Scandinavian journal of infectious diseases. Supplementum最新文献

Besides the current classification of cytomegalovirus (CMV) infection and disease we defined "CMV antigenaemia" as the marker for initiation of antiviral therapy (CMV hyperimmune globulin 2 ml/kg/d and ganciclovir 1000 mg/d), and "episodes of CMV antigenaemia"(the time from detection of antigenaemia until a subsequent antigenaemia assay tested negative again) indicated the time period of antiviral treatment. Patients were at highest risk for antigenaemia at day 38.2 +/- 20.9 after heart transplantation. We observed 50 episodes of antigenaemia in 18 patients. The mean duration was 7.3 +/- 6.4 days. No antigenaemia associated symptoms and no anti-CMV IgM was observed without preceding evidence of antigenaemia. Antigenaemia-associated symptoms and antigenaemia disappeared after antiviral therapy was initiated. Our therapy did not prevent CMV infection, but despite the repeated evidence of active CMV infection, no patient suffered CMV disease.

To evaluate the diagnostic relevance and the clinical impact of the cerebrospinal fluid (CSF) polymerase chain reaction (PCR) for cytomegalovirus (CMV) DNA in the diagnosis of CMV infection of the central nervous system (CNS), 220 acquired immune deficiency syndrome (AIDS) patients with neurological disease were examined. CSF was drawn 1-180 days before death, concomitantly with clinical neurological disease, and autopsy was performed in all the cases. CMV DNA was detected in the CSF from 36 of 45 patients (82%) with CMV infection of the CNS, and in 2 of 175 without CMV infection of the CNS at autopsy. The sensitivity of the method was 82%, the specificity 99%, the positive predictive value 95%, and the negative predictive value 96%. An extensive CMV ventriculitis or encephalitis was shown by histopathology in the majority of the CSF PCR-positive patients with overt clinical encephalitis. Minor CMV lesions only, not likely to cause relevant clinical symptoms, were observed in some CSF PCR-positive patients, concomitant with other opportunistic CNS diseases. CSF PCR is a reliable means for diagnosis of CMV infection of the CNS in patients with AIDS. A positive PCR result, however, requires careful interpretation in the individual clinical context.

Animal models offer the opportunity to study the interaction of the virus and the host and to unravel the mechanism in processes such as persistence of the virus and virus-induced pathology. Primary infection results in a generalized infection as shown by the presence of virus in many organs. During viraemia the virus is present in mononuclear cells by which it is transported through the body. In neonates and in immuno-suppressed animals the infection results in multiorgan failure, leading to death. Recent data have shown that infection of endothelial cells in the microvasculature and mononuclear cells seems to be important in the pathogenesis of cytomegalovirus (CMV)-induced disease. After primary infection the virus persists in the body. Although the exact localization of the latent virus is unknown it is clear that during latency viral DNA is present in many organs. By immune suppression the virus can reactivate from its latent state. In addition to the direct complications attributable to the virus itself, CMV has modulating effects on the immune response. Although in some instances the infection leads to immune suppression, the virus infection can also accelerate inflammatory and immune responses. Studies in mice have shown that CMV infection can exacerbate graft-versus-host reactions, and experiments in rats using allogeneic transplants indicate that CMV infection results in enhanced chronic rejection in which acceleration of the immune response is involved. Although the exact mechanism is not clear, recent data indicate that cytokines, such as tumor necrosis factor alpha are involved in these processes.

The relationship between cytomegalovirus (CMV) DNA in leucocytes and CMV disease in AIDS patients was sought. In 195 HIV-1 infected, mostly AIDS patients, CMV nPCR was performed in 477 peripheral EDTA blood samples which were collected also for CD4 cell counts (403), classic (410) and rapid virus isolation (270), and antigenemia tests (190). Most patients who died were autopsied. Immunohistopathology for CMV was performed. The first 43 patients were classified clinically according to having (A) verified organ involvement of CMV (15), (B) suspected CMV disease due to symptoms (4), or no CMV-associated disease (24). CMV-DNA was detected in the majority of samples (66%) and patients (68%). In contrast, CMV in the samples was detected in only 16% by classical and 11% by rapid isolation and in 8.4% by the antigenemia test. Acquisition of CMV DNA in leucocytes became more common as the CD4 cell counts fell. Detection of CMV DNA was significantly associated with CMV-associated symptoms and later mortality. In conclusion, CMV PCR of DNA in leucocytes is a sensitive and early marker of CMV disease in HIV-infected AIDS patients. It might be a marker to be added to CD4 cell counts for initiation of preemptive therapy.

Four human cytomegalovirus strains with double resistance to both ganciclovir and foscarnet were recovered from acquired immunodeficiency syndrome (AIDS) patients. The four isolates were genetically unrelated and each of them consisted of a single viral population. In addition, for each isolate, UL97 and UL54 open reading frames sequencing showed a single aminoacid change in a conserved domain of each of the two genes.

Although several methods have been utilized for the detection and quantification of human cytomegalovirus (HCMV) DNA, all of them can be divided into three groups: (i) detection of HCMV DNA directly in tissues by in situ hybridization or in situ polymerase chain reaction (PCR); (ii) detection of HCMV DNA in cell or tissue lysates by hybridization with DNA or RNA probes differently labelled-labels were progressively modified in order to provide an increasing sensitivity (hybridization products were revealed by radioactive, colorimetric or chemiluminescent procedures); (iii) detection of HCMV DNA in cell or tissue lysates by qualitative (single-step and nested) and quantitative (semiquantitative, competitive or noncompetitive) PCR. The selection of the methods to be employed depends primarily on the clinical situation which must be evaluated. Clinical samples for HCMV genome detection must vary accordingly.

Cytomegalovirus (CMV) infection is known to be a major risk factor for the development of chronic transplant rejection in heart and lung transplantation. A possible mechanism for the induction of lung transplant rejection by CMV infection is the inflammatory upregulation of adhesion ligand molecules by the viral infection leading to an increased endothelial-leucocyte interaction. To study this question, an experimental model was established in the rat using a rat cytomegalovirus (RCMV) infection and acute lung transplant rejection in left single lung transplantation. The distribution of RCMV, intercellular adhesion molecule-1 (ICAM-1) and its leucocyte receptor CD11a (LFA-1) were investigated by immunohistochemistry. The viral infection was observed in transplant lungs of infected hosts as early as day 11. The expression of ICAM-1 on endothelial cells was induced and enhanced by RCMV infection, and infiltration of CD11a-positive leucocytes found to be increased in infected recipients. An acceleration of the rejection of the allografts by the hosts was found.

Patients with either deficient or immature immune systems need protection against cytomegalovirus (CMV) disease. That maternal immunization prior to pregnancy will protect newborns from congenital disease is suggested by the fact that newborns who acquire CMV either via transfusion or transplacentally are relatively protected if their mothers had antibodies to CMV prior to pregnancy. For patients becoming partially immunocompromised following solid organ transplantation, protection against severe CMV disease is afforded by immunity acquired either by wild-type infection prior to transplantation or passive or active immunization. In three randomized placebo-controlled studies, live attenuated CMV vaccine has successfully protected seronegative recipients of kidneys from seropositive donors from severe CMV disease by efficiently inducing humoral and cellular immunity. Subunit vaccines comprised of glycoprotein gB, the viral component containing the majority of viral neutralizing epitopes, are in the early phases of study, as are strategies to provide patients with CD8+ deficiency immunoprophylaxis via adoptive transfer of cytotoxic T-cells expanded in vitro against CMV structural proteins. Given all of these facts, safe and effective CMV immunoprophylaxis against CMV disease is possible.

Retinal cytomegalovirus (CMV) disease is one of the major manifestations of viral pathogenesis in immunosuppressed patients with the acquired immunodeficiency syndrome (AIDS). CMV infection of the retina causes directional destruction which begins at the optic nerve head adjacent to the retinal capillaries and progresses, if untreated, to retinal detachment and blindness. Infection does not occur across the basal membrane of the retinal pigment epithelium (RPE), adjacent to the highly vascularized choroid. CMV replicates in polarized RPE cells, and progeny virions cross apical and lateral membranes of RPE cells grown on permeable filter supports, but not basal membranes. Cell-cell junctions of CMV-infected RPE cells are permeabilized, and the tight junction protein zonula occludens (ZO-1) is disassembled; progeny virions then spread to neighboring cells through the lateral cell membranes, which in polarized cells differ significantly in lipid and protein composition from the apical cell membranes. We found that CMV mutants with deletions in US9 and US8/US9 failed to spread from cell to cell, exhibiting a small-plaque phenotype in polarized RPE cells. Immunofluorescence confocal microscopy staining of ZO-1 protein revealed that RPE cells infected with CMV deletion mutants RV35, RV80, and RV61 did not exhibit altered tight junctions, in contrast to RPE cells infected with wild-type strain AD169 virus. Our findings indicate that US9, which is an accessory glycoprotein in infected foreskin fibroblasts, is required for transmission of virus across cell-cell junctions of polarized RPE cells. The relationship between US9 expression and virus transmission across cell-cell boundaries suggests that US9 may directly or indirectly permeabilize tight junction complexes of polarized RPE cells.

The incidence of tuberculosis has continued to decline in the Swedish-born population, but there has been an increase in the foreign-born population, especially among young adults and children. Multidrug-resistant tuberculosis is still rare in Sweden. The annual number of patients with culture confirmed atypical mycobacteria, especially of M. avium-intracellulare, has increased. The increased incidence of atypical mycobacteria observed in non-BCG vaccinated Swedish children seems to be related to the restricted BCG policy brought into force in 1975.