[THE SPECTRUM OF MARKERS OF HERPES VIRAL INFECTIONS AND ALGORITHM OF THEIR LABORATORY DIAGNOSTIC IN CHILDREN WITH INFLAMMATORY PROCESSES OF UPPER RESPIRATORY WAYS AND ENT-ORGANS].

The purpose of study is to explore markers of persistent herpes viral infections in children with inflammatory processes of upper respiratory ways and ENT-organs. The sampling included 118 examined patients aged from 1 month to 17 years. The complex of standardized viral, immunological, molecular genetic methods was applied to detect (to exclude) herpes infection: cytomegalovirus infection, Epstein-Barre virus infection, simplex herpes virus infection. The diagnostic algorithm of examination of children with diseases of upper respiratory ways for herpes infection is presented. The dominating significance of simplex herpes virus and Epstein-Barre virus and also Staphylococcus aureus and Streptococcus haemolyticus-ß group A at the analysis of microbial landscape. In 83.9% of children with diseases of upper respiratory ways chronic infections of simplex herpes virus, Epstein-Barre virus, cytomegalovirus; in39.39% - mixed-infection; in 41.03% - combination of simplex herpes virus and Epstein-Barre virus infections; in 33.33% - combination of simplex herpes virus and cytomegalovirus infections; in 7.69% - combination of simplex herpes virus and Epstein-Barre virus and cytomegalovirus infections; in 17.94% - combination of Epstein-Barre virus and cytomegalovirus infections; The particularity of course of persistent herpes infection in children had to do with absence of specific symptoms of nosologic form in 59.2% of cases. The results of analysis of smears from nasopharynx of children infected with herpes viruses permitted to detect: Staphylococcus aureus in 36.36%; Streptococcus haemolyticus-ß in 32.32%; Streptococcus haemolyticus-α in 11.11%; Candida albicans of mucous membranes in 4.04% of children. The viral bacterial mixed-infection was detected in 44.44%. The laboratory signs of activity of immune inflammation were detected: increasing of content of TNАα and decreasing of level of IFNγ. The results of study substantiate necessity of individual approach to therapy of children with diseases of upper respiratory ways and ENT-organs and with implementation of complex of curative rehabilitating activities.The purpose of study is to explore markers of persistent herpes viral infections in children with inflammatory processes of upper respiratory ways and ENT-organs. The sampling included 118 examined patients aged from 1 month to 17 years. The complex of standardized viral, immunological, molecular genetic methods was applied to detect (to exclude) herpes infection: cytomegalovirus infection, Epstein-Barre virus infection, simplex herpes virus infection. The diagnostic algorithm of examination of children with diseases of upper respiratory ways for herpes infection is presented. The dominating significance of simplex herpes virus and Epstein-Barre virus and also Staphylococcus aureus and Streptococcus haemolyticus-ß group A at the analysis of microbial landscape. In 83.9% of children with diseases of upper respiratory ways chronic infections of simplex herpes virus, Epstein-Barre virus, cytomegalovirus; in39.39% - mixed-infection; in 41.03% - combination of simplex herpes virus and Epstein-Barre virus infections; in 33.33% - combination of simplex herpes virus and cytomegalovirus infections; in 7.69% - combination of simplex herpes virus and Epstein-Barre virus and cytomegalovirus infections; in 17.94% - combination of Epstein-Barre virus and cytomegalovirus infections; The particularity of course of persistent herpes infection in children had to do with absence of specific symptoms of nosologic form in 59.2% of cases. The results of analysis of smears from nasopharynx of children infected with herpes viruses permitted to detect: Staphylococcus aureus in 36.36%; Streptococcus haemolyticus-ß in 32.32%; Streptococcus haemolyticus-α in 11.11%; Candida albicans of mucous membranes in 4.04% of children. The viral bacterial mixed-infection was detected in 44.44%. The laboratory signs of activity of immune inflammation were detected: increasing of content of TNАα and decreasing of level of IFNγ. The results of study substantiate necessity of individual approach to therapy of children with diseases of upper respiratory ways and ENT-organs and with implementation of complex of curative rehabilitating activities.

Development of the suppository form of human immunoglobulin preparation with high titers of antibodies to herpes simplex virus types 1 and 2 for the treatment of chronic forms of herpetic disease.

In spite of the vast arsenal of therapeutic agents, therapy of herpes virus infection (HVI) is very difficult, particularly in pregnant women, newborns and children in the first years of life, as well as in patients with immune deficiency. In this regard, possibility of using immunoglobulins for the treatment of HVI is currently attracting the attention of doctors. The aim of this work was to develop a suppository form of the drug containing donor immunoglobulins with high levels of neutralizing antibodies to herpes simplex virus types 1 and 2 for the treatment of chronic forms of herpetic disease. The study included the following steps: 1) selection of gamma-globulins with high antibody titer for HSV-1 and HSV-2 ELISA test; 2) determination of the level of neutralizing antibodies in the selected series of gamma-globulins in tests in tissue cultures and animals; 3) lyophilization of immunoglobulins; 4) development of the suppository form of the preparation containing gamma-globulin donors with high levels of neutralizing antibodies to HSV-1 and HSV-2; 5) study of the safety of the activity of neutralizing antibodies to HSV-1 and HSV-2 in the suppository form of the drug with hyaluronic acid used as immunomodulator. As the result of this work, immunoglobulin preparation in the suppository form was developed. The developed preparation meets the requirements for safety and efficacy. It is not toxic or pyrogenic. The problems of clinical use of this drug as a method of HVI therapy are discussed.

[Evaluating the effectiveness of Solanum tuberosum shoots extract in experimental ocular herpes].

UNLABELLED: Ocular herpes (OH) is an infectious disease caused by the herpes simplex virus (HSV) characterized by a variable clinical presentation and often accompanied by complications that may lead to deterioration of visual functions, cataract development, or even blindness. Its treatment is arduous. The aim of this work was to evaluate the effectiveness, tolerability, and safety of Panavir eye drops in a rabbit model of OH. MATERIAL AND METHODS: Ocular infection was induced with HSV-1 (EU strain) in grey rabbits (all males, 2.5-3.0 kg) according to the standard technique. The treatment included Panavir-GLA (Panavir-gamma-linolenic acid) and Panavir medications. RESULTS: Panavir eye drops instilled 6 times daily for 8 days showed a pronounced therapeutic effect and prevented the development of severe corneal opacities. The most rapid and significant results were seen in rabbits with epithelial keratitis and those with short-term persistence of the virus. Generally, the effectiveness of Panavir eye drops was comparable with that of the reference drug (Oftalmoferon). Panavir instillations caused no irritation, toxic and/or allergic effects and were well tolerated by the rabbits. CONCLUSION: The data obtained suggest that Panavir eye drops may be included in OH treatment schemes.

[Results of using Solanum tuberosum sprouts extract for the treatment of ophthalmoherpes].

The efficacy, tolerability and safety of the extract of Solanum tuberosum sprouts (Panavir eyedrops) have been studied on the model of ophthalmic disorder in rabbits caused by herpes simplex virus (HSV) type 1. It is established that Panavir applied via 6 instillations per day for a period of days has potent therapeutic efficacy and prevents the development of gross corneal opacity in rabbits. Instillation of Panavir eyedrops does not cause irritation, toxic and allergic effects and are well tolerated by rabbits. The fastest and most pronounced effect of Panavir eyedrops was observed in the treatment of epithelial keratitis, as well as for not prolonged persistence of HSV. The effectiveness of Panavir eyedrops is comparable with that of the reference preparation OphthalmoferonR.

[Vaccines as an approach to the immunocorrection in herpetic infections].

Development of vaccines for immunologic correction in herpetic infections is an important problem that raises a growing concern worldwide. The data on the experimental studies of the efficacy of an inactivated whole-virion vaccine against herpes simplex viruses types 1 and 2 (HSV-1 and -2) using an animal model are discussed. The results of the multiyear application of the vaccine to ophthalmology and dermatology practice are also presented. The results unambiguously show a high efficacy of the vaccine in the prevention of recurrences of the infections based on activation of specific T-cell response. A live vaccine against the varicella zoster virus (VZV) was developed for control of the infection in children. For the cytomegalovirus (CMV) infection in adults, inactivated whole-virion vaccines are at the stage of development. An important part of the study addresses a combined application of the inactivated vaccines with immunomodulators.

[Immunomodulators and specific inactivated vaccines in urgent prophylaxis under experimental arboviral infection].

A reliable protective activity of the home-manufactured immunomodulators (ridostin, polyribonate glucosemuramyl-dipeptide, Mylife, and peptidoglycane-160) was detected in mice. The mice were infected with the equine eastern encephalomyelitis virus (EEEV, an alphavirus), or with the tick-borne encephalitis virus (TBEV), or the yellow fever (YF) virus (both flaviviruses). The effect of the urgent vaccination reliably increases when the vaccination is combined with the immunomodulators listed above. Under the alphavirus infection, the combined effects of the vaccine and ridostin were accompanied with increased specific humoral and cellular immune response (virus-specific antibodies and adoptive transfer of immune lymphocytes). The combined application of the specific vaccine and ridostin can be recommended for clinical trials of TBE in the foci of Infection.

[Efficiency of coadministration of immunomodulators and vaccine in an experiment on tick-borne encephalitis].

Experiments on a tick-borne encephalitis (TBE) model in CBA and BALB/c mice demonstrated that immunomodulators (ridostin, polyribonate, and peptidoglycan-160) and a specific vaccine against TBE were significantly effective in increasing the level of a protective effect and life expectancy in the experimental group as compared to the control group. The findings allow one to recommend the immunomodulator ridostin in combination with the inactivated vaccine for the emergency prophylaxis of TBE in its virus-infected subjects in the foci of infection.

[Combined effects of immunomodulators and specific inactivated vaccines against alpha- and flavivirus infections].

The combined effects of immunomodulators, such as ridostin, polyribonate, glucose muramyl dipeptide, and peptidoglycan-160, and specific vaccines on survival of mice with alpha- (eastern equine encephalitis) and flavivirus (tick-borne encephalitis (TBE) infections were found to be significant. In alphavirus infection, the combined effects of the specific vaccine and ridostin were accompanied by increases in specific humoral immunity (specific antibodies) and cellular immunity (adoptive transfer of immune lymphocytes). The concurrent use of the specific vaccine and the immunomodulator ridostin is recommended in clinical trials of TBE in the foci of infection.

[The antiviral activity of peptide immunomodulator "Gepon" in experimental infections caused by herpes simplex viruses types 1 and 2]. / Protivovirusnaia aktivnost' peptidnogo immunomoduliatora "Gepon" pri éksperimental'nykh infektsiiakh, vyzvannykh virusami prostogo gerpesa tipov 1 i 2.

Experimental data are reported on the antiviral activity of peptide immune-modulator "Gepon" in infections caused by herpes simplex virus (HSV), types 1 and 2, in vitro and in vivo. The drug proved to be non-toxic and did not possess any viricidal action. Its antiviral effect was registered in experiments with a multiple-infection cells' culture. The maximal effect was a 100-fold reduction of the viral titer when it was used in a concentration of 6.25 mcg/I as a preventive measure 24 hours before triggering the infection. The mentioned drug's effect was reliably higher than its use within a treatment scheme (1 hour after the infection onset). "Gepon" possessed the reliable protecting qualities (36% of protection with a mean increase of the infected mouse life by 1.9 days) in experiments with intraperitoneally infected mice (10 LD50/mouse of HSV, type 2), when the drug was administered in doses of 0.1 and 1 mcg/mouse.

[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.

[Effectiveness of the interferon inducers ridostin and camedon in prevention and treatment of experimental alpha- and flavivirus infections]. / Effektivnost' induktorov interferona ridostina i kamedona v profilaktike i lechenii éksperimental'nykh al'fa- i flavivirusnykh infektsii.

Antiviral activity of rybamidil (virasol) and interferon inducers ridostine and camedone developed in Russia and introduced in practical medicine has been studied in mice with experimentally induced arboviral infections, flavivirus (tick-borne encephalitis-TBE, and yellow fever-YF) and alphavirus ones (Western and Eastern equine encephalomyelitis-WEE and EEE). Rybamidil injected subcutaneously proved to be ineffective both for prevention and treatment of these infections. Early interferon inducers ridostine and camedone (larifan) with a peak of interferon production 4 hours after injection, when used in doses of 5 and 150 mg/ kg, respectively, had a clear-cut prophylactic antiviral effect if injected 24 or 4 hours before infection. Ridostine had a distinct antiviral effect, providing up to 40% protection from TBE, YF, and WEE.

[Design of a recombinant strain of the vaccinia virus containing an expressible gene for influenza A virus hemagglutinin]. / Konstruirovanie rekombinantnogo shtamma virusa ospovaktsiny, soderzhashchego ékspressiruemyi gen gemaggliutinina virusa grippa A.

A recombinant vaccinia virus (VV) strain containing a cloned gene of influenza A/Udorn/307/72 (H3N2) hemagglutinin (HA) gene has been produced. HA expression in CV-1 cells infected with the recombinant virus was determined by enzyme immunoassay. The influenza virus HA titer was 1:64-1:128. When rabbits were inoculated intravenously with the recombinant VaV, antibody titres were 1:5120. The recombinant VaV preparation may be used for generation of monospecific antibody to influenza virus.

Leukogenic properties of purified BLV and possible routes of its transmission with blood cells present in milk.

The results of five years studies on the possibility of experimental induction of bovine leukemia with purified BLV and different BLV-containing materials demonstrated that inoculation of calves with purified BLV (structures of 1.14-1.17 g/ml density in 20-60% sucrose gradient) can induce oncornavirus infection and bovine leukemia. From 41 experimentally infected calves 9 showed evidence of bovine leukemia. 5 of these 9 animals were from a group of 22 calves inoculated with purified BLV. Diagnosis of bovine leukemia in these 9 animals was established by hematologic (3 animals) and histologic method (6 animals). BLV was isolated from leukocytes of all of them. It was shown also that before the development of bovine leukemia the development of oncornavirus infection takes place. But only a small part of the animals with oncornavirus infection and presence of antibodies became ill with typical forms of hemoblastosis. The investigation of the role of milk and blood cells in milk in bovine leukemia transmission was also carried out. The presence was demonstrated of oncornavirus structures antigenically identical with BLV in milk and reproduction of these structures in blood cells being present in milk. These results, and also the induction of bovine leukemia, in cattle by rearing with raw milk from cattle with leukemia, allow us to suppose the possible routes of bovine leukemia transmission in nature.