Herpes Patients Research Articles

Detection of herpes viruses in patients with classical trigeminal neuralgia

A comparison of the presence frequency of herpes viruses HSV1/2, VZV, HHV-6, HHV-7, EBV, CMV was conducted in 430 patients with classical trigeminal neuralgia (TN) using RT PCR method. In the venous blood of patients with paroxysmal pain syndrome (TNP) and persistent background pain (TNB), herpes viruses were detected in 36.3% (97/267) and 80.4% (131/163) cases, respectively. The effectiveness of microvascular decompression and long-term outcomes were assessed depending on the presence of herpes viruses. Pain syndrome completely regressed in 404 out of 430 patients (93.9%), partially in 25 patients (5.8%), and persisted in 1 patient (0.2%). In TNB group, pain recurrence and partial regression were observed more frequently (20.2% (34/163) and 12.8% (21/163), respectively) if compared to TNP group (1.8% (5/267) and 1.5% (4/267), respectively). Complete pain regression in TNB group was less than in TNP group: 86.5% (141/163) and 98% (263/267), respectively. The presence of herpes viruses in patients with TN, a higher frequency of detection of herpes viruses, as well as a higher percentage of patients with recurrence of pain in TNB versus TNP group suggest a potential role of herpes viruses in the development of pain syndrome. Thus, studying herpes viruses in the blood could be recommended for improving the diagnostics and therapy of patients with classical TN.

Active herpesviruses are associated with intensive care unit (ICU) admission in patients pulmonary infection and alter the respiratory microbiome.

The Herpesviridae family contains several human-related viruses, which are able to establish colonizing and latency in the human body, posing a significant threat to the prognosis of patients. Pulmonary infections represent one of the predominant infectious diseases globally, characterized by diverse and multifaceted clinical manifestations that have consistently attracted clinician's concern. However, the relationship of herpesviruses on the prognosis of pulmonary infections and the respiratory microbiota remains poorly understood. Here, we retrospectively analyzed respiratory samples from 100 patients with pulmonary infection detected by metagenomic next-generation sequencing (mNGS). Employing mNGS, five herpesvirus species were detected: Human alphaherpesvirus 1 (HSV-1), Human gammaherpesvirus 4 (EBV), Human betaherpesvirus 5 (CMV), Human betaherpesvirus 7 (HHV-7), and Human betaherpesvirus 6B (HHV-6B). Regression analysis showed that the age and positivity of herpesviruses in patients were independently correlated with ICU admission rates. In addition, positivity of herpesvirus was related with increased ICU days and total hospital stay. The herpesvirus-positive group demonstrated markedly higher incidences of co-infections and fungi-positive, predominantly involving Pneumocystis jirovecii and Aspergillus fumigatus. Analysis of respiratory microbiota revealed a substantially altered community composition within the herpesvirus-positive group, and herpesviruses were significantly positively correlated with the diverse respiratory opportunistic pathogens. Overall results substantiate that the active herpesviruses in patients with pulmonary infections were significantly associated with high ICU admission rate. Moreover, the herpesviruses promotes the dysbiosis of the respiratory microbiota and an increased proportion of co-infections. These insights could contribute to unraveling the underlying mechanisms connecting active herpesviruses to the progression of severe illnesses.

T-cell immunity status of children with combined infection with SARS-CoV-2 and human herpesviruses

There is an opinion that COVID-19 may be the cause of the reactivation of herpesviruses. Purpose. To study the state of the cellular link of adaptive immunity in the combined course of herpesvirus infections and COVID-19, to describe the clinical and laboratory characteristics of such conditions. Material and methods. In 2022–2023 a cross-sectional study was conducted. 71 patients aged from 1 month to 16 years were selected. Inclusion criteria: presence of signs of acute respiratory disease associated with SARS-CoV-2 and/or mononucleosis-like syndrome associated with active herpesvirus infection. All patients underwent a standard laboratory examination, determined by nosology, and an additional assessment of the cellular link of adaptive immunity (CD3+, CD4+, CD8+, CD3+HLA-DR+, CD3- CD16+CD56+ and CD20+) on a flow cytometer using monoclonal antibodies. Results and conclusion. The clinical pattern of the combined course of herpesvirus infection and SARS-CoV-2 differs little from monoinfections. Only at the first encounter with the Epstein-Barr virus, lymphoproliferative syndrome and hepatomegaly were more often recorded (p<0.05). Comparing the nature of the cellular immune response in patients with COVID-19 and herpesvirus infection, we observed pronounced differences. In patients with primary herpesvirus infection, the T-cell immune response was an order of magnitude higher than in acute COVID-19, herpesvirus reactivation, and co-infection, and this was true for all studied lymphocyte subpopulations. With SARS-CoV-2, a decrease in the total number of T-lymphocytes, T-helpers, and cytotoxic lymphocytes was observed. This condition, of course, cannot be called immunosuppression, but some parallel is clearly traced. And even with the combined course of SARS-CoV-2 and herpesvirus infection, the absolute values of T-cell immunity indicators do not reach the same indicators in patients without COVID-19. It is likely that this reason underlies the phenomenon of reactivation of persistent herpesviruses in patients infected with SARS-CoV-2.

Determination of serotype distribution of aggregatibacter actinomycetemcomitans and its relationship to Herpes virus in patients with aggressive periodontitis

Aggregatibacter actinomycetemcomitans (A. a) and its serotypes were commonly associated with Aggressive Periodontitis (AgP). Herpes virus along with A.a in sites of destruction, suggested that their co-occurence reduces the ability of macrophages to respond to bacteria and inhibits their phagocytic activity. JP2 clone is a highly leukotoxic strain of A.a, associated with Keywincreased progression of periodontal disease. The aim of the study was to determine the serotype distribution of A.a and its relationship to the presence of Herpes virus [Epstein Barr virus (EBV) and Cytomegalovirus (CMV)] in patients with AgP. The study included 20 patients with AgP and 20 periodontally healthy subjects. Subgingival plaque samples were collected from deepest pockets using Gracey curettes and transferred to transport media. The cDNA was extracted and analysed by PCR. Serotype d and JP2 were found to be significantly more prevalent among the participants and showed a positive correlation with increased PD and CAL, suggesting an association with the severity of AgP. Though CMV and EBV were also found to be associated with AgP, the results were insignificant. Females showed more association with disease severity than males, but the results were insignificant. There was a positive correlation between serotype d and JP2 with the periodontal status. CMV and EBV were also associated with the severity of AgP, but the results were insignificant. Further quantitative studies should prove the exact role of co- occurrence of serotypes with CMV and EBV and their effect on AgP.

The incidence of infection in tumor and eye fluid system, and specific humoral immunity to herpes viruses in patients with uveal melanoma

Studies aimed at a direct research of human herpes viruses (HHVs) in the tumor material and eye media have not been carried out so far. Research goal to establish the frequency of detection HHVs DNA in the biomaterial of the eye and blood and to assess the specific humoral immunity to the causative agents of herpes virus infections in patients with uveal melanoma. 38 patients with the uveal tract tumor were examined for the presence of DNA of HHV types 1 and 2 (HSV-1, 2), Cytomegalovirus (CMV), Varicella Zoster virus (VZV), EpsteinBarr virus (EBV) and herpes viruses 6 and 8 types (HHV-6, HHV-8) in tumor tissue, vitreous body, aqueous humour and blood plasma by real-time polymerase chain reaction; blood serum was studied by enzyme-linked immunosorbent assay (ELISA) for IgG and IgM antibodies to HHVs. EBV DNA was present in tumor tissue in 20.6% of cases, in vitreous body in 4.2%, in blood plasma in 2.7%, and was not found in aqueous humor. Ig G antibodies to HSV-1, 2 and CMV were detected in 97.3% of cases, VZV 94.6%, HHV-6 32.4%, antibodies to HHV-8 were not detected. 20 patients (55.6%) had reactivation of chronic HSV-1, 2 infection, and 14 (38.9%) patients had reactivation of CMV infection. Markers of chronic EBV infection were found in all patients, its atypical reactivation was observed in 2 cases (5.4%). Our findings suggest the possible participation of EBV in the oncogenesis of the uveal tract and emphasize the need for further in-depth study of this problem.

Herpesvirus and neurological manifestations in patients with severe coronavirus disease.

BackgroundCertain clinical manifestations of coronavirus disease (COVID-19) mimic those associated with human herpesvirus (HHV) infection. In this study, we estimated the prevalence of herpesvirus in patients with COVID-19 and determined if coinfection is associated with poorer outcomes and neurological symptoms.MethodsWe analyzed samples of 53 patients diagnosed with COVID-19. The samples were evaluated for the presence of alphaherpesviruses, betaherpesviruses, and gammaherpesviruses, and the viral loads were quantified using quantitative polymerase chain reaction (qPCR) method.ResultsAmong the patients, in 79.2% had detection at least one type of herpesvirus. HHV-6 (47.2%), cytomegalovirus (43.3%), and HHV-7 (39.6%) showed the highest detection rates. Patients with a high severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) load were more likely to show herpes simplex virus 1 detection (p = 0.037). Among patients coinfected with SARS-CoV-2 and HHVs, 26.4% showed central nervous system-associated neurological symptoms and herpetic manifestations. A statistically significant association was observed between neurological changes and HHV-6 detection (p = 0.034).ConclusionsThe findings showed a high prevalence of herpesvirus in patients with COVID-19. Furthermore, even though SARS-CoV-2 and HHV coinfection was not associated with poorer outcomes, the findings demonstrated the association between neurological symptoms and HHV-6 detection.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12985-022-01828-9.

Herpesviruses in patients after renal transplantation

To estimate graft function after kidney transplantation during active herpesviruses or superinfection Materials and methods. The study included 32 patients (men 21, women 11) with end-stage chronic kidney disease. The median age was 43 years. Cytomegalovirus (CMV), EpsteinBarr virus (EBV) and human herpes virus 6 (HHV-6) DNAs were screened by RT-PCR in the donor's transplant biopsy, and recipients peripheral blood and urine after kidney transplantation (KT) on 0, 1, 2, 4, 6, 12 months. Antiviral antibodies (IgM and IgG) were also screened by Enzyme-linked immunoassay analysis (ELISA) along with PCR. The 500 or less copies of viral DNA per 105 nuclear cells or 1 ml of urine was considered as low, more than 1000 copies high. On the first month after KT CMV DNA was detected in 50% of pts., EBV DNA in 40% and HHV-6 DNA in 33%. During first year after KT two or three viruses simultaneously were found in 12 recipients: CMV, EBV, and HHV-6 were detected in 5 recipients; CMV and EBV in 4 patients; CMV and HHV-6 in 2 pts; EBV and HHV-6 in 1 pt. Graft dysfunction was observed in 9 patients with a high concentration of viral DNA of one, two or three viruses simultaneously. An upraise of the concentration of virus DNA (CMV, EBV and HHV 6) was detected primarily in the urine, while in the blood its concentration was less than 500 cop or undetectable. Renal dysfunction was not observed on the background of low concentrations of viral DNA in urine and blood. However, with an increase of DNA concentration, an impaired graft function in 8 of 12 patients appeared. Low viral DNA level proved to be a background for another virus activation or bacterial/fungal superinfection. Graft dysfunction occurs at high viral DNA levels detection during mono-or superinfection. Low viral load can serve as a background for another virus activation and/or bacterial/fungal superinfection.

Oral shedding of herpesviruses and clinical outcomes in hematopoietic stem cell transplant patients.

To characterize the oral shedding of herpes viruses in patients who underwent allogeneic hematopoietic stem cell transplantation (alloHSCT) and investigate its relationship with clinical outcomes. Polymerase chain reaction and enzymatic digestion were performed to identify the oral shedding of the members of the Herpesviridae family in 31 patients. The samples were collected from the oral cavity at five timestamps. The presence of each herpesvirus in the oral cavity was observed in 3.2%, 12.9%, 19.3%, 32.2%, 54.8% and 93.5% patients for human herpesvirus (HHV)-6A, herpes simplex virus-1, HHV-6B, cytomegalovirus (CMV), Epstein-Barr virus (EBV) and HHV-7, respectively. Oral shedding of herpes virus was not uncommon after alloHSCT. There was a statistically significant association between the EBV and CMV oral shedding at C1 and the cumulative incidence of acute graft-versus-host disease (aGVHD). The results suggested that the presence of HSV-1 at C2 was related to a relapse. The HHV-7 oral shedding at C2 suggests a possible link between relapse, progression-free survival and overall survival of the patients. Patients who developed aGVHD showed higher CMV and EBV shedding in the oral cavity at aplasia, suggesting modifications to the pattern of immune cell response and inflammatory microenvironment.

Oral shedding of CMV and HSV-1 in hematopoietic stem cell transplantation patients.

To evaluate the oral shedding of herpesviruses in patients undergoing hematopoietic stem cell transplantation (HSCT) and correlate it with oral mucositis (OM). Saliva samples were collected before the HSCT and on day D+8. Multiplex Polymerse Chain Reaction (PCR) was performed to detect herpes simplex virus (HSV)-1 and HSV-2, Epstein-Barr virus (EBV), Cytomegalovirus (CMV), Variella-zoster virus (VZV), and human herpesvirus (HHV)-6, HHV-7, and HHV-8. OM was assessed according to WHO criteria. Thirty one patients were enrolled, in which 20 of 31 (64.5%) were males; median age was 50 (21-70) years; 16 of 31 (51.6%) underwent allo-HSCT; and 15 of 31 (48.4%) underwent auto-HSCT. On D+8, OM grades III and IV were observed in 8 of 31 (25.8%) patients. In the first salivary collection, EBV was found in 24 of 31 (77.4%), followed by HHV-6 (7/31, 22.6%) and HHV-7 (8/31 25.8%). In the second collection, EBV was found in 24 of 27(89%), followed by HSV-1 (8/27, 30%) and CMV, HHV-6, and HHV-7 (5/27, 18.5%, each one). On D+8, OM grades II and IV were associated with the presence of HSV-1. HSV-1 was also associated with worsening degrees of OM on D+15. The presence of HSV-1 and CMV in oral samples was more frequent on day D+8 after HSCT. HSV-1 detection was associated with severity and worsening of OM. HSV-1 and CMV seem to be associated with oral dysbiosis due to HSCT.

Prevalence of seropositivity of selected herpesviruses in patients with multiple sclerosis in the North of Jordan

BackgroundMultiple sclerosis (MS) is a neurological disease that is caused by an autoimmune response that results in the neuron’s demyelination in the central nervous system. The exact etiology of MS is not clear; however, several environmental and genetic factors are believed to participate in its initiation and development, including exposure to viruses. This study aims to investigate the association between the seropositivity and antibody titer of selected herpesviruses and MS in Jordanian MS patients.MethodIn this study, 55 MS patients and 40 age- and gender-matching apparently healthy volunteers were recruited from two main hospitals in the north of Jordan. MS patients were grouped into three types of MS based on the clinical presentation of the disease. Blood samples were collected from the participants and the IgG antibodies for human herpesvirus 6 (HHV-6), Epstein-Barr virus (EBV) nuclear antigen (EBNA), EBV viral capsid antigen (VCA) and varicella-zoster virus (VZV) were assayed by ELISA. The prevalence of seropositivity and the antibody level for each of the antibodies were compared between MS patients and controls and between the three types of MS.ResultsThere was no significant difference in the prevalence of seropositivity and in the levels of antibodies for HHV-6, EBNA and VCA between MS patients and controls and between the three types of MS. In contrast, the number of seropositive patients and the level of IgG antibodies for VZV were significantly higher in MS patients compared to the control.ConclusionThis study showed that patients with MS in the north of Jordan were more likely to be seropositive for VZV than the general population. Based on this finding, we recommend further studies to evaluate the seropositivity to VZV to be carried out in other parts of Jordan and the greater middle east to find out if there is a correlation between MS and previous infection with VZV.

Periodontal disease and detection of human herpesviruses in saliva and gingival crevicular fluid of chronic kidney disease patients.

Patients with chronic kidney disease (CKD) have inability to maintain the normal levels of protein metabolism products, blood pressure and hematocrit. Periodontal disease involves an inflammatory destructive process. Identification of opportunistic viruses is extremely important as they are associated with co-morbidities. The objective of this study was to analyse the presence of human herpesviruses in saliva and gingival crevicular fluid (GCF) from patients with CKD. One hundred and thirty one individuals were divided depending on the stage of CKD: Group 1 (clearance of creatinine>75mL/min) patients with no renal disease (n=24); Group 2 (clearance of creatinine of 11-75mL/min) patients with renal disease (n=67); Group 3 (clearance of creatinine<10mL/min) patients on hemodialysis (n=40). The parameters of periodontal disease were evaluated. The viral detection was assessed by PCR. considering the three groups, the prevalence of herpes simplex virus 1 (HSV-1) were 9% in saliva and 5% in GCF; Epstein-Barr virus 36% in saliva and 39% in GCF; human cytomegalovirus (HCMV) 11% in GCF; varicella zoster virus 6% in saliva and 3% in GCF; of human herpesvirus-6 (HHV-6) 6% in saliva and 2% in GCF; and HHV-7 44% in saliva and 8% in GCF. Of these patients, 46.48% presented with severe periodontitis. A statistically significant association between HSV-1 and HCMV was found in hemodialysis patients and severe periodontitis was also more frequent among them. These findings show the importance of evaluating the periodontal disease and detecting herpesviruses in patients with CKD as the inflammatory process observed in these clinical conditions may worsen the course of both periodontal disease and CKD.

Herpesviruses in the oral cavity of patients subjected to allogeneic hematopoietic stem cell transplantation and its relationship with oral mucositis.

This study was performed to characterise oral shedding of herpesviruses in patients who underwent allogeneic hematopoietic stem cell transplantation (alloHSCT) and to investigate its relationship with oral mucositis (OM). PCR and enzymatic digestion were conducted to identify oral shedding of herpesviruses and its correlation with OM development in 31 patients. The samples were collected at three sites in the oral cavity and at 5 times during follow-up; two additional collections were made from patients who developed ulcerative OM. HSV-1, EBV, CMV, HHV-6A, HHV-6B, and HHV-7 were detected in 4.97%, 16.02%, 4.41%, 2.20%, 3.31%, and 68% of the oral mucosal samples, respectively; 4.41%, 16.57%, 5.52%, 2.20%, 5.52%, and 63.53% of supragingival samples, respectively, and 4.41%, 18.23%, 2.76%, 1.65%, 2.75%, and 35.91% of subgingival samples, respectively. OM was diagnosed in 13 patients. The presence of HHV-7 in C1 (oral mucosa: p = 0.032) and C2 (supragingival: p = 0.009; subgingival: p = 0.002) was significantly increased in patients who developed OM, and patients exhibiting HHV-7 shedding in the oral cavity were 3.32-fold more likely to develop OM. Patients who developed OM showed higher HHV-7 shedding in the oral cavity at nadir (immediately prior to OM development), suggesting modifications to the inflammatory microenvironment. HHV-7 may be involved in oral dysbiosis in HSCT-related OM; enhanced understanding of its role in the pathogenesis of OM may lead to the development of strategies for managing and preventing this common side effect of alloHSCT.

Seroprevalence to herpesviruses in patients with primary brain gliomas

Purpose of the study . The purpose of the study was to assess the level of seroprevalence and the frequency of detection of serological markers of acute herpesvirus infection in patients with PGBT in comparison with those in patients with chronic non-tumor diseases. Materials and methods . Before conducting antitumor therapy, the blood serum of 42 patients with PGBT (the main group) was studied. The comparison group consisted of 137 patients with chronic non-tumor diseases. Antibodies of classes M and G to herpes simplex virus types 1, 2 (HSV-1,2), cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpes virus type 6 (HHV-6) were determined by ELISA using JSC Vector-Best reagent kits. Results . Among patients with PGBT, seropositive for HSV-1,2 were 95.2%, CMV — 92.9%, EBV — 100%, HHV-6-40.5% of patients. No statistically significant differences in seroprevalence and the presence of markers of acute infection (IgM) were found either in comparison with non-tumor diseases or depending on the malignancy grade. Antibodies to HSV-1,2, CMV and EBV in patients with gliomas were significantly more often found in the medium range, and in the comparison group — in the high values of coefficient of positivity (CP) for IgG. In all the studied groups, antibodies to HHV-6 were determined statistically significantly less frequently than to other herpes viruses. Conclusion . The absence of statistically significant differences in seropositivity between groups of patients and their presence between pathogens is most likely a reflection of general trends in the population, and the question of the involvement of various representatives of the Herpesviridae family in neuro-oncogenesis of primary glial brain tumors still remains open.

Frequency of Type 8 Human Herpes Virus in Patients with Pemphigus Vulgaris in Tabriz Sina Hospital since 2016-2017

Background: Pemphigus vulgaris is the most common form of autoimmune vesiculobullous skin disease. Human herpesvirus-8 (HHV-8) has a well-known association with Kaposi's sarcoma. Considering the reports about the incidence of Kaposi's sarcoma in patients with pemphigus and bolus pemphigoid without evidence of HIV infection, this study was designed to investigate the presence of HHV-8 in patients with pemphigus. Methods: In this cross-sectional and descriptive-analytic study, 27 patients with newly diagnosed pemphigus vulgaris were selected. The control group included 27 patients with benign non- vesiculobullous skin lesions. IHC (Immunohistochemistry) staining was performed to detect HHV-8 in tissue samples taken from skin lesions or mucosal lesions in both groups. Results: IHC showed HHV-8 in 12 patients in case group with pemphigus vulgaris (44.4%) and 9 patients in control group (33.3%) (P=0.402). Conclusion: Although HHV-8 prevalence was higher in Pemphigus vulgaris patients, this difference was not statistically significant, and there is unlikely to be a causal relationship between HHV-8 and Pemphigus.

Polymerase chain reaction for the diagnosis of herpesvirus infections in dermatology : Analysis of clinical data.

SummaryBackgroundRapid identification of human herpesviruses from lesion swabs is necessary for timely initiation of antiviral treatment, especially with infections involving neonates and immunocompromised individuals. The aim of the study was to investigate the results of an in-house polymerase chain reaction (PCR) test for herpesviruses in patients with symptoms suggestive for a herpesvirus infection.Patients and methodsIn this single center retrospective study the results of 3677 lesion swab specimens tested for human herpes simplex virus 1 and 2 (HSV 1 and 2) and varicella zoster virus (VZV) were analyzed in the context of data sheets giving details of the suspected diagnosis, medical history as well as the demographic data of the patients. The PCR procedures for cytomegalovirus (CMV), Epstein-Barr virus (EBV) and human herpes virus 8 (HHV-8) were applied on special occasions.ResultsOf the samples 3369 (91.6%) were swabs and a minority were tissue or blood samples. Of the 3015 samples tested for HSV‑1, HSV‑2 and VZV concomitantly, 52.3% were positive for at least one of these viruses. Clinically distinct conditions, such as herpes zoster and varicella had a high rate of positive PCR results, ranging from 81% to 88%, respectively. Among HSV‑2 positive samples, 23.7% derived from human immunodeficiency virus (HIV) positive patients, in contrast to the 10.8% originating from immunocompetent patients, the difference being statistically significant (p < 0.002). The HSV‑2 was detected more often in women than in men.ConclusionDistinct clinical diagnoses have a high correlation rate with positive PCR results. A significantly higher number of HSV‑2 positive results were found in HIV positive patients and in women.

Clinical Infections by Herpesviruses in Patients Treated with Valproic Acid: A Nested Case-Control Study in the Spanish Primary Care Database, BIFAP

The objective of this study is to evaluate the risk of clinical infections by herpesviruses in patients exposed to valproic acid (VPA). We performed a case-control study nested in a primary cohort selected from the Spanish primary care population-based research database BIFAP (Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria) over the period 2001–2015. The events of interest were those diseases caused by any herpesviruses known to infect humans. For each case, up to 10 controls per case matched by age, gender, and calendar date were randomly selected. A conditional logistic regression was used to compute adjusted odds ratios (OR) and their 95% confidence intervals (95% CI). Current use of VPA was associated with a trend towards a reduced risk of clinical infections by herpesviruses as compared with non-users (OR 0.84; CI 95% 0.7–1.0; p = 0.057). Among current users, a trend to a decreased risk with treatment durations longer than 90 days was also observed. The results show a trend to a reduced risk of clinical infection by herpesviruses in patients exposed to VPA. These results are consistent with those in vitro studies showing that, in cultured cells, VPA can inhibit the production of the infectious progeny of herpesviruses. This study also shows the efficient use of electronic healthcare records for clinical exploratory research studies.

Reactivation of herpesvirus in patients with hepatitis C treated with direct-acting antiviral agents.

BackgroundWe performed a case-series analysis of reactivation of herpesvirus in patients with hepatitis C virus (HCV) infection treated with direct-acting antiviral (DAA) agents.MethodsEight cases were detected among 100 treated patients with DAA regimens in Qena University Hospital from June 2016 to June 2017. Herpesvirus was reactivated in eight patients who received DAA therapy. None of the cases had risk factor for herpes zoster reactivation.ResultsThe DAA regimens used were sofosbuvir/daclatasvir in six cases and sofosbuvir/ledipasvir in two cases. Immune changes that follow HCV clearance might lead to reactivation of other viruses, such as herpesvirus.ConclusionPatients with HCV infection suspected of having herpesvirus infection should be treated promptly.

Clinical Results and Utility of Herpesviruses Multiplex Polymerase Chain Reaction: Assessment of Aqueous Humor Samples From Patients With Corneal Endotheliitis and High Intraocular Pressure.

The main purpose of this study was to evaluate herpesvirus infection in patients with corneal endotheliitis and high intraocular pressure (IOP) using multiplex polymerase chain reaction (PCR) in aqueous humor samples. This was a retrospective, observational study of immunocompetent patients living in South Korea. Eligible subjects had typical corneal endotheliitis with an IOP≥21 mm Hg or required antiglaucoma medication. Multiplex PCR was performed using aqueous humor samples obtained at first visit to detect the DNA of 6 herpesviruses. Forty-two eyes from 42 patients with >6 months' follow-up were analyzed. Of these, 16 were herpesvirus-positive: 3 herpes simplex virus 1, 3 varicella-zoster virus, 9 cytomegalovirus, and 1 Epstein-Barr virus. Eyes with coin-shaped or fine keratic precipitates (kps), high IOP, and a low baseline endothelial cell count were more likely to show a positive result on multiplex PCR. Univariate analysis showed that male sex (P=0.014), a previous history of uveitic glaucoma (P=0.048), and the presence of fine kps (P=0.031) were significantly associated with a positive PCR result. On multivariate analysis, male sex (P=0.010) and a previous history of uveitic glaucoma (P=0.031) showed a significant positive association. Cytomegalovirus was the most commonly detected herpesvirus in patients with corneal endotheliitis and high IOP. A positive PCR result was seen more frequently in male individuals and patients with fine kps or a history of uveitic glaucoma.

Herpesvirus Infections in Patients Treated with the Mood Stabilizer Valproic Acid: A Nested Case-Control Study in the Spanish Primary Care Database, BIFAP

Purpose: The objective of this study is to evaluate the risk of infections for herpesviruses in patients exposed to Valproic acid and derivatives (VPA) in the Spanish research database BIFAP. Methods: We performed a case-control study nested in a primary cohort selected from the Spanish primary care population-based research database BIFAP over the period 2001 to 2015. The events of interest were those diseases caused by any of the herpesviruses known to infect humans, specifically. For each case, up to 10 controls per case matched by age, gender and calendar date were randomly selected using risk set sampling. A conditional logistic regression was used to compute adjusted odds ratios (OR) and their 95% confidence intervals (95%CI) for infection for herpesviruses associated to the use of VPA after adjusting for potential confounders. Results: Current use of VPA was associated with a trend towards a reduced risk of infection by herpesviruses as compared to non-users (OR 0.84; CI95% 0.7-1.0), being these differences marginally significant (p=0.053). Among current users, a trend to a decreased risk with treatment durations longer than 90 days was also observed. Conclusions: The results of this study show a trend to a reduced risk of infection for herpesviruses in patients exposed to VPA, especially in those with treatment durations longer than 90 days. These results are consistent with in vitro studies showing that, in cultured cells, VPA inhibits the production of infectious progeny of different enveloped viruses causing relevant human and veterinary diseases, including herpesviruses. Funding Statement: Work at Centro de Biologia Molecular Severo Ochoa was supported by grants from the Spanish Ministerio de Economia y Competitividad (AGL2014-52395-C2-1-R and AGL2017-84097-C2-1- R), and by an institutional grant from the Fundacion Ramon Areces and Banco Santander Central Hispano. Work at INIA (MAM-A) was supported by grant AGL2014-56518-JIN. Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The scientific committee of BIFAP granted a positive opinion to the study protocol (#08/2015). The investigators had access to only fully anonymized data, and under this condition, no specific ethics review was required according to Spanish law.

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-1β, IL-2, IL-4, IL-6, MCP-1, MIP-1α, MIP-1β, 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-1β (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-1β and TNF-α in saliva.