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.

Atypical paronychia: don't forget herpesvirus.

Paronychia is usually caused by bacterial infections. Herpetic whitlow is an acute infection of the fingers or toes caused by herpes simplex viruses and it typically presents with vesicles. We report the case of a 78-year-old woman with gingivostomatitis and atypical paronychia in several fingers without blisters.

Brush Samples of Oral Lesions to FTA Elute Card for High-risk Human Papilloma Virus Diagnosis.

AIM: To investigate the level of agreement between three non-invasive methods for hrHPV diagnosis in oral and oropharyngeal squamous cell carcinoma (OSCC, OPSCC) and in oral mucosal lesions. MATERIALS AND METHODS: For hrHPV DNA FTA Elute card™ and Anyplex II HPV28™ were used and for hrHPV mRNA PreTect SEE™ in tumour patients (n=60), non-tumour lesions (n=51), immunosuppression or previous hrHPV-infection (n=32). RESULTS: The level of agreement between the DNA-methods was 82.2% (k=0.54, p=0.001). Pair-wise comparison for the FTA Elute card were close to the reference (AUC=0.83, 95% CI=0.73-0.90). hrHPV mRNA was diagnosed in 50% of the tumours, with an agreement level of 58.3%, compared to Anyplex II (k=0.17, p=0.04). The hrHPV positivity in oral lesions was 3.9% for immunosuppression and for previous HPV infection 9.4%. CONCLUSION: The FTA card is reliable for hrHPV DNA diagnosis while mRNA gives an insight into viral activity and correlates with severity of the lesion.

Topical Treatment of Acyclovir-Resistant Herpes Simplex Virus Stomatitis after Allogeneic Hematopoietic Cell Transplantation.

INTRODUCTION: We report on patients who developed severe acyclovir-resistant (ACVr) herpes simplex virus 1 (HSV-1) stomatitis after allogeneic hematopoietic cell transplantation (HCT). PATIENTS: HCT patients suffering from HSV-1 stomatitis without response after 1 week of high-dose acyclovir (ACV) were tested for ACV resistance. Patients with proven ACV resistance were treated either topically with cidofovir solution and gel or with topical foscavir cream or with intravenous foscavir. RESULTS: Among 214 consecutive HCT patients, 6 developed severe ACVr HSV-1 stomatitis (WHO grade III n = 1, WHO grade IV n = 5). All 6 patients suffered from relapse of acute myeloid leukemia (AML) after HCT. ACVr stomatitis was treated topically with first-line (n = 4) or second-line (n = 2) cidofovir. Topical foscavir cream was applied as first-line (n = 1) or second-line (n = 1) therapy. Intravenous foscavir was used in 3 patients (first-line therapy, n = 1; second-line therapy, n = 2). Complete remission was reached by topical cidofovir (n = 3), topical foscavir (n = 1), and intravenous foscavir (n = 1), respectively. Five of the 6 patients died due to progression of leukemia. Only 1 patient survived. CONCLUSIONS: ACVr HSV-1 stomatitis is a severe complication in AML patients relapsing after HCT. It reflects the seriously impaired general condition of these patients. This analysis shows that topical treatment with cidofovir or foscavir might be a sufficient first-line therapy approach in ACVr HSV-1 stomatitis. It might serve as a less toxic alternative to intravenous foscavir.

Investigations into the presence of nidoviruses in pythons.

BACKGROUND: Pneumonia and stomatitis represent severe and often fatal diseases in different captive snakes. Apart from bacterial infections, paramyxo-, adeno-, reo- and arenaviruses cause these diseases. In 2014, new viruses emerged as the cause of pneumonia in pythons. In a few publications, nidoviruses have been reported in association with pneumonia in ball pythons and a tiger python. The viruses were found using new sequencing methods from the organ tissue of dead animals. METHODS: Severe pneumonia and stomatitis resulted in a high mortality rate in a captive breeding collection of green tree pythons. Unbiased deep sequencing lead to the detection of nidoviral sequences. A developed RT-qPCR was used to confirm the metagenome results and to determine the importance of this virus. A total of 1554 different boid snakes, including animals suffering from respiratory diseases as well as healthy controls, were screened for nidoviruses. Furthermore, in addition to two full-length sequences, partial sequences were generated from different snake species. RESULTS: The assembled full-length snake nidovirus genomes share only an overall genome sequence identity of less than 66.9% to other published snake nidoviruses and new partial sequences vary between 99.89 and 79.4%. Highest viral loads were detected in lung samples. The snake nidovirus was not only present in diseased animals, but also in snakes showing no typical clinical signs. CONCLUSIONS: Our findings further highlight the possible importance of snake nidoviruses in respiratory diseases and proof multiple circulating strains with varying disease potential. Nidovirus detection in clinical healthy individuals might represent testing during the incubation period or reconvalescence. Our investigations show new aspects of nidovirus infections in pythons. Nidoviruses should be included in routine diagnostic workup of diseased reptiles.

Contribution of herpesviruses in the progression of periodontal and peri-implant diseases in systemically healthy individuals.

The aim of this review was to assess the contribution of herpesviruses in the subgingival oral biofilm in the progression of periodontal and peri-implant diseases in systemically healthy individuals. The literature review was customized to summarize the pertinent information for the following reasons: (1) A systematic review regarding the role of herpesviruses in the etiopathogenesis of periodontal disease has recently been published; and (2) a limited number of studies have assessed the association of herpesviruses with peri-implant diseases. To date, five observational studies have assessed the presence of herpesviruses in the subgingival oral biofilm of individuals with peri-implant diseases. In these studies, dental implants were in place for up to approximately 8 years. In two studies, human cytomegalovirus (HCMV) was more often isolated from the peri-implant sulci of sites with than without peri-implantitis. In one study, a low prevalence of HCMV compared with Epstein-Barr virus (EBV) was associated with the progression of peri-implantitis. In previous studies, the presence of EBV in the subgingival oral biofilm was associated with the onset of peri-implantitis and peri-implant mucositis, respectively. Major limitations of the studies assessed were the absence of blinding and lack of power analysis for sample size estimation. In conclusion, the presence of herpesviruses in the periodontal and peri-implant subgingival oral biofilm is an indicator of periodontal and peri-implant diseases in systemically healthy individuals; however, further studies with a statistically justified sample-size are needed to understand and refine this association.

The Natural History of Oral Human Papillomavirus in Young Costa Rican Women.

BACKGROUND: Oral human papillomavirus (HPV) infection and related oropharyngeal cancer are uncommon in lower-income countries, particularly compared to HPV-associated cervical cancer. However, little is known about the natural history of oral HPV in less-developed settings and how it compares to the natural history of cervical HPV. METHODS: Three hundred fifty women aged 22 to 33 years from the Costa Rica Vaccine Trial provided exfoliated cells from the cervical and oral regions at 2 visits 2 years apart. Samples from both visits were tested for 25 characterized α HPV types by the SPF10 PCR-DNA enzyme immunoassay-LiPA25 version 1 system. Risk factors for oral HPV persistence were calculated utilizing generalized estimating equations with a logistic link. RESULTS: Among the 82 women with characterized α oral HPV DNA detected at baseline, 14 persisted and were detected 2 years later (17.6%; 95% confidence interval [CI], 10.9-28.5%) and was similar to the persistence of α cervical HPV (40/223; 17.7%; 95% CI, 13.1-23.9%; P = 0.86). Acquisition of new α oral HPV type was low; incident infection (1.7%; 95% CI, 0.6-3.7%). CONCLUSIONS: Oral HPV DNA is uncommon in young women in Latin America, and often appears to clear within a few years at similar rates to cervical HPV.

Prevalence of feline herpesvirus-1, feline calicivirus, Chlamydophila felis and Mycoplasma felis DNA and associated risk factors in cats in Spain with upper respiratory tract disease, conjunctivitis and/or gingivostomatitis.

Objectives Our objective was to perform the first multicentric study in Spain to evaluate the prevalence of feline herpesvirus-1 (FHV-1), feline calicivirus (FCV), Chlamydophila felis and Mycoplasma felis in cats with upper respiratory tract disease (URTD), conjunctivitis and/or gingivostomatitis (GS) compared with control cats; and to evaluate risk factors for these clinical conditions. Methods Conjunctival and oropharyngeal swabs were collected and a questionnaire regarding signalment, lifestyle, vaccination history and clinical signs was obtained for each cat. Swabs were tested for each pathogen by real-time PCR. Results The study population consisted of 358 cats, including 98 control cats. Among the 260 diseased cats, 127 cats presented with URTD, 149 cats had conjunctivitis, 154 cats were suffering GS; many cats presented more than one clinical condition. The prevalence observed of FHV-1, FCV, C felis and M felis was, respectively, 28.3%, 48.0%, 20.5% and 46.5% in cats with URTD; 24.2%, 43.6%, 19.5% and 38.3% in cats with conjunctivitis; and 15.6%, 58.4%, 9.1% and 37.7% in cats with GS. Prevalences in the control group were 6.1%, 15.3%, 2.0% and 20.4%, respectively. Coinfections were common among all groups of cats. Risk factors were identified for all groups. FHV-1, FCV and C felis were associated with URTD and conjunctivitis. FCV was strongly associated with GS. M felis was present in a high percentage of the population in all groups, but its role in these clinical conditions remains uncertain. Vaccination was protective for URTD and GS but not for conjunctivitis. Conclusions and relevance This epidemiological study describes, for the first time, prevalence for FHV-1, FCV, C felis and M felis in Spain. In general, the prevalences found are similar to those reported in other countries. Factors associated with disease expression were also identified, which are relevant for practitioners.

Oral shedding of human herpesviruses in patients undergoing radiotherapy/chemotherapy treatment for head and neck squamous cell carcinoma.

OBJECTIVE: Opportunistic infections may affect the oral mucosa of patients undergoing radio/chemotherapy through exacerbation of oral mucositis. The aim of this study is to evaluate the oral shedding of all eight human herpesviruses and its possible association with oral mucositis. MATERIALS AND METHODS: In this prospective cohort study, we analyzed oral rinse samples, collected weekly, from 20 patients during radiotherapy treatment. Serologic status to HSV1 and HSV2, EBV, CMV, and VZV in three different periods was performed by ELISA assay. PCR and enzymatic digestion was performed to detect HSV1, HSV2, EBV, CMV, VZV, HHV6, HHV7, and HHV8. Oral mucositis was evaluated according to the WHO criteria. RESULTS: Oral shedding of EBV, HHV6, and HHV7 was observed in all weeks of radiotherapy. Considering the episodes of shedding, the highest frequency was found in patients with EBV excretion (55.0%). No virus reactivation was observed by serological analysis. EBV oral shedding frequency was significantly higher than that of other viruses and showing a positive correlation with oral mucositis grade ≥2. CONCLUSIONS: There was a positive correlation between EBV oral shedding and oral mucositis grade ≥2, particularly after 3 weeks of radiotherapy, a period in which the severity of mucositis was statistically higher. These findings allow us to infer that the local inflammatory environment in mucositis grade ≥2 is more favorable for EBV replication. CLINICAL RELEVANCE: Mucositis is a frequent and important side effect of radio/chemotherapy treatment. Understanding the possible participation of viruses in the mechanism of this condition is important to develop strategies for treatment and prevention.

Reactivation of polyomavirus in the genitourinary tract is significantly associated with severe GvHD and oral mucositis following allogeneic stem cell transplantation.

PURPOSE: BK-virus and JC-virus are the most common polyomaviridae associated with hemorrhagic cystitis in the allogeneic transplant setting. Hemorrhagic cystitis and symptomatic viruria caused by these viruses are a major cause of morbidity in patients undergoing allogeneic stem cell transplantation. METHODS: We performed a retrospective evaluation on a highly uniform study population of 73 patients receiving allogeneic stem cell transplantation. Patients were treated according to the FLAMSA-RIC-protocol, and were examined for the incidence of BK-/JC-viruria and late-onset BK-positive hemorrhagic cystitis within a two-year period. RESULTS: The occurrence of BK-viruria was correlated with published risk factors (acute GvHD, oral mucositis, donor type, conditioning, age, gender). Thirty patients (41 %) were found to excrete either BK-virus (n = 17), JC-virus (n = 3) or both (n = 10), of whom 18 patients (60 %) developed higher-grade hemorrhagic cystitis as opposed to none in the virus-negative control group. Higher grade GvHD (grade B-D) was more common in patients with viruria (p = 0.013) and also more common in patients with manifest hemorrhagic cystitis (p = 0.048). Similarly, oral mucositis was associated both with viruria (p = 0.014) and hemorrhagic cystitis (p = 0.005). Manifest cystitis but not viruria was significantly associated with male gender (p = 0.016). No significant correlation was found with age, conditioning with busulfane vs total body irradiation or related vs unrelated donor. CONCLUSIONS: Severe GvHD and oral mucositis are significantly associated with reactivation of polyomaviridae in the genitourinary-tract already at the level of asymptomatic viruria.

Herpes simplex 1 stomatitis after cleft palate repair: a case report and guidelines for management.

Herpes simplex virus (HSV) primary infection and reactivation has been associated with the inflammation and transient decrease in immunocompetence after surgery and local trauma. In addition, HSV infection is known to impair wound healing, increase risk of scarring, and impede connective tissue graft transplantation. To our knowledge, this is the first case of HSV infection complicating cleft palate repair presented in literature. In this report, we present a case of primary HSV infection occurring in a healthy 26-month-old patient after repair of the secondary cleft palate with mucoperichondrial flaps and V-Y pushback. The patient developed high fever on postoperative day 1, which was followed by perioral vesicular lesions and multiple intraoral ulcerations involving the lips, palate, and posterior pharynx. Unknown to the surgeons, the patient was exposed to HSV before surgery by a sibling with orolabial HSV infection. The infective cause was ascertained via polymerase chain reaction for HSV-1 DNA, and the infection was treated with topical and intravenous acyclovir for 1 week. The patient recovered well with adequate flap healing, good aesthetic outcome, and no complications on 1-month follow-up. This report underscores the importance of prompt recognition of herpetic infections in the patient with craniofacial surgery and reviews the association and complications of HSV infection in surgical healing. Early identification with prompt antiviral therapy and meticulous wound care are essential to ameliorate the scarring and delayed wound healing associated with HSV infection.

Seroprevalence of HSV-1/2 and correlation with aggravation of oral mucositis in patients with squamous cell carcinoma of the head and neck region submitted to antineoplastic treatment.

PURPOSE: Oral mucositis (OM) is a frequent side effect resulting from antineoplastic treatment and is described as an acute alteration characterized by ulcerative lesions, with the presence of a persistent chronic inflammatory infiltrate, erythema, and pain. AIMS: The purpose of the study was to evaluate the presence of the herpes simplex virus (HSV-1/2) in patients with squamous cell carcinoma of the head and neck region (SCC) and its influence on the aggravation of oral mucositis after radiotherapy or radio/chemotherapy treatment. METHODS: In this prospective cohort study, 91 patients were evaluated with regard to their serological status for IgG before treatment (initial time interval--TI) and for IgM before treatment (T1) and on the 30th day after the first day of radiotherapy application/radiation therapy (final time interval--TF), using immunoenzymatic assay (ELISA), and the results were correlated with the intensity of OM. RESULTS: The seroprevalence for IgG was 97.8 %. IgM (TI) was positive in 18.7% and IgM (TF) in 20.9% of patients. All the patients developed some degree of oral mucositis; however, there was statistically significant correlation between positivity for IgM and degree of severity of OM, irrespective of the type of treatment to which the patient was submitted. CONCLUSION: The reactivation of HSV-1/2 was shown to be relatively infrequent and there was no correlation between presence of the virus and aggravation of oral mucositis resulting from antineoplastic treatment.

Herpes simplex virus-related oral mucositis in patients with lymphoma.

A 58-year-old man named J.S. was diagnosed with non-Hodgkin lymphoma and underwent treatment with standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy. He presented to his local outpatient clinic for evaluation and laboratory tests on day 10 after cycle 3. During this visit, J.S. reported great difficulty opening his mouth with significant gingival and lingual pain when eating and drinking in spite of prophylactic oral care. Laboratory test results revealed a white blood cell count of 0.9 k/ul, hemoglobin level of 8.9 g/dl, platelets of 100 k/ul, serum creatinine level of 1 mg/dl, and blood urea nitrogen level of 29 mg/dl.

HSV-1 as well as HSV-2 is frequent in oral mucosal lesions of children on chemotherapy.

PURPOSE: Prevalence data of herpes simplex virus (HSV) in oral mucositis in children on treatment for cancer is limited. Quantitative polymerase chain reaction (PCR) has been seldom utilized for detection of HSV-1/2 in oral mucosa. METHODS: Children on treatment for cancer with oral mucositis were enrolled as cases and healthy children as controls. An oral swab from the lesion in cases and mucosal scraping in controls were obtained. Both qualitative and real-time quantitative PCR for HSV-1/2 were performed. Serum ELISA-IgG/IgM for HSV-1/2 antibodies (NovaLisa™-Dietzenbach-Germany) were measured. RESULTS: Thirty-two cases (Age, 6.3±3.4 years) and 30 controls were enrolled. Majority (69%) of cases had ALL. All patients had febrile neutropenia, except two. ELISA-IgM-HSV-1/2 was not positive in any case or control. ELISA-IgG-HSV-1/2 was positive in 11 (34%) cases and nine (30%) controls (p=1.0). Qualitative PCR for HSV-1 detected the virus in eight (25%) cases and nil controls (p=0.009). HSV-2 was not detected in any case/control by qualitative PCR. Quantitative PCR detected HSV-1 in 21 (66%) and HSV-2 in 22 (69%) cases. In controls, quantitative PCR detected HSV-1 in three (10%) and HSV-2 in none. In patients, the mean viral load of HSV-1 (5,500±15,987×10(4) copies/nanogram DNA) was more than HSV-2 (4.03±8.5×10(4)) (p=0.11). There was no correlation of HSV-1/2 with grading of mucositis. CONCLUSIONS: Both HSV-1/2 are commonly shed from oral mucosal lesions in children receiving chemotherapy. In a novel finding, real-time PCR detected copies of HSV-2 in 69% cases, all missed by conventional PCR. Implication for morbidity, if any, or treatment needs to be determined.

Seroprevalence of herpes virus associated with the presence and severity of oral mucositis in children diagnosed with acute lymphoid leukemia.

INTRODUCTION: Acute lymphoid leukemia (ALL) is the hematologic neoplasia most commonly diagnosed in children. Among the secondary side effects of chemotherapy, mucositis is the most frequent complication. The aim of this study was to evaluate the seroprevalence of herpes viruses HSV-1, EBV, and CMV and the presence and severity of oral mucositis in children and adolescents diagnosed with ALL. METHODOLOGY: Ninety-two patients diagnosed with ALL were evaluated. Serum samples were collected before chemotherapy and tested by ELISA method. Presence of mucositis was observed on the first day before antineoplastic therapy (D0) and on 7th day post-therapy (D7). Classification of mucositis intensity was performed according to toxicity criteria established by the National Cancer Institute. RESULTS: 70.7% of the patients presented mucositis on the D7, and of these, 60% were classified as Grade I and 40% as Grade II; of the 92 individuals tested, 59 (64.1%) presented antibodies for HSV-1, 57 (62%) for EBV, 75 (81.5%) for CMV_IgG, and 21 (22.8%) for CMV_IgM. Using a logistic regression model, the presence of HSV-1 was observed to be 4.10 times greater in Grade II mucositis severity than in Grade I (P = 0.03). CONCLUSION: Based on the findings of this study, it was possible to conclude that infection by the herpes viruses HSV-1, EBV, and CMV is ubiquitous in the studied population and that HSV-1 may be a risk factor for aggravating the severity of mucositis.

Oral human papillomavirus infection among drug users in Puerto Rico.

OBJECTIVE: The prevalence of human papillomavirus (HPV) in the oral cavity has not been as well studied as genital infection and its prevalence among drug users is uncertain. This study describes the prevalence and correlates of oral HPV infection among a sample of drug users in Puerto Rico (PR). METHODS: Cross-sectional study of 271 drug users aged 18-35 years, not undergoing substance abuse treatment, living in the San Juan metropolitan area. Oral samples were collected through an oral rinse and HPV infection status was detected through PCR and HPV typing. Information on covariates was obtained through face-to-face interviews and serum analyses. RESULTS: A total of 34 participants were positive for any HPV type (12.5%), whereas 13 individuals (4.8%) were positive for one of the 38 type-specific HPV probes evaluated. Among those HPV positive, the most common HPV type detected was non-oncogenic HPV 72 (11.8%, n = 4). Oncogenic HPV types detected were 35 (5.9%) and 56 (2.9%). Factors associated with oral HPV infection included binge drinking (OR = 3.85, 95% CI = 1.40, 10.58), HIV positivity (OR = 4.67, 95% CI = 1.58, 13.74) and ever having engaged in commercial sex (OR = 3.55, 95% CI = 1.46, 8.67); infection did not differ by age or gender. CONCLUSION: Consistent with previous studies in the genital and oral tract, HIV infection, alcohol abuse and commercial sex practices were strongly associated with oral HPV infection. Future studies should assess the implications of oral HPV infection on oral cancer risk in this population.