Epstein-Barr Virus and Peri-Implantitis: A Systematic Review and Meta-Analysis.

The exponential growth in the use of dental implants in the last decades has been accompanied by an increase in the prevalence of peri-implant disease. It appears that viruses may have pathogenic potential for the development of this pathology. The objective of this systematic review is to study the possible association between the presence of Epstein-Barr virus and the development of peri-implantitis. An electronic search was conducted in PubMed/MEDLINE, Scielo and Embase databases for cross-sectional and case-control studies in humans published up to and including 4 January 2021. Five studies were included in the qualitative analysis. The meta-analysis did not show a statistically significant difference regarding the prevalence of Epstein-Barr virus in the peri-implant sulcus between implants with peri-implantitis and healthy implants. In conclusion, no association between the human herpesvirus 4 and peri-implantitis was found. Further research on this topic is essential to develop more effective treatments.

Current weight of evidence of viruses associated with peri-implantitis and peri-implant health: A systematic review and meta-analysis.

The pathological role of human herpesviruses (HHVs) (Epstein-Barr virus [EBV], Human cytomegalovirus [CMV], and Herpes simplex virus [HSV]) in peri-implant health needs clarification quantitatively. To determine the weight of evidence for HHVs in patients with peri-implantitis (PI) and substantiate the significance of HHVs in peri-implant inflammation, electronic databases including EMBASE, MEDLINE, Cochrane Oral Health Group Trials Register, and Cochrane Central Register of Controlled Trials were searched from 1964 up to and including November 2018. Meta-analyses were conducted for prevalence of HHVs in PI and healthy controls. Forest plots were generated that recorded risk difference (RD) of outcomes and 95% confidence intervals (CI). Five clinical studies were considered and included. Four clinical studies reported data on EBV while three clinical studies reported data on CMV. Considering the risk of these viruses in PI, significant heterogeneity for CMV (χ2  = 53.37, p < 0.0001, I2  = 96.25%) and EBV (χ2  = 14.14, p = 0.002, I2  = 78.79%) prevalence was noticed between PI and healthy control sites. The overall RD for only EBV (RD = 0.20, 95% CI, 0.01-0.40, p = 0.03) was statistically significant between both groups. Frequencies of the viruses were increased in patients with PI compared with healthy nondiseased sites. However, the findings of the present study should be interpreted with caution because of significant heterogeneity and small number of included studies.

Cytokine Levels and Human Herpesviruses in Saliva from Clinical Periodontal Healthy Subjects with Peri-Implantitis: A Case-Control Study.

This study evaluated the presence of cytokines (IL-1ß, IL-2, IL-4, IL-6, MCP-1, MIP-1α, MIP-1ß, and TNF-α) and human herpesvirus (HSV1, HSV2, EBV, CMV, VZV, HHV6, HHV7, and HHV8) in saliva samples taken from subjects with and without peri-implantitis. Forty-two periodontally healthy subjects were divided according to peri-implant condition: healthy and peri-implantitis groups. The clinical parameters as probing depth, clinical attachment level, plaque index, gingival bleeding, bleeding on probing, and suppuration were evaluated. For cytokine detection, multiplex analysis was performed, and PCR assay was used to identify herpesviruses. No significant differences were found in cytokine levels between groups (p > 0.05). The presence of herpesvirus was 1.97-fold higher in patients with peri-implantitis (odds ratio, CI 0.52-7.49). The association of the presence or absence of herpesvirus with the salivary markers was statistically significant for MIP-1ß (p = 0.0087) and TNF-α (p = 0.0437) only in the peri-implantitis group. The presence of herpesviruses in patients with peri-implantitis suggests the development of a proinflammatory environment, which is characterized by increased expression of MIP-1ß and TNF-α in saliva.

What is the Impact of Epstein-Barr Virus in Peri-implant Infection?

PURPOSE: To compare the qualitative and quantitative profile of Epstein-Barr virus (EBV) at external and internal implant surfaces between participants with peri-implantitis and healthy peri-implant tissues and to quantitatively assess the relation between EBV and periopathogens inside the microbiologic profile associated with peri-implantitis. MATERIALS AND METHODS: Microbiologic specimens were retrieved from 84 patients wearing 190 implants to estimate the levels of EBV and 10 periopathogens in the peri-implant pocket and internal-implant connection using quantitative polymerase chain reaction. RESULTS: The study sample consisted of 113 healthy and 77 peri-implantitis-affected implants. Statistical significance was not reached in EBV prevalence between peri-implantitis and healthy controls. EBV-positive participants demonstrated higher levels of Prevotella intermedia (Pi) and Campylobacter rectus (Cr) compared with EBV-negative participants. A positive correlation was demonstrated among EBV and Tannerella forsythia (Tf), Parvimonas micra (Pm), Fusobacterium nucleatum (Fn), and Cr levels in peri-implantitis-affected implants, while healthy controls demonstrated a positive correlation between EBV and Aggregatibacter actinomycetemcomitans (Aa), Pi, and Pm. CONCLUSION: EBV cannot be considered as a microbiologic marker of peri-implantitis. However, EBV could be considered as a risk factor and a peri-implantitis enhancer based on its positive correlations with pathogens associated with peri-implantitis.

Herpes Simplex 1 and Periopathogen Role in Peri-implantitis.

INTRODUCTION: The objectives of this study were to compare the qualitative and quantitative profiles of herpes simplex virus type I (HSV-1) in implant surfaces between participants with peri-implantitis (PI) and Healthy peri-implant tissues and to quantitatively assess the relation between HSV-1 and periopathogens inside the microbiological profile associated with PI. MATERIALS AND METHODS: A total of 40 patients with PI and 40 with healthy peri-implant tissues (HI) were recruited. Plaque samples from peri-implant sulcus and internal implant connections were analyzed using quantitative real-time polymerase chain reaction to detect and quantify HSV-1 and periodonto-pathogens. Frequencies of detection and levels of microorganisms were compared between PI and HI; the frequencies and levels of periodontopathogens were compared between HSV-1+ and HSV-1- PI to assess qualitative relations between HSV-1 and bacteria. Correlation between HSV-1 and periodontopatho-gens levels was assessed in PI and HI. RESULTS: A total of 77 dental implants affected by PI, and 113 HIs were included. The HSV-1 prevalence was slightly higher in PI compared with controls (33.3 vs 23.8%; p > 0.05); HSV-1 was detected in external samples more frequently compared with internal samples. The HSV-1-positive patients revealed higher median loads of Prevotella intermedia (Pi) and Campylobacter rectus (Cr) compared with HSV-1-negative patients. In the PI group, a significant positive correlation was evidenced between HSV-1 and Tannerella forsythia, Parvimonas micra (Pm), Fusobacterium nucleatum, and Cr levels, while in the HI, positive correlation between HSV-1 and Aggregatibacter actinomycetemcomitans, Pi, and Pm was established. CONCLUSION: The HSV-1 prevalence cannot be used to identify PI. The HSV-1 was found in similar levels of PI and HI patients after an average of 6 years of loaded implants. The HSV-1 prevalence cannot be used to identify implants with or without the presence of PI. CLINICAL SIGNIFICANCE: Although HSV-1 is detected in PI site, HSV-1 may represent an unspecific indicator for the host response to the bacterial challenge observed in PI.

Periodontopathogen and Epstein-Barr virus-associated periapical periodontitis may be the source of retrograde infectious peri-implantitis.

BACKGROUND: Herpesviral-bacterial synergism may play a role in periodontitis and peri-implantitis etiopathogenesis. Periapical periodontitis (PP) lesions can predict future apical peri-implantitis complications. PURPOSE: This pilot study aimed to substantiate herpesviral-bacterial coinfection in symptomatic (SP) and asymptomatic (AP) PP and assess associations with periodontopathogen salivary contamination in patients receiving implants. MATERIALS AND METHODS: Polymerase chain reaction (PCR)-based identification was performed on PP granulation tissue (GT) from 33 SP and AP patients and compared with unstimulated whole saliva. Quantitative PCR evaluated Epstein-Barr virus (EBV) and cytomegalovirus copy counts. RESULTS: SP GT had higher proportions of periodontopathogens. Symptomatic patients were 3.7 times more likely to be infected with EBV than AP (p = .07; 95% CI: 0.8-16.2). SP were 2.9, 2.1, 3.6, and 1.6 times more likely to be infected with Treponema denticola, Prevotella intermedia, Aggregatibacter actinomycetemcomitans, and Porphyromonas gingivalis, respectively. The odds ratio of EBV infecting PP lesions was two times higher in those positive for the virus in saliva. Saliva Tannerella forsythia-positive patients were 15 times more likely to present this pathogen in PP lesions (p = .038). Saliva EBV-positive individuals were 7 and 3.5 times more likely to yield GT contamination with T. forsythia and T. denticola, respectively. EBV copy counts were significantly higher in SP (p < .01). CONCLUSIONS: A causal association between EBV, specific bacterial anaerobic infection, and symptomatic PP is likely. EBV high prevalence underscores the viral etiological importance. Salivary EBV contamination is likely to be associated with viral and bacterial GT infection. Saliva PCR analysis can be a good predictor of GT specific infection and help establish antimicrobial therapy. If confirmed by prospective longitudinal clinical trials, antiviral therapy could possibly benefit SP and nonresponsive to treatment individuals and help prevent potential peri-implant infectious complications.

Epstein-Barr virus associated peri-implantitis: a split-mouth study.

OBJECTIVES: Herpesviral-bacterial synergism may play a potential role in periodontitis and peri-implantitis (PI) etiopathogenesis. PI lesions can worsen depending on specific microbial challenge and host susceptibility. This cross-sectional split-mouth study aimed to substantiate herpesviral-bacterial co-infection in PI patients and assess associations with periodontopathogen salivary contamination. METHODS: PCR-based identification was performed on 23 patients presenting PI and contralateral healthy implants, and compared to unstimulated whole saliva. Clinical evaluation included probing depths, bleeding on probing, and suppuration. Radiographs were assessed for the presence of lamina dura and bone loss. Three sample sites per patient were tested: PI lesions, healthy implant sulci, and saliva. Quantitative PCR evaluated Epstein-Barr virus (EBV) and cytomegalovirus (CMV) copy counts. Significance of group comparisons for binary-dependent variables, within-subjects designs, was determined by McNemar's chi-square test. Risk analysis was evaluated through odds ratios (OR). RESULTS: PI lesions were 14.2 (P = 0.001; 95 % confidence interval [CI], 1.6-124.1) and 3 times (P = 0.03; 95 % CI, 0.7-11.9) more likely to harbor EBV than healthy implants and saliva, respectively. EBV positive predictive value was 90 %. PI was associated with absence of lamina dura and higher periodontopathogen proportions. Saliva sampling showed high agreement with PI bacterial detection (89-100 % rate) but not with EBV (44.4 %). The OR of PI lesions harboring Treponema denticola or Tannerella forsythia was 6.79 (P = 0.007; 95 % CI, 1.8-25.0) and 3.3 (P < 0.0001; 95 % CI, 0.3-34.3) times higher than healthy implants, respectively. Saliva of patients with PI was 5.6 times more likely to be contaminated with Prevotella nigrescens than healthy peri-implant sulci (P = 0.002). PI lesions were 1.92 times more likely to harbor Prevotella nigrescens than healthy implants (P = 0.04). CONCLUSIONS: EBV is a potential candidate in peri-implantitis etiopathogenesis. Saliva PCR analysis is useful in predicting peri-implantitis-specific bacterial infection but not EBV or CMV. CLINICAL SIGNIFICANCE: Herpesviral-bacterial synergism may favor ongoing microbial challenge in peri-implant disease and exacerbate its progression. EBV infection may explain non-responsive to treatment PI. Peri-implantitis individuals may benefit from antiviral therapy.

Correlation between different genotypes of human cytomegalovirus and Epstein-Barr virus and peri-implant tissue status.

BACKGROUND: The purpose of this study was to estimate the prevalence of different genotypes of human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) in peri-implantitis and mucositis sites, and to evaluate the correlation between herpesvirus presence and clinical parameters. METHODS: A total of 80 dental implants (mean time of loading, 4.16 ± 1.8 years) were evaluated during the course of the study (30 peri-implantitis, 25 mucositis and 25 healthy peri-implant sites). The following clinical parameters were assessed: visible plaque index, bleeding on probing, suppuration and probing depth. A polymerase chain reaction (PCR) assay was used to identify the presence of different HCMV and EBV genotypes in peri-implant tissue plaque samples. RESULTS: HCMV-2 was detected in 53.3% and EBV-1 in 46.6% of the 30 peri-implantitis sites evaluated. By contrast, HCMV-2 was not detected in healthy periodontal sites and EBV-1 was detected in one healthy site. A statistically significant correlation was found between the presence of HCMV-2 and EBV-1 genotypes and clinical parameters of peri-implantitis. CONCLUSIONS: The results from the present study confirmed the high prevalence of HCMV-2 and EBV-1 in the peri-implant tissue plaque of peri-implantitis sites and suggests a possible active pathogenic role of the viruses in peri-implantitis.

Prevalence of human cytomegalovirus and Epstein-Barr virus in subgingival plaque at peri-implantitis, mucositis and healthy sites. A pilot study.

This study evaluated the prevalence of human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) in peri-implantitis and mucositis sites and the correlation between herpesvirus and clinical parameters. Fifty-six dental implants (mean time of loading, 4.27±1.6 years) were evaluated (20 peri-implantitis, 18 mucositis, 18 healthy peri-implant sites.) The clinical parameters assessed were: visible plaque index (PI), bleeding on probing (BOP), suppuration (SUP), probing depth (PD). A polymerase chain reaction assay identified HCMV and EBV in subgingival plaque samples. The percent of sites with plaque and BOP was significantly higher around mucositis and peri-implantitis compared with healthy implants (p<0.05). The mean PD around the implants was significantly higher in peri-implantitis, followed by mucositis and healthy implants (p<0.05). HCMV was detected in 13 (65%) and EBV in 9 (45%) of the 20 peri-implantitis sites. HCMV was found in 1 of the 18 (6%) healthy periodontal sites and EBV in 2 (11%). A statistically significant correlation was found between presence of HCMV and EBV subgingivally and clinical parameters of peri-implantitis and healthy sites. These results confirm the high prevalence of HCMV and EBV in subgingival plaque of peri-implantitis sites and suggest the viruses have a possible active pathogenic role in peri-implantitis.