Correlation of cytomegalovirus and human herpesvirus 7 with CD3+ and CD3+ CD4+ cells in chronic periodontitis patients.

BACKGROUND AND OBJECTIVE: Human chronic periodontitis is an inflammatory process characterized by dense accumulation of immune cells in the periodontal tissue. The periodontitis can lead to loss of teeth in the patient and the pathogenesis of this disease is not completely known. This study tested the hypothesis that chronic periodontitis-affected sites can harbor betaherpesviruses and that viruses are linked to a profile of the inflammatory infiltrate. MATERIAL AND METHODS: Biopsies of periodontal tissue were taken from periodontitis-affected patients and from healthy subjects. Immunohistochemistry was performed to count CD19(+) B cells, CD3(+) total T cells, T-CD4(+) and T-CD8(+) cell subsets, and PCR was performed to detect cytomegalovirus and human herpesvirus 6 and 7 in the samples. One slide of each sample was stained with Giemsa for histopathological examination and to evaluate the quality of the cellular infiltrate. RESULTS: As expected, tissues collected from healthy subjects presented no significant level of inflammatory infiltration and were therefore excluded from immunostaining procedures. Results showed that CD19(+) B cells were in higher number than CD3(+) T cells in the periodontitis-affected tissue, but this was not statistically significant. The T-CD4(+) lymphocyte subset was significantly higher than the T-CD8(+) lymphocyte subset (p = 0.004) in the samples. Cytomegalovirus and human herpesvirus 7 were found at periodontitis-affected sites, but not in tissue collected from healthy subjects (p = 0.04 and p = 0.04, respectively). Human herpesvirus 6 was rarely detected. We found a correlation between cytomegalovirus and lower CD19(+) /CD3(+) ratios (ratio < 0.9, p = 0.003) and between human herpesvirus 7 and lower CD19(+) /CD3(+) ratios (ratio < 0.9, p = 0.003) and higher CD4(+) /CD8(+) ratios (ratio > 1.1, p = 0.002). CONCLUSION: This study shows that cytomegalovirus and human herpesvirus 7 can be present at periodontitis-affected sites but are uncommon at healthy periodontal sites. Moreover, our data suggest that cytomegalovirus can be related to an inflammatory infiltrate with predominance of CD3(+) T cells, whereas human herpesvirus 7 can be associated with an infiltrate with predominance of T-CD4(+) cells. However, further studies are necessary to support this hypothesis. Herpesviruses could play a role in human chronic periodontitis by modulation of the T cell response.

Human herpesvirus-7 in Brazilian liver transplant recipients: a follow-up comparison between molecular and immunological assays.

Human herpesvirus-6 and -7 (HHV-6, HHV-7) remain latent after primary infection and can reactivate after transplantation. HHV-6 active infection has been related to some clinical manifestation, but the role of HHV-7 remains unclear. The clinical significance of HHV-7 DNAemia is not completely known and the immune response against HHV-7 has been poorly studied in transplantation. In this study, we investigated HHV-7 DNAemia in liver transplant recipients and evaluated the immunoglobulin (Ig) G and IgM response against HHV-7. A total of 22 adult liver transplant recipients were followed up for 90 days. HHV-7 DNAemia was detected by nested polymerase chain reaction (PCR) in DNA extracted from sera. IgG and IgM detection was performed by immunofluorescent assay using HHV-7-infected cord blood mononuclear cells. A significant virus antibody response was defined as either a positive IgM or a > or =4-fold rise in the virus IgG antibody. All patients had pre-transplant HHV-7-positive serostatus. Nine of 22 (40.9%) patients presented HHV-7 DNAemia during follow-up. All these patients had anti-HHV-7-positive IgM and/or significant increase in IgG titers with concurrent or subsequent DNAemia. In patients without DNAemia and low persistent IgG antibody titers, IgM was not detected. Correlation between nested PCR and IgM detection was statistically significant (P=0.01). Our study indicates that nested PCR in DNA extraction from serum can be useful to detect and monitor HHV-7 active infection in liver transplant recipients. IgM antibody detection also can be useful as a first immunological technique to detect active infection, especially if combined with PCR.

Detection and monitoring of human herpesvirus 7 in adult liver transplant patients: impact on clinical course and association with cytomegalovirus.

We herein have described HCMV and HHV-7 detection during the follow-up of 29 adult liver recipients in our transplant unit. For basic immunosuppression, the patients received cyclosporine and symptomatic HCMV infection was treated with gancyclovir. The most prevalent etiology for liver transplantation was hepatitis C or alcohol abuse (45% of patients). The laboratory monitoring to 180 days after transplantation was performed by nested-polymerase chain reaction to HCMV or HHV-7. HCMV DNA was detected in 19/29 of patients (65.5%) and HHV-7 DNA, in 14/29 of patients (48.2%). The time-related appearance of HHV-7 and HCMV DNA differed significantly (P = .02); their detection was considered independent (P = .2). The results showed that few patients remained free of HHV-7 or HCMV after liver transplantation, indicating that most patients were actively infected with more then one virus sequentially and not concurrently. Graft dysfunction, fever, gastrointestinal system abnormalities, and interstitial pneumonitis dominated the clinical pictures. Thirteen of 29 patients (44.8%) developed symptomatic HCMV active infections. The relationship between the detection of HCMV DNA, and HCMV disease development was significant (P = .0004). In HCMV-free patients, no symptoms or significant laboratory findings were linked with HHV-7. However, HHV-7 was frequently detected sequentially after HCMV, and an interaction of HCMV and/or HHV-6 to increase their pathogenic effects could not be excluded. Further studies should be performed including HHV-6 to evaluate the relationship, among beta herpesviruses.

Polyarteritis nodosa and cytomegalovirus: diagnosis by polymerase chain reaction.

We investigated the occurrence of an active cytomegalovirus (CMV) infection in patients with polyarteritis nodosa (PAN). Eleven patients with PAN were screened for the presence of CMV-DNA in their blood using the polymerase chain reaction (PCR). Serum anti-CMV IgG and anti-CMV IgM antibodies were determined by enzyme-linked immunosorbent assays (ELISA). The ELISA for IgM was negative in all cases whereas that for IgG was positive in eight cases. Only one patient was positive for CMV-DNA by PCR. He presented with myalgia, polyarthralgia, fever and weight loss, suggesting PAN activity. CMV infection was uncommon in our series of patients with PAN, despite disease activity and immunosuppressor therapy. The finding of a transient CMV infection in one case at the beginning of PAN activity suggests that CMV may be involved in the pathogenesis of PAN.

Identification of bacterial infections and clinical manifestation associated with cytomegalovirus in liver transplantation patients.

INTRODUCTION: Liver transplantation has become the most effective therapy for the treatment of patients with end-stage liver disease. With new immunosuppressive agents the incidence of acute rejection has been significantly reduced, but infection has become a serious problem. OBJECTIVE: Our objective was to correlate cytomegalovirus (CMV) positivity of antigenemia and polymerase chain reaction (PCR) with clinical manifestations and bacterial infections among patients undergoing liver transplantation. METHODS: This prospective study included patients monitored for 6 months for early detection of CMV infection. Sample collections were performed at the time of surgery and weekly until the second month followed by fortnightly in the third month, and monthly in the fourth to sixth month. CMV infection was defined by positive antigenemia (>3 cells) or 2 positive PCR tests associated or not with clinical symptoms. The methodology for the diagnosis of bacterial infection was through biochemical tests and the automated VITEK/bioMérieux (identification and antibiogram) using samples of urine and blood cultures. Chi-square test was used for dicotomic variables with significant differences when P < .05. RESULTS: Sixteen patients (32%) had CMV infections, including 13 (81%) with concomitant infections. Thirty-four patients (68%) did not have CMV infections and 8 of these (24%) had bacterial infection. There was a high correlation with bacterial infections among CMV-positive patients. CONCLUSION: Bacterial infections after liver transplantation were associated with CMV infection.

Co-infection and clinical impact of human herpesvirus 5 and 6 in liver transplantation.

BACKGROUND: Human herpesvirus (HHV) 5 and 6 remain latent after primary infection and can be reactivated after immunosuppression for organ transplantation. An association between HHV-5 and HHV-6 has been reported in liver transplant patients. The coinfection is associated with clinical manifestations and graft dysfunction. OBJECTIVE: The aim of this study was to monitor herpesviruses in liver transplant recipients to better understand issues involving coinfection with HHV-5/6 and correlations with acute cellular rejection episodes and bacterial infections. METHODS: Forty-five adult liver transplant patients of median age 47 years (range, 18-66), gave blood samples and liver biopsies in the first 6 months after their surgeries. Viremia was detected with the use of nested PCR and antigenemia; the Banff classification was used to detect allograft rejection. RESULTS: IgG positive for HHV-5 was observed in 94% of subjects whose main indication (67%) for transplantation was hepatitis C. Twenty-three (51.1%) displayed cytomeg virus (CMV) infections and 12 (26.7%) HHV-6 infection. There were 6 patients (13.3%) with HHV-5/6 coinfections. Eighteen of the 23 patients had CMV disease, showing a strong correlation between a positive test and CMV disease; 6 displayed an acute cellular rejection episode in the same period (χ(2) = 6.62; P < .03). Four out of 6 patients who displayed coinfections (HHV-5/6) had concomitant bacterial infections; 3/6 experienced graft rejection episodes. During follow-up, 1 patient had HHV-6 infection diagnosed as encephalitis followed by fever on the 24th day after surgery. The median 32 days for HHV-6 detection by nested PCR positivity was shorter than 38 days for HHV-5. CONCLUSIONS: HHV-5/6-infected patients displayed more allograft rejection episodes, coinfections, and concomitant bacterial infections, besides an higher risk for CMV disease.

Monitoring and detection of cytomegalovirus in liver transplant recipients.

Cytomegalovirus (CMV) is a ß-herpesvirus. CMV infections are a common complication contributing to morbidity and mortality after liver transplantation. Among organ transplant recipients, CMV can reactivate from latency during the first 6 months. This prospective study performed from February 2008 to December 2009 examined liver transplant recipients during the first 6 months. Two methods were performed to detect CMV infections: antigenemia (AGM) and nested (PCR). Ninety-four patients, including 72 men (76.6%) and 22 women (23.4%) underwent liver transplantation during this period. We analyzed 575 samples including 465 for AGM and PCR. Forty-three (9.25%) showed positive AGM as detected 2 to 179 days posttransplantation with a mean of 50 days and a median of 35 days, and 93/465 (20%) showed positive PCR at 0 to 186 days posttransplantation with a mean of 31 days and a median of 38 days. Among the 43 antigenemia patients, 38 samples were positive for up to 5 cells 18 of which were PCR-positive. Five samples were positive with more than 5 cells, including 3 that were PCR-positive. Only 4.51% had AGM and were PCR-positive in the same sample. Despite only 9.25% (43/465) showing AGM, the current study suggested the utility of routine monitoring to detect early CMV infection among liver transplantation patients seeking to reduce morbidity and mortality.