Objective To identify fetal cord blood prognostic markers of symptomatic congenital human cytomegalovirus infection (HCMV).Design Retrospective observational study.Setting Fetal medicine unit in Milan and Medical virology unit in Pavia, Italy.Population HCMV-infected and -uninfected fetuses of mothers with primary HCMV infection during the period 1995-2009.Methods Overall, 94 blood samples from as many fetuses of 93 pregnant women experiencing primary HCMV infection were examined for multiple immunological, haematological and biochemical markers as well as virological markers. Congenital HCMV infection was diagnosed by detection of virus in amniotic fluid, and symptomatic/asymptomatic infections were determined by ultrasound scans, nuclear magnetic resonance imaging, histopathology or clinical examination at birth. Blood sample markers were retrospectively compared in symptomatic and asymptomatic fetuses with congenital infection.Main outcome measures A statistical analysis was performed to determine the value of each parameter in predicting outcome.Results Univariate analysis showed that most nonviral and viral markers were significantly different in symptomatic (n = 16) compared with asymptomatic (n = 31) fetuses. Receiver operator characteristics analysis indicated that, with reference to an established cutoff for each marker, the best nonviral factors for differentiation of symptomatic from asymptomatic congenital infection were b 2 -microglobulin and platelet count, and the best virological markers were immunoglobulin M antibody and DNAaemia. b 2 -Microglobulin alone or the combination of these four markers reached the optimal diagnostic efficacy.
ConclusionsThe determination of multiple markers in fetal blood, following virus detection in amniotic fluid samples, is predictive of perinatal outcome in fetuses with HCMV infection.
In 7 of 18 solid-organ transplant recipients with primary human cytomegalovirus (HCMV) infection, HCMV antigenemia levels were unexpectedly found to rise significantly (P = 0.018) during a mean time of 7.3 ± 3.2 days after initiation of specific antiviral treatment, whereas corresponding levels of viremia dropped significantly (P = 0.043). Thus, shifting to an alternative antiviral drug based solely on increasing antigenemia levels is not justified in this group of patients.
A new technique for in vitro activation of cytotoxic T lymphocytes (CTLs) specific for herpes simplex virus type 1 (HSV-1) is described. Autologous phytohemagglutinin (PHA)-activated, HSV-1-infected peripheral blood mononuclear cells (PBMC) were used, after fixation with 1% paraformaldehyde, to activate virus-specific CTLs in short-term cultures. The same unfixed PBMC were used as target cells in the cytotoxicity assay. By using this technique high levels of HSV-1-specific cytotoxic activity (50.06 +/- 16.76% at 30:1 effector:target ratio) were repeatedly obtained in 24 experiments using PBMC from 16 HSV-1 antibody-positive healthy donors, while no cytotoxic activity was observed using PBMC from 3 HSV-1 antibody-negative donors. HSV-1-induced CTLs were shown to be virus-specific as they did not lyse autologous, PHA-activated PBMC infected with influenza A virus or autologous Epstein-Barr virus (EBV) lymphoblastoid cell line (LCL), while they were able to lyse both HSV-1-infected, autologous PHA-activated PBMC and EBV-LCL. HSV-1-specific cytotoxicity was mediated by T lymphocytes, since depletion of CD3-positive cells from the effector population completely removed the killing of HSV-1-infected target cells. CD8-positive CTLs were primarily involved in the killing of HSV-1-infected targets since depletion of CD8-positive cells caused a strong reduction of virus-specific cytotoxic activity while elimination of CD4-positive lymphocytes increased killing capacity. Finally, this technique has proven to be highly reproducible, easy to perform, and thus suitable for clinical investigations.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.