[Complex treatment of recurrent herpetic stomatitis with dysbiosis]. / Analiz kompleksnoi metodiki lecheniia retsidiviruiushchego gerpeticheskogo stomatita s disbakteriozom.

Research objective was to study the effectiveness of complex treatment of recurrent herpetic stomatitis with dysbiosis. The study included 147 patients aged from 18 to 45 years with recurrent herpetic stomatitis (RGS) and disbyosis divided in 3 groups. Group 1 received conventional antiviral and symptomatic treatment of RGS, in group 2 complex immunoglobulins (IgA (15-25%), IgM (15-25%) and Ig (50-70%)) were added to conventional therapy, group 3 received immunoglobulins only. Clinical and immunological efficiency was estimated by values of oral local immunity (SlgA, lysozyme), humoral immunity (IgE and IgG) and cellular immunity (RBTL with FGA, defined T-lymphocytes). Significant (p<0.05) increase of lisozyme and SlgA, RBTL with FGA, number of T-lymphocytes and IgG concentration was observed in group 2. The obtained data allow improving quality of treatment of recurrent herpetic stomatitis with related dysbiosis.

[Prevention of the recurrent herpetic stomatitis in employees of Kazan city industrial enterprises frequently suffering from acute respiratory viral infections]. / Profilaktika retsidiviruyushchego gerpeticheskogo stomatita u rabotnikov promyshlennykh predpriyatii goroda Kazani, chasto boleyushchikh ostrymi respiratornymi zabolevaniyami.

Research objective was to study the efficacy of ingavirin for prevention of recurrent herpetic stomatitis in employees of Kazan city industrial enterprises frequently suffering from acute respiratory viral infections. 128 employees aged from 18 to 56 years were included in the study. Clinical and immunological efficiency of ingavirin prevention of recurrent herpetic stomatitis is proved by estimation of oral cavity local immunity (SlgA, lisozyme), humoral immunity (IgE and IgG) and cellular immunity (RBTL with FGA, defined T-lymphocytes). After administration of ingavirin significant (p<0.05) increase of lisozyme and SlgA, RBTL with FGA, number of T-lymphocytes and IgG concentration was observed. The obtained data allow to recommend ingavirin for prevention of recurrent herpetic stomatitis.

Frequency of Oral Mucositis and Local Virus Reactivation in Herpes Simplex Virus Seropositive Children with Myelosuppressive Therapy.

BACKGROUND: Oral mucositis (OM) is a common chemo- and radiotherapy adverse effect in oncological pediatric patients. Herpes simplex virus (HSV) infection can cause a severe clinical course. We hypothesize, that HSV seropositivity is a risk factor for local HSV-1 reactivation and increased frequency of OM in patients with myelosuppressive therapies. PATIENTS AND METHOD: We evaluated the prevalence of seropositivity of HSV-1 between June 2011 and April 2014 in patients with potential oncological disease and correlated it to the frequency of OM and local viral reactivation in OM under myelosuppressive therapy. RESULTS: The overall rate of HSV-seropositivity in our cohort was 22%. 48 patients underwent myelosuppressive therapy. Of these, 7 were HSV-1 IgG positive and 41 negative. All patients with OM under myelosuppressive therapy and positive local swab for viral HSV (l-PCR) were HSV-1 IgG positive before the start of therapy (100%). The absolute risk for OM in HSV-1 IgG positive patients was increased by 58.5% (95%CI: 20.0 - 72.2%) corresponding to a relative risk (RR) of 2.4 (95%CI: 1.7-3.5, P=0.009). The multivariable adjusted OR to suffer 2 or more OM episodes in HSV-1 IgG positivity was 8.8 (95%CI: 1.5-95.8, P=0.014). DISCUSSION AND CONCLUSION: In HSV-1 IgG positive patients half of the OM episode showed HSV reactivation, and the risk for multiple OM episodes was increased. These patients should be investigated for HSV-infection in every OM episode. Prophylactic and preemptive therapeutic measures should be discussed early, but prospective data on HSV prophylaxis and preemptive treatment is required.

Striated muscle involvement in experimental oral infection by herpes simplex virus type 1.

Herpes simplex virus type 1 is one of the most frequent causes of oral infection in humans, especially during early childhood. Several experimental models have been developed to study the pathogenesis of this virus but all of them employed adult animals. In this work, we developed an experimental model that uses mice younger than 4 days old, to more closely resemble human infection. Mice were infected subcutaneously with the prototype strain McIntyre of Herpes simplex-1, and the progression of infection was studied by immunoperoxidase. All animals died within 24-72 h post-infection, while viral antigens were found in the oral epithelium, nerves and brain. The most striking result was the finding of viral antigens in the nucleus and cytoplasm of cells belonging to striated muscles. Organotypic cultures of striated muscles were performed, and viral replication was observed in them by immunocytochemistry, electron microscopy and viral isolation. We conclude that the infection of striated muscles is present from the onset of oral infection and, eventually, could explain some clinical observations in humans.

[State of local immunity in herpetic stomatitis patients].

It was set by us, that at intensifying of herpetic stomatititis of mucous membrane of oral cavity for patients the deficit of lysozyme and antibodies of class is marked A in the mixed saliva. At what the degree of expressed of the exposed violations of local immunity correlated with frequency of relapses of viral infection and its duration.

[The role of local immunity in chronic recurrent intraoral herpes].

Chronic recurrent herpetic stomatitis is an acute infectious disease caused by various types of herpes simplex virus. Patients showed various manifestations of immunodeficiency indicating that herpes infection as a disease of immune system. Our results confirm the influence of herpes on the state of the local immunity of the oral cavity. The correlation of the severity of chronic recurrent herpes sores and the amount of virus excreted allows determining the expected duration of the disease and treatment time.

[The evaluation of secretory immunity under herpetic affection of oral cavity].

The study is based upon the results of clinical laboratory examination of 33 patients with diagnosis of recurrent herpetic stomatitis. The control group included 26 healthy persons. In patients with manifestations of herpetic infection of mucous tunic of oral cavity the pronounced abnormalities of indicators of secretory immunity (lactoferrin, secretory immunoglobulin A) correlating with hygiene index are established. At the same time, indicator of antiviral immunity (alpha-interferon) characterized by absence of significant changes in this group of patients.

Effects of herpes simplex virus type 1 infection on immune functions of human neutrophils.

BACKGROUND AND OBJECTIVE: Herpesviruses may play roles in the development of periodontal diseases. This study analyzed the effects of herpes simplex virus type 1 (HSV-1) infection on neutrophil function. The effects of lipopolysaccharide (LPS) from the periodontal pathogen, Porphyromonas gingivalis, during HSV-1 infection were also determined. MATERIAL AND METHODS: Purified HSV-1 was pretreated with buffer containing no serum, with HSV-1 immunoglobulin G (IgG)-positive serum (HSV-1 antiserum) or with control serum. Neutrophils were mock-infected or infected with the pretreated HSV-1. Viral binding and phagosome formation were detected using immunostaining. Intracellular reactive oxygen species (ROS) were determined using 2',7'-dichlorofluorescin diacetate and fluorometry. Leukotriene B(4) (LTB(4)) and interleukin-8 (IL-8) were detected using enzyme immunoassays. Release of matrix metalloproteinase-9 (MMP-9) was examined using gelatin zymography. Phosphorylation of Akt/glycogen synthase kinase-3 (GSK-3) was determined using western blotting. RESULTS: HSV-1 bound directly to neutrophils and enhanced the release of MMP-9. HSV-1 immune complexes, formed in the HSV-1 antiserum, bound neutrophils and induced the formation of early phagosome more effectively than did HSV-1 alone. The relative levels of ROS and phosphorylation of Akt/GSK-3 were increased significantly in neutrophils after infection with HSV-1 immune complexes. Infection with HSV-1 and HSV-1 immune complexes also stimulated the production of inflammatory mediators, LTB(4) and IL-8. Moreover, LPS enhanced the HSV-1-stimulatory production of IL-8. CONCLUSION: This study demonstrated differences in neutrophils infected with HSV-1 alone or with HSV-1 immune complexes, suggesting that opsonization of HSV-1 might enhance its effects on neutrophils. The in vitro findings suggest that HSV-1 infection may induce the inflammatory response and affect periodontal health.

[Improvement of treatment of inflammatory diseases in oral cavity].

In order to determine the anti-pathogenic clinical efficacy of cycloferon liniment in the combined treatment of herpetic stomatitis and periodontitis, medical examination and treatment of these disorders have been carried out in a group of 80 patients. It is established that the use of cycloferon liniment in the combined treatment of herpetic stomatitis and periodontitis decreases the infectious load in parodontal recess, reduces the manifestations of local inflammation, normalizes the immunity indices, and decreases the level of endogenous intoxication, which ensures the acceleration of recuperation processes and lowers the frequency of recurrences.

[Improvement of herpetic stomatitis therapy in patients with chronic tonsillitis].

To determine the clinicopathogenetic efficacy of cycloferon liniment in combined therapy of herpetic stomatitis, 60 patients with herpetic stomatitis and chronic tonsillitis were examined and treated. It was shown that the use of cycloferon liniment in the combined therapy of herpetic stomatitis in the patients with chronic tonsillitis allowed to lower the infection load in the parodontal recesses and the local inflammation, to normalize the immunity indices and to reduce the level of the endogenous intoxication, that provided acceleration of the recuperation processes and decreased the frequency of stomatitis backsets.

Immunodominant epitopes in herpes simplex virus type 2 glycoprotein D are recognized by CD4 lymphocytes from both HSV-1 and HSV-2 seropositive subjects.

In human recurrent cutaneous herpes simplex, there is a sequential infiltrate of CD4 and then CD8 lymphocytes into lesions. CD4 lymphocytes are the major producers of the key cytokine IFN-gamma in lesions. They recognize mainly structural proteins and especially glycoproteins D and B (gD and gB) when restimulated in vitro. Recent human vaccine trials using recombinant gD showed partial protection of HSV seronegative women against genital herpes disease and also, in placebo recipients, showed protection by prior HSV1 infection. In this study, we have defined immunodominant peptide epitopes recognized by 8 HSV1(+) and/or 16 HSV2(+) patients using (51)Cr-release cytotoxicity and IFN-gamma ELISPOT assays. Using a set of 39 overlapping 20-mer peptides, more than six immunodominant epitopes were defined in gD2 (two to six peptide epitopes were recognized for each subject). Further fine mapping of these responses for 4 of the 20-mers, using a panel of 9 internal 12-mers for each 20-mers, combined with MHC II typing and also direct in vitro binding assay of these peptides to individual DR molecules, showed more than one epitope per 20-mers and promiscuous binding of individual 20-mers and 12-mers to multiple DR types. All four 20-mer peptides were cross-recognized by both HSV1(+)/HSV2(-) and HSV1(-)/HSV2(+) subjects, but the sites of recognition differed within the 20-mers where their sequences were divergent. This work provides a basis for CD4 lymphocyte cross-recognition of gD2 and possibly cross-protection observed in previous clinical studies and in vaccine trials.

Erythema Nodosum: As an Extraintestinal Manifestation or Complication in Ulcerative Colitis?

In our case, we want to highlight the importance of screening for opportunistic infectious diseases in these immunosuppressed patients. We present the case of an erythema nodosum triggered by reactivation of Herpes Simplex Virus (HSV) in a patient with ulcerative colitis.

Herpes Simplex Virus Type 1 and Host Antiviral Immune Responses: An Update.

Herpes simplex virus type 1 (HSV-1) infection activates a rapid stimulation of host innate immune responses and a delicate interplay between virus and host immune elements regulates the whole events. Although host immune elements play well in limiting the HSV-1 infection by interfering viral replication, they are still unable to remove the virus completely, because HSV-1 proteins are efficient enough to bypass the host antiviral immune responses and virus succeed to reactivate again from latency at opportune time. Type 1 interferon signaling pathway is the central point of innate immunity along with some of the activated neutrophils, monocytes, macrophages, and dendritic cells, and some natural killer cells play role, while the CD8+ T cells are crucial in adaptive immunity. In this review, the current knowledge of host and HSV-1 interaction has been described that how the host antiviral immune responses occur and what are the mechanisms of viral evasion adapted by virus to counteract with both arms of immunity.

A comparative study between viral isolation and indirect immunofluorescence in the diagnosis of herpes simplex virus.

Fifty patients with oral ulcers were studied clinically and investigated for the detections of Herpes Simplex Virus (HSV) through virus isolation from their lesions (vesicles and ulcers) and detection of the presence of antiviral antibodies (both, IgM and IgG) in their sera using the indirect immunofluorescene (IIF) technique. The results of this study proved that virus isolation is the most reliable method for diagnosis, though the use of antibody serological tests could be a useful adjunct to virus isolation in situations where a rapid laboratory diagnosis is needed. Oral Herpes Simplex virus infection can be viewed, in the main, as a trivial disorder causing patients minor physical discomfort. The prevalence of HSV may be high in innocent infections, as high as 1/3 of the population. However, HSV infection and its complications with troublesome recurrences may make the problem worse. The apparent increase in HSV infection over recent years may be partly due to increased publicity about the disease, the current antiviral treatment, the inclusion of both primary and recurrent cases in clinic follow up and the increased use of viral cultures for diagnosis. The aim of this work is to share in the study of the detection of HSV through virus isolation and detection of antiviral antibodies using IIF technique, as well as the evaluation of the diagnosis by the above mentioned methods.

[Efficacy study of immunomodulator Gepon in treatment of oral membrane diseases in patients with complications in the form of filling material extrusion into mandibular canal].

Experience in new domestic immunomodulator Gepon application in practice of treatment of virus diseases and their manifestations in oral cavity of patients with complications in the form of filling material extrusion into mandibular canal is submitted. In a combination to traditional techniques of the treatment the preparation has shown high efficacy.

Oral ulcers in children under chemotherapy: clinical characteristics and their relation with Herpes Simplex Virus type 1 and Candida albicans.

OBJECTIVE: The objective of this study was to determine the clinical characteristics of oral ulcers in pediatric oncology patients undergoing chemotherapy and their relation with the presence of Herpes Simplex Virus (HSV) type 1 and Candida albicans. STUDY DESIGN: The sample consisted of 20 ulcerative lesions from 15 children treated with chemotherapy in the Pediatric Service of the Regional Hospital of Concepción, Chile. Two calibrated clinicians performed clinical diagnosis of the ulcers and registered general data from the patients (age, general diagnosis, absolute neutrophil count, and number of days after chemotherapy) and clinical characteristic of the ulcers: number, size, location, presence or absence of pain and inflammatory halo, edge characteristics, and exudate type. Additional to clinical diagnosis, culture for Candida albicans (C) and polymerase chain reaction (PCR) for Herpes Simplex Virus type 1 was performed. RESULTS: Ten ulcers occurred in patients with acute lymphoblastic leukemia, five in patients with acute myeloblastic leukemia and five in patients with other neoplastic diseases. Eight ulcers were HSV (+) / C (-), 6 HSV (-) / C (-), 4 HSV (+) / C (+) and 2 HSV (-) / C (+). Preferential location was the hard palate. Most lesions were multiple, painful, with inflammatory halo, irregular edges and fibrinous exudate. The average size was 6,5 millimeters, and the mean number of days after chemotherapy was 7.5 days. CONCLUSIONS: Oral ulcers in children with oncological diseases did not present a specific clinical pattern. They were strongly associated with HSV.

Oral recrudescent herpes simplex virus infection.

OBJECTIVE: The objective of this study is to determine the frequency of involvement of different intraoral sites by oral recrudescent herpes simplex virus in immunocompromised patients and whether keratinized intraoral sites are always affected by this virus. STUDY DESIGN: The records of 30 hospitalized patients who had oral ulcers culture positive for herpes simplex virus were reviewed for the location of oral ulcers, febrile episodes, and medical diagnoses. RESULTS: The data revealed that oral recrudescent herpes simplex virus may involve any intraoral site in immunocompromised patients with nonkeratinized sites representing approximately half of all sites; this is more frequent than has been previously reported. Twenty-six (86.7%) of 30 patients had no evidence of herpes labialis, and 13 (43.3%) of 30 patients were afebrile. CONCLUSION: It is recommended that all oral ulcers, in immunocompromised patients should be cultured for herpes simplex virus regardless of their location. Early diagnosis reduces patient morbidity because effective treatment in the form of acyclovir is readily available.

Clinical and immunological evaluation of oral ribavirin administration in recurrent herpes simplex infections.

A total of 38 out-patients with recurrent oral or genital Herpes simplex virus infections received either oral ribavirin (800-1600 mg/day for 7 days) or placebo following a randomized and balanced protocol. Clinical and laboratory parameters, including haematological, metabolic and immunological tests, were checked in order to estimate tolerance to and efficacy of ribavirin on recurrent Herpes simplex virus infection and on the number of recurrences during the 12 months following treatment. Ribavirin showed definite superiority in the treatment of recurrent Herpes simplex virus 1, when compared to placebo, its efficacy being enhanced if treatment is started as soon as possible after infection has started. No significant modification of the parameters used to assess tolerance was noted; moreover there was no modification of the immunological parameters evaluated.

Oral herpes simplex infections in patients with leukemia.

Thirty patients hospitalized for induction chemotherapy of acute leukemia were studied for incidence, severity, and clinical features of oral herpes simplex virus infections. In 50% of the patients with evidence of past herpes infection, recurrent oral herpes developed during the study. Herpes simplex virus was the major cause of oral mucosal lesions seen in patients with leukemia. A majority of the episodes involved multiple oral sites and caused large atypical lesions. All lesions healed after topical or intravenous acyclovir therapy. Herpes simplex infection should be ruled out in all cases of oral ulcers detected in patients being treated for leukemia.

Lymphoproliferative responses in recrudescent orofacial herpetic infections.

The relationship between antibody (Ab) and lympho-proliferative responses to herpes simplex virus (HSV) and recrudescent orofacial HSV lesions were investigated in 65 patients. All had HSV-specific Ab and cell mediated immune responses (CMIR) demonstrated by ELISA and in vitro lymphoproliferation respectively. Thirteen control subjects were negative in both tests. Thirty-three patients were repeatedly investigated for 6-38 months during which time they suffered 1-8 recrudescences. HSV-induced lymphoproliferation was depressed during recrudescences, rose to a peak several weeks later, and declined slowly to a background level. However, ELISA titres and lymphoproliferative responses to Concanavalin A (Con A) were high throughout and circulating peripheral blood mononuclear cell (PBMC) subsets did not change. Depressed lymphoproliferative responses to HSV antigen (Ag) during recrudescences were enhanced by removal of CD8+ cells from PBMC using either a panning technique or cell sorting; reconstitution of CD8+ cells suppressed the HSV-specific lymphoproliferative response. CD8+ cell depletion affected neither HSV-induced lymphoproliferation recrudescence, nor lymphoproliferative responses to another Ag (PPD) during recrudescence. Depressed HSV-induced lymphoproliferation during recrudescences might thus be due to CD8+ suppressor T cell (Ts) function rather than low numbers of circulating lymphocytes. Suppression or delay of normal CMIR to asymptomatic recurrent epidermal HSV infection by Ts might allow development of recrudescent HSV lesions.