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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.

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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.

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.

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., (© Georg Thieme Verlag KG Stuttgart · New York.)

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.

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., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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.

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.

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., (© 2012 John Wiley & Sons A/S.)

Aim and Objective: This study was carried out with the primary aim of correlating oral changes and general changes of HIV-infected patients with their CD4 count., Materials and Methods: 124 patients were selected, and after taking their informed consent, they were subjected to detailed history taking and thorough clinical examination. Specific oral lesions and general physical changes were recorded. Every patient was subjected to laboratory investigation for CD4 count. All these findings were tabulated. The clinical observation and laboratory findings were subjected to critical analysis and correlated. Statistical test, i.e. Student's " t" test, was applied and objective conclusions were drawn., Result: Out of 124 patients, 40 had oral candidiasis, 6 had oral hairy leukoplakia, 12 had periodontal disease, 20 had xerostomia, 30 had melanin pigmentation, while 4 had HSV2, and atypical ulceration. Out of 40 patients with oral candidiasis, 28 patients had CD4 count <200 (group A), 10 patients were in group, B (CD4 count 200-500 cell/mm 3 ) and 2 patients in group C(CD4 >500 cell/mm 3 ). Oral hairy leukoplakia occurred in equal proportions in group A and B. These periodontal diseases were more commonly in group B; xerostomia and melanin pigmentation was equally seen in group A and B., Conclusion: Oral candidiasis, oral hairy leukoplakia, linear gingival erythema, necrotizing ulcerative gingivitis, and necrotizing ulcerative periodontitis are specific oral indicators which will definitely suggest to the dental surgeon that the disease is running a rapid downhill course and due to this the oral physician is in a position to raise a suspicion and alert the general physician regarding the declining immune status of patient.

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.

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.

Background: Primary immune deficiencies of natural killer (NK) cells have been described in patients with a susceptibility to herpes infections., Aims: To assess the diagnostic utility of measurement of NK cytotoxicity in patients with recurrent oral herpes infections., Methods: A retrospective audit was carried out on results obtained over an 18-month period, from 28 NK cell cytotoxicity assays (24 patients; all with a history of recurrent oral herpes infections), and 24 control samples (three healthy donors). Percentage specific cytotoxicity (PSC) was determined by measurement of the percentage of K562 target cells lysed by NK cells after incubation, using the NK TEST. Comparison of PSC was made with reference ranges provided., Results: No patient with absent NK/NKT cells or NK cell cytotoxicity was identified (95% CI 0 to 14.8%). Two patients had persistently low PSC. Two patients with reduced PSC showed PSC within the normal reference range on repeat testing. Patient and control samples were seen both above and below the reference ranges. A relationship was expected between NK cell percentage and PSC; however this correlation was not significant (r(s)=0.29, p=0.18, 95% CI -0.14 to 0.63)., Conclusions: A deficiency of NK cell cytotoxicity has not been identified in this cohort. An apparent reduction in cytotoxicity may be due to normal interpersonal and intersample variability in NK cytotoxicity. Without reference ranges established from a large population of control samples to account for this, a reduction in PSC is difficult to define. Further studies are required to identify if a correlation exists between the percentage of NK cells and PSC.

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.

We present a case of serious treatment-refractory acyclovir- and foscarnet-resistant herpes simplex virus (HSV) type-1 orolingual infection that responded to oral cidofovir rinses after failure of acyclovir and foscarnet therapy. The use of 3% cidofovir in a saline rinse for refractory mucosal HSV infection appears promising but needs prospective evaluation.

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.

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.

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.

Microflora of oral cavity of people of 45-65 years with removable denture and children with acute herpetic stomatitis, its dependence upon the degree of local immunity, presence and severity of inflammatory process have been studied. Percentage of leucocyte subpopulations activity of bactericide enzymes of granulocytes, average anticolonization ratio, correlation of Gram-positive and Gram-negative bacteria, degree of colonization with Candida fungi have been determined is smear-simprints of mucous membrane. The intensity of growth of optional anaerobic microorganisms has been investigated in bacteriological studies of material taken from mucous membrane. Their identification has been performed using morphological-cultural and biochemical indices. Significant changes in microbiocenosis of oral cavity such as disappearance of autochthonous microflora, appearance and intensive growth of pathogenic and opportunistic microorganisms are to be observed in conditions of decrease of non-specific resistance and presence of inflammatory process in persons with removable denture and acute herpetic stomatitis.

The efficiency of licopide in combination with traditional treatment was evaluated in 59 children aged 1-14 years suffering from allergic diseases and relapsing herpetic stomatitis. Immunological studies were carried out before and after a course of therapy: local oral immunity, cellular immunity (in the blast transformation test with phytohemagglutinin), lymphocyte populations and subpopulations, humoral immunity values (IgA, IgM, IgG, and IgE), and C3 complement component were evaluated. The results indicate that licopide in complex with traditional methods normalized the immunological values, had a favorable impact on the course of relapsing herpetic stomatitis, and led to a stable remission of allergic diseases (p<0.001).

Clinical and immunological efficiency of leukinferone in combination with polyoxidonium (immunomodulator) was studied in patients with relapsing herpetic stomatitis (RHS). The levels of alpha- and gamma-IFN were decreased, levels of IgM, IgG, and IgE were increased, active oxygen forms were actively produced, and the count of CD8(+)-cells was increased in patients with RHS. Treatment with polyoxidonium and leukinferone led to an increase of the blood levels of alpha- and gamma-IFN, decrease of IgM, IgG, and IgE levels, normalization of phagocytosis, and decrease of CD8(+)-cell count. The treatment had a pronounced clinical effect in patients with RHS of any severity, which indicates the efficiency of these drugs in combined therapy of patients with RHS.

Oral manifestations often found in HIV-infected children are frequently the first clinical sign of the infection. This article aims to report the prevalence of oral manifestations in soft tissues and their relationship with the degree of immunosuppression in 80 HIV-infected patients (average age 6.30 +/- 3.32 years old) at the IPPMG-UFRJ. Thirty children (38%) presented some type of oral lesion and the percentage of CD4 was lower than that found in lesion-free children (p < 0.05); 22.5% presented candidiasis, 17.5% gingivitis, 8.8% enlargement of parotids, 1.3% herpes simplex and 1.3% hairy leukoplakia. Of the 30 children with lesions, 70% showed severe immunosuppression, 23.3% moderate immunosuppression and in only 6.7% was immunosuppression absent. Oral manifestations were directly related to the degree of immunosuppression and such lesions can be considered as indicators of the progression of the HIV infection in children.

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.

Lymphotropic therapy with trental was administered to patients with chronic herpetic stomatitis. Trental was injected near the mastoid process after preinjection with lidase (total dose no more than 1 ml on each side, 6 sessions per course). The treatment normalized the immune status, clinical symptoms regressed sooner than after treatment with an antiviral agent bonafton, remissions were prolonged, and in 5 out of 18 patients no more relapses occurred.

Two immunocompromised patients with herpetic geometric glossitis, a clinically distinctive form of lingual herpes simplex virus (HSV) type 1 infection, are described. The significant features of herpetic geometric glossitis are summarized, the clinical differential diagnosis of this form of HSV infection is reviewed, and the possible pathogenesis of these lingual lesions is discussed. Both of our patients, as well as all previously described patients with this condition, had extremely painful cross-hatched, branched, and/or linear fissures on the dorsal aspect of the tongue. Symptoms promptly resolved within 1 to 2 days, and the fissures subsequently healed within 3 to 12 days after systemic acyclovir therapy was initiated. In contrast to tongue lesions of herpetic geometric glossitis, similar-appearing lingual lesions of other conditions are usually asymptomatic. The similar morphology of corneal dendrites in herpetic epithelial keratitis and linear fissures in herpetic geometric glossitis suggest the possibility that these HSV mucosal lesions may have a common pathogenesis.

The anatomical basis for facial itch after epidural morphone is outlined. CNS nuclear events which reactivate latent herpes simplex and immune inhibition resulting in maternal mouth vesicles or neonatal infections are described. Morphine is hypothesized to affect these processes and facial itch is only a marker, not a trigger of this trigeminal opioid activity.

Twenty-seven patients with chronic herpetic stomatitis were treated using routine protocols including traditional autohemotherapy (controls, n = 12) and magnetic autohemotherapy (main group, n = 15) developed by the authors. Local therapy was identical in both groups and corresponded to the disease stage. Treatment with magnetic autohemotherapy proved to be highly effective: it prolonged the remission and reduced the incidence and duration of exacerbations. Cytological findings indicate that such an exposure activated the processes of regeneration of the buccal and labial mucosal epithelium. A trend to normalization of some parameters of cellular and humoral immunity was observed.

Serum levels of soluble intercellular adhesion molecule-1, soluble interleukin-2 receptor, and cytokines such as interleukin-3, interleukin-4, interleukin-6, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor were examined in patients with oral disorders with 20 healthy persons used as control subjects. Patients studied included 30 with squamous cell carcinoma, 26 with oral lichen planus, 20 with recurrent aphthous ulcer, 19 with acute odontogenic bacterial infection, 16 with pseudomembranous candidiasis, and 16 with herpetic gingivostomatitis. Compared with levels in control subjects, detectable serum levels of interleukin-3 (> or = 10 pg/ml) existed more frequently in pseudomembranous candidiasis (13/16), acute odontogenic bacterial infection (14/19), and squamous cell carcinoma (24/30) and of granulocyte-macrophage colony-stimulating factor (> or = 4 pg/ml) more frequently in recurrent aphthous ulcer (15/20) and squamous cell carcinoma (21/30). These cytokine levels were increased with T stage of squamous cell carcinoma. About 20 pg/ml of interleukin-4 was detected in serum from one third to one fourth of patients with oral lichen planus, recurrent aphthous ulcer, and squamous cell carcinoma. Tumor necrosis factor-alpha was hardly detected in most patients except those with oral lichen planus and squamous cell carcinoma in which about one third of the patients had more than 40 pg/ml of tumor necrosis factor-alpha in serum. More than 10 pg/ml of interleukin-6 was frequently detected in all disorders, especially recurrent aphthous ulcer (18/20), pseudomembranous candidiasis (12/16), and acute odontogenic bacterial infection (17/19).(ABSTRACT TRUNCATED AT 250 WORDS)

Herpes simplex virus (HSV)-specific immunoglobulin A, immunoglobulin G, and secretory-component-containing immunoglobulins were identified in cervical and salivary secretions from six subjects with oral HSV type 1 (HSV-1) infections. Anamnestic cervical and salivary antibody responses were detected in two HSV-1-seropositive women with newly acquired genital HSV-2 infections. These data implicate the common mucosal immune system in antibody responses to HSV.

Background: Oral lesions are common findings in HIV-related disease, but little is known about their significance in predicting immune suppression among a representative group of HIV-infected persons., Methods: Oral examinations were performed on 454 patients who came to an outpatient dental clinic for dental care. CD4+ cell counts were obtained within 2 months of the examination., Results: In persons with a specific lesion and a CD4+ cell count below 200 cells/mm3 the corresponding mean CD4+ cell counts and predictive values were 149.5 cells/mm3 and 69.9% for candidiasis, 143.3 cells/mm3 and 70.1% for oral hairy leukoplakia, 126.0 cells/mm3 and 69.4% for xerostomia, 51.8 cells/mm3 and 95.1% for necrotizing ulcerative periodontitis, 98.7 cells/mm3 and 87.0% for long-standing herpes simplex virus infections, 66.6 cells/mm3 and 93.6% for Kaposi's sarcoma, and 33.7 cells/mm3 and 100% for major aphthous ulcers. The mean CD4+ cell count declined with increased numbers of different concurrent lesions., Conclusion: The presence of specific oral manifestations and the number of different concurrent intraoral lesions among HIV-infected persons are associated with severe immune suppression and AIDS. Oral examinations are an essential component for early recognition of disease progression and comprehensive evaluation of HIV-infected patients.

Thymalin, a polypeptide drug obtained by extraction from cattle thymus, was used in therapy of 44 children with acute and relapsing herpetic stomatitis. Laboratory studies included direct analysis of fluorescent antibodies in buccal mucosa epithelium to verify the clinical diagnosis and enzyme immunoassay of specific antigen in salivary samples before and after therapy. Enzyme immunoassay was also used to assay antibodies to herpes simplex virus in the blood serum over the course of treatment. Immunity status over the course of treatment was assessed by indirect immunofluorescence with monoclonal antibodies used to study lymphocyte subpopulations CD4+ inductor-helpers, CD8+ natural killers, and CD4+/CD8+ ratio. Thumalin therapy was not conducive to a rapid abatement of acute symptoms in stomatitis; but such therapy is justified, for in helps attain a stable antirelapse effect in children at a high risk of developing stomatitis recurrences.

Herpes simplex virus (HSV) infections causing severe disease are reported frequently in patients suffering from human immunodeficiency virus (HIV) infection. This disease pattern may also be seen in an immunocompromised disease state with other causes, however, as in the case presented in this paper. An 84-year-old woman had hepatic cirrhosis resulting from chronic hepatitis C virus infection. The woman developed ulcerative lesions in and around her mouth and in the genito-anal region, and these persisted for some months. Diagnosis of HSV infection was not obtained until after extensive laboratory investigations. Aciclovir infusion therapy started immediately afterwards led to dramatic improvement of the skin and mucous membrane changes. Complete clearing of lesions was not obtained, however, because the patient died as a result of the immunosuppression.

Peripheral blood mononuclear cell parameters were examined in 17 adult patients with primary herpes simplex virus-1 (HSV-1) infection. Two-color flow cytometry revealed an increase in HLA-DR+ T cell and Leu8+ T cell subsets, and a decrease in CD57+CD16+ subset in the patients. In the symptomatic phase of HSV-1 infection, serum interferon gamma (IFN-gamma) level increased in many patients, and the mean serum level in the patients (0.26 +/- 0.12 U/ml) was significantly higher than the mean control level (0.14 +/- 0.06 U/ml). Soluble intercellular adhesion molecule-1 (sICAM-1) in patients' serum also was increased to a mean level of 398 +/- 130 ng/ml at the first visit. Both the IFN-gamma and sICAM-1 levels fell to near the control levels after the disappearance of oral inflammation. Natural killer (NK) activity was at first increased (mean 46.1 +/- 17.9%), and later decreased to the control level (mean 38.4 +/- 10.6%). In contrast, lymphokine activated killer (LAK) activity at the first visit (mean 53.2 +/- 15.7%) was significantly lower than the control level (mean 69.5 +/- 10.3%). PHA- or ConA-stimulated lymphocytes from the patients incorporated less thymidine than control lymphocytes. These reduced lymphocyte reactivities recovered to the control levels after the disappearance of the acute infection. These results indicate some of the characteristics of lymphocyte pathophysiology in primary HSV-1 infection.

Immunoglobulin with a high titer of antiherpetic antibodies (1:640 to 1:1280) was used for the treatment of children with acute and recurrent herpetic stomatitis. The agent was injected intramuscularly, 2 to 4 injections, depending on the disease severity. The results evidence a favorable effect of the drug on the clinical and immunologic parameters of patients suffering from the acute condition and permit a conclusion that this immunoglobulin prevented the development of recurrent forms in the children with the acute disease.

Clinical efficacies of ointments containing alpha- and gamma-interferon and characterized by antiviral activity (2.0 x 10(4) IU) were studied. Antiviral effect of these ointments used in the treatment of 168 children suffering from herpetic stomatitis was assessed from the clinical and immunologic viewpoints. Measurements of secretory IgG carried out over the course of therapy evidenced positive changes in local immunity.

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.

Recovery from epidermal herpes simplex virus (HSV) infection depends primarily on development of an effective cell-mediated immune response, possibly generated following antigen (Ag) presentation by epidermal cells (EC). The ability of EC to present HSV Ag was investigated in 12 subjects with occasional recrudescent facial HSV infections. All had circulating HSV specific antibodies and cell-mediated immunity to the virus. Peripheral blood mononuclear cell suspensions, depleted of antigen presenting cells (APC) by glass adherence and then enriched for T cells by adsorption on nylon wool columns, did not proliferate in response to HSV Ag. Both EC suspensions, prepared from suction blister roofs, and glass-adherent peripheral blood mononuclear cells (AC) preincubated with ultraviolet-inactivated HSV, reconstituted the T-cell proliferative response to HSV. EC were more efficient than AC at presenting HSV Ag to T cells. Depletion of CD1+ cells from EC suspensions by cell sorting reduced their ability to present HSV Ag and augmentation of CD1+ cell numbers supplemented it. Preincubation of EC or AC with monoclonal antibodies to major histocompatibility complex class II antigens DP, DQ or DR, blocked the lymphoproliferative response to HSV Ag. Evidence was obtained that cells co-ordinately expressing products of the DP, DQ and DR loci are involved in presentation of HSV Ag by both EC and AC.

Herpes simplex virus (HSV) antigens were sought in 15 biopsy specimens from both lesional mucosa and clinically healthy looking oral mucosa between attacks in patients with erythema multiforme (EM). Four of the eight biopsy specimens obtained from lesional EM mucosa stained positively with HSV-1-and/or HSV-2-specific antisera applied in direct immunoperoxidase staining. Of the 16 tissue specimens used as controls, two displayed positive staining with HSV-1 and/or HSV-2. Five of the seven biopsy specimens from macroscopically healthy oral mucosa obtained between attacks from patients with recurrent EM stained positively with HSV-1 and/or HSV-2. Of the six tissue specimens used as controls, three stained positively. Most of the local inflammatory mononuclear cells belonged to the T cell series, mainly to the CD-4 subset. A small proportion of the local T cells were blast transformed as assessed by CD-25 expression and [3H]thymidine incorporation. This, together with the findings showing a lower degree of activation in the biopsy from macroscopically healthy looking mucosa between attacks suggest an active role of the cell-mediated immune response in the genesis of oral lesions in EM. The persistence of HSV antigens, and the well-established role of HSV as a precipitating factor in recurrent EM, suggest that HSV may be involved, but since HSV seems to be present in other mucosal lesions as well as in clinically healthy mucosa, quite frequently an additional, hitherto unknown factor must be present in order that EM may occur.

A comparative study of various factors of humoral immunity in human chronic herpes stomatitis (CHS) in periods of relapses and remission of the infection showed the exacerbations of the disease to occur in the presence of complement-fixing (CF) and virus-neutralizing (VN) antibodies in the blood serum the titres of which moderately rose with the progress of the infection. A relapse of the disease occurs during marked decline in the content of secretory IgA and true secretory Sc-IgA, serum and secretory IgG, low levels of serum interferon, and a small rise in titres of 19S specific CF antibodies. Remission comes as these values become normal. Although specific immunological changes do occur in CHS, they are not very marked, whereas the factors of nonspecific host resistance change considerably in close correlation with the periods of relapse and remission of the infection.

Transfer factor potentiates cellular immunity and induces interferon. It was because of these properties that transfer factor was tried in 17 patients with recurrent herpes simplex types 1 and 2. Transfer factor was administered in doses ranging from 5 to 10 U/m2 i. m. The interval between injections varied from 1 week to 3 months. 16 patients could be evaluated clinically in whom the recurrence rate decreased from 10.7 +/- 6.1 to 2.1 +/- 2.5 (mean SD). The reduction was statistically significant. 8 patients were completely free of disease while the other 8 had reduced number of episodes during the period of observation, 7 patients had abnormal T cell function as reflected by the low number of T cells or low lymphocyte transformation. Statistically significant improvement in the T cell function was observed. Delayed hypersensitivity skin test reactions also improved significantly.

Subjects with oral herpes lesions at the time of serum sampling had higher-efficiency antibody (higher proportion of neutralizing antibody as determined by plaque reduction, compared with total antibody as detected by radioimmunoassay) to herpes simplex virus type 1 (HSV-1) than did subjects with no lesions at the time of serum sampling. These higher-efficiency sera also had higher antibody titers to structural components of herpes simplex virus type 1 than did the low-efficiency sera. Absorption of high- and low-efficiency sera with purified herpes simplex virus type 1 particles removed all neutralizing antibody but not all antibody detected by radioimmunoassay. High-efficiency serum was depleted of more antibody to particulate antigen that was the low-efficiency serum, indicating that the high-efficiency serum contained a higher proportion of antibody to the virus particle.

Specimens of mixed untreated saliva from 3 groups of children were tested for antibodies to herpes virus by the fluorescent antibody technique (33 children with acute herpes stomatitis, 64 with recurrent herpes stomatitis, and 30 in the control group). Herpes virus antibodies were found in the saliva in 27.2 +/- 7.7% of the cases at the peak of acute stomatitis and in 77.7 +/- 10.0% of cases in the period of epithelization, in 84.6 +/- 10.0% of the examined subjects the antibodies were detected 2-4 months after the disease. Examinations of 64 saliva specimens obtained from the children during one of the relapses of chronic stomatitis demonstrated antibodies more frequently (59.3 +/- 8.0%) than in children at the peak of acute stomatitis disease. A trend for increased antibody content in the saliva of children by the period of epithelization of lesions in the buccal cavity both in acute stomatitis and during relapses of chronic disease was observed. No herpes antibodies were found in saliva specimens from 30 children of the control group.