaplasia. The molecular pathogenesis appears to center around the activation of canonical and, perhaps more importantly, noncanonical NFκB. Further, COX-2 and IL-6 are important downstream effectors of embryopathology. At the cellular level, there appears to be a consequential interplay between the transformed SMG cells and the surrounding extracellular matrix, resulting in the nuclear translocation of β-catenin. From these studies, a tentative framework has emerged within which additional studies may be planned and performed.

  13. Impact of HIV on CD8+ T cell CD57 expression is distinct from that of CMV and aging.

    Directory of Open Access Journals (Sweden)

    Sulggi A Lee

    Full Text Available Chronic antigenic stimulation by cytomegalovirus (CMV is thought to increase "immunosenesence" of aging, characterized by accumulation of terminally differentiated CD28- CD8+ T cells and increased CD57, a marker of proliferative history. Whether chronic HIV infection causes similar effects is currently unclear.We compared markers of CD8+ T cell differentiation (e.g., CD28, CD27, CCR7, CD45RA and CD57 expression on CD28- CD8+ T cells in healthy HIV-uninfected adults with and without CMV infection and in both untreated and antiretroviral therapy (ART-suppressed HIV-infected adults with asymptomatic CMV infection.Compared to HIV-uninfected adults without CMV (n=12, those with asymptomatic CMV infection (n=31 had a higher proportion of CD28-CD8+ T cells expressing CD57 (P=0.005. Older age was also associated with greater proportions of CD28-CD8+ T cells expressing CD57 (rho: 0.47, P=0.007. In contrast, untreated HIV-infected CMV+ participants (n=55 had much lower proportions of CD28- CD8+ cells expressing CD57 than HIV-uninfected CMV+ participants (P<0.0001 and were enriched for less well-differentiated CD28- transitional memory (TTR CD8+ T cells (P<0.0001. Chronically HIV-infected adults maintaining ART-mediated viral suppression (n=96 had higher proportions of CD28-CD8+ T cells expressing CD57 than untreated patients (P<0.0001, but continued to have significantly lower levels than HIV-uninfected controls (P=0.001. Among 45 HIV-infected individuals initiating their first ART regimen, the proportion of CD28-CD8+ T cells expressing CD57 declined (P<0.0001, which correlated with a decline in percent of transitional memory CD8+ T cells, and appeared to be largely explained by a decline in CD28-CD57- CD8+ T cell counts rather than an expansion of CD28-CD57+ CD8+ T cell counts.Unlike CMV and aging, which are associated with terminal differentiation and proliferation of effector memory CD8+ T cells, HIV inhibits this process, expanding less well

  14. Association between cytomegalovirus antibody levels and cognitive functioning in non-elderly adults.

    Directory of Open Access Journals (Sweden)

    Faith Dickerson

    Full Text Available BACKGROUND: Elevated levels of antibodies to Cytomegalovirus (CMV have been associated with cognitive impairment, but the quantitative relationship between CMV antibody levels and domains of cognitive functioning in younger adults has not been established. METHODS: We measured IgG class antibodies to Cytomegalovirus in 521 individuals, mean age 32.8 years. Participants were selected for the absence of psychiatric disorder and of a serious medical condition that could affect brain functioning. Cognitive functioning was measured with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS, the Wisconsin Card Sorting Test, Trail Making Test part A, and the WAIS III Letter Number Sequencing subtest. Linear regression analyses were used to measure the quantitative association between cognitive scores and Cytomegalovirus IgG antibody level. Logistic regression analyses were used to measure the odds of low cognitive scores and elevated antibody levels defined as an antibody level > = 50th, 75th, and 90th percentile of the group. RESULTS: Higher levels of CMV antibodies were associated with lower performance on RBANS Total (coefficient -1.03, p<.0002, Delayed Memory (coefficient -0.94, p<.001, Visuospatial/Constructional (coefficient -1.77, p<5×10(-7, and Letter Number Sequencing (coefficient -0.15, p<.03. There was an incremental relationship between the level of CMV antibody elevation and the odds of a low RBANS Total score. The odds of a low total cognitive score were 1.63 (95th % CI 1.01, 2.64; p<.045, 2.22 (95th % CI 1.33, 3.70; p<.002, and 2.46 (95th % CI 1.24, 4.86; p<.010 with a CMV antibody level greater than or equal to the 50th, 75th, and 90th percentile respectively. CONCLUSIONS: Higher levels of Cytomegalovirus antibodies are associated with lower levels of cognitive functioning in non-elderly adults. Methods for the prevention and treatment of CMV infection should be evaluated to determine if they result in an

  15. Association between Cytomegalovirus Antibody Levels and Cognitive Functioning in Non-Elderly Adults

    Science.gov (United States)

    Dickerson, Faith; Stallings, Cassie; Origoni, Andrea; Katsafanas, Emily; Schweinfurth, Lucy A. B.; Savage, Christina L. G.; Yolken, Robert

    2014-01-01

    Background Elevated levels of antibodies to Cytomegalovirus (CMV) have been associated with cognitive impairment, but the quantitative relationship between CMV antibody levels and domains of cognitive functioning in younger adults has not been established. Methods We measured IgG class antibodies to Cytomegalovirus in 521 individuals, mean age 32.8 years. Participants were selected for the absence of psychiatric disorder and of a serious medical condition that could affect brain functioning. Cognitive functioning was measured with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), the Wisconsin Card Sorting Test, Trail Making Test part A, and the WAIS III Letter Number Sequencing subtest. Linear regression analyses were used to measure the quantitative association between cognitive scores and Cytomegalovirus IgG antibody level. Logistic regression analyses were used to measure the odds of low cognitive scores and elevated antibody levels defined as an antibody level > = 50th, 75th, and 90th percentile of the group. Results Higher levels of CMV antibodies were associated with lower performance on RBANS Total (coefficient −1.03, p<.0002), Delayed Memory (coefficient −0.94, p<.001), Visuospatial/Constructional (coefficient −1.77, p<5×10−7), and Letter Number Sequencing (coefficient −0.15, p<.03). There was an incremental relationship between the level of CMV antibody elevation and the odds of a low RBANS Total score. The odds of a low total cognitive score were 1.63 (95th % CI 1.01, 2.64; p<.045), 2.22 (95th % CI 1.33, 3.70; p<.002), and 2.46 (95th % CI 1.24, 4.86; p<.010) with a CMV antibody level greater than or equal to the 50th, 75th, and 90th percentile respectively. Conclusions Higher levels of Cytomegalovirus antibodies are associated with lower levels of cognitive functioning in non-elderly adults. Methods for the prevention and treatment of CMV infection should be evaluated to determine if they result in an

  16. Age can be a Problem: Clostridium difficile and Cytomegalovirus Colitis Coinfection in an Immunocompetent 90-year-old Patient

    Directory of Open Access Journals (Sweden)

    Po-Hsun Chen

    2015-06-01

    Full Text Available Clostridium difficile colitis and cytomegalovirus colitis coinfection has been documented in immunocompromised patients. However, this kind of coinfection has rarely been reported in immunocompetent patients. We present a 90-year-old, critically ill, immunocompetent patient, who had a C. difficile and cytomegalovirus colitis coinfection. Although the common risk factors of both types of colitis are well known, clinical physicians still need to be alert to this coinfection because severe complications of CMV colitis have been reported previously. Physicians should be more aggressive in the management of elderly immunocompetent patients with refractory symptoms of colitis.

  17. Cytomegalovirus pneumonia as the first manifestation of severe combined immunodeficiency

    Science.gov (United States)

    Jończyk-Potoczna, Katarzyna; Ossowska, Lidia; Bręborowicz, Anna; Bartkowska-Śniatkowska, Alicja; Wachowiak, Jacek

    2014-01-01

    Severe combined immunodeficiency (SCID) is characterized by the absence of functional T lymphocytes and impairment of adaptive immunity. While heterogeneity of the genetic background in SCID leads to the variability of immune phenotypes, most of affected newborns appear healthy but within the first few months they develop life-threatening opportunistic respiratory or gastrointestinal tract infections. The objective of the study was to define the presenting features and etiology of infections in children with SCID. We retrospectively reviewed five children in whom the diagnosis of SCID had been established in our pediatric immunology clinic over the last 10-year period. A viral respiratory tract infection was the first manifestation of SCID in all the children studied. Cytomegalovirus (CMV) pneumonia was recognized in as many as 4 cases and coronavirus pulmonary infection was diagnosed in one case, whereas Pneumocystis jiroveci was identified as a co-pathogen in one CMV-infected patient. Severe combined immunodeficiency is a pediatric emergency condition and given the significant impact of pulmonary CMV infection in SCID children, establishing an accurate etiological diagnosis is of essential importance in instituting the specific treatment and improving the outcome. PMID:26155153

  18. EPSTEIN-BARR VIRUS AND CYTOMEGALOVIRUS – TWO HERPES VIRUSES WITH ORAL MANIFESTATIONS.

    Directory of Open Access Journals (Sweden)

    Assya Krasteva

    2013-09-01

    Full Text Available Diseases caused by cytomegalovirus and Epstein-Barr virus are reported with increasing frequency. Epstein-Barr virus damages usually are due to reactivation of latent infection. while cytomegalovirus disease result from primary or reactivated infection in susceptible hosts. The booth infections can have oral manifestations.

  19. Cytomegalovirus viral load kinetics in patients with HIV/AIDS admitted to a medical intensive care unit: a case for pre-emptive therapy.

    Directory of Open Access Journals (Sweden)

    Simnikiwe H Mayaphi

    Full Text Available BACKGROUND: Cytomegalovirus (CMV infection is associated with severe diseases in immunosuppressed patients; however, there is a lack of data for pre-emptive therapy in patients with HIV/AIDS. METHOD: This was a retrospective study, which enrolled patients diagnosed with HIV/AIDS (CD41,000 copies/ml at baseline testing had significantly higher mortality compared to those who had 5,100 copies/ml and did not receive ganciclovir had 100% mortality compared to 58% mortality in those who received ganciclovir at VLs of >5,100 copies/ml, 50% mortality in those who were not treated and had low VLs of <5,100 copies/ml, and 44% mortality in those who had ganciclovir treatment at VLs of <5,100 copies/ml (p = 0.084, 0.046, 0.037, respectively. CONCLUSION: This study showed a significantly increased mortality in patients with HIV/AIDS who had high CMV VLs, and suggests that a threshold value of 1,000 copies/ml may be appropriate for pre-emptive treatment in this group.

  20. Cytomegalovirus coinfecting with disseminated herpes simplex virus in one case%巨细胞病毒感染合并播散性单纯疱疹病毒感染一例

    Institute of Scientific and Technical Information of China (English)

    唐旭华; 周晖; 杨建; 李巧飞; 高谦; 何定阳

    2014-01-01

    巨细胞病毒(CMV)合并播散性单纯疱疹病毒(HSV)感染往往发生于HIV感染的患者,HIV阴性患者少见。该文报道1例肾病患者给予糖皮质激素治疗导致CMV和HSV重新激活,给予伐昔洛韦、更昔洛韦、亚胺培南、利奈唑胺等抗感染治疗后CMV-DNA复制数降至正常,皮疹有好转,但50 d后因并发重症免疫抑制宿主肺炎、Ⅰ型呼吸衰竭死亡。该例提示CMV合并播散性HSV感染预后差,应引起临床重视。%Cytomegalovirus (CMV)coinfecting with herpes simplex virus (HSV)usually occurred in patients with human immunodeficiency virus (HIV)infection,while rarely occurred in patients with negative HIV and haven't been reported in mainland China to our best knowledge. We presented an immunocompromised patient with renal disorder treated with corticosteroid resulting in reactivation of CMV and HSV. The CMV-DNA replication number of the patient was reduced to the normal level by valacyclovir,ganciclovir,imipenem,lin-ezolid. Howeve the patient die in the 50th day,who dead for severe complications of pneumonia. We should pay more attention to the disease because of its poor prognosis.

  1. Inflammatory bowel disease — is there something new in the immunological background?

    Directory of Open Access Journals (Sweden)

    Michał Drews

    2011-07-01

    Full Text Available In the present paper we correlate clinical data, as well as histopathological, immunohistochemical and molecular biology methods, with the occurrence of both forms of inflammatory bowel disease (IBD i.e. ulcerative colitis and Crohn’s disease. We found that patients with a history of Epstein-Barr virus (EBV or cytomegalovirus (CMV infections, as well as steroid treatment, had increased susceptibility to the development of IBD. The diagnosis of IBD was confirmed by histopathology. Previous infections by EBV and CMV, as well as M. tuberculosis, were proved by PCR-based techniques and in situ hybridization. We found PCR-proved latent viral infections in 30–50% of the IBD patients we studied. However, we were unable to prove the presence of viral antigens by immunohistochemistry for EBV or CMV. We found positive correlations between the presence of anti-CMV IgG, as well as PCR-positive results for M. tuberculosis with an ulcerative colitis diagnosis. Additionally, up to 80% of IBD patients used steroids, which was found to be correlated with a diagnosis of Crohn’s disease. Our data may support the theory that IBD could be related to previous viral infections and the use of steroids. (Folia Histochemica et Cytobiologica 2011, Vol. 49, No. 2, 357–362

  2. 母乳喂养对婴儿唾液巨细胞病毒载量的影响%Effect of breastfeeding on infant cytomegalovirus viral load

    Institute of Scientific and Technical Information of China (English)

    张琳; 王淮燕; 梅涛; 杨利民; 史烨; 虞斌

    2014-01-01

    目的 对先天性巨细胞病毒(CMV)感染的新生儿进行随访监测,探讨母乳喂养对CMV载量变化的影响.方法 采集2010年11月至2012年2月在常州市妇幼保健院山生的新生儿唾液进行CMV感染筛查,排除早产、严重感染性疾病或畸形等,对阳性感染且.无症状的足月新生儿根据母亲自主选择分成人工喂养组及母乳喂养组,随访至6个月,分别在出生1个月内、3个月、6个月采集唾液及母乳,采取实时荧光定量PCR法检测CMV-DNA的载量变化,同时行体格检查、头颅B超检查、耳声发射听力筛查、肝功能、血常规分析等检查.结果 30例婴儿在随访的6个月中均末发现有CMV感染性疾病的表现.人工喂养组与母乳喂养组婴儿在出生1个月内、3个月、6个月唾液巨细胞DNA载量末见明显变化(t=2.832、3.161、3.475,P均>0.05).母乳喂养组乳汁在山生1个月内、3个月、6个月CMV-DNA载量分别为3.125×103±2.017×102、2.688×103±2.251×102、3.016×103 ±2.613×102,三者比较差异无统计学意义(F=1.725,P=0.667).头颅B超检查、耳声发射听力筛查、肝功能、血常规分析等检查末见明显异常.结论 CMV感染的足月无症状新生儿,即便母乳中CMV 阳性,继续母乳喂养后婴儿体内的病毒载量也不会增加,也末发现继发性的症状感染.%Objective Follow-up monitoring was carried out in infants infected with cytomegalovirus (CMV) so as to find out whether breastfeeding could bring about changes of CMV viral load.Methods Saliva of the neonates born in Changzhou Maternal and Child Health Hospital from Nov.2010 to Feb.2012,was collected for CMV screening.Premature infants,or the infants with seriously infectious diseases and deformities were excluded,such as severe intrauterine infection,congenital immune deficiency disease and so on.The full-term infants with aymptomatic infection were divided into the artificial feeding group and the breastfeeding group

  3. Breakage of resistance to Cucumber mosaic virus by co-infection with Zucchini yellow mosaic virus: enhancement of CMV accumulation independent of symptom expression.

    Science.gov (United States)

    Wang, Y; Lee, K C; Gaba, V; Wong, S M; Palukaitis, P; Gal-On, A

    2004-02-01

    Resistance to the cucumovirus Cucumber mosaic virus (CMV) in cucumber cv. Delila was manifested as a very low level of accumulation of viral RNA and capsid protein, and an absence of CMV-induced symptoms. In addition, resistance was observed at the single cell level, with a reduction in accumulation of CMV RNAs, compared to accumulation in cells of the susceptible cucumber cv. Bet Alpha. Resistance to CMV in cv. Delila was broken by co-infection with the potyvirus Zucchini yellow mosaic virus (ZYMV). Resistance breakage in cv. Delila plants was manifested by an increase in the accumulation of (+) and (-) CMV RNA as well as CMV capsid protein, with no increase in the level of accumulation of ZYMV. Resistance breakage in the resistant cultivar by ZYMV also occurred at the single cell level. Thus, synergistic interactions known to occur between a potyvirus and a cucumovirus led to resistance breakage during a double infection. However, resistance breakage was not accompanied by an increase in disease symptoms beyond those induced by ZYMV itself. On co-inoculation with an asymptomatic variant of ZYMV-AG an enhancement of CMV infection occurred without disease manifestation. Consequently, intensification of viral RNA and capsid protein accumulation can occur without a corresponding increase in disease development, suggesting that different host genes regulate viral accumulation and disease development in the CMV-resistant cucumber plants.

  4. Comparison of high-resolution computed tomography findings between Pseudomonas aeruginosa pneumonia and Cytomegalovirus pneumonia

    Energy Technology Data Exchange (ETDEWEB)

    Omeri, Ahmad Khalid; Okada, Fumito; Takata, Shoko; Ono, Asami; Sato, Haruka; Mori, Hiromu [Oita University Faculty of Medicine, Department of Radiology, Yufu, Oita (Japan); Nakayama, Tomoko [Oita Red Cross Hospital, Department of Radiology, Oita (Japan); Ando, Yumiko [Oita Nishibeppu National Hospital, Department of Radiology, Oita (Japan); Hiramatsu, Kazufumi [Oita University Hospital, Hospital Infection Control Center, Oita (Japan)

    2014-12-15

    To compare pulmonary high-resolution CT (HRCT) findings in patients with Pseudomonas aeruginosa pneumonia to HRCT findings in patients with Cytomegalovirus (CMV) pneumonia. We studied 124 patients (77 men, 47 women; age range, 20-89 years; mean age, 65.4 years) with P. aeruginosa pneumonia and 44 patients (22 men, 22 women; age range, 36-86 years; mean age, 63.2 years) with CMV pneumonia. CT findings of consolidation (p < 0.005), bronchial wall thickening (p < 0.001), cavity (p < 0.05), and pleural effusion (p < 0.001) were significantly more frequent in patients with P. aeruginosa pneumonia than in those with CMV pneumonia. Centrilobular nodules, a crazy-paving appearance, and nodules were significantly more frequent in patients with CMV pneumonia than in those with P. aeruginosa pneumonia (all p < 0.001). Pulmonary HRCT findings, such as bronchial wall thickening, crazy-paving appearance, and nodules may be useful in distinguishing between P. aeruginosa pneumonia and CMV pneumonia. (orig.)

  5. Dried Urine Spots for Detection and Quantification of Cytomegalovirus in Newborns

    Science.gov (United States)

    Forman, Michael; Valsamakis, Alexandra; Arav-Boger, Ravit

    2012-01-01

    Dried urine spots (DUS) have been reported to provide a simple screening tool for congenital cytomegalovirus (CMV) infection. We developed a standardized method for CMV quantification from DUS. Two applications of 20 μ L urine remained within the rim of the filter paper disc and were used to determine the analytical performance of Towne CMV spiked into urine and applied on the discs. The measurable range spanned 3.7 to ≥8.0 log10 copies/mL. The detection limit was 22 DNA copies/disc. Urine samples from congenitally-infected newborns and negative controls were either diluted 1:10 or applied on filter paper at the same volume. DNA copy number from DUS correlated well with copy number from 1:10 diluted urine, although there was a trend for lower levels from DUS (0.3 log10 difference). Our standardized method for CMV detection and quantification may facilitate CMV studies in resource-limited areas and allow for longitudinal monitoring of viral loads in treated infants. PMID:22658885

  6. Cystoid macular edema secondary to immune recovery uveitis in a man with cytomegalovirus retinitis and AIDS

    Directory of Open Access Journals (Sweden)

    Kathir Yoganathan

    2010-09-01

    Full Text Available Kathir YoganathanHIV/Genito-Urinary Medicine, Abertawe Bro Morgannwg University Health Board, Singleton hospital, Swansea, UKAbstract: Cytomegalovirus (CMV is the most common intraocular opportunistic infection in profoundly immunocompromised patients with AIDS. It is characterized by an acute, progressive, necrotizing retinitis in patients with a CD4 count of <50 cells/µL. Although the incidence of CMV retinitis has declined because of the introduction of antiretroviral therapy (ART, a new syndrome of intraocular inflammation has emerged in patients with rising CD4 lymphocyte counts following ART. This is called immune recovery uveitis (IRU. It is thought to occur as a result of restored immunity to various infectious agents, commonly mycobacterial, Cryptococcus, and herpes virus infections. We report a man who was treated for CMV retinitis and later developed IRU in the form of cystoid macular edema (CMO even though his CMV retinitis remained inactive. His CMO resolved and visual acuity improved 2 years after the onset of CMO without any treatment interventions.Keywords: HIV, cystoid macular edema, AIDS, CMV retinitis

  7. Polymorphisms in Toll-like receptor genes influence antibody responses to cytomegalovirus glycoprotein B vaccine

    Directory of Open Access Journals (Sweden)

    Arav-Boger Ravit

    2012-03-01

    Full Text Available Abstract Background Congenital Cytomegalovirus (CMV infection is an important medical problem that has yet no current solution. A clinical trial of CMV glycoprotein B (gB vaccine in young women showed promising efficacy. Improved understanding of the basis for prevention of CMV infection is essential for developing improved vaccines. Results We genotyped 142 women previously vaccinated with three doses of CMV gB for single nucleotide polymorphisms (SNPs in TLR 1-4, 6, 7, 9, and 10, and their associated intracellular signaling genes. SNPs in the platelet-derived growth factor receptor (PDGFRA and integrins were also selected based on their role in binding gB. Specific SNPs in TLR7 and IKBKE (inhibitor of nuclear factor kappa-B kinase subunit epsilon were associated with antibody responses to gB vaccine. Homozygous carriers of the minor allele at four SNPs in TLR7 showed higher vaccination-induced antibody responses to gB compared to heterozygotes or homozygotes for the common allele. SNP rs1953090 in IKBKE was associated with changes in antibody level from second to third dose of vaccine; homozygotes for the minor allele exhibited lower antibody responses while homozygotes for the major allele showed increased responses over time. Conclusions These data contribute to our understanding of the immunogenetic mechanisms underlying variations in the immune response to CMV vaccine.

  8. An In Vitro Mouse Model of Congenital Cytomegalovirus-induced Pathogenesis of the Inner Ear Cochlea

    Science.gov (United States)

    Melnick, Michael; Jaskoll, Tina

    2015-01-01

    Congenital human cytomegalovirus (CMV) infection is the leading nongenetic etiology of sensorineural hearing loss (SNHL) at birth and prelingual SNHL not expressed at birth. The paucity of temporal bone autopsy specimens from infants with congenital CMV infection has hindered the critical correlation of histopathology with pathogenesis. Here, we present an in vitro embryonic mouse model of CMV-infected cochleas that mimics the human sites of viral infection and associated pathology. There is a striking dysplasia/hyperplasia in mouse CMV-infected cochlear epithelium and mesenchyme, including organ of Corti hair and supporting cells and stria vascularis. This is concomitant with significant dysregulation of p19, p21, p27, and Pcna gene expression, as well as proliferating cell nuclear antigen (PCNA) protein expression. Other pathologies similar to those arising from known deafness gene mutations include downregulation of KCNQ1 protein expression in the stria vascularis, as well as hypoplastic and dysmorphic melanocytes. Thus, this model provides a relevant and reliable platform within which the detailed cell and molecular biology of CMV-induced deafness may be studied. PMID:23281115

  9. [Epstein Barr and cytomegaloviruses in ocular pathology].

    Science.gov (United States)

    Magdei, Corina; Cuşnir, Valeriu; Bârcâ, Ludmila

    2010-01-01

    Epstein-Barr virus (EBV) and Citomegalovirus (CMV) are Herpesviridae family representative and presents a real danger for human. A very high infect risk of population farther the danger The ocular pathology induced by them can affect all media and tunics of optic analyzer. An etiologic differentiation is necessary for the mentioned viruses induced diseases. The etiologic differentiation has like purpose the enforcement of an effective and optimal antiviral and immunomodulating therapy.

  10. Xenotransplantation and porcine cytomegalovirus.

    Science.gov (United States)

    Denner, Joachim

    2015-01-01

    Porcine microorganisms may be transmitted to the human recipient when xenotransplantation with pig cells, tissues, and organs will be performed. Most of such microorganisms can be eliminated from the donor pig by specified or designated pathogen-free production of the animals. As human cytomegalovirus causes severe transplant rejection in allotransplantation, considerable concern is warranted on the potential pathogenicity of porcine cytomegalovirus (PCMV) in the setting of xenotransplantation. On the other hand, despite having a similar name, PCMV is different from HCMV. The impact of PCMV infection on pigs is known; however, the influence of PCMV on the human transplant recipient is unclear. However, first transplantations of pig organs infected with PCMV into non-human primates were associated with a significant reduction of the survival time of the transplants. Sensitive detection methods and strategies for elimination of PCMV from donor herds are required.

  11. Cytomegalovirus and herpes simplex virus effect on the prognosis of mechanically ventilated patients suspected to have ventilator-associated pneumonia.

    Directory of Open Access Journals (Sweden)

    Yannael Coisel

    Full Text Available OBJECTIVE: Cytomegalovirus (CMV and herpes simplex virus (HSV are common viruses that can affect critically ill patients who are not immunocompromised. The aim of this study was to determine whether the identification of CMV and/or HSV in mechanically ventilated critically ill patients suspected of having pneumonia was associated with an increased mortality. DESIGN: Prospective epidemiological study. SETTING: Medical intensive care unit of a tertiary medical center. PATIENTS: Ninety-three patients with suspected pneumonia. INTERVENTIONS: Patients with suspected pneumonia had bronchoalveolar lavage and blood samples taken to confirm the diagnosis. Antigenemia was used to detect CMV in the blood. Bronchoalveolar lavage samples were submitted to testing using quantitative real-time Polymerase Chain Reaction. MEASUREMENTS AND MAIN RESULTS: We identified 22 patients with a CMV infection, 26 patients with an HSV infection and 45 patients without CMV or HSV infection (control group. Mortality at day 60 was higher in patients with a CMV infection than in patients from the control group (55% vs. 20%, P<0.01. Mortality at day 60 was not significantly increased in the group with HSV infection. Duration of ICU stay and ICU mortality were significantly higher in patients with CMV infections when compared to patients from the control group, whereas ventilator free days were significantly lower in patients with CMV infections when compared to patients from the control group. CONCLUSIONS: In critically ill patients, a CMV infection is associated with an increased mortality. Further interventional studies are needed to evaluate whether treatment could improve the prognosis.

  12. Comparison of two molecular assays for detection of cytomegalovirus DNA in whole blood and plasma samples from transplant recipients.

    Science.gov (United States)

    Costa, Cristina; Sidoti, Francesca; Mantovani, Samantha; Gregori, Gabriella; Proietti, Alex; Ghisetti, Valeria; Cavallo, Rossana

    2016-07-01

    In immunosuppressed patients, pre-emptive therapy and a strict follow-up of CMV infection are the standard of care for the prevention of CMV disease. Several real-time PCR assays for CMV DNA quantification on whole blood (WB) and plasma (PL) are commercially available. This study compared and correlated CMV viral loads obtained by the Cobas AmpliPrep/Cobas TaqMan (CAP/CTM) platform on plasma specimens with those obtained on corresponding whole blood specimens by the real-time PCR assay (ELITe MGB-CMV) in 185 sequential samples from 41 immunosuppressed patients. Correlation between the two assays was good. Kinetics of CMV DNA within the same patient was similar, but PL viral load was constantly 1 log lower than WB. In patients under antiviral therapy, low level of CMV DNA persisted in WB, while it was absent in PL. The good correlation between CMV DNA detected on both PL and WB supports the reliability of the two matrices for viral monitoring and the therapeutic management of CMV infection. Nevertheless, due to significant quantification differences between PL and WB CMV DNA, the same biological specimen should be used for a sequential and reliable follow-up of patients at high risk of CMV infection.

  13. Cytomegalovirus and Langerhans Cell Histiocytosis: Is There a Link?

    Science.gov (United States)

    Khoddami, Maliheh; Nadji, Seyed-Alireza; Dehghanian, Paria; Vahdatinia, Mahsa; Shamshiri, Ahmad-Reza

    2016-01-01

    Background: Langerhans cell histiocytosis is a rare proliferative histiocytic disease of unknown etiology. Histologically, it is characterized by granuloma-like proliferation of Langerhans-type dendritic cells derived from bone marrow. Many investigators have suggested the possible role of viruses such as Epstein-Barr virus, human herpesvirus-6 (HHV-6), herpes simplex virus (HSV) types 1 and 2, and Cytomegalovirus in the pathogenesis of Langerhans cell histiocytosis. Objectives: In this study, we have investigated the presence of Cytomegalovirus in Langerhans cell histiocytosis in Iranian children. Patients and Methods: In this retrospective study, we have investigated the presence of Cytomegalovirus DNA expression, using paraffin-embedded tissue samples of 30 patients with Langerhans cell histiocytosis and 30 age and site-matched controls by qualitative Polymerase Chain Reaction (PCR) method. Results: No significant difference in prevalence of Cytomegalovirus presence between patients and controls was found. Cytomegalovirus was found by qualitative PCR in only 2 (6.66%) out of 30 patients and in 1 (3.3%) of 30 control samples with a P value of 1 (1.00 > 0.05) using chi-square test with OR: 2.07; 95% CI of OR: 0.18 - 24.15. Conclusions: Our findings do not support the hypothesis of a possible role for Cytomegalovirus in the pathogenesis of Langerhans cell histiocytosis. PMID:27307972

  14. Cytomegalovirus and Langerhans Cell Histiocytosis: Is There a Link?

    Directory of Open Access Journals (Sweden)

    Maliheh Khoddami

    2016-02-01

    Full Text Available Background: Langerhans cell histiocytosis is a rare proliferative histiocytic disease of unknown etiology. Histologically, it is characterized by granuloma-like proliferation of Langerhans-type dendritic cells derived from bone marrow. Many investigators have suggested the possible role of viruses such as Epstein-Barr virus, human herpesvirus-6 (HHV-6, herpes simplex virus (HSV types 1 and 2, and Cytomegalovirus in the pathogenesis of Langerhans cell histiocytosis. Objectives: In this study, we have investigated the presence of Cytomegalovirus in Langerhans cell histiocytosis in Iranian children. Patients and Methods: In this retrospective study, we have investigated the presence of Cytomegalovirus DNA expression, using paraffin-embedded tissue samples of 30 patients with Langerhans cell histiocytosis and 30 age and site-matched controls by qualitative Polymerase Chain Reaction (PCR method. Results: No significant difference in prevalence of Cytomegalovirus presence between patients and controls was found. Cytomegalovirus was found by qualitative PCR in only 2 (6.66% out of 30 patients and in 1 (3.3% of 30 control samples with a P value of 1 (1.00 > 0.05 using chi-square test with OR: 2.07; 95% CI of OR: 0.18 - 24.15. Conclusions: Our findings do not support the hypothesis of a possible role for Cytomegalovirus in the pathogenesis of Langerhans cell histiocytosis.

  15. Postmortem diagnosis of cytomegalovirus and accompanying other infection agents by real-time PCR in cases of sudden unexpected death in infancy (SUDI).

    Science.gov (United States)

    Yagmur, Gulhan; Ziyade, Nihan; Elgormus, Neval; Das, Taner; Sahin, M Feyzi; Yildirim, Muzaffer; Ozgun, Ayse; Akcay, Arzu; Karayel, Ferah; Koc, Sermet

    2016-02-01

    As an opportunistic pathogen with high mortality rates, Cytomegalovirus (CMV) may lead to fatal disseminated CMV infection of the premature and newborn; thus necessitating the demonstration of CMV-DNA with clinical history and/or histopathological findings of CMV infection and defining other bacterial and viral infection agents with real-time polymerase chain reaction (RT-PCR) in udden unexpected death in infancy (SUDI) cases as we aimed in this study. 314 (144 female, 170 male) SUDI cases were prospectively investigated from January 2013 to January 2015 in Istanbul Forensic Medicine Institution. The study includes 87 tissue samples of 39 cases for post-mortem histopathological examination of interstitial pneumonia, myocarditis, meningitis, encephalitis, hepatitis, colitis or tubulointerstitial nephritis and/or accompanying chronic sialadenitis. CMV-DNA