Cytomegalovirus (CMV) reactivation in immune compromised patients such as those undergoing hematopoietic progenitor cell transplantation (HPCT) and those with HIV infections can cause severe morbidity and mortality despite treatment with appropriate antiviral agents. The recovery of Cytomegalovirus (CMV) specific cytotoxic T lymphocytes (CTL) plays an important role in the reconstitution of CMV specific immunity in immunocompromised patients. Recent studies have reported that CMV reactivation can be successfully treated by adoptive transfer of CMV-specific T cell clones from CMV seropositive donors expanded in vitro with CMV infected fibroblasts or lysates of CMV infected cells. Other studies have used immune dominant CMV proteins or peptides to expand CMV-specific cytotoxic T lymphocytes. This review describes the clinical manifestations of CMV disease in immunocompromised patients, recent advances of antiviral therapy for CMV disease, the principals of the induction of cellular immune response to CMV, and the clinical application of CMV immunotherapy.
Cytomegalovirus Infections/*immunology/*therapy ; Humans ; *Immunocompromised Host ; *Immunotherapy, Adoptive

BACKGROUNDThere 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.

METHODSSix 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.

RESULTSIn 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.

CONCLUSIONSPoor 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, immunosuppressants should be given again but immunoenhancement therapy ceased. Individualized immunomodulatory therapy is essential to the treatment of CMV pneumonia after LT.

Adjuvants, Immunologic ; therapeutic use ; Adult ; Cytomegalovirus Infections ; drug therapy ; immunology ; Humans ; Liver Transplantation ; adverse effects ; immunology ; Lymphocyte Activation ; Male ; Middle Aged ; Pneumonia, Viral ; drug therapy ; immunology

BACKGROUNDRheumatic diseases involve multiple organs that are affected by immunological mechanisms. Treatment with corticosteroids and immunosuppressive agents may also increase the frequency of infection. Cytomegalovirus (CMV) is a widespread herpes virus and a well-recognized pathogen, which causes an opportunistic and potentially fatal infection in immunocompromised patients. This retrospective study aimed to investigate the clinical and laboratory characteristics of CMV pneumonia in patients with rheumatic diseases after immunosuppressive therapy in a single center in Shanghai, China.

METHODSEight hundred and thirty-four patients with rheumatic diseases who had undergone CMV-DNA viral load tests were included, and the medical records of 142 patients who were positive for CMV-DNA in plasma samples were evaluated. GraphPad Prism version 5.013 (San Diego, CA, USA) was used to conduct statistical analysis. The correlation between CMV-DNA viral loads and lymphocyte counts was assessed using the Spearman rank correlation coefficient test. Significance between qualitative data was analyzed using Pearson's Chi-squared test. The cut-off thresholds for CMV-DNA viral load and lymphocyte count were determined by receiver operating characteristic (ROC) curve analysis.

RESULTSOne 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 < 0.01). The symptomatic group had lower lymphocyte counts, especially CD4+ T-cells, than the asymptomatic group (P < 0.01). By ROC curve analysis, when CD4+ T-cell count was <0.39 × 109/L, patients with rheumatic diseases were at high risk for symptomatic CMV infection. The CMV-DNA load was significantly higher in the symptomatic patients than that in asymptomatic patients (P < 0.01; threshold viral loads: 1.75 × 104 copies/ml). Seven patients had a fatal outcome, and they had lower peripheral lymphocyte counts (P < 0.01), including CD4+ and CD8+ T-cells (P < 0.01).

CONCLUSIONSWhen CD4+ T-cell count is <0.39 × 109/L, patients are at high risk for pulmonary CMV infection. Patients are prone to be symptomatic with CMV-DNA load >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.

CD4-Positive T-Lymphocytes ; metabolism ; China ; Cytomegalovirus ; pathogenicity ; Cytomegalovirus Infections ; genetics ; immunology ; therapy ; virology ; Humans ; Immunosuppression ; methods ; Pneumonia ; genetics ; immunology ; therapy ; virology ; Polymerase Chain Reaction ; Retrospective Studies ; Rheumatic Diseases ; genetics ; immunology ; therapy ; virology ; Viral Load

Administration, Oral ; Anti-Bacterial Agents ; administration & dosage ; Cytomegalovirus Infections ; drug therapy ; immunology ; virology ; Erythromycin ; administration & dosage ; Female ; Humans ; Infant ; Male ; T-Lymphocyte Subsets ; immunology ; Virus Replication

BACKGROUND: Quantitation of cytomegalovirus (CMV) DNA using real-time PCR has been utilized for monitoring CMV infection. However, the CMV antigenemia assay is still the 'gold standard' assay. There are only a few studies in Korea that compared the efficacy of use of real-time PCR for quantitation of CMV DNA in whole blood with the antigenemia assay, and most of these studies have been limited to transplant recipients. METHOD: 479 whole blood samples from 79 patients, falling under different disease groups, were tested by real-time CMV DNA PCR using the Q-CMV real-time complete kit (Nanogen Advanced Diagnostic S.r.L., Italy) and CMV antigenemia assay (CINA Kit, ArgeneBiosoft, France), and the results were compared. Repeatedly tested patients were selected and their charts were reviewed for ganciclovir therapy. RESULTS: The concordance rate of the two assays was 86.4% (Cohen's kappa coefficient value=0.659). Quantitative correlation between the two assays was a moderate (r=0.5504, P<0.0001). Among 20 patients tested repeatedly with the two assays, 13 patients were transplant recipients and treated with ganciclovir. Before treatment, CMV was detected earlier by real-time CMV DNA PCR than the antigenemia assay, with a median difference of 8 days. After treatment, the antigenemia assay achieved negative results earlier than real-time CMV DNA PCR with a median difference of 10.5 days. CONCLUSIONS: Q-CMV real-time complete kit is a useful tool for early detection of CMV infection in whole blood samples in transplant recipients.
Antiviral Agents/therapeutic use ; Cytomegalovirus/*genetics ; Cytomegalovirus Infections/drug therapy/pathology/virology ; DNA, Viral/*blood/metabolism ; Ganciclovir/therapeutic use ; Humans ; *Immunoassay ; Organ Transplantation ; Phosphoproteins/genetics/immunology/*metabolism ; *Real-Time Polymerase Chain Reaction ; Viral Matrix Proteins/genetics/immunology/*metabolism ; Virology/*methods

The aim of the study was to investigate the correlation between prognosis of human cytomegalovirus (HCMV) infection and zinc in mature women, in order to explore the effect of serum zinc on HCMV infection. 900 mature woman were examined for zinc level and serum HCMV specific antibodies (IgG and IgM). 63 HCMV-IgM positive cases were divided into 3 subgroups according to their serum zinc level, and HCMV-IgM was observed for conversion after treatment with a Chinese traditional medicine (Jinyebadu). Our results showed that the mean concentration of zinc in serum was significantly lower in HCMV-IgM(+) group than that in HCMV-IgM(-) group (P<0.001). A positive correlation was found between the response of mature females with HCMV infection to the treatment and the levels of serum zinc (P<0.001). The response of mature women with HCMV is poor when the serum zinc is lower than 0.70.
Adult ; Antibodies, Viral ; blood ; Antiviral Agents ; therapeutic use ; Cytomegalovirus ; immunology ; Cytomegalovirus Infections ; blood ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Immunoglobulin G ; blood ; Immunoglobulin M ; blood ; Phytotherapy ; Zinc ; blood

No abstract available.
Adult ; Antineoplastic Combined Chemotherapy Protocols/*adverse effects ; Appendicitis/diagnosis/*etiology/therapy ; Bacteremia/*etiology/therapy ; Consolidation Chemotherapy/adverse effects ; Cytomegalovirus Infections/diagnosis/*etiology/therapy ; Humans ; Immunocompromised Host ; Male ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/*drug therapy/immunology/therapy

Cytomegaloviral hepatitis is an infantile liver disease commonly encountered in China, which could be differentiated into 4 patterns with different clinical conditions. Along with the progress of laboratory diagnostic techniques, multiple diagnostic approaches are available for this disease, but accurate diagnosis can only be made when individual patients' realities are taken into consideration. Clinical treatments are various, and the Western medicine used is mainly anti-viral agents such as Ganciclovir, and so far no unified therapeutic program has been formed. More and more ways of regarding Chinese medicine treatment of cytomegaloviral hepatitis have been published increasingly in recent years, though further research to seek preferable treatment programs is still expected.
Cytomegalovirus Infections ; complications ; diagnosis ; immunology ; therapy ; Diagnostic Techniques and Procedures ; trends ; Drugs, Chinese Herbal ; therapeutic use ; Hepatitis, Viral, Human ; diagnosis ; etiology ; immunology ; therapy ; Humans ; Immune System ; physiology ; physiopathology ; Infant ; Medicine, Chinese Traditional ; methods ; trends ; Professional Practice ; Western World

OBJECTIVEIdiopathic thrombocytopenic purpura (ITP) is a hemorrhagic disease in children with blood platelets redundant destruction caused by chaotic immunological mechanism. However, some patients with ITP with negative platelet-associated antibody and ineffective adrenal cortical hormone therapy probably have special pathogenesis. It is indicated that the human cytomegalovirus (HCMV) can incubate in haemopoietic stem cell/ancestral cell to inhibit its generation and differentiation. Therefore, the study was designed to investigate HCMV-late mRNA expression in megakaryoblast for the purpose of examining the pathogenesis of ITP and to examine the effectiveness of ganciclovir on ITP.

METHODSColony forming unit-megakaryocyte (CFU-MK) of 46 ITP patients with HCMV infection were incubated. Reverse transcription-polymerase chain reaction (RT-PCR) was subsequently used for HCMV-late mRNA detection. Ganciclovir therapy was given to both positive group and negative group for comparison of therapeutic effectiveness.

RESULTSNineteen out of 46 CFU-MK culture cell specimens with positive HCMV-DNA by PCR or positive CMV-IgM by enzyme linked immunosorbent assay (ELISA) from serum of peripheral blood showed positive for HCMV-late mRNA. While, the remaining 27 were negative. Sixteen positive responders to ganciclovir therapy were observed amongst those with positive HCMV-DNA. Whereas, only 4 positive responders to ganciclovir therapy were noticed amongst those with negative HCMV-DNA. The curative effectiveness in positive group was significantly higher than that in negative group (P < 0.01).

CONCLUSIONHCMV can directly infect CFU-MK, which might be one of the mechanisms responsible for ITP. Ganciclovir is an effective therapy resulting in an increase in thrombocyte in ITP patients whose HCMV-late mRNA was positive in their CFU-MK.

Adolescent ; Antibodies, Viral ; immunology ; Antiviral Agents ; therapeutic use ; Blood Platelets ; drug effects ; immunology ; Cells, Cultured ; Child ; Child, Preschool ; Cytomegalovirus ; drug effects ; genetics ; pathogenicity ; Cytomegalovirus Infections ; drug therapy ; genetics ; immunology ; Enzyme-Linked Immunosorbent Assay ; Female ; Ganciclovir ; therapeutic use ; Humans ; Immunoglobulin M ; immunology ; Infant ; Male ; Megakaryocyte Progenitor Cells ; drug effects ; metabolism ; Purpura, Thrombocytopenic, Idiopathic ; complications ; drug therapy ; immunology ; RNA, Messenger ; RNA, Viral ; drug effects ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction

We report five cases of cytomegalovirus infection in immunocompromised patients which were detected by either cytomegalovirus antigenemia assay or in situ hybridization. Four cases had leukemia and the other had chronic renal failure. All the three BMT recipients suffered from GvHD. Interestingly, there was an unique case of CMV disease without a history of BMT, which reminded us that CMV could attack immunocompromised patients who had not undergone transplantation, too. Four out of five cases died. We think that cytomegalovirus infection or disease should not be regarded as a minor problem in post-transplantation infection in Korea.
Adolescent ; Adult ; Antigens, Viral/*blood ; *Bone Marrow Transplantation ; Case Report ; Cytomegalovirus/*immunology ; Cytomegalovirus Infections/complications/*diagnosis ; Fatal Outcome ; Graft vs Host Disease/complications ; Human ; Immunocompromised Host ; In Situ Hybridization ; Kidney Failure, Chronic/complications ; Kidney Transplantation ; Leukemia/*complications/therapy ; Leukemia, Lymphocytic, Acute, L2/complications/therapy ; Leukemia, Myelocytic, Acute/complications/therapy ; Leukemia, Myeloid, Chronic/complications/therapy ; Male ; Viremia/*diagnosis