Cytomegalovirus (CMV) is the most prevalent infectious agent causing neurological dysfunction in the developing brain. This study analysed the different patterns of tissue damage, particularly in the ...brain, of fetuses with documented CMV infection. We studied 45 fetuses at 20-21 weeks of gestation with congenital CMV infection documented by invasive positive prenatal diagnosis. At the time of amniocentesis, abnormal ultrasound findings had been recorded for 13 of the 45 fetuses (29%). Histological and immunohistochemical characterization was performed on the placenta, brain, heart, lung, liver, kidney, and pancreas. The different degrees of brain damage were correlated with tissue viral load, inflammatory response, placental functionality, and extramedullary haematopoiesis. Even though a high CMV load was detected in all amniotic fluids, brain infection occurred in only 62% of the fetuses and with different degrees of severity. Tissues with a low viral load showed a globally weak inflammatory response, and fetuses had only mild brain damage, whereas tissues with a high CMV load showed prominent infiltration of the activated cytotoxic CD8+ T-lymphocytes responsible for immune-mediated damage. Furthermore, severe placental infection was associated with diffuse villitis and necrosis, consistent with functional impairment and possible consequent hypoxic cerebral damage. Brain injury induced by CMV congenital infection may be the result of uncontrolled viral replication, immune-mediated damage by cytotoxic CD8+ T-lymphocytes, and, in the presence of placental insufficiency, fetal hypoxia.
Abstract Background Cytomegalovirus (CMV) is a major cause of graft failure and posttransplantation mortality in intestinal/multivisceral transplantation. CMV infection exhibits a wide range of ...clinical manifestations from asymptomatic infection to severe CMV disease. Study's Purpose The purposes of this study were to assess the utility of measuring CMV-specific cellular immunity in bowel/multivisceral transplant recipients and to provide additional information on the risk of infection and development of CMV disease. Methods We studied 10 bowel/multivisceral transplant recipients to investigate the kinetics of CMV infection using real-time polymerase chain reaction (on blood and biopsy tissue samples) and CMV-specific T-cell reconstitution by Enzyme-linked ImmunoSPOT Assay (ELISPOT) that enumerates Interferon-γ–secreting CMV-specific T cells upon in vitro stimulation with viral antigens (pp65 and IE-1). Results All patients were seropositive for CMV. According to the pattern of T-cell reconstitution occurring either within the first month after transplantation or later, patients were classified as early (n = 7) or late responders (n = 3). Clinically, early responder patients (3/7; 43%) experienced asymptomatic or mild CMV infections, whereas all late responders (3/3; 100%) developed moderate or severe CMV disease. A reduction in mean and peak CMV viral load was observed in early responders, whereas the onset time of infection did not differ significantly between early and late CMV responders. Conclusions A good and early reconstitution of CMV-specific T-cell immune responses after transplantation is a critical determinant in controlling CMV infections. Simultaneous monitoring of CMV infection and CMV-specific T-cell immunity predicts T-cell–mediated control of CMV infection.
Congenital infection with human cytomegalovirus (CMV) is a major cause of morbidity and mortality. In an uncontrolled study published in 2005, administration of CMV-specific hyperimmune globulin to ...pregnant women with primary CMV infection significantly reduced the rate of intrauterine transmission, from 40% to 16%.
We evaluated the efficacy of hyperimmune globulin in a phase 2, randomized, placebo-controlled, double-blind study. A total of 124 pregnant women with primary CMV infection at 5 to 26 weeks of gestation were randomly assigned within 6 weeks after the presumed onset of infection to receive hyperimmune globulin or placebo every 4 weeks until 36 weeks of gestation or until detection of CMV in amniotic fluid. The primary end point was congenital infection diagnosed at birth or by means of amniocentesis.
A total of 123 women could be evaluated in the efficacy analysis (1 woman in the placebo group withdrew). The rate of congenital infection was 30% (18 fetuses or infants of 61 women) in the hyperimmune globulin group and 44% (27 fetuses or infants of 62 women) in the placebo group (a difference of 14 percentage points; 95% confidence interval, -3 to 31; P=0.13). There was no significant difference between the two groups or, within each group, between the women who transmitted the virus and those who did not, with respect to levels of virus-specific antibodies, T-cell-mediated immune response, or viral DNA in the blood. The clinical outcome of congenital infection at birth was similar in the two groups. The number of obstetrical adverse events was higher in the hyperimmune globulin group than in the placebo group (13% vs. 2%).
In this study involving 123 women who could be evaluated, treatment with hyperimmune globulin did not significantly modify the course of primary CMV infection during pregnancy. (Funded by Agenzia Italiana del Farmaco; CHIP ClinicalTrials.gov number, NCT00881517; EudraCT no. 2008-006560-11.).
Abstract Background Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are the major causes of graft failure and posttransplantation mortality among small bowel and multivisceral transplantations ...(SB/MVT). Little is known about human herpes virus 6 (HHV-6) infections in transplant recipients. Study Purpose The purposes of this study were to analyze the clinical relevance of CMV, EBV, and HHV-6 infections after small bowel transplantation and to establish whether routine monitoring for HHV-6 infection should be recommended for the prevention of severe complications in this population. Methods Ten adult patients were monitored based on CMV, EBV, and HHV6 DNA quantifications in blood and biopsy tissue samples. Three patients were monitored for at least 5 months (early period) and 7 patients were monitored for 1 to 5 years after transplantation (late period). Results In the early period, despite prophylaxis all 3 patients developed symptomatic CMV infections: 1 fever/diarrhea, 1 enteritis and rejection, as well as 1 fever and pneumonia. Only 1 patient developed EBV and HHV-6 infections. The average time of onset of CMV infection was 3 months after transplantation and only 24 days for HHV6 infection. In the late period, of the 7 SB/MVT recipients only 1 developed an EBV infection at 2 years after transplantation. No CMV or HHV-6 infections were identified in any patient. Conclusions CMV infection is a major cause of organ disease and rejection in the early period after transplantation. EBV infection in adult recipients must be considered also in the late period, particularly in association with severe immunosuppression. Because HHV-6 infection occurs earlier than CMV/EBV, it may serve as an indicator for more intense virological surveillance.
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