[Mixed infections and inflammatory ophthalmic diseases: clinical and laboratory observations]. / Mikst-infektsii i vospalitel'naia oftal'mopatologiia: kliniko-laboratornye nabliudeniia.

In recent years, all medical specialists, including ophthalmologists, have been facing the problem of mixed infections. Recurrent inflammation in the anterior and posterior eye segments is often a result of infection by more than one variety of pathogens. MATERIAL AND METHODS: Over the period 2013-2016, 34 patients (14 men and 20 women) with different inflammatory processes in the eye who appeared DNA-positive for mycoplasmas (Mycoplasma hominis, Ureaplasma urealyticum) and/or chlamydiae (Chlamydia trachomatis) (PCR testing of tear fluid and/or urine) were followed up. All patients were examined for intensive production of herpesvirus, adenovirus, and enterovirus DNA in biological fluids. After being consulted by related specialists, all the patients started local and systemic (antibacterial and antiviral) therapy. In the end of the latter, laboratory tests were repeated. RESULTS: Among all the clinical forms, anterior segment inflammation (i.e. of conjunctiva, cornea, and the anterior vascular tract) prevailed - 76%. In most patients, mycoplasmas and/or chlamydiae formed associations with herpesviruses (n=19; 56%). Bacterial DNA alone (mycoplasma and/or chlamydia) was detected in 12 cases (35%). In 4 cases, mycoplasma and/or chlamydia DNA was detected in tear fluid, in 19 patients - in urine, and in 10 patients - in both secreta. Local and systemic causal treatment enabled resolution of the complaints and symptoms and yielded negative results of follow-up laboratory tests. CONCLUSION: More than a half of the patients demonstrated concomitant viral-bacterial infection (22 cases). The presence of bacterial/viral DNA in biological secreta, as revealed by PCR, reflects the systemic nature of the infection process and, thus, necessitates engagement of related specialists (dermatologists, urologists, gynecologists).

[Clinical presentations of Herpes Zoster Ophthalmicus (diagnosis and therapy)]. / Klinicheskie proyavleniya Herpes Zoster Ophthalmicus (diagnostika i terapiya).

Approximately a quarter of the world's population at some point in life is at risk of developing shingles (Herpes Zoster). In 10-20% of cases the first branch of the trigeminal nerve gets involved (Herpes Zoster Ophthalmicus, HZO). Ophthalmic complications of HZO are able to cause a significant reduction in visual function. AIM: To study and summarize clinical features of HZO (including the rate of complications and their nature) and to determine the relationship between clinical and laboratory data from these patients. MATERIAL AND METHODS: The study included 133 patients with ophthalmic and neurological complications of HZO (group 1 (n=28) - retrospective analysis of outpatient records for the period 1995-2005; group 2 (n=95) - a prospective study for the period 2005-2015), who received a course of conservative treatment in either the Botkin City Hospital, branch № 1, or in the ophthalmic department of the Moscow herpes centre (Gerpeticheskiy Tsentr Ltd.). Laboratory tests were performed only in patients from group 2 and included: examination of biological fluids for six types of herpes viruses by polymerase chain reaction, examination of tears and urine for DNA of Chlamydia, Mycoplasma, and Ureaplasma, and serological blood testing for markers of herpes virus infection. Patients from group 1 were prescribed topical antiviral, antibacterial, and anti-inflammatory therapy, in rare cases - acyclovir per os. In group 2, the treatment included systemic antiviral medications and immune correction therapy. Anti-inflammatory therapy consisted of local and systemic non-steroidal agents (NSAIDs). RESULTS: The most common ophthalmic complications of HZO in both groups were stromal keratitis and keratoiridocyclitis, neurological - III and VI cranial nerves palsies. The duration of the disease in the first group ranged from 2 months to 3 years; in the second group, patients were divided into two subgroups: subgroup A with the disease duration of no more than one month (n=81) and subgroup B with the disease duration from 1.5 to 9 months (n=14). Varicella-zoster virus (VZV) DNA was present in tears and/or other biological fluids of patients from group 2 in more than 70% of cases (n=67). Particularly, in 27.4% of cases the virus was isolated in two fluids and in 7.4% of cases - in three fluids. The duration of virus production in tears and other biological fluids (saliva, blood, and urine) ranged from 10 days to 4 months. CONCLUSION: Topical non-steroidal anti-inflammatory drugs and systemic etiological treatment in case of intraocular inflammation in HZO patients may reduce the risk of severe consequences of VZV reactivation and help avoid recurrences later in life.

[Herpesviruses in ophthalmology].

The article presents the current data on seven main human herpesviruses, capable of causing ocular inflammation. Features of intraocular production and anterior segment involvement associated with each of the viruses and modern aspects of antiviral therapy for herpetic keratitis are discussed.

[Mechanisms for the therapeutic effect of herpes polyvaccines in chronic ophthalmic herpes and genital herpes]. / Mekhanizm lechebnogo éffekta gerpeticheskoi polivaktsiny pri khronicheskom oftal'mogerpese i gerpes genitalii.

Commercial inactivated culture polyvaccine against herpes simplex viruses (types 1 and 2) developed at D. I. Ivanovsky Institute of Virology promoted cessation of viremia. During the first vaccination viremia coincided with appearance of a focal allergic test on the retina, which is proposed for the diagnosis of herpetic involvement of the posterior compartment of the eye. T-cellular immunity normalized after a course of vaccination. Experimental immunization of rats and vaccination of patients with chronic ophthalmic and genital herpes demonstrated the therapeutic activity of inactivated herpetic polyvaccine in suppositoria.

[Development of a suppository form of the interferon inducer poludan and potentiation of its action by hyaluronic acid]. / Razrobotka svechevoi formy induktora interferona poludan i potentsirovanie ego deistviia gialuronovoi kislotoi.

A promising dosage form of interferon inductor poludan has been developed for the treatment of patients with genital herpes and ophthalmic herpes: suppositoria. High interferon-producing and antiviral activity of poludan in suppositoria is potentiated by hyaluronic acid and antioxidants.

[The detection of the herpes simplex virus 1 and 2 antigens in clinical specimens by using monoclonal antibodies]. / Detektsiia antigena virusa prostogo gerpesa 1 i 2 tipa pri pomoshchi monoklonal'nykh antitel v klinicheskikh obraztsakh.

The possibility of using monoclonal antibodies (McAb), obtained earlier, for the detection of herpes simplex virus (HSV) in clinical specimens taken from sick and infected persons was studied. The examination of 90 persons revealed that the mixture of McAb 4A and 2C could effectively detect the presence of HSV antigen in the indirect immunofluorescence assay (IFA) directly in cells contained in cytological preparations (smears, scrapes, impressions) obtained from different organs of patients. The search of optimum combinations of McAb for the detection of HSV antigens by the method of the solid-phase enzyme immunoassay (EIA) was carried out. This study, made on purified HSV used as an experimental model, revealed that the maximum sensitivity could be achieved with the use of two McAb (4f6 and 7c4) out of three McAb (4f6, 7c4 and 3d10). The approbation of both variants of EIA on clinical specimens taken from 99 patients (blood clots, seminal fluid, scrapes of cervical canal cells, peripheral blood lymphocytes) showed that the addition of McAb 3d10 made it possible to detect 8 more positive specimens. 754 specimens from 337 patients were studied with the use of McAb-based EIA, and in 204 of these patients (61%) HSV antigen was detected. The results obtained with the use of our McAb were compared with the data obtained with certified commercial test systems. The coincidence of the EIA data with those obtained with the use of the Murex Wellcozyme HSV test system (UK) was registered in 75% of cases (in 15 out of 20 cases). The coincidence of the IFA data with those obtained with the use of the Sanofi test system (France) was observed in all 19 cases (100%).

[Viral antigens in kidney biopsies of children with glomerulonephritis]. / Virusnye antigeny v bioptatakh pochechnoi tkani u detei s glomerulonefritom.

A relationship between clinical forms of glomerulonephritis and incidence of viral antigens in renal tissue was revealed: Hepatitis B virus antigens (HBsAg) are more frequently detected in the glomeruli in the patients with nephrotic glomerulonephritis, Herpes simplex antigens are detected in the glomeruli in mixed glomerulonephritis, and cytomegaloviral and Herpes simplex antigens are detected in the epithelium of the proximal canaliculi in patients with hematuric glomerulonephritis. No correlations between the persistence of Herpes simplex type 1, cytomegalovirus, and HBsAg in the renal tissue were detected. HBsAg is detected in the renal tissue mainly in the children without free HBsAg in the blood serum. This may be indicative of an important role of specific immune complexes in the pathogenesis of glomerulonephritis associated with hepatitis B viral infection. The results point to an appreciable contribution of a persistent viral infection to the progress of glomerulonephritis.

[The use of immunostimulants for enhancing the immunogenicity of a herpes vaccine]. / Ispol'zovanie immunostimuliatorov dlia povysheniia immunogennosti gerpeticheskoi vaktsiny.

National immunostimulators and interferon inducers (poludan, ridostin, larifan, myelopide, vegetan) in combination with a commercial herpes vaccine (HV) were used for experimental immunization of mice. A 3-fold or greater rise of specific antibody titres was observed after a single immunization of intact BALB/c mice. In experiments in chronically infected animals a single inoculation of HV resulted in a 3-fold rise of specific antibody titres at 6 days postimmunization but not in later periods (20, 30 days). Administration of larifan, an interferon inducer, but not the immunostimulator myelopide, induced a synergic effect in these experiments. Activation of alpha-interferon production was observed early after combined use of HV and immunostimulators. It is concluded that combined experimental use of HV and immunostimulators activated both specific antibody production and interferon production.

[Indices of the immune status of recurrent herpes patients being treated with a herpes polyvaccine]. / Nekotorye pokazateli immunnogo statusa bol'nykh retsidiviruiushchim gerpesom pri lechenii gerpeticheskoi polivaktsinoi.

Patients with dermal and genital forms of recurring herpes were found to have decreased levels of leukocytes and changed balance of the peripheral blood lymphocyte populations. Treatment with herpes inactivated cultural polyvaccine produced a therapeutic effect in a significant number of patients which was accompanied by a correcting effect of the vaccine on their immune status.

[Protective effect of a commercial vaccine, poludan and their combinations in an experimental herpes infection]. / Izuchenie zashchitnogo éffekta kommercheskoi vaktsiny, poludana i ikh kombinatsii pri éksperimental'noi gerpeticheskoi infektsii.

The antiviral action of herpes vaccine and poludan, an interferon-inducing agent, has been studied in experimental herpes infection, and the synergic effect of these preparations has been obtained. The best result (survival rate equal to 100% after the intraperitoneal inoculation of herpes simplex virus and 85.7% after its intracerebral inoculation) has been registered after the multiple vaccination of experimental animals and the injection of poludan 1 day before the challenge of the animals with the virus. The protective effect of the synergic action of the preparations under study coincides with the period of the maximum content of antibodies in the blood sera of the animals.

[Use of a conjugate of staphylococcal protein A with peroxidase in an immunoenzyme test system for determining antibodies to the herpes simplex virus]. / Ispol'zovanie kon"iugata belka A stafilokokka s peroksidazoi v immunofermentnoi test-sisteme dlia opredeleniia antitel k virusu prostogo gerpesa.

An enzyme-immunoassay system for the detection of specific antibody to herpes simplex virus was developed in which the antigen layered on the solid phase consisted of a crude extract of infected cells, and the detecting agent was a conjugate of protein A with horseradish peroxidase. This assay system was used for serological examination of 22 serum specimens from patients suffering from either meningoencephalitis or recurrent herpes of the skin and mucous membranes of the genitalia, as well as 6 specimens of the cerebrospinal fluid from patients with meningoencephalitis. The enzymeimmunoassay was found to be more sensitive than CFT. The advantages of using protein A/peroxidase conjugate for rapid estimation of the total amount of specific antibodies at any stage of herpes infection are discussed.

[Indices of lymphocyte functional activity in patients with recurrent cutaneous-genital herpes during treatment with a herpes vaccine]. / Pokazateli funktsional'noi aktivnosti limfotsitov bol'nykh retsidiviruiushchim kozhno-genital'nym gerpesom v protsesse lecheniia gerpeticheskoi vaktsinoi.

The functional activity of lymphocytes of patients with severe forms of recurrent cutaneous-genital herpes was studied in the course of treatment with inactivated polyvalent herpes vaccine on the basis of lymphocyte blast-transformation response to polyclonal mitogens and herpes simplex virus antigen. In the group of patients who showed a marked therapeutic effect as a result of the treatment the initially high values of the antigen-dependent lymphocyte blast-transformation test declined and became normal. Thus, in some cases the herpes vaccine exerts an immunomodulating effect normalizing the functions of different lymphocyte subpopulations.