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Infections continue to be one of the leading causes of morbidity and mortality in liver transplant recipients. We retrospectively reviewed the symptomatic infectious episodes that occurred during the first year post-transplant to determine time of onset, causative pathogens and cell-mediated immunity response patterns. Ninety-eight of the 202 (48.5%) recipients enrolled developed at least one infectious episode. The total number of infectious episodes was 135: 77 (57.1%) bacterial, 45 (33.3%) viral and 13 (9.6%) fungal. The most frequently isolated bacteria were Escherichia coli (21 isolates) and Klebsiella pneumoniae (19 isolates). Overall, extended-spectrum beta lactamase-producing and methicillin-resistant organisms were responsible for 29 (29/77; 37.7%) infectious episodes. Members of the herpes virus group, in particular cytomegalovirus (34/45 viral infections, 75.5%), were detected. Candida species (9 isolates) followed by Aspergillus species (4 isolates) were isolated. The majority of infections (63%) occurred during the early post-transplant phase (

Background: The Congenital Human Cytomegalovirus Infection Prevention (CHIP) study, a randomized, blinded, placebo-controlled trial, demonstrated that the efficacy of hyperimmune globulin (HIG) was not different from that of placebo regarding transmission of cytomegalovirus (CMV) from mothers to newborns. Our aim was to analyze histologically HIG effects on placentas collected for the CHIP study. Materials and Methods: Virological and histological analyses were performed on 40 placentas from transmitter and nontransmitter HIG-treated and untreated mothers by assessing the number of CMV-positive cells, tissue viral load, tissue damage, and compensatory mechanisms. Results: The HIG and placebo groups showed no significant differences in the number of CMV-positive cells (median number in 10 fields at 10 high-power fields: 2.5 vs. 2, p = 0.969) and viral load (median load: 5 copies/5 ng vs. 10.5 copies/5 ng, p = 0.874). Regarding histological examination, the scores of parameters related to tissue damage and hypoxic parenchymal compensation were higher in transmitters except for chorangiosis, with statistically significant differences observed for chronic villitis (p = 0.007), calcification (p = 0.011), and the total score of tissue damage (p < 0.001). The HIG and placebo groups showed no significant differences for all tissue damage and compensation parameters and overall scores. Discussion: HIGs are not able to reduce placental viral load and histological damage, which was significantly associated only with infection.

Background We performed serological and molecular pretransplant screening in solid organ transplant (SOT) donors and recipients in north central Italy and a surveillance program for human herpesvirus 8 (HHV8) infection after transplant, aiming to establish an optimal management of HHV8 infection in SOT recipients. Methods For pretransplant HHV8 screening in both donors and recipients, 6 serological (4 indirect immunofluorescent assays [IFA] and 2 enzyme-linked immunosorbent assays-both HHV8 lytic and latent antigen based) and 2 molecular assays were used. A reference standard to identify HHV8-positive patients was defined by at least 2 positive assays. All transplant patients at risk to develop HHV8-related disease underwent virological posttransplant monitoring by quantitative real-time polymerase chain reaction (PCR) assay. Results Human herpesvirus 8 seroprevalence was 4% (10/249) in donors and 18% (93/517) in organ recipients. The best performance was obtained by 2 lytic antigen-based IFAs that showed almost perfect agreement to the reference standard (0.943 and 0.931 Cohen kappa). Human herpesvirus 8-DNA was detected in 6.8% and 2.9% of HHV8-seropositive donor samples by in-house nested PCR and quantitative real-time PCR assays, respectively. After transplant, 3 (25%) of 12 HHV8-mismatch patients (seropositive donor/seronegative recipient) developed a primary infection, one of whom developed a lethal nonmalignant illness. Two of 93 HHV8-seropositive recipients (2.1%) had viral replication in posttransplant period, one of whom developed Kaposi sarcoma. Conclusions Serological assays, specifically lytic IFAs, were the best methodological approach to identify HHV8-infected SOT donors and recipients. A very low incidence (1.9%) of posttransplant HHV8-related disease was observed.

Clin Microbiol Infect 2012; 18: E419-E427 ABSTRACT: 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.

Background Congenital cytomegalovirus (CMV) infection is a major cause of central nervous system damage leading to sensorineural hearing loss, mental retardation and cerebral palsy. Objectives Identify the type of organ involvement and understand the histopathogenesis of damage in foetuses of women with a CMV-highly positive amniotic fluid. Study design 34 foetuses with congenital CMV infection documented by prenatal diagnosis were studied. Three foetuses died in utero . The remaining pregnancies were electively terminated at 20–21 weeks gestation. Results Foetal organs positive for CMV antigens were: placenta (100%), pancreas (100%), lung (87%), kidney (87%), liver (71%), brain (55%) and heart (44%). Inflammatory infiltrate was almost always present in CMV-infected foetal organs and the severity of the inflammatory response was correlated with the organ damage. Brain damage with necrosis was observed in 33% (9/27) and a mild telencephalic leukoencephalopathy in 22% (6/27) of foetuses studied. Conclusions Focal necrosis was observed very frequently in organs such as pancreases, livers, hearts and kidneys. However the damage in these organs is likely to be resolved by parenchymal regeneration. Brain damage, which seems to be the results of a combined effect of viral infection, inflammatory infiltration and hypoxia due to severe placentitis, is less likely to be resolved because of the low regeneration ability of this organ.

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.