[The role of herpesviruses in development of diseases of the urogenital tract and infertility in women].

This review presents the data on the spreading of all known human herpesviruses (НHVs) in female urogenital tract. According to the WHO almost 500 million people worldwide suffer from genital infection caused by НHVs. НHVs were detected in various inflammatory diseases of female upper and lower genital tract (vaginitis and cervicitis), in extrauterine pregnancy (in fallopian tubes), in infertility (cervical channel, endometrium and ovaries). Herpes simplex virus 1 (HSV­1) was identified for the first time in oocytes after failed in vitro fertilization (IVF). НHVs produce negative effect on the entire reproductive process from conception to childbirth. It was established that HSV, cytomegalovirus (CMV) and human herpesvirus 6 (HHV-6) markedly increase the risk of spontaneous abortion, preterm birth and stillbirth. Intrauterine НHV infection is a major cause of congenital malformations. Data on humoral and cell immunity in genital herpesvirus infections (НHVI) are also reviewed. Intravaginal HSV­2 infection changes cell composition of vaginal mucosa, i.e., together with cells mobilized from the blood, protective role is performed by resident memory T­cells (TRM), natural killer cells (NK­cells) and regulatory T­cells (Treg) whose function consists in maintaining the balance of the activities of lymphocytes. Constant НHVI spreading is largely explained by transition of primary infection to potentially reactivating latent form, since latent virus is unavailable to immune recognition and medicines. The genome editing system CRISPR/Cas9 can recognize and modify not only active but also latent viruses. The promising pilot results with the use of this system offer the possibility of developing innovative technologies for НHV elimination and НHVI eradication.

[HUMAN CYTOMEGALOVIRUS INFECTION AND SPONTANEOUS ABORTION IN PREGNANT WOMEN OF I AND II TRIMESTER].

The goal of this work was the evaluation of the frequency of human CMV infection among the women, whose pregnancy ended in miscarriage, detection of active forms of infection and treatment before pregnancy. Virological and sero-immunological techniques were used. A total of 116 women who had miscarriages before the 28 week of pregnancy were submitted to the CMV test. 109 women (94.0%) demonstrated positive results. 49 women (42.2%) had active form of the cytomegalovirus infection. 13 women (26.5%) had the recurrent form and 36 patients (73.5%) had the persistent form of CMV infection (stage of productive replication). All the women with active CMVI were treated before the next pregnancy. Immunomodulatory therapy for the treatment was used.

[Perinatal transmission of hepatitis C virus].

The perinatal transmission of hepatitis C virus (HCV) is the major route of infection in infants. The understanding of the risk factors of perinatal infection and the continuation of studies in this area allow one to propose immunological algorithms of prediction and to work outa follow-up strategy of infected children. The authors have made virological and Immunological studies of infants born to mothers with HCV infection.

[Clinical and laboratory evaluation of efficiency and tolerance of the "Nikavir" in acute hepatitis B]. / Kliniko-laboratornaia otsenka terapevticheskoi éffectivnosti i perenosimosti protivovirusnogo preparata "Nikavir" pri ostrom gepatite B.

New antiviral drug "Nikavir" was clinically tested in acute hepatitis B (AHB). A total of 60 AHB patients were followed up; 30 patients were in the main group and 30 persons were in the control group. The treatment with Nikavir of AHB patients was shown to ensure a favorable clinical disease course and it was accompanied by a quicker rate in reduction of the activity of serum enzymes AIAT, AcAT, alkaline phosphatase and of gamma-glutamil-transpeptidase; besides, it was accompanied by an early elimination of such serum markers of AHB like HBeAg, HbsAg and HBV DNA. Wikavir can be used in the treatment of patients with mild and moderate forms of AHB.

[Cytomegalovirus infection in pregnant women. Diagnosis and interpretation of examination results]. / Tsitomegalovirusnaia infektsiia u beremennykh. Diagnostika, traktovka rezul'tatov obsledovaniia.

Changes of the immune status are decisive in the pathogenesis of cytomegalovirus infection, which is a cause for the intrauterine infection. Therefore, complex immunological and virological examinations are advisable to make in pregnant women with compromised obstetrics history, pathological pregnancy course and with indirect signs of intrauterine fetus infection for the sake of choosing an optimal tactics of observation and treatment.

[Acute hepatitis C in the presence of chronic HBV infection]. / Ostryi gepatit C na fone khronitseskoi GBV-infektsii.

Acute HCV superinfection was studied in 23 patients with chronic hepatitis B virus infection. HBsAg, anti-HCV (C-100, core, NS3, NS5) were detected in patients' sera at first investigation. Predominant replication of HBV DNA was detected in the sera of 68% patients and HCV RNA in only 24% patients. The clinical course of acute hepatitis C in patients with chronic HBV infection in general corresponded to HCV monoinfection except for more pronounced biochemical shifts and shorter intoxication. The role of HBV and HCV in infectious process is discussed.

[Acute hepatitis B in anti-HCV-positive patients]. / Ostryi gepatit B u anti-HCV-pozitivnykh patsientov.

Seventy-six anti-HCV-positive patients with acute hepatitis B were observed. HBsAg, anti-HBc IgM, and anti-HCV were detected in the sera of all patients. During the acute phase of illness, HBV DNA was present in the sera of 90.8% patients, but not HCV RNA. The clinical picture of acute hepatitis B in anti-HCV-positive patients corresponded to HBV monoinfection with prolonged intoxication and a more benign biochemical course. Out of 10 patients observed during 2 years chronic mixed HBV/HCV hepatitis was diagnosed in 1 patient, in 8 patients only HCV infection was diagnosed, and in 6 cases HCV RNA was detected. Virus interference may be responsible for successive alternative dominant replication of HBV and HCV.

[Clinico-laboratory characteristics of viral hepatitis C with various HCV genotypes]. / Kliniko-laboratornaia kharakteristika virusnogo gepatita C pri razlichnykh genotipakh HCV.

Clinical and biochemical features of the acute phase of icteric hepatitis C in various HCV genotypes have been studied. The HCV genotypes determine the duration of incubation period and some clinical signs in the preicteric and icteric periods of acute hepatitis C. The biochemical picture and formation of chronic hepatitis virtually did not depend on the virus genotype.

[Effect of hepatitis G virus on the course of acute hepatitis B and C]. / Vliianie virusa gepatita G na techenie ostrogo gepatita B i C.

Examinations of 204 patients with acute viral hepatitis revealed HGV RNA in 65 (32%) cases. Clinical and laboratory data in HBV or HCV monoinfection virtually did not differ from these in co-infection with HBV + HGV and HCV + HGV.

[Cytomegalovirus infection in women of reproductive age with an at-risk obstetrical history]. / Tsitomegalovirusnaia infektsiia u zhenshchin reproduktivnogo vozrasta s otiagoshchennym akusherskim anamnezom.

Studies aimed at the detection of cytomegalovirus infection (CMVI) in women of reproductive age with obstetric complications in their medical history were carried out. 230 women aged 17-44 years were examined with the use of virological and serological tests. As the result of complex examination, CMVI markers were detected in 159 (69%) of women. Three forms of CMVI were detected in the examined women: latent (30%), reactivated (14%) and persistent (25%). This investigation revealed that the most complete detection of CMVI and the evaluation of its activity in women with obstetric complications in their medical history requires the combined use of virological and serological tests.

[The characteristics of the immune response in acute viral hepatitis B]. / Nekotorye osobennosti immunnogo otveta pri ostrom virusnom gepatite B.

The clinical and pathogenetic importance of a number of features characterizing cell-mediated immunity and nonspecific protective factors in acute virus hepatitis B. 124 patients with hepatitis B virus (HBV) infection were placed under observation. Of these, 115 patients had acute virus hepatitis B, 6 patients had acute virus hepatitis of mixed etiology (B + delta) and 3 patients had chronic virus hepatitis B. The study included, besides the detection of virus hepatitis markers and the biochemical analysis of blood, the determination of subpopulations of peripheral blood lymphocytes (CD3, CD4, CD8, CD57), the functional activity of natural killers, characteristics of the interferon status, serum neopterin and beta 2-microglobulin in blood serum. Considerable changes in cell-mediated immunity and the interferon system were found to occur and the optimum immune response in acute virus hepatitis B was characterized.

[The interferon reaction of the leukocytes and the natural killer activity in patients with acute viral hepatitis B undergoing interferon treatment]. / Interferonovaia reaktsiia leikotsitov i aktivnost' estestvennykh killerov u bol'nykh ostrym virusnym gepatitom B pri lechenii interferonom.

The interferon response of leukocytes (IRL) alpha and gamma as well as the functional activity of natural killers (NK) were studied in patients with the verified diagnosis of acute viral hepatitis B (AVH-B) treated with leukinferon (a preparation of natural interferon-alpha and cytokines) and reaferon (recombinant alpha 2 interferon). The effect of therapy with LF and RF in patients with AVH-B manifested by an increase in the functional activity of NK up to complete normalization after termination of the course of therapy. In the group of patients treated with LF as a result of therapy IRL-alpha increased by the end of the treatment and in the convalescence period. The observed activation of NK and the IF-alpha system under the effect of IF preparations in patients with AVH-B correlated with enhanced elimination of HBsAg.

[Clinical trials of recombinant gamma-interferon. Circulating interferon and the 2,5-oligoadenylate synthetase activity after intramuscular and inhalation administrations]. / Klinicheskie ispytaniia rekombinantnogo gamma-interferona. Tsirkuliruiushchii interferon i aktivnost' fermentov 2,5-oligoadenilatsintetazy pri vnutrimyshechnom i ingaliatsionnom vvedeniiakh.

It was shown that human recombinant gamma IFN given to volunteers intramuscularly (90 x 10(3) IU) and by inhalation (120 x 10(3) IU) induced 5-10-fold increase circulating IFN (up to 40-60 IU/ml); the activities of 2,5-oligoadenylate synthetase increased 1.5-2 fold and protein kinase of lymphocytes--3-5-fold. The repeated doses of gamma IFN at 12-15-hour intervals maintained a relatively stable IFN status, the inhalatory route of application being more effective. Convalescents after influenza different from healthy donors by a higher level of serum interferon and activity of 2.5-oligoadenylate synthetase but the activity of protein kinase was lowered in lymphocytes and plasma. The side effects induced by IFN administration were more marked only after intramuscular injections of 90 10 IU and were absent after inhalation of IFN (120,000 IU).

[The use of a virazole aerosol in young children with a respiratory syncytial virus infection]. / Primenenie aérozolia virazola u detei rannego vozrasta s respiratorno-sintsitial'noi virusnoi infektsiei.

The therapeutic effect of aerosol virasol was studied in young infants suffering from RS virus infection with concomitant broncho-obstructive syndrome. The study involved 60 children between 1 month and 4 years of age of whom 30 were treated with virasol and another 30 made a control group. Virasol was shown to reduce the severity of the clinical picture to a considerable degree and speed up the recovery in infants with RS virus disease. Virasol is recommended for inhalation treatment of infants with RS virus infection and concomitant broncho-obstructive syndrome. The daily dose of virasol is 10 mg per kilo of body weight. The duration of one course is 3 to 5 days.

[Clinico-biochemical evaluation of the effectiveness of plasmapheresis in the treatment of severe forms of viral hepatitis]. / Kliniko-biokhimicheskaia otsenka éffektivnosti plazmafereza v terapii tiazhelykh form virusnogo gepatita.

The study was performed of clinico-biochemical effect of plasmapheresis (PA) in severe viral hepatitis B, mixed hepatitis and hepatitis delta. Altogether 24 patients, all of them HBsAg carriers, were examined. With associated acute hepatic encephalopathy, clinical effect in hepatitis of PA was insignificant notwithstanding positive biochemical changes. In the absence of hepatic encephalopathy PA effect was pronounced both clinically and biochemically.

[Perinatal infection with hepatitis B virus and the problem of its specific prevention]. / Perinatal'noe infitsirovanie detei virusom gepatita B i voprosy spetsificheskoi profilaktiki.

The incidence of HBs- and HBe-antigens detection in future mothers was studied in Moscow, Uzbekistan, and Moldavia, and the incidence of hepatitis B (HB) virus transmission from mothers with persisting HBs-antigenemia to their offspring. In reverse passive hemagglutination test, HBsAg was detected in 1.1% of pregnancies in Moscow, in 6.3% of pregnancies in Uzbekistan, and in 5.4% of pregnancies in Moldavia. In these regions, immunofluorescence revealed HBe-antigen in HBsAg carriers in 5.2, 13.9, and 16.3%, respectively. Perinatal infection with HB virus was found in 26.1% of births to HBsAg carriers in Moscow and in 40% in Uzbekistan and Moldavia; in the latter two regions 16.0% and 13.3% of these births were found to become chronic carriers of HBsAg. In the presence of persistence of HBeAg in HSsAg carriers, from 89 to 100% births to these mothers showed the development of durable HBs-antigenemia, while in the presence of anti-HBe such outcome was noted in only 3%. Specific anti-HBs-immunoglobulin administered to infants born to HBsAg carriers exerted a protective effect by reducing the HB virus infection rate in the first 6 months of life, but failed to prevent completely the development of HB virus infection. The necessity of a wide-scale vaccination against HB in order to prevent HB virus infection of neonates is emphasized.

Class-specific antibody responses in school children vaccinated with an A/Brazil/11/78 (H1N1)-like recombinant influenza virus prepared from the A/Leningrad/134/57 paediatric cold-adapted donor strain.

Forty-three school children from 8 to 11 years old were vaccinated intranasally with two doses of a paediatric attenuated influenza vaccine developed by reassortment between cold-adapted A/Leningrad/134/57(H2N2) and an A/Brazil/11/78(H1N1)-like strain. Two vaccine doses were administered 1 month apart in a randomized, blind, placebo-controlled study. Although the first vaccine dose had a low infectivity titre, overall 65% of children who received two doses of vaccine showed serological evidence of infection by HI tests. Serum IgA antibody responses against the vaccine strain were detected in nearly 50% of the vaccines and serum IgG antibody responses were detected in approximately equal to 40% by an enzyme immunoassay.